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

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.

[Transcranial magnetic stimulation and motor cortex stimulation in neuropathic pain].

PubMed

Mylius, V; Ayache, S S; Teepker, M; Kappus, C; Kolodziej, M; Rosenow, F; Nimsky, C; Oertel, W H; Lefaucheur, J P

2012-12-01

Non-invasive and invasive cortical stimulation allows the modulation of therapy-refractory neuropathic pain. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the contralateral motor cortex yields therapeutic effects at short-term and predicts the benefits of epidural motor cortex stimulation (MCS). The present article summarizes the findings on application, mechanisms and therapeutic effects of cortical stimulation in neuropathic pain.

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.

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

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.

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.

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.

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.

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.

Stimulating Conversation: Enhancement of Elicited Propositional Speech in a Patient with Chronic Non-Fluent Aphasia following Transcranial Magnetic Stimulation

ERIC Educational Resources Information Center

Hamilton, Roy H.; Sanders, Linda; Benson, Jennifer; Faseyitan, Olufunsho; Norise, Catherine; Naeser, Margaret; Martin, Paula; Coslett, H. Branch

2010-01-01

Although evidence suggests that patients with left hemisphere strokes and non-fluent aphasia who receive 1Hz repetitive transcranial magnetic stimulation (rTMS) over the intact right inferior frontal gyrus experience persistent benefits in naming, it remains unclear whether the effects of rTMS in these patients generalize to other language…

The effects of combined repetitive transcranial magnetic stimulation and transcranial direct current stimulation on motor function in patients with stroke.

PubMed

Kwon, Tae Gun; Park, Eunhee; Kang, Chung; Chang, Won Hyuk; Kim, Yun-Hee

2016-11-22

Both transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), when provided to stroke patients in combination with motor training, enhance therapeutic efficacy and motor function. However, the majority of previous studies have only examined a single treatment modality. The authors investigated the modulating influence of combination dual-mode brain stimulation upon bihemispheric stimulation with motor training in stroke patients. Twenty stroke patients with hemiparesis underwent five randomly arranged sessions of diverse combinations of rTMS and tDCS. We applied cathodal or anodal tDCS over the contralesional primary motor cortex (cM1) and 10 Hz rTMS over the ipsilesional primary motor cortex (iM1) in a simultaneous or preconditioning method including sham stimulation. Immediately after dual-mode stimulation, sequential hand motor training was performed for 5 minutes. The total pulses of rTMS and the duration of tDCS and motor training were the same for all sessions. Cortical excitability and sequential motor performance were evaluated before and after each session. Motor function and corticomotor excitability following simultaneous stimulation via cathodal tDCS over the cM1 combined with 10 Hz rTMS over the iM1 were significantly increased after the intervention, with significantly greater motor improvement than seen with other treatment conditions (P < 0.05). For the combination of bihemispheric rTMS and tDCS, simultaneous stimulation of cathodal tDCS and 10 Hz rTMS results in better motor performance in stroke patients than other combination methods. This result seemed to be related to effective modulation of interhemispheric imbalance of cortical excitability by dual-mode stimulation.

Left prefrontal repetitive transcranial magnetic stimulation in schizophrenia.

PubMed

Holi, Matti M; Eronen, Markku; Toivonen, Kari; Toivonen, Päivi; Marttunen, Mauri; Naukkarinen, Hannu

2004-01-01

In a double-blind, controlled study, we examined the therapeutic effects of high-frequency left prefrontal repetitive transcranial magnetic stimulation (rTMS) on schizophrenia symptoms. A total of 22 chronic hospitalized schizophrenia patients were randomly assigned to 2 weeks (10 sessions) of real or sham rTMS. rTMS was given with the following parameters: 20 trains of 5-second 10-Hz stimulation at 100 percent motor threshold, 30 seconds apart. Effects on positive and negative symptoms, self-reported symptoms, rough neuropsychological functioning, and hormones were assessed. Although there was a significant improvement in both groups in most of the symptom measures, no real differences were found between the groups. A decrease of more than 20 percent in the total PANSS score was found in 7 control subjects but only 1 subject from the real rTMS group. There was no change in hormone levels or neuropsychological functioning, measured by the MMSE, in either group. Left prefrontal rTMS (with the used parameters) seems to produce a significant nonspecific effect of the treatment procedure but no therapeutic effect in the most chronic and severely ill schizophrenia patients.

Shaped magnetic field pulses by multi-coil repetitive transcranial magnetic stimulation (rTMS) differentially modulate anterior cingulate cortex responses and pain in volunteers and fibromyalgia patients

PubMed Central

2013-01-01

Background Repetitive transcranial magnetic stimulation (rTMS) has shown promise in the alleviation of acute and chronic pain by altering the activity of cortical areas involved in pain sensation. However, current single-coil rTMS technology only allows for effects in surface cortical structures. The ability to affect activity in certain deep brain structures may however, allow for a better efficacy, safety, and tolerability. This study used PET imaging to determine whether a novel multi-coil rTMS would allow for preferential targeting of the dorsal anterior cingulate cortex (dACC), an area always activated with pain, and to provide preliminary evidence as to whether this targeted approach would allow for efficacious, safe, and tolerable analgesia both in a volunteer/acute pain model as well as in fibromyalgia chronic pain patients. Methods Part 1: Different coil configurations were tested in a placebo-controlled crossover design in volunteers (N = 16). Tonic pain was induced using a capsaicin/thermal pain model and functional brain imaging was performed by means of H215O positron emission tomography – computed tomography (PET/CT) scans. Differences in NRS pain ratings between TMS and sham treatment (NRSTMS-NRSplacebo) which were recorded each minute during the 10 minute PET scans. Part 2: 16 fibromyalgia patients were subjected to 20 multi-coil rTMS treatments over 4 weeks and effects on standard pain scales (Brief Pain Inventory, item 5, i.e. average pain NRS over the last 24 hours) were recorded. Results A single 30 minute session using one of 3 tested rTMS coil configurations operated at 1 Hz consistently produced robust reduction (mean 70% on NRS scale) in evoked pain in volunteers. In fibromyalgia patients, the 20 rTMS sessions also produced a significant pain inhibition (43% reduction in NRS pain over last 24 hours), but only when operated at 10 Hz. This degree of pain control was maintained for at least 4 weeks after the final session

[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.

Effects of low frequency repetitive transcranial magnetic stimulation (rTMS) on gamma frequency oscillations and event-related potentials during processing of illusory figures in autism.

PubMed

Sokhadze, Estate M; El-Baz, Ayman; Baruth, Joshua; Mathai, Grace; Sears, Lonnie; Casanova, Manuel F

2009-04-01

Previous studies by our group suggest that the neuropathology of autism is characterized by a disturbance of cortical modularity. In this model a decrease in the peripheral neuropil space of affected minicolumns provides for an inhibitory deficit and a readjustment in their signal to noise bias during information processing. In this study we proposed using low frequency transcranial magnetic stimulation (rTMS) as a way increasing the surround inhibition of minicolumns in autism. Thirteen patients (ADOS and ADI-R diagnosed) and equal number of controls participated in the study. Repetitive TMS was delivered at 0.5 Hz, 2 times per week for 3 weeks. Outcome measures based on event-related potentials (ERP), induced gamma activity, and behavioral measures showed significant post-TMS improvement. The results suggest that rTMS offers a potential therapeutic intervention for autism.

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.

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.

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.

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 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

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.

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

Combined noninvasive language mapping by navigated transcranial magnetic stimulation and functional MRI and its comparison with direct cortical stimulation.

PubMed

Ille, Sebastian; Sollmann, Nico; Hauck, Theresa; Maurer, Stefanie; Tanigawa, Noriko; Obermueller, Thomas; Negwer, Chiara; Droese, Doris; Zimmer, Claus; Meyer, Bernhard; Ringel, Florian; Krieg, Sandro M

2015-07-01

Repetitive navigated transcranial magnetic stimulation (rTMS) is now increasingly used for preoperative language mapping in patients with lesions in language-related areas of the brain. Yet its correlation with intraoperative direct cortical stimulation (DCS) has to be improved. To increase rTMS's specificity and positive predictive value, the authors aim to provide thresholds for rTMS's positive language areas. Moreover, they propose a protocol for combining rTMS with functional MRI (fMRI) to combine the strength of both methods. The authors performed multimodal language mapping in 35 patients with left-sided perisylvian lesions by using rTMS, fMRI, and DCS. The rTMS mappings were conducted with a picture-to-trigger interval (PTI, time between stimulus presentation and stimulation onset) of either 0 or 300 msec. The error rates (ERs; that is, the number of errors per number of stimulations) were calculated for each region of the cortical parcellation system (CPS). Subsequently, the rTMS mappings were analyzed through different error rate thresholds (ERT; that is, the ER at which a CPS region was defined as language positive in terms of rTMS), and the 2-out-of-3 rule (a stimulation site was defined as language positive in terms of rTMS if at least 2 out of 3 stimulations caused an error). As a second step, the authors combined the results of fMRI and rTMS in a predefined protocol of combined noninvasive mapping. To validate this noninvasive protocol, they correlated its results to DCS during awake surgery. The analysis by different rTMS ERTs obtained the highest correlation regarding sensitivity and a low rate of false positives for the ERTs of 15%, 20%, 25%, and the 2-out-of-3 rule. However, when comparing the combined fMRI and rTMS results with DCS, the authors observed an overall specificity of 83%, a positive predictive value of 51%, a sensitivity of 98%, and a negative predictive value of 95%. In comparison with fMRI, rTMS is a more sensitive but less specific

Active and placebo transcranial magnetic stimulation effects on external and internal auditory hallucinations of schizophrenia.

PubMed

Paillère-Martinot, M-L; Galinowski, A; Plaze, M; Andoh, J; Bartrés-Faz, D; Bellivier, F; Lefaucheur, J-P; Rivière, D; Gallarda, T; Martinot, J-L; Artiges, E

2017-03-01

Repetitive transcranial magnetic stimulation (rTMS) over the left temporo-parietal region has been proposed as a treatment for resistant auditory verbal hallucinations (AVH), but which patients are more likely to benefit from rTMS is still unclear. This study sought to assess the effects of rTMS on AVH, with a focus on hallucination phenomenology. Twenty-seven patients with schizophrenia and medication-resistant AVH participated to a randomized, double-blind, placebo-controlled, add-on rTMS study. The stimulation targeted a language-perception area individually determined using functional magnetic resonance imaging and a language recognition task. AVH were assessed using the hallucination subscale of the Scale for the Assessment of Positive Symptoms (SAPS). The spatial location of AVH was assessed using the Psychotic Symptom Rating Scales. A significant improvement in SAPS hallucination subscale score was observed in both actively treated and placebo-treated groups with no difference between both modalities. Patients with external AVH were significantly more improved than patients with internal AVH, with both modalities. A marked placebo effect of rTMS was observed in patients with resistant AVH. Patients with prominent external AVH may be more likely to benefit from both active and placebo interventions. Cortical effects related to non-magnetic stimulation of the auditory cortex are suggested. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Resting State Dense Array Gamma Oscillatory Activity as a Response Marker for Cerebellar-Repetitive Transcranial Magnetic Stimulation (rTMS) in Schizophrenia.

PubMed

Tikka, Sai Krishna; Garg, Shobit; Sinha, Vinod Kumar; Nizamie, S Haque; Goyal, Nishant

2015-12-01

As cerebellum and its abnormalities have been implicated in the pathophysiology of schizophrenia, repetitive transcranial magnetic stimulation (rTMS) of this alternate site has been suggested as a novel target for treating patients with this disorder. As resting state gamma activity measures functional brain connectivity, it could be used as a specific treatment marker. To investigate the effect of cerebellar-rTMS on resting state gamma activity, while studying its efficacy in recent onset schizophrenia patients. This rater-blinded prospective study was completed by 11 schizophrenia patients. They received 10 sessions of high-frequency (theta patterned) rTMS to midline cerebellum over 2 weeks. Resting state EEG was recorded using high (192-channel) resolution EEG at baseline and post rTMS. Gamma spectral power was calculated using fast Fourier transformation, Hanning window averaged over 8 scalp segments corresponding 8 lobes. Clinical improvement rated on the Positive and Negative Syndrome Scale and depressive symptoms assessed using the Calgary Depression Scale for Schizophrenia were other outcome variables. Nonparametric statistics were used. Over the treatment course, significant reduction was seen on negative syndrome and depression scores. Gamma spectral power in left frontal and temporal segments reduced significantly. Spearman correlation analysis showed that percentage reduction in psychopathology scores had significant positive correlation with percentage reduction in gamma spectral power. Cerebellar-rTMS might be an effective adjunct to treat intricate and lingering negative and affective symptoms. Resting state gamma spectral power in frontal and temporal regions might be used as a biomarker for treatment response.

Repetitive transcranial magnetic stimulation modulates the impact of a negative mood induction

PubMed Central

Lacomblé, Lylis; Meyer, Thomas; Schutter, Dennis J.L.G.; Gielkens, Tom; Becker, Eni S.; Tendolkar, Indira; van Eijndhoven, Philip

2017-01-01

Abstract High frequency repetitive Transcranial Magnetic Stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been found to alleviate depressive symptoms. However, the mechanisms driving these effects are still poorly understood. In the current study, we tested the idea that this intervention protects against negative mood shifts following emotional provocation. We furthermore explored changes in EEG activity (frontal alpha asymmetry) and effects on attentional processing (emotional Stroop). To this end, 23 healthy individuals participated in two sessions separated by one week, whereby they once received 15 min of 10Hz rTMS stimulation (1500 pulses) at 110% of the individual motor threshold, and once sham stimulation. Then, negative mood was induced using sad movie clips. The results revealed a significantly stronger mood decline following rTMS compared to sham stimulation. No changes were observed in frontal alpha asymmetry and attentional processing. Our findings are at odds with the view that high frequency rTMS over the left DLPFC directly protects against the induction of negative mood, but rather suggest that it enhances the effects of emotional provocation. Possibly, in healthy young individuals, this stimulation protocol heightens susceptibility to mood induction procedures in general. PMID:28008080

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

[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.

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

Blood flow and oxygenation changes due to low-frequency repetitive transcranial magnetic stimulation of the cerebral cortex

NASA Astrophysics Data System (ADS)

Mesquita, Rickson C.; Faseyitan, Olufunsho K.; Turkeltaub, Peter E.; Buckley, Erin M.; Thomas, Amy; Kim, Meeri N.; Durduran, Turgut; Greenberg, Joel H.; Detre, John A.; Yodh, Arjun G.; Hamilton, Roy H.

2013-06-01

Transcranial magnetic stimulation (TMS) modulates processing in the human brain and is therefore of interest as a treatment modality for neurologic conditions. During TMS administration, an electric current passing through a coil on the scalp creates a rapidly varying magnetic field that induces currents in the cerebral cortex. The effects of low-frequency (1 Hz), repetitive TMS (rTMS) on motor cortex cerebral blood flow (CBF) and tissue oxygenation in seven healthy adults, during/after 20 min stimulation, is reported. Noninvasive optical methods are employed: diffuse correlation spectroscopy (DCS) for blood flow and diffuse optical spectroscopy (DOS) for hemoglobin concentrations. A significant increase in median CBF (33%) on the side ipsilateral to stimulation was observed during rTMS and persisted after discontinuation. The measured hemodynamic parameter variations enabled computation of relative changes in cerebral metabolic rate of oxygen consumption during rTMS, which increased significantly (28%) in the stimulated hemisphere. By contrast, hemodynamic changes from baseline were not observed contralateral to rTMS administration (all parameters, p>0.29). In total, these findings provide new information about hemodynamic/metabolic responses to low-frequency rTMS and, importantly, demonstrate the feasibility of DCS/DOS for noninvasive monitoring of TMS-induced physiologic effects.

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 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

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

PubMed

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

2017-01-13

The treatment of depression remains a challenge since at least 40% of patients do not respond to initial antidepressant therapy and 20% present chronic symptoms (more than 2 years despite standard treatment administered correctly). Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy but still not ideal. Intermittent Theta Burst Stimulation (iTBS), which has only been used recently in clinical practice, could have a faster and more intense effect compared to conventional protocols, including 10-Hz high-frequency rTMS (HF-rTMS). However, no controlled study has so far highlighted the superiority of iTBS in resistant unipolar depression. This paper focuses on the design of a randomised, controlled, double-blind, single-centre study with two parallel arms, carried out in France, in an attempt to assess the efficacy of an iTBS protocol versus a standard HF- rTMS protocol. Sixty patients aged between 18 and 75 years of age will be enrolled. They must be diagnosed with major depressive disorder persisting despite treatment with two antidepressants at an effective dose over a period of 6 weeks during the current episode. The study will consist of two phases: a treatment phase comprising 20 sessions of rTMS to the left dorsolateral prefrontal cortex, localised via a neuronavigation system and a 6-month longitudinal follow-up. The primary endpoint will be the number of responders per group, defined by a decrease of at least 50% in the initial score on the Montgomery and Asberg Rating Scale (MADRS) at the end of rTMS sessions. The secondary endpoints will be: response rate 1 month after rTMS sessions; number of remissions defined by a MADRS score of <8 at the endpoint and 1 month after; the number of responses and remissions maintained over the next 6 months; quality of life; and the presence of predictive markers of the therapeutic response: clinical (dimensional scales), neuropsychological (evaluation of cognitive functions), motor

The effects of high-frequency transcranial magnetic stimulation combined with transcutaneous electrical stimulation in a severe stroke patient.

PubMed

Koyama, Soichiro; Tanabe, Shigeo; Takeda, Kazuya; Warashina, Hiroaki; Sakurai, Hiroaki; Kanada, Yoshikiyo; Okumura, Ryuji; Shinoda, Jun; Nagata, Junji; Kanno, Tetsuo

2012-10-12

The case report describes the effects of 5 Hz repetitive transcranial magnetic stimulation (rTMS) combined with transcutaneous electrical stimulation (TES) in a patient with severe stroke. The patient was a 69-year-old male who was affected by a left middle cerebral artery infarction. The patient had no movement in his right hand. To assess the effects, cerebral blood flow and motor function were measured before and after treatment. This treatment delivered rTMS over the affected M1 with TES at the paretic wrist extensor muscles for 10 days. The regional cerebral blood flow (rCBF) in the entire brain was measured by positronemission tomography. To evaluate the motor function, the Fugl-Meyer assessment (FMA) was used. After treatment, the rCBF was increased (except for the stimulated region), and the FMA score was slightly improved. These results suggest the potential therapeutic use of rTMS combined with TES for recovery in severe stroke.

Repetitive Transcranial Magnetic Stimulation Improves Handwriting in Parkinson's Disease

PubMed Central

Randhawa, Bubblepreet K.; Farley, Becky G.; Boyd, Lara A.

2013-01-01

Background. Parkinson disease (PD) is characterized by hypometric movements resulting from loss of dopaminergic neurons in the substantia nigra. PD leads to decreased activation of the supplementary motor area (SMA); the net result of these changes is a poverty of movement. The present study determined the impact of 5 Hz repetitive transcranial magnetic stimulation (rTMS) over the SMA on a fine motor movement, handwriting (writing cursive “l”s), and on cortical excitability, in individuals with PD. Methods. In a cross-over design, ten individuals with PD were randomized to receive either 5 Hz or control stimulation over the SMA. Immediately following brain stimulation right handed writing was assessed. Results. 5 Hz stimulation increased vertical size of handwriting and diminished axial pressure. In addition, 5 Hz rTMS significantly decreased the threshold for excitability in the primary motor cortex. Conclusions. These data suggest that in the short term 5 Hz rTMS benefits functional fine motor task performance, perhaps by altering cortical excitability across a network of brain regions. Further, these data may provide the foundation for a larger investigation of the effects of noninvasive brain stimulation over the SMA in individuals with PD. PMID:23841021

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

Repetitive transcranial magnetic stimulation modulates the impact of a negative mood induction.

PubMed

Möbius, Martin; Lacomblé, Lylis; Meyer, Thomas; Schutter, Dennis J L G; Gielkens, Tom; Becker, Eni S; Tendolkar, Indira; van Eijndhoven, Philip

2017-04-01

High frequency repetitive Transcranial Magnetic Stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been found to alleviate depressive symptoms. However, the mechanisms driving these effects are still poorly understood. In the current study, we tested the idea that this intervention protects against negative mood shifts following emotional provocation. We furthermore explored changes in EEG activity (frontal alpha asymmetry) and effects on attentional processing (emotional Stroop). To this end, 23 healthy individuals participated in two sessions separated by one week, whereby they once received 15 min of 10Hz rTMS stimulation (1500 pulses) at 110% of the individual motor threshold, and once sham stimulation. Then, negative mood was induced using sad movie clips. The results revealed a significantly stronger mood decline following rTMS compared to sham stimulation. No changes were observed in frontal alpha asymmetry and attentional processing. Our findings are at odds with the view that high frequency rTMS over the left DLPFC directly protects against the induction of negative mood, but rather suggest that it enhances the effects of emotional provocation. Possibly, in healthy young individuals, this stimulation protocol heightens susceptibility to mood induction procedures in general. © The Author (2016). Published by Oxford University Press.

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

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.

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.

A case of cerebral reversible vasoconstriction syndrome triggered by repetition transcranial magnetic stimulation.

PubMed

Sato, Mamiko; Yamate, Koji; Hayashi, Hiromi; Miura, Toyoaki; Kobayashi, Yasutaka

2017-08-31

A 75-year-old man was admitted for combined low-frequency repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy. Five days after the initiation of rTMS, he developed hypotension and temporary exacerbation of the right hemiplegia with thunderclap headache. MRA showed segmental stenosis of the left middle cerebral artery, which findings were improved at 9 days after the onset of the headache. He was diagnosed as having the reversible cerebral vasoconstriction syndrome (RCVS). The rTMS was recognized as safe rehabilitation treatment. However, it is necessary to recognize that RCVS can become one of the precipitants. This is the first report of RCVS triggered by rTMS.

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 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

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.

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.

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

Impairment of preoperative language mapping by lesion location: a functional magnetic resonance imaging, navigated transcranial magnetic stimulation, and direct cortical stimulation study.

PubMed

Ille, Sebastian; Sollmann, Nico; Hauck, Theresa; Maurer, Stefanie; Tanigawa, Noriko; Obermueller, Thomas; Negwer, Chiara; Droese, Doris; Boeckh-Behrens, Tobias; Meyer, Bernhard; Ringel, Florian; Krieg, Sandro M

2015-08-01

Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is increasingly used and has already replaced functional MRI (fMRI) in some institutions for preoperative mapping of neurosurgical patients. Yet some factors affect the concordance of both methods with direct cortical stimulation (DCS), most likely by lesions affecting cortical oxygenation levels. Therefore, the impairment of the accuracy of rTMS and fMRI was analyzed and compared with DCS during awake surgery in patients with intraparenchymal lesions. Language mapping was performed by DCS, rTMS, and fMRI using an object-naming task in 27 patients with left-sided perisylvian lesions, and the induced language errors of each method were assigned to the cortical parcellation system. Subsequently, the receiver operating characteristics were calculated for rTMS and fMRI and compared with DCS as ground truth for regions with (w/) and without (w/o) the lesion in the mapped regions. The w/ subgroup revealed a sensitivity of 100% (w/o 100%), a specificity of 8% (w/o 5%), a positive predictive value of 34% (w/o: 53%), and a negative predictive value (NPV) of 100% (w/o: 100%) for the comparison of rTMS versus DCS. Findings for the comparison of fMRI versus DCS within the w/ subgroup revealed a sensitivity of 32% (w/o: 62%), a specificity of 88% (w/o: 60%), a positive predictive value of 56% (w/o: 62%), and a NPV of 73% (w/o: 60%). Although strengths and weaknesses exist for both rTMS and fMRI, the results show that rTMS is less affected by a brain lesion than fMRI, especially when performing mapping of language-negative cortical regions based on sensitivity and NPV.

Mapping of cortical language function by functional magnetic resonance imaging and repetitive navigated transcranial magnetic stimulation in 40 healthy subjects.

PubMed

Sollmann, Nico; Ille, Sebastian; Boeckh-Behrens, Tobias; Ringel, Florian; Meyer, Bernhard; Krieg, Sandro M

2016-07-01

Functional magnetic resonance imaging (fMRI) is considered to be the standard method regarding non-invasive language mapping. However, repetitive navigated transcranial magnetic stimulation (rTMS) gains increasing importance with respect to that purpose. However, comparisons between both methods are sparse. We performed fMRI and rTMS language mapping of the left hemisphere in 40 healthy, right-handed subjects in combination with the tasks that are most commonly used in the neurosurgical context (fMRI: word-generation = WGEN task; rTMS: object-naming = ON task). Different rTMS error rate thresholds (ERTs) were calculated, and Cohen's kappa coefficient and the cortical parcellation system (CPS) were used for systematic comparison of the two techniques. Overall, mean kappa coefficients were low, revealing no distinct agreement. We found the highest agreement for both techniques when using the 2-out-of-3 rule (CPS region defined as language positive in terms of rTMS if at least 2 out of 3 stimulations led to a naming error). However, kappa for this threshold was only 0.24 (kappa of <0, 0.01-0.20, 0.21-0.40, 0.41-0.60, 0.61-0.80 and 0.81-0.99 indicate less than chance, slight, fair, moderate, substantial and almost perfect agreement, respectively). Because of the inherent differences in the underlying physiology of fMRI and rTMS, the different tasks used and the impossibility of verifying the results via direct cortical stimulation (DCS) in the population of healthy volunteers, one must exercise caution in drawing conclusions about the relative usefulness of each technique for language mapping. Nevertheless, this study yields valuable insights into these two mapping techniques for the most common language tasks currently used in neurosurgical practice.

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

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.

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.

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.

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.

Emotional memory retrieval. rTMS stimulation on left DLPFC increases the positive memories.

PubMed

Balconi, Michela; Ferrari, Chiara

2012-09-01

A suggestive hypothesis proposed that the lateral prefrontal cortex (LPFC) may be identified as the site of emotion-memory integration, since it was shown to be sensitive to the encoding and retrieval of emotional content. In the present research we explored the role of the dorsolateral prefrontal cortex (DLPFC) in memory retrieval of positive vs. negative emotional stimuli. This effect was analyzed by using an rTMS paradigm that induced a cortical activation of the left DLPFC. Subjects were required to perform a task consisting of two experimental phases: an encoding phase, where some lists composed by positive and negative emotional words were presented to the subjects; a retrieval phase, where the old stimuli and the new stimuli were presented for a recognition performance. The rTMS stimulation was provided during the retrieval phase over the left DLPFC. We found that the rTMS stimulation over this area affects the memory retrieval of positive emotional material, with higher memory efficiency (reduced RTs). This result suggested that left DLPFC activation promotes the memory retrieval of emotional information. Secondly, the valence model of emotional cue processing may explain decreasing of RTs, by pointing out the distinct role the left hemisphere has in positive emotional cue processing.

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.

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

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.

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.

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.

Repetitive Transcranial Magnetic Stimulation for Wernicke-Korsakoff Syndrome: A Case Report.

PubMed

Chung, So Won; Park, Shin Who; Seo, Young Jae; Kim, Jae-Hyung; Lee, Chan Ho; Lim, Jong Youb

2017-02-01

A 57-year-old man who was diagnosed with Wernicke-Korsakoff syndrome showed severe impairment of cognitive function and a craving for alcohol, even after sufficient supplementation with thiamine. After completing 10 sessions of 10 Hz repetitive transcranial magnetic stimulation (rTMS) at 100% of the resting motor threshold over the left dorsolateral prefrontal cortex, dramatic improvement in cognitive function and a reduction in craving for alcohol were noted. This is the first case report of the efficacy of a high-frequency rTMS in the treatment of Wernicke-Korsakoff syndrome.

Repetitive Transcranial Magnetic Stimulation for Wernicke-Korsakoff Syndrome: A Case Report

PubMed Central

2017-01-01

A 57-year-old man who was diagnosed with Wernicke-Korsakoff syndrome showed severe impairment of cognitive function and a craving for alcohol, even after sufficient supplementation with thiamine. After completing 10 sessions of 10 Hz repetitive transcranial magnetic stimulation (rTMS) at 100% of the resting motor threshold over the left dorsolateral prefrontal cortex, dramatic improvement in cognitive function and a reduction in craving for alcohol were noted. This is the first case report of the efficacy of a high-frequency rTMS in the treatment of Wernicke-Korsakoff syndrome. PMID:28289650

rTMS stimulation on left DLPFC affects emotional cue retrieval as a function of anxiety level and gender.

PubMed

Balconi, Michela; Ferrari, Chiara

2012-11-01

Anxiety behaviour showed a consistent attentional bias toward negative and aversive memories, induced by a right dorsolateral prefrontal cortex (DLPFC) hyperactivation. In the present research, we explored the possible effect of rTMS (repeated transcranial magnetic stimulation) on the left DLPFC in memory retrieval of positive versus negative emotional words, to induce a balanced response between the two hemispheres. Moreover, the gender effect in emotional memory processing was verified as a function of the stimulus valence. Thirty subjects, who were divided in two different groups depending on their anxiety level (high/low anxiety, State-Trait-Anxiety Inventory (STAI)), were required to perform a task consisting of two experimental phases: an encoding phase (lists composed by positive and negative emotional words); and a retrieval phase (old stimuli and new stimuli to be recognized). We found that the rTMS stimulation over left DLPFC affects the memory retrieval. Specifically, high-anxiety subjects benefitted in greater measure to the frontal left stimulation with a reduced negative bias (increased accuracy and reduced response time (RT) for the positive stimuli). Whereas females showed a significant bias toward the negative memories, they did not benefit in greater measure to the TMS stimulation on the left hemisphere. These results suggested that left DLPFC activation favors the memory retrieval of positive emotional information and may limit the "unbalance effect" induced by a right frontal hemispheric superiority in high levels of anxiety. © 2012 Wiley Periodicals, Inc.

Understanding hypnosis metacognitively: rTMS applied to left DLPFC increases hypnotic suggestibility.

PubMed

Dienes, Zoltan; Hutton, Sam

2013-02-01

According to the cold control theory of hypnosis (Dienes and Perner, 2007), hypnotic response occurs because of inaccurate higher order thoughts of intending. The dorsolateral prefrontal cortex (DLPFC) is a region likely involved in constructing accurate higher order thoughts. Thus, disrupting DLPFC with low frequency repetitive transcranial magnetic stimulation (rTMS) should make it harder to be aware of intending to perform an action. That is, it should be easier to respond to a hypnotic suggestion. Twenty-four medium hypnotisable subjects received low frequency rTMS to the left DLPFC and to a control site, the vertex, in counterbalanced order. The hypnotist was blind to which site had been stimulated. Subjects rated how strongly they expected to respond to each suggestion, and gave ratings on a 0-5 scale of the extent to which they experienced the response, for four suggestions (magnetic hands, arm levitation, rigid arm and taste hallucination). The experimenter also rated behavioural response. Low frequency rTMS to the DLPFC rather than vertex increased the degree of combined behavioural and subjective response. Further, subjects did not differ in their expectancy that they would respond in the two conditions, so the rTMS had an effect on hypnotic response above and beyond expectancies. The results support theories, including cold control theory, postulating a component of hypofrontality in hypnotic response. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

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.

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.

Electrical or repetitive transcranial magnetic stimulation of primary motor cortex for intractable neuropathic pain.

PubMed

Saitoh, Youichi; Maruo, Tomoyuki; Yokoe, Masaru; Matsuzaki, Taiga; Sekino, Masaki

2013-01-01

To assess the pain-relieving effects of motor cortex electrical stimulation (MCS) and the predictive factors retrospectively. Thirty-four patients with intractable neuropathic pain underwent MCS; 19 patients had cerebral lesions, and 15 had non-cerebral lesions. In selected 12 patients, test electrodes were implanted within the central sulcus and on the precentral gyrus. Twelve patients received both MCS and repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex. Pain reduction of >50% was observed in 12 of 32 (36%) patients with >12 months follow-ups (2 patients were excluded because of short follow-up). In 10 of the 12 patients who received test electrodes within the central sulcus and on the precentral gyrus, the optimal stimulation was MCS within the central sulcus. In 4 of these (40%) patients, positive effects were maintained at follow-ups. The pain reduction of rTMS significantly correlated with that of MCS during test stimulation. The test stimulation within the central sulcus was more effective than that of the precentral gyrus. In the selected patients, chronic stimulation within the central sulcus did not significantly improve long-term results. Repeated rTMS seems to be same effective as MCS.

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.

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.

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

Safety and preliminary efficacy of deep transcranial magnetic stimulation in MS-related fatigue

PubMed Central

Gaede, Gunnar; Tiede, Marina; Lorenz, Ina; Brandt, Alexander U.; Pfueller, Caspar; Dörr, Jan; Bellmann-Strobl, Judith; Piper, Sophie K.; Roth, Yiftach; Zangen, Abraham; Schippling, Sven

2017-01-01

Objective: To conduct a randomized, sham-controlled phase I/IIa study to evaluate the safety and preliminary efficacy of deep brain H-coil repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC) and the primary motor cortex (MC) in patients with MS with fatigue or depression (NCT01106365). Methods: Thirty-three patients with MS were recruited to undergo 18 consecutive rTMS sessions over 6 weeks, followed by follow-up (FU) assessments over 6 weeks. Patients were randomized to receive high-frequency stimulation of the left PFC, MC, or sham stimulation. Primary end point was the safety of stimulation. Preliminary efficacy was assessed based on changes in Fatigue Severity Scale (FSS) and Beck Depression Inventory scores. Randomization allowed only analysis of preliminary efficacy for fatigue. Results: No serious adverse events were observed. Five patients terminated participation during treatment due to mild side effects. Treatment resulted in a significant median FSS decrease of 1.0 point (95%CI [0.45,1.65]), which was sustained during FU. Conclusions: H-coil rTMS is safe and well tolerated in patients with MS. The observed sustained reduction in fatigue after subthreshold MC stimulation warrants further investigation. ClinicalTrials.gov identifier: NCT01106365. Classification of evidence: This study provides Class III evidence that rTMS of the prefrontal or primary MC is not associated with serious adverse effects, although this study is underpowered to state this with any precision. PMID:29259998

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).

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

Focal hand dystonia: individualized intervention with repeated application of repetitive transcranial magnetic stimulation.

PubMed

Kimberley, Teresa Jacobson; Borich, Michael R; Schmidt, Rebekah L; Carey, James R; Gillick, Bernadette

2015-04-01

To examine for individual factors that may predict response to inhibitory repetitive transcranial magnetic stimulation (rTMS) in focal hand dystonia (FHD); to present the method for determining optimal stimulation to increase inhibition in a given patient; and to examine individual responses to prolonged intervention. Single-subject design to determine optimal parameters to increase inhibition for a given subject and to use the selected parameters once per week for 6 weeks, with 1-week follow-up, to determine response. Clinical research laboratory. A volunteer sample of subjects with FHD (N = 2). One participant had transcranial magnetic stimulation responses indicating impaired inhibition, and the other had responses within normative limits. There were 1200 pulses of 1-Hz rTMS delivered using 4 different stimulation sites/intensity combinations: primary motor cortex at 90% or 110% of resting motor threshold (RMT) and dorsal premotor cortex (PMd) at 90% or 110% of RMT. The parameters producing the greatest within-session increase in cortical silent period (CSP) duration were then used as the intervention. Response variables included handwriting pressure and velocity, subjective symptom rating, CSP, and short latency intracortical inhibition and facilitation. The individual with baseline transcranial magnetic stimulation responses indicating impaired inhibition responded favorably to the repeated intervention, with reduced handwriting force, an increase in the CSP, and subjective report of moderate symptom improvement at 1-week follow-up. The individual with normative baseline responses failed to respond to the intervention. In both subjects, 90% of RMT to the PMd produced the greatest lengthening of the CSP and was used as the intervention. An individualized understanding of neurophysiological measures can be an indicator of responsiveness to inhibitory rTMS in focal dystonia, with further work needed to determine likely responders versus nonresponders. Copyright �

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

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.

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.

rTMS For PTSD: Induced Merciful Oblivion or Elimination of Abnormal Hypermnesia?

PubMed Central

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. PMID:17148840

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.

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.

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.

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.

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.

Contralateral versus ipsilateral rTMS of temporoparietal cortex for the treatment of chronic unilateral tinnitus: comparative study.

PubMed

Khedr, E M; Abo-Elfetoh, N; Rothwell, J C; El-Atar, A; Sayed, E; Khalifa, H

2010-07-01

Repetitive transcranial magnetic stimulation (rTMS) applied over left temporoparietal cortex has been reported to have a long-term therapeutic effect on tinnitus. We compare the impact of 1 and 25 Hz rTMS delivered either contralateral or ipsilateral to symptoms in 62 patients with unilateral chronic tinnitus. Patients were randomly assigned to one of four treatment groups: with stimulation at 1 or 25 Hz applied either ipsilateral or contralateral to symptoms. Two thousand pulses per session were given daily for 2 weeks. Changes in tinnitus handicap inventory (THI), self-rating scores of loudness, awareness, and annoyance were measured monthly for 10 months. Duration of residual inhibition (RI) and psychiatric morbidity were evaluated monthly for 3 months. There was a significant main effect of time (P < 0.0001) and a significant time x side interaction (P = 0.032) between groups. This was because of the fact that contralateral stimulation had a greater effect on THI than ipsilateral stimulation; it was also superior to left side stimulation (P = 0.027). Ratings of loudness improved more after contralateral rTMS (P = 0.037). Twenty patients had no remaining tinnitus after 3 months; the remainder had a significant increase in RI. Patients with the shortest history of tinnitus tended to respond better to rTMS. There was a significant correlation between changes in THI score and changes in Hamilton anxiety and depression scores. Ten daily treatments of 1 and 25 Hz rTMS contralateral to the side of tinnitus have a greater beneficial effect on symptoms than either ipsilateral or left side stimulation.

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

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.

Clinical effects of non-invasive cerebellar magnetic stimulation treatment combined with neuromotor rehabilitation in traumatic brain injury. A single case study.

PubMed

Martino Cinnera, Alex; Bonnì, S; Iosa, M; Ponzo, V; Fusco, A; Caltagirone, Carlo; Koch, Giacomo

2016-01-01

Multimodal treatments are emerging as effective approaches for motor recovery in traumatic brain injury (TBI). Various evidence has demonstrated that repetitive transcranial magnetic stimulation (rTMS) may improve outcomes in people with motor disorders. Behavioral gains from rTMS protocols may be maximized when brain stimulation is coupled with carefully designed occupational/physical therapy. We present the case of a 25-year-old man with chronic TBI (a bilateral corticosubcortical parieto-occipital lesion) who underwent three weeks of cerebellar intermittent theta burst stimulation (iTBS), a form of rTMS, combined with neurorehabilitation treatment. The Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS), Jebsen-Taylor Hand Function Test, and accelerometer gait analysis were administered before and after treatment. The results showed improvements in balance performance (BBS: T0=47; T1=53; +10.72%), motor recovery (FMA: T0=93/100; T1=96/100; +3.00%), step length (T0=50.4±7.2; T1=53.8±2.2 cm, p<0.001), and walking speed (T0=0.87±0.06; T1=0.91±0.04 m/sec,p<0.001). Combined cerebellar rTMS and neurore-Clinical effects of non-invasive cerebellar magnetic stimulation treatment combined with neuromotor rehabilitation in traumatic brain injury. A single case study. habilitation seems to be a promising treatment for motor and balance dysfunctions in TBI patients.

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.

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.

Effective treatment of narcolepsy-like symptoms with high-frequency repetitive transcranial magnetic stimulation

PubMed Central

Lai, Jian-bo; Han, Mao-mao; Xu, Yi; Hu, Shao-hua

2017-01-01

Abstract Rationale: Narcolepsy is a rare sleep disorder with disrupted sleep-architecture. Clinical management of narcolepsy lies dominantly on symptom-driven pharmacotherapy. The treatment role of repetitive transcranial magnetic stimulation (rTMS) for narcolepsy remains unexplored. Patient concerns: In this paper, we present a case of a 14-year-old young girl with excessive daytime sleepiness (EDS), cataplexy and hypnagogic hallucinations. Diagnoses: After excluding other possible medical conditions, this patient was primarily diagnosed with narcolepsy. Interventions: The patient received 25 sessions of high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC). Outcomes: The symptoms of EDS and cataplexy significantly improved after rTMS treatment. Meanwhile, her score in the Epworth sleep scale (ESS) also remarkably decreased. Lessons: This case indicates that rTMS may be selected as a safe and effective alternative strategy for treating narcolepsy-like symptoms. Well-designed researches are warranted in future investigations on this topic. PMID:29145290

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.

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.

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.

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

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.

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.

Single Session Low Frequency Left Dorsolateral Prefrontal Transcranial Magnetic Stimulation Changes Neurometabolite Relationships in Healthy Humans

PubMed Central

Bridges, Nathaniel R.; McKinley, Richard A.; Boeke, Danielle; Sherwood, Matthew S.; Parker, Jason G.; McIntire, Lindsey K.; Nelson, Justin M.; Fletchall, Catherine; Alexander, Natasha; McConnell, Amanda; Goodyear, Chuck; Nelson, Jeremy T.

2018-01-01

Background: Dorsolateral prefrontal cortex (DLPFC) low frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise as a treatment and investigative tool in the medical and research communities. Researchers have made significant progress elucidating DLPFC LF-rTMS effects—primarily in individuals with psychiatric disorders. However, more efforts investigating underlying molecular changes and establishing links to functional and behavioral outcomes in healthy humans are needed. Objective: We aimed to quantify neuromolecular changes and relate these to functional changes following a single session of DLPFC LF-rTMS in healthy participants. Methods: Eleven participants received sham-controlled neuronavigated 1 Hz rTMS to the region most activated by a 7-letter Sternberg working memory task (SWMT) within the left DLPFC. We quantified SWMT performance, functional magnetic resonance activation and proton Magnetic resonance spectroscopy (MRS) neurometabolite measure changes before and after stimulation. Results: A single LF-rTMS session was not sufficient to change DLPFC neurometabolite levels and these changes did not correlate with DLPFC activation changes. Real rTMS, however, significantly altered neurometabolite correlations (compared to sham rTMS), both with baseline levels and between the metabolites themselves. Additionally, real rTMS was associated with diminished reaction time (RT) performance improvements and increased activation within the motor, somatosensory and lateral occipital cortices. Conclusion: These results show that a single session of LF-rTMS is sufficient to influence metabolite relationships and causes widespread activation in healthy humans. Investigating correlational relationships may provide insight into mechanisms underlying LF-rTMS. PMID:29632477

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

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

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.

Improvement of white matter and functional connectivity abnormalities by repetitive transcranial magnetic stimulation in crossed aphasia in dextral.

PubMed

Lu, Haitao; Wu, Haiyan; Cheng, Hewei; Wei, Dongjie; Wang, Xiaoyan; Fan, Yong; Zhang, Hao; Zhang, Tong

2014-01-01

As a special aphasia, the occurrence of crossed aphasia in dextral (CAD) is unusual. This study aims to improve the language ability by applying 1 Hz repetitive transcranial magnetic stimulation (rTMS). We studied multiple modality imaging of structural connectivity (diffusion tensor imaging), functional connectivity (resting fMRI), PET, and neurolinguistic analysis on a patient with CAD. Furthermore, we applied rTMS of 1 Hz for 40 times and observed the language function improvement. The results indicated that a significantly reduced structural and function connectivity was found in DTI and fMRI data compared with the control. The PET imaging showed hypo-metabolism in right hemisphere and left cerebellum. In conclusion, one of the mechanisms of CAD is that right hemisphere is the language dominance. Stimulating left Wernicke area could improve auditory comprehension, stimulating left Broca's area could enhance expression, and the results outlasted 6 months by 1 Hz rTMS balancing the excitability inter-hemisphere in CAD.

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.

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.

Magnetic Resonance Imaging-Guided, Open-Label, High-Frequency Repetitive Transcranial Magnetic Stimulation for Adolescents with Major Depressive Disorder.

PubMed

Wall, Christopher A; Croarkin, Paul E; Maroney-Smith, Mandie J; Haugen, Laura M; Baruth, Joshua M; Frye, Mark A; Sampson, Shirlene M; Port, John D

2016-09-01

Preliminary studies suggest that repetitive transcranial magnetic stimulation (rTMS) may be an effective and tolerable intervention for adolescents with treatment-resistant depression. There is limited rationale to inform coil placement for rTMS dosing in this population. We sought to examine and compare three localization techniques for coil placement in the context of an open-label trial of high-frequency rTMS for adolescents with treatment-resistant depression. Ten adolescents with treatment-resistant depression were enrolled in an open-label trial of high-frequency rTMS. Participants were offered 30 rTMS sessions (10 Hz, 120% motor threshold, left 3000 pulses applied to the dorsolateral prefrontal cortex) over 6-8 weeks. Coil placement for treatment was MRI guided. The scalp location for treatment was compared with the locations identified with standard 5 cm rule and Beam F3 methods. Seven adolescents completed 30 rTMS sessions. No safety or tolerability concerns were identified. Depression severity as assessed with the Children's Depression Rating Scale Revised improved from baseline to treatment 10, treatment 20, and treatment 30. Gains in depressive symptom improvement were maintained at 6 month follow-up visits. An MRI-guided approach for coil localization was feasible and efficient. Our results suggest that the 5 cm rule, Beam F3, and the MRI-guided localization approaches provided variable scalp targets for rTMS treatment. Open-label, high-frequency rTMS was feasible, tolerable, and effective for adolescents with treatment-resistant depression. Larger, blinded, sham-controlled trials are needed for definitive safety and efficacy data. Further efforts to understand optimal delivery, dosing, and biomarker development for rTMS treatments of adolescent depression are warranted.

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

PubMed

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

2018-01-15

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

Effective treatment of narcolepsy-like symptoms with high-frequency repetitive transcranial magnetic stimulation: A case report.

PubMed

Lai, Jian-Bo; Han, Mao-Mao; Xu, Yi; Hu, Shao-Hua

2017-11-01

Narcolepsy is a rare sleep disorder with disrupted sleep-architecture. Clinical management of narcolepsy lies dominantly on symptom-driven pharmacotherapy. The treatment role of repetitive transcranial magnetic stimulation (rTMS) for narcolepsy remains unexplored. In this paper, we present a case of a 14-year-old young girl with excessive daytime sleepiness (EDS), cataplexy and hypnagogic hallucinations. After excluding other possible medical conditions, this patient was primarily diagnosed with narcolepsy. The patient received 25 sessions of high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC). The symptoms of EDS and cataplexy significantly improved after rTMS treatment. Meanwhile, her score in the Epworth sleep scale (ESS) also remarkably decreased. This case indicates that rTMS may be selected as a safe and effective alternative strategy for treating narcolepsy-like symptoms. Well-designed researches are warranted in future investigations on this topic.

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.

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.

Using repetitive transcranial magnetic stimulation to study the underlying neural mechanisms of human motor learning and memory.

PubMed

Censor, Nitzan; Cohen, Leonardo G

2011-01-01

In the last two decades, there has been a rapid development in the research of the physiological brain mechanisms underlying human motor learning and memory. While conventional memory research performed on animal models uses intracellular recordings, microfusion of protein inhibitors to specific brain areas and direct induction of focal brain lesions, human research has so far utilized predominantly behavioural approaches and indirect measurements of neural activity. Repetitive transcranial magnetic stimulation (rTMS), a safe non-invasive brain stimulation technique, enables the study of the functional role of specific cortical areas by evaluating the behavioural consequences of selective modulation of activity (excitation or inhibition) on memory generation and consolidation, contributing to the understanding of the neural substrates of motor learning. Depending on the parameters of stimulation, rTMS can also facilitate learning processes, presumably through purposeful modulation of excitability in specific brain regions. rTMS has also been used to gain valuable knowledge regarding the timeline of motor memory formation, from initial encoding to stabilization and long-term retention. In this review, we summarize insights gained using rTMS on the physiological and neural mechanisms of human motor learning and memory. We conclude by suggesting possible future research directions, some with direct clinical implications.

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

Metabolic changes of cerebrum by repetitive transcranial magnetic stimulation over lateral cerebellum: a study with FDG PET.

PubMed

Cho, Sang Soo; Yoon, Eun Jin; Bang, Sung Ae; Park, Hyun Soo; Kim, Yu Kyeong; Strafella, Antonio P; Kim, Sang Eun

2012-09-01

To better understand the functional role of cerebellum within the large-scale cerebellocerebral neural network, we investigated the changes of neuronal activity elicited by cerebellar repetitive transcranial magnetic stimulation (rTMS) using (18)F-fluorodeoxyglucose (FDG) and positron emission tomography (PET). Twelve right-handed healthy volunteers were studied with brain FDG PET under two conditions: active rTMS of 1 Hz frequency over the left lateral cerebellum and sham stimulation. Compared to the sham condition, active rTMS induced decreased glucose metabolism in the stimulated left lateral cerebellum, the areas known to be involved in voluntary motor movement (supplementary motor area and posterior parietal cortex) in the right cerebral hemisphere, and the areas known to be involved in cognition and emotion (orbitofrontal, medial frontal, and anterior cingulate gyri) in the left cerebral hemisphere. Increased metabolism was found in cognition- and language-related brain regions such as the left inferior frontal gyrus including Broca's area, bilateral superior temporal gyri including Wernicke's area, and bilateral middle temporal gyri. Left cerebellar rTMS also led to increased metabolism in the left cerebellar dentate nucleus and pons. These results demonstrate that rTMS over the left lateral cerebellum modulates not only the target region excitability but also excitability of remote, but interconnected, motor-, language-, cognition-, and emotion-related cerebral regions. They provide further evidence that the cerebellum is involved not only in motor-related functions but also in higher cognitive abilities and emotion through the large-scale cerebellocereberal neural network.

rTMS with Motor Training Modulates Cortico-Basal Ganglia-Thalamocortical Circuits in Stroke Patients

PubMed Central

Chang, Won Hyuk; Kim, Yun-Hee; Yoo, Woo-Kyoung; Goo, Kyoung-Hyup; Park, Chang-hyun; Kim, Sung Tae; Pascual-Leone, Alvaro

2013-01-01

Background and Purpose Repetitive transcranial magnetic stimulation (rTMS) may enhance plastic changes in the human cortex and modulation of behavior. However, the underlying neural mechanisms have not been sufficiently investigated. We examined the clinical effects and neural correlates of high-frequency rTMS coupled with motor training in patients with hemiparesis after stroke. Methods Twenty-one patients were randomly divided into two groups, and received either real or sham rTMS. Ten daily sessions of 1,000 pulses of real or sham rTMS were applied at 10 Hz over the primary motor cortex of the affected hemisphere, coupled with sequential finger motor training of the paretic hand. Functional MRIs were obtained before and after training using sequential finger motor tasks, and performances were assessed. Results Following rTMS intervention, movement accuracy of sequential finger motor tasks showed significantly greater improvement in the real group than in the sham group (p<0.05). Real rTMS modulated areas of brain activation during performance of motor tasks with a significant interaction effect in the sensorimotor cortex, thalamus, and caudate nucleus. Patients in the real rTMS group also showed significantly enhanced activation in the affected hemisphere compared to the sham rTMS group. Conclusion According to these results, a 10 day course of high-frequency rTMS coupled with motor training improved motor performance through modulation of activities in the cortico-basal ganglia-thalamocortical circuits. PMID:22555430

Intermittent theta-burst transcranial magnetic stimulation for treatment of Parkinson disease.

PubMed

Benninger, D H; Berman, B D; Houdayer, E; Pal, N; Luckenbaugh, D A; Schneider, L; Miranda, S; Hallett, M

2011-02-15

To investigate the safety and efficacy of intermittent theta-burst stimulation (iTBS) in the treatment of motor symptoms in Parkinson disease (PD). Progression of PD is characterized by the emergence of motor deficits, which eventually respond less to dopaminergic therapy and pose a therapeutic challenge. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS. In this randomized, double-blind, sham-controlled study, we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks (evidence Class I). Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson's Disease Rating Scale (UPDRS), and additional clinical, neuropsychological, and neurophysiologic measures. We investigated 26 patients with mild to moderate PD: 13 received iTBS and 13 sham stimulation. We found beneficial effects of iTBS on mood, but no improvement of gait, bradykinesia, UPDRS, and other measures. EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity. Few reported discomfort or pain and one experienced tinnitus during real stimulation. iTBS of the motor and prefrontal cortices appears safe and improves mood, but failed to improve motor performance and functional status in PD. This study provides Class I evidence that iTBS was not effective for gait, upper extremity bradykinesia, or other motor symptoms in PD.

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.

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.

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

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.

[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

rTMS treatments combined with speech training for a conduction aphasia patient

PubMed Central

Zhang, Hui; Chen, Ying; Hu, Ruiping; Yang, Liqing; Wang, Mengxing; Zhang, Jilei; Lu, Haifeng; Wu, Yi; Du, Xiaoxia

2017-01-01

Abstract Rationale: To date, little is known regarding the neural mechanisms of the functional recovery of language after repetitive transcranial magnetic stimulation (rTMS) in aphasia. Our aim was to investigate the mechanism that underlies rTMS and speech training in a case report. Patient concerns and diagnoses: We report the case of a 39-year-old woman who was initially diagnosed with conduction aphasia following a left hemisphere stroke. Interventions: The rTMS location comprised the left Broca area, and a frequency of 5 Hz for 20 min/d for 10 days during a 2-week period was used. She had received speech rehabilitation training 1 month after stroke. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging were used to investigate the functional and microstructural changes before and after rTMS treatment. Outcomes: The results demonstrated that the Western Aphasia Battery scores significantly improved for language ability at 2 weeks post-treatment, and the gains were steadily increased at 2.5 months post-treatment. The fMRI results indicated a more focused activation pattern and showed significant activation in the left dominant hemisphere relative to the right hemisphere, especially in the perilesional areas, post-treatment during 2 language tasks compared with pretreatment. Moreover, the fractional anisotropy increased in the left superior temporal gyrus, which comprises an important area that is involved in language processing. Lessons: Our findings suggest that rTMS combined with speech training improved the speech-language ability of this chronic conduction aphasia patient and enhanced the cerebral functional and microstructural reorganization. PMID:28796033

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.

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

One-year follow up of patients with chronic tinnitus treated with left temporoparietal rTMS.

PubMed

Khedr, E M; Rothwell, J C; El-Atar, A

2009-03-01

Although there are a number of positive reports on the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) for treatment of tinnitus, there are few details about the duration of treatment effects or the relative efficiency of different rTMS protocols. Sixty six patients with chronic tinnitus were divided into four groups, receiving sham rTMS, 1, 10 and 25 Hz rTMS applied each day for 10 days over left temporoparietal cortex. They were followed up at 4 months and 1 year using the tinnitus questionnaire [Tinnitus Handicap Inventory(THI)] and self ratings of annoyance as well as measures of residual inhibition. A two factor anova revealed a significant 'rTMS' x 'time' interaction indicating that real and sham rTMS had different effects on the THI scale and annoyance of tinnitus (P = 0.026 and 0.046 respectively). After 1 year, the tinnitus was absent in one or both ears of 10 patients who had received real rTMS: one of these was in the 1 Hz group, four patients were in the 10 Hz group and five patients were in the 25 Hz group. Some patients show a lasting benefit at 1 year after 10 days of rTMS treatment. It appears that treatment at 10 or 25 Hz may be more beneficial than at 1 Hz, although more work is necessary to validate this conclusion.

Moderate therapeutic efficacy of positron emission tomography‐navigated repetitive transcranial magnetic stimulation for chronic tinnitus: a randomised, controlled pilot study

PubMed Central

Plewnia, C; Reimold, M; Najib, A; Reischl, G; Plontke, S K; Gerloff, C

2007-01-01

Background Tinnitus has been shown to respond to modulations of cortical activity by high‐frequency and low‐frequency repetitive transcranial magnetic stimulation (rTMS). Objective To determine the tinnitus‐attenuating effects of a 2‐week daily regimen of rTMS, navigated to the maximum of tinnitus‐related increase in regional cerebral blood flow. Methods Six patients with chronic tinnitus were enrolled in this sham‐controlled crossover study and treated with 2×2 weeks of suprathreshold 1 Hz rTMS (30 min) applied to the region with maximal tinnitus‐related increase in regional cerebral blood flow delineated by functional imaging with [15O]H2O positron emission tomography and a control area. Tinnitus‐related distress was assessed before and after each treatment and 2 weeks after the end of the 4‐week course of stimulation using a validated tinnitus questionnaire. Additional self‐assessment scores of tinnitus change, loudness and annoyance were obtained. Results In five of six patients, rTMS induced greater reduction of the tinnitus questionnaire score than sham stimulation. In two patients, all parameters measured (tinnitus change score, tinnitus loudness, tinnitus annoyance) showed unequivocal improvement. At the group level, the degree of response in the tinnitus questionnaire score was correlated with tinnitus‐associated activation of the anterior cingulate cortex. Two weeks after the final stimulation, tinnitus had returned to baseline in all patients but one. Conclusion Tinnitus can be attenuated by low‐frequency rTMS navigated to each person's maximum tinnitus‐related cortical hyperactivity. The effects are only moderate; interindividual responsiveness varies and the attenuation seems to wear off within 2 weeks after the last stimulation session. Notably, tinnitus‐related anterior cingulate cortex activation seems to predict the response to rTMS treatment. PMID:16891384

Combined rTMS treatment targeting the Anterior Cingulate and the Temporal Cortex for the Treatment of Chronic Tinnitus

PubMed Central

Kreuzer, Peter M.; Lehner, Astrid; Schlee, Winfried; Vielsmeier, Veronika; Schecklmann, Martin; Poeppl, Timm B.; Landgrebe, Michael; Rupprecht, Rainer; Langguth, Berthold

2015-01-01

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a tinnitus treatment option. Promising results have been obtained by consecutive stimulation of lateral frontal and auditory brain regions. We investigated a combined stimulation paradigm targeting the anterior cingulate cortex (ACC) with double cone coil rTMS, followed by stimulation of the temporo-parietal junction area with a figure-of-eight coil. The study was conducted as a randomized, double-blind pilot trial in 40 patients suffering from chronic tinnitus. We compared mediofrontal stimulation with double-cone-coil, (2000 stimuli, 10 Hz) followed by left temporo-parietal stimulation with figure-of-eight-coil (2000 stimuli, 1 Hz) to left dorsolateral-prefrontal-cortex stimulation with figure-of-eight-coil (2000 stimuli, 10 Hz) followed by temporo-parietal stimulation with figure-of-eight-coil (2000 stimuli, 1 Hz). The stimulation was feasible with comparable dropout rates in both study arms; no severe adverse events were registered. Responder rates did not differ in both study arms. There was a significant main effect of time for the change in the TQ score, but no significant time x group interaction. This pilot study demonstrated the feasibility of combined mediofrontal/temporoparietal-rTMS-stimulation with double cone coil in tinnitus patients but failed to show better outcome compared to an actively rTMS treated control group. PMID:26667790

Alteration of Duration Mismatch Negativity Induced by Transcranial Magnetic Stimulation Over the Left Parietal Lobe.

PubMed

Oshima, Hirokazu; Shiga, Tetsuya; Niwa, Shin-Ichi; Enomoto, Hiroyuki; Ugawa, Yoshikazu; Yabe, Hirooki

2017-01-01

Mismatch negativity (MMN) is generated by a comparison between an incoming sound and the memory trace of preceding sounds stored in sensory memory without any attention to the sound. N100 (N1) is associated with the afferent response to sound onset and reflects early analysis of stimulus characteristics. MMN generators are present in the temporal and frontal lobe, and N1 generators are present in the temporal lobe. The parietal lobe is involved in MMN generation elicited by a change in duration. The anatomical network connecting these areas, lateralization, and the effect of the side of ear stimulation on MMN remain unknown. Thus, we studied the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the left parietal lobe on MMN and N1 in 10 healthy subjects. Low-frequency rTMS over the left parietal lobe decreased the amplitude of MMN following right ear sound stimulation, but the amplitude was unaffected with left ear sound stimulation. We observed no significant changes in the amplitude of N1 or the latency of MMN or N1. These results suggest that low-frequency rTMS over the left parietal lobe modulates the detection of early auditory changes in duration in healthy subjects. Stimulation that is contralateral to the side of the ear experiencing sound may affect the generation of duration MMN more than ipsilateral stimulation. © EEG and Clinical Neuroscience Society (ECNS) 2016.

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

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.

Repetitive Transcranial Magnetic Stimulation for the Treatment of Executive Function Deficits in Autism Spectrum Disorder: Clinical Trial Approach.

PubMed

Ameis, Stephanie H; Daskalakis, Zafiris J; Blumberger, Daniel M; Desarkar, Pushpal; Drmic, Irene; Mabbott, Donald J; Lai, Meng-Chuan; Croarkin, Paul E; Szatmari, Peter

2017-06-01

Executive function (EF) deficits in patients with autism spectrum disorder (ASD) are ubiquitous and understudied. Further, there are no effective, neuroscience-based treatments to address this impairing feature of ASD. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated promise in addressing EF deficits in adult neuropsychiatric disorders. This article will outline the design of a novel randomized-controlled trial of bilateral, 20 Hz, rTMS applied to the dorsolateral prefrontal cortex (DLPFC) for treatment of EF deficits in ASD that is currently ongoing. We describe prior therapeutic rTMS research for ASD and prior rTMS trials targeting EFs in adult neuropsychiatric disorders. A neurophysiological rationale for rTMS treatment of EF deficits in ASD is presented. An ongoing protocol will enroll participants aged 16-35 with ASD and no intellectual disability. Psychotropic medications will be continued during the 4-week trial of active 20 Hz versus sham rTMS applied to the DLPFC. Twenty, active treatment sessions consisting of 25 stimulation trains at a 90% motor threshold will be administered. The primary outcome measure is the Cambridge Neuropsychological Test Automated Battery (CANTAB) spatial working memory task. At present, recruitment, enrollment, and treatment within the described clinical trial are ongoing. EF deficits are common and impairing symptoms of ASD. There are no evidence-based treatments for EF deficits in ASD. The protocol described here will provide important preliminary data on the feasibility and efficacy of 20 Hz rTMS to DLPFC for EF deficits in ASD.

Right prefrontal rTMS treatment for refractory auditory command hallucinations - a neuroSPECT assisted case study.

PubMed

Schreiber, Shaul; Dannon, Pinhas N; Goshen, Elinor; Amiaz, Revital; Zwas, Tzila S; Grunhaus, Leon

2002-11-30

Auditory command hallucinations probably arise from the patient's failure to monitor his/her own 'inner speech', which is connected to activation of speech perception areas of the left cerebral cortex and to various degrees of dysfunction of cortical circuits involved in schizophrenia as supported by functional brain imaging. We hypothesized that rapid transcranial magnetic stimulation (rTMS), by increasing cortical activation of the right prefrontal brain region, would bring about a reduction of the hallucinations. We report our first schizophrenic patient affected with refractory command hallucinations treated with 10 Hz rTMS. Treatment was performed over the right dorsolateral prefrontal cortex, with 1200 magnetic stimulations administered daily for 20 days at 90% motor threshold. Regional cerebral blood flow changes were monitored with neuroSPECT. Clinical evaluation and scores on the Positive and Negative Symptoms Scale and the Brief Psychiatric Rating Scale demonstrated a global improvement in the patient's condition, with no change in the intensity and frequency of the hallucinations. NeuroSPECT performed at intervals during and after treatment indicated a general improvement in cerebral perfusion. We conclude that right prefrontal rTMS may induce a general clinical improvement of schizophrenic brain function, without directly influencing the mechanism involved in auditory command hallucinations.

Intermittent theta-burst transcranial magnetic stimulation for treatment of Parkinson disease

PubMed Central

Berman, B.D.; Houdayer, E.; Pal, N.; Luckenbaugh, D.A.; Schneider, L.; Miranda, S.; Hallett, M.

2011-01-01

Objective: To investigate the safety and efficacy of intermittent theta-burst stimulation (iTBS) in the treatment of motor symptoms in Parkinson disease (PD). Background: Progression of PD is characterized by the emergence of motor deficits, which eventually respond less to dopaminergic therapy and pose a therapeutic challenge. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS. Methods: In this randomized, double-blind, sham-controlled study, we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks (evidence Class I). Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson's Disease Rating Scale (UPDRS), and additional clinical, neuropsychological, and neurophysiologic measures. Results: We investigated 26 patients with mild to moderate PD: 13 received iTBS and 13 sham stimulation. We found beneficial effects of iTBS on mood, but no improvement of gait, bradykinesia, UPDRS, and other measures. EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity. Few reported discomfort or pain and one experienced tinnitus during real stimulation. Conclusion: iTBS of the motor and prefrontal cortices appears safe and improves mood, but failed to improve motor performance and functional status in PD. Classification of evidence: This study provides Class I evidence that iTBS was not effective for gait, upper extremity bradykinesia, or other motor symptoms in PD. PMID:21321333

Repetitive Transcranial Magnetic Stimulation to the Primary Motor Cortex Interferes with Motor Learning by Observing

ERIC Educational Resources Information Center

Brown, Liana E.; Wilson, Elizabeth T.; Gribble, Paul L.

2009-01-01

Neural representations of novel motor skills can be acquired through visual observation. We used repetitive transcranial magnetic stimulation (rTMS) to test the idea that this "motor learning by observing" is based on engagement of neural processes for learning in the primary motor cortex (M1). Human subjects who observed another person learning…

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

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.

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

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

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.

A Pilot Study of Peripheral Muscle Magnetic Stimulation as Add-on Treatment to Repetitive Transcranial Magnetic Stimulation in Chronic Tinnitus

PubMed Central

Vielsmeier, Veronika; Schecklmann, Martin; Schlee, Winfried; Kreuzer, Peter M.; Poeppl, Timm B.; Rupprecht, Rainer; Langguth, Berthold; Lehner, Astrid

2018-01-01

While brain stimulation techniques have been examined as treatment options for chronic tinnitus for many years, they have recently been extended to multimodal treatment approaches. As chronic tinnitus is often accompanied by comorbid muscular tension in the neck and back, we performed a one-arm pilot study to explore the feasibility of a new multimodal treatment approach. In detail, repetitive peripheral magnetic stimulation (rPMS) of the back was performed before and after each session of repetitive transcranial magnetic stimulation (rTMS) of the brain. Data of 41 patients were analyzed, all of which were treated with ten sessions of rTMS of the left prefrontal and left temporoparietal cortex followed by rPMS of the neck and back muscles. Tinnitus severity was measured using the tinnitus questionnaire (TQ). Neck pain was assessed using the neck pain and disability scale (NPAD). The new treatment approach was feasible and well accepted by the majority of patients. However, the overall patient group did not improve significantly in either of the questionnaires. If patients were divided in different subgroups depending on whether they were suffering from neck pain or somatosensory tinnitus, explorative post-hoc tests suggested differential effects: patients with both neck pain and somatosensory tinnitus had better outcomes than patients without those conditions or with neck pain only. This was true for both the TQ and the NPAD. This effect was of transient nature though: the TQ score went back to its baseline level after a follow-up period of 12 weeks. Based on our results we recommend that in studies that investigate tinnitus treatments targeting somatosensory afferents patients should be stratified according to somatic co-morbidities and somatosensory influence on the tinnitus percept. Clinical trial registration: www.clinicaltrials.gov, NCT02306447. PMID:29515350

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

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.

Low-Frequency Repetitive Transcranial Magnetic Stimulation Targeted to Premotor Cortex Followed by Primary Motor Cortex Modulates Excitability Differently Than Premotor Cortex or Primary Motor Cortex Stimulation Alone.

PubMed

Chen, Mo; Deng, Huiqiong; Schmidt, Rebekah L; Kimberley, Teresa J

2015-12-01

The excitability of primary motor cortex (M1) can be modulated by applying low-frequency repetitive transcranial magnetic stimulation (rTMS) over M1 or premotor cortex (PMC). A comparison of inhibitory effect between the two locations has been reported with inconsistent results. This study compared the response secondary to rTMS applied over M1, PMC, and a combined PMC + M1 stimulation approach which first targets stimulation over PMC then M1. Ten healthy participants were recruited for a randomized, cross-over design with a one-week washout between visits. Each visit consisted of a pretest, an rTMS intervention, and a post-test. Outcome measures included short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). Participants received one of the three interventions in random order at each visit including: 1-Hz rTMS at 90% of resting motor threshold to: M1 (1200 pulses), PMC (1200 pulses), and PMC + M1 (600 pulses each, 1200 total). PMC + M1 stimulation resulted in significantly greater inhibition than the other locations for ICF (P = 0.005) and CSP (P < 0.001); for SICI, increased inhibition (group effect) was not observed after any of the three interventions, and there was no significant difference between the three interventions. The results indicate that PMC + M1 stimulation may modulate brain excitability differently from PMC or M1 alone. CSP was the assessment measure most sensitive to changes in inhibition and was able to distinguish between different inhibitory protocols. This work presents a novel procedure that may have positive implications for therapeutic interventions. © 2015 International Neuromodulation Society.

Whole-brain haemodynamic after-effects of 1-Hz magnetic stimulation of the posterior superior temporal cortex during action observation.

PubMed

Arfeller, Carola; Schwarzbach, Jens; Ubaldi, Silvia; Ferrari, Paolo; Barchiesi, Guido; Cattaneo, Luigi

2013-04-01

The posterior superior temporal sulcus (pSTS) is active when observing biological motion. We investigated the functional connections of the pSTS node within the action observation network by measuring the after-effect of focal repetitive transcranial magnetic stimulation (rTMS) with whole-brain functional magnetic resonance imaging (fMRI). Participants received 1-Hz rTMS over the pSTS region for 10 min and underwent fMRI immediately after. While scanned, they were shown short video clips of a hand grasping an object (grasp clips) or moving next to it (control clips). rTMS-fMRI was repeated for four consecutive blocks. In two blocks we stimulated the left pSTS region and in the other two the right pSTS region. For each side TMS was applied with an effective intensity (95 % of motor threshold) or with ineffective intensity (50 % of motor threshold). Brain regions showing interactive effects of (clip type) × (TMS intensity) were identified in the lateral temporo-occipital cortex, in the anterior intraparietal region and in the ventral premotor cortex. Remote effects of rTMS were mostly limited to the stimulated hemisphere and consisted in an increase of blood oxygen level-dependent responses to grasp clips compared to control clips. We show that the pSTS occupies a pivotal relay position during observation of goal-directed actions.

Cathodal Transcranial Direct Current Stimulation of the Right Wernicke's Area Improves Comprehension in Subacute Stroke Patients

ERIC Educational Resources Information Center

You, Dae Sang; Kim, Dae-Yul; Chun, Min Ho; Jung, Seung Eun; Park, Sung Jong

2011-01-01

Previous studies have shown the appearance of right-sided language-related brain activity in right-handed patients after a stroke. Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been shown to modulate excitability in the brain. Moreover, rTMS and…

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

Repeated mapping of cortical language sites by preoperative navigated transcranial magnetic stimulation compared to repeated intraoperative DCS mapping in awake craniotomy

PubMed Central

2014-01-01

Background Repetitive navigated transcranial magnetic stimulation (rTMS) was recently described for mapping of human language areas. However, its capability of detecting language plasticity in brain tumor patients was not proven up to now. Thus, this study was designed to evaluate such data in order to compare rTMS language mapping to language mapping during repeated awake surgery during follow-up in patients suffering from language-eloquent gliomas. Methods Three right-handed patients with left-sided gliomas (2 opercular glioblastomas, 1 astrocytoma WHO grade III of the angular gyrus) underwent preoperative language mapping by rTMS as well as intraoperative language mapping provided via direct cortical stimulation (DCS) for initial as well as for repeated Resection 7, 10, and 15 months later. Results Overall, preoperative rTMS was able to elicit clear language errors in all mappings. A good correlation between initial rTMS and DCS results was observed. As a consequence of brain plasticity, initial DCS and rTMS findings only corresponded with the results obtained during the second examination in one out of three patients thus suggesting changes of language organization in two of our three patients. Conclusions This report points out the usefulness but also the limitations of preoperative rTMS language mapping to detect plastic changes in language function or for long-term follow-up prior to DCS even in recurrent gliomas. However, DCS still has to be regarded as gold standard. PMID:24479694

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.

Daily left prefrontal repetitive transcranial magnetic stimulation for medication-resistant burning mouth syndrome.

PubMed

Umezaki, Y; Badran, B W; Gonzales, T S; George, M S

2015-08-01

Burning mouth syndrome (BMS) is a persistent and chronic burning sensation in the mouth in the absence of any abnormal organic findings. The pathophysiology of BMS is unclear and its treatment is not fully established. Although antidepressant medication is commonly used for treatment, there are some medication-resistant patients, and a new treatment for medication-resistant BMS is needed. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technology approved by the US Food and Drug Administration (FDA) for the treatment of depression. Recent studies have found beneficial effects of TMS for the treatment of pain. A case of BMS treated successfully with daily left prefrontal rTMS over a 2-week period is reported here. Based on this patient's clinical course and a recent pain study, the mechanism by which TMS may act to decrease the burning pain is discussed. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Treating anxious depression using repetitive transcranial magnetic stimulation.

PubMed

Diefenbach, Gretchen J; Bragdon, Laura; Goethe, John W

2013-10-01

A subset of patients given a clinical diagnosis of major depressive disorder (MDD) are described as having "anxious depression," a presentation that, in some studies, has been an indicator of poor response to pharmacotherapy. The aim of this study was to determine if anxious depression is associated with attenuated response to repetitive transcranial magnetic stimulation (rTMS), an FDA-approved treatment for MDD. Participants were 32 adult outpatients with treatment resistant MDD who were referred for rTMS. The Hamilton Rating Scale for Depression (HAMD) was administered to assess treatment response, and anxious depression was defined as a score of seven or above on the anxiety/somatization factor of the HAMD. A quarter of the sample met the anxious depression criterion at pretreatment. Both depression (total score) and anxiety symptoms improved from pre- to post-treatment with moderate to large treatment effects. Patients with and without anxious depression demonstrated similar rates of improvement in depression. Patients with versus without anxious depression demonstrated larger improvements in anxiety. The sample size was small, and assessments did not include structured diagnostic interview or independent measures of anxiety symptoms. For the sample as a whole, there were significant improvements in both depression and anxiety. Anxious depression was not associated with attenuated treatment response to rTMS. © 2013 Elsevier B.V. All rights reserved.

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

The Emerging Role for rTMS in Optimizing the Treatment of Adolescent Depression

PubMed Central

Croarkin, Paul E.; Wall, Christopher A.; McClintock, Shawn M.; Kozel, F. Andrew; Husain, Mustafa M.; Sampson, Shirlene M.

2010-01-01

Major depressive disorder (MDD) in adolescents is a common illness and significant public health problem. Treatment is challenging due to recurrences and limited modalities. Selective serotonin reuptake inhibitors (SSRIs) and Cognitive Behavioral Therapy (CBT) are considered the standard of care in severe or treatment resistant MDD in this age group. However, responses to these interventions are often suboptimal. A growing body of research supports the efficacy of repetitive transcranial magnetic stimulation for the treatment of MDD in adults. Induced seizures are a primary safety concern, although this is rare with appropriate precautions. There is, however, limited experience with rTMS as a therapeutic intervention for adolescent psychiatric disturbances. This review will summarize the rTMS efficacy and safety data in adults and describe all published experience with adolescent MDD. Applications in other adolescent psychiatric illnesses such as schizophrenia and attention-deficit/hyperactivity disorder (ADHD) are reviewed. Safety and ethical issues are paramount with investigational treatments in adolescent psychiatric illnesses. However, further research with rTMS in adolescent MDD is imperative to establish standards for optimal stimulation site, treatment parameters, and its role in treatment algorithms. These may diverge from adult data. Early intervention with neuromodulation could also hold the promise of addressing the developmental course of dysfunctional neurocircuitry. PMID:20418774

Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment in Enduring Anorexia Nervosa: A Case Series.

PubMed

McClelland, Jessica; Kekic, Maria; Campbell, Iain C; Schmidt, Ulrike

2016-03-01

This case series examined the therapeutic potential of repetitive transcranial magnetic stimulation in five women with enduring anorexia nervosa. Participants received ~20 sessions of neuronavigated high-frequency repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex. Body mass index, eating disorder (ED) symptoms and mood were assessed pre-treatment and post-treatment, at 6-month and 12-month follow-up (FU). Qualitative feedback regarding the intervention was obtained from participants and carers. From pre-treatment to post-treatment, ED and affective symptoms improved significantly, and body mass index remained stable. Further improvements in ED symptoms/mood were seen at 6-month FU with 3/5 and 2/5 participants deemed 'recovered' on the Eating Disorders Examination Questionnaire and Depression, Anxiety and Stress Scale, respectively. However, most participants had lost some weight, and therapeutic effects on psychopathology had waned by 12-month FU. Qualitative feedback regarding the intervention was encouraging. Repetitive transcranial magnetic stimulation was well tolerated, and preliminary evidence is provided for its therapeutic potential in anorexia nervosa. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

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

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

Neural Correlates of the Antinociceptive Effects of Repetitive Transcranial Magnetic Stimulation on Central Pain After Stroke

PubMed Central

Ohn, Suk Hoon; Chang, Won Hyuk; Park, Chang-hyun; Kim, Sung Tae; Lee, Jung Il; Pascual-Leone, Alvaro; Kim, Yun-Hee

2013-01-01

Background Repetitive transcranial magnetic stimulation (rTMS) modulates central neuropathic pain in some patients after stroke, but the mechanisms of action are uncertain. Objective The authors used diffusion tensor imaging (DTI) and functional MRI (fMRI) to evaluate the integrity of the thalamocortical tract (TCT) and the activation pattern of the pain network in 22 patients with poststroke central pain. Methods Each patient underwent daily 10-Hz rTMS sessions for 1000 pulses on 5 consecutive days over the hotspot for the first dorsal interosseus muscle. Pain severity was monitored using the Visual Analogue Scale (VAS). Mood was assessed by the Hamilton Depression Rating Scale. Results Clinical data from all participants along with the DTI and fMRI findings from 10 patients were analyzed. VAS scores decreased significantly, if modestly, following administration of rTMS in 14 responders, which lasted for 2 weeks after the intervention. Regression analysis showed a significant correlation between less initial depression and higher antalgic effect of rTMS. Integrity of the superior TCT in the ipsilesional hemisphere showed significant correlation with change of VAS score after rTMS. fMRI showed significantly decreased activity in the secondary somatosensory cortex, insula, prefrontal cortex, and putamen in rTMS responders, whereas no change was noted in nonresponders. Conclusion Mood may affect the modest antinociceptive effects of rTMS that we found, which may be mediated by the superior TCT through modulation of a distributed pain network. PMID:21980153

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

Low-Intensity Repetitive Transcranial Magnetic Stimulation Improves Abnormal Visual Cortical Circuit Topography and Upregulates BDNF in Mice

PubMed Central

Makowiecki, Kalina; Harvey, Alan R.; Sherrard, Rachel M.

2014-01-01

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used as a treatment for neurological and psychiatric disorders. Although the induced field is focused on a target region during rTMS, adjacent areas also receive stimulation at a lower intensity and the contribution of this perifocal stimulation to network-wide effects is poorly defined. Here, we examined low-intensity rTMS (LI-rTMS)-induced changes on a model neural network using the visual systems of normal (C57Bl/6J wild-type, n = 22) and ephrin-A2A5−/− (n = 22) mice, the latter possessing visuotopic anomalies. Mice were treated with LI-rTMS or sham (handling control) daily for 14 d, then fluorojade and fluororuby were injected into visual cortex. The distribution of dorsal LGN (dLGN) neurons and corticotectal terminal zones (TZs) was mapped and disorder defined by comparing their actual location with that predicted by injection sites. In the afferent geniculocortical projection, LI-rTMS decreased the abnormally high dispersion of retrogradely labeled neurons in the dLGN of ephrin-A2A5−/− mice, indicating geniculocortical map refinement. In the corticotectal efferents, LI-rTMS improved topography of the most abnormal TZs in ephrin-A2A5−/− mice without altering topographically normal TZs. To investigate a possible molecular mechanism for LI-rTMS-induced structural plasticity, we measured brain derived neurotrophic factor (BDNF) in the visual cortex and superior colliculus after single and multiple stimulations. BDNF was upregulated after a single stimulation for all groups, but only sustained in the superior colliculus of ephrin-A2A5−/− mice. Our results show that LI-rTMS upregulates BDNF, promoting a plastic environment conducive to beneficial reorganization of abnormal cortical circuits, information that has important implications for clinical rTMS. PMID:25100609

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.

Short duration repetitive transcranial magnetic stimulation for tinnitus treatment: a prospective Asian study.

PubMed

Ting, S K S; Chan, Y M; Cheong, P W T; Wong, M; Fook-Chong, S; Lo, Y L

2011-09-01

Tinnitus is a subjective auditory perception of sounds or noise not triggered by external auditory stimuli. To date, treatment in severe cases is generally unsatisfactory. Characteristic functional brain imaging changes associated with tinnitus include hyperactivity encompassing both the primary auditory cortex (AC) and the secondary or associative cortex. Brief repetitive transcranial magnetic stimulation (rTMS) trains applied to the scalp overlying the hyperactive left AC is known to produce moderate tinnitus attenuation. Although Western studies have documented the value of rTMS in tinnitus treatment, we evaluate the efficacy of a short duration rTMS protocol for the first time in the Asian setting. Consecutive patients were recruited at our tinnitus clinic. Detailed history, examination, audiogram and baseline tinnitus scales were recorded. RTMS consisted of 1000 pulses/day at 1 Hz and 110% of the motor threshold, for five consecutive days over the left temporoparietal cortex. Tinnitus ratings were determined weekly for 4 weeks after rTMS. Fifteen patients completed the trial; none experienced significant side effects. Repeated measures ANOVA showed significant linear decrease in Tinnitus Handicap Inventory (THI) scores over the time period (F((1,14))=4.7, p=0.04). However, none of the other parameters (severity, annoyance, effect on lifestyle and overall impression: visual analogue scale) showed beneficial outcomes. Our findings point to a positive effect of short duration rTMS in tinnitus treatment using the THI. However, no significant benefits were demonstrated for other subjective patient ratings. Although well tolerated and convenient, short duration rTMS may prove inadequate for modulating maladaptive plastic changes at the cortical level, and our results suggest the need for delivery of more stimuli. Future studies will utilize at least 2000 pulses/day, in line with previous experience in Western settings. Copyright © 2011 Elsevier B.V. All rights

A measure of acoustic noise generated from transcranial magnetic stimulation coils.

PubMed

Dhamne, Sameer C; Kothare, Raveena S; Yu, Camilla; Hsieh, Tsung-Hsun; Anastasio, Elana M; Oberman, Lindsay; Pascual-Leone, Alvaro; Rotenberg, Alexander

2014-01-01

The intensity of sound emanating from the discharge of magnetic coils used in repetitive transcranial magnetic stimulation (rTMS) can potentially cause acoustic trauma. Per Occupational Safety and Health Administration (OSHA) standards for safety of noise exposure, hearing protection is recommended beyond restricted levels of noise and time limits. We measured the sound pressure levels (SPLs) from four rTMS coils with the goal of assessing if the acoustic artifact levels are of sufficient amplitude to warrant protection from acoustic trauma per OSHA standards. We studied the SPLs at two frequencies (5 and 10 Hz), three machine outputs (MO) (60, 80 and 100%), and two distances from the coil (5 and 10 cm). We found that the SPLs were louder at closer proximity from the coil and directly dependent on the MO. We also found that in all studied conditions, SPLs were lower than the OSHA permissible thresholds for short (<15 min) acoustic exposure, but at extremes of use, may generate sufficient noise to warrant ear protection with prolonged (>8 h) exposure. Copyright © 2014 Elsevier Inc. All rights reserved.

The positive effects of high-frequency right dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation on memory, correlated with increases in brain metabolites detected by proton magnetic resonance spectroscopy in recently detoxified alcohol-dependent patients.

PubMed

Qiao, Jun; Jin, Guixing; Lei, Licun; Wang, Lan; Du, Yaqiang; Wang, Xueyi

2016-01-01

To explore the effect of right dorsolateral prefrontal cortex (DLPFC) repetitive transcranial magnetic stimulation (rTMS) on memory, and its correlation with levels of hippocampal brain metabolites detected by proton magnetic resonance spectroscopy ( 1 H-MRS) in recently detoxified alcohol-dependent patients. In this randomized, double-blind sham-controlled trial, alcohol-dependent patients were enrolled and randomized into two groups: the experimental group (rTMS, 10 Hz, on right DLPFC, 20 sessions) and the control group (sham stimulation). Memory function was assessed using Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) before and after treatment. 1 H-MRS was used to detect the levels of N -acetyl aspartic acid (NAA), choline (Cho), and creatine (Cr) in bilateral hippocampi before and after treatment. Thirty-eight patients (18 in the experimental group and 20 in the control group) were included in the analyses. The experimental group showed significantly greater changes in HVLT-R, BVMT-R, NAA/Cr, and Cho/Cr after rTMS from baseline than the control group. The percentage change in BVMT-R and HVLT-R correlated with the percentage change in NAA/Cr and Cho/Cr in the right brain. High-frequency right DLPFC rTMS was associated with improvement in memory dysfunction, which is correlated with levels of hippocampal brain metabolites detected by 1 H-MRS in recently detoxified alcohol-dependent patients.

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

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.

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

Right secondary somatosensory cortex-a promising novel target for the treatment of drug-resistant neuropathic orofacial pain with repetitive transcranial magnetic stimulation.

PubMed

Lindholm, Pauliina; Lamusuo, Salla; Taiminen, Tero; Pesonen, Ullamari; Lahti, Ari; Virtanen, Arja; Forssell, Heli; Hietala, Jarmo; Hagelberg, Nora; Pertovaara, Antti; Parkkola, Riitta; Jääskeläinen, Satu

2015-07-01

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex has analgesic effect; however, the efficacy of other cortical targets and the mode of action remain unclear. We examined the effects of rTMS in neuropathic orofacial pain, and compared 2 cortical targets against placebo. Furthermore, as dopaminergic mechanisms modulate pain responses, we assessed the influence of the functional DRD2 gene polymorphism (957C>T) and the catechol-O-methyltransferase (COMT) Val158Met polymorphism on the analgesic effect of rTMS. Sixteen patients with chronic drug-resistant neuropathic orofacial pain participated in this randomized, placebo-controlled, crossover study. Navigated high-frequency rTMS was given to the sensorimotor (S1/M1) and the right secondary somatosensory (S2) cortices. All subjects were genotyped for the DRD2 957C>T and COMT Val158Met polymorphisms. Pain, mood, and quality of life were monitored throughout the study. The numerical rating scale pain scores were significantly lower after the S2 stimulation than after the S1/M1 (P = 0.0071) or the sham (P = 0.0187) stimulations. The Brief Pain Inventory scores were also lower 3 to 5 days after the S2 stimulation than those at pretreatment baseline (P = 0.0127 for the intensity of pain and P = 0.0074 for the interference of pain) or after the S1/M1 (P = 0.001 and P = 0.0001) and sham (P = 0.0491 and P = 0.0359) stimulations. No correlations were found between the genetic polymorphisms and the analgesic effect in the present small clinical sample. The right S2 cortex is a promising new target for the treatment of neuropathic orofacial pain with high-frequency rTMS.

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.

Results on the spatial resolution of repetitive transcranial magnetic stimulation for cortical language mapping during object naming in healthy subjects.

PubMed

Sollmann, Nico; Hauck, Theresa; Tussis, Lorena; Ille, Sebastian; Maurer, Stefanie; Boeckh-Behrens, Tobias; Ringel, Florian; Meyer, Bernhard; Krieg, Sandro M

2016-10-24

The spatial resolution of repetitive navigated transcranial magnetic stimulation (rTMS) for language mapping is largely unknown. Thus, to determine a minimum spatial resolution of rTMS for language mapping, we evaluated the mapping sessions derived from 19 healthy volunteers for cortical hotspots of no-response errors. Then, the distances between hotspots (stimulation points with a high error rate) and adjacent mapping points (stimulation points with low error rates) were evaluated. Mean distance values of 13.8 ± 6.4 mm (from hotspots to ventral points, range 0.7-30.7 mm), 10.8 ± 4.8 mm (from hotspots to dorsal points, range 2.0-26.5 mm), 16.6 ± 4.8 mm (from hotspots to apical points, range 0.9-27.5 mm), and 13.8 ± 4.3 mm (from hotspots to caudal points, range 2.0-24.2 mm) were measured. According to the results, the minimum spatial resolution of rTMS should principally allow for the identification of a particular gyrus, and according to the literature, it is in good accordance with the spatial resolution of direct cortical stimulation (DCS). Since measurement was performed between hotspots and adjacent mapping points and not on a finer-grained basis, we only refer to a minimum spatial resolution. Furthermore, refinement of our results within the scope of a prospective study combining rTMS and DCS for resolution measurement during language mapping should be the next step.

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.

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.

One hertz repetitive transcranial magnetic stimulation over dorsal premotor cortex enhances offline motor memory consolidation for sequence-specific implicit learning.

PubMed

Meehan, S K; Zabukovec, J R; Dao, E; Cheung, K L; Linsdell, M A; Boyd, L A

2013-10-01

Consolidation of motor memories associated with skilled practice can occur both online, concurrent with practice, and offline, after practice has ended. The current study investigated the role of dorsal premotor cortex (PMd) in early offline motor memory consolidation of implicit sequence-specific learning. Thirty-three participants were assigned to one of three groups of repetitive transcranial magnetic stimulation (rTMS) over left PMd (5 Hz, 1 Hz or control) immediately following practice of a novel continuous tracking task. There was no additional practice following rTMS. This procedure was repeated for 4 days. The continuous tracking task contained a repeated sequence that could be learned implicitly and random sequences that could not. On a separate fifth day, a retention test was performed to assess implicit sequence-specific motor learning of the task. Tracking error was decreased for the group who received 1 Hz rTMS over the PMd during the early consolidation period immediately following practice compared with control or 5 Hz rTMS. Enhanced sequence-specific learning with 1 Hz rTMS following practice was due to greater offline consolidation, not differences in online learning between the groups within practice days. A follow-up experiment revealed that stimulation of PMd following practice did not differentially change motor cortical excitability, suggesting that changes in offline consolidation can be largely attributed to stimulation-induced changes in PMd. These findings support a differential role for the PMd in support of online and offline sequence-specific learning of a visuomotor task and offer converging evidence for competing memory systems. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: a systematic review and meta-analysis.

PubMed

Ren, Juanjuan; Li, Hui; Palaniyappan, Lena; Liu, Hongmei; Wang, Jijun; Li, Chunbo; Rossini, Paolo Maria

2014-06-03

Electroconvulsive therapy (ECT) is the most effective treatment of depression. During the last decades repetitive transcranial magnetic stimulation (rTMS), an alternative method using electric stimulation of the brain, has revealed possible alternative to ECT in the treatment of depression. There are some clinical trials comparing their efficacies and safeties but without clear conclusions, mainly due to their small sample sizes. In the present study, a meta-analysis had been carried out to gain statistical power. Outcomes were response, remission, acceptability and cognitive effects in depression. Following a comprehensive literature search that included both English and Chinese language databases, we identified all randomized controlled trials that directly compared rTMS and ECT for major depression. 10 articles (9 trials) with a total of 425 patients were identified. Methodological quality, heterogeneity, sensitivity and publication bias were systematically evaluated. ECT was superior to high frequency rTMS in terms of response (64.4% vs. 48.7%, RR = 1.41, p = 0.03), remission (52.9% vs. 33.6%, RR = 1.38, p = 0.006) while discontinuation was not significantly different between the two treatments (8.3% vs. 9.4%, RR = 1.11, p = 0.80). According to the subgroup analysis, the superiority of ECT was more apparent in those with psychotic depression, while high frequency rTMS was as effective as ECT in those with non-psychotic depression. The same results were obtained in the comparison of ECT with low frequency rTMS. ECT had a non-significant advantage over high frequency rTMS on the overall improvement in HAMD scores (p = 0.11). There was insufficient data on medium or long term efficacy. Both rTMS and ECT were well tolerated with only minor side effects reported. Results based on 3 studies suggested that specific cognitive domains such as visual memory and verbal fluency were more impaired in patients receiving ECT. In conclusion, ECT seemed more effective than and

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

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.

Efficacy of deep rTMS for neuropathic pain in the lower limb: a randomized, double-blind crossover trial of an H-coil and figure-8 coil.

PubMed

Shimizu, Takeshi; Hosomi, Koichi; Maruo, Tomoyuki; Goto, Yuko; Yokoe, Masaru; Kageyama, Yu; Shimokawa, Toshio; Yoshimine, Toshiki; Saitoh, Youichi

2017-11-01

OBJECTIVE Electrical motor cortex stimulation can relieve neuropathic pain (NP), but its use requires patients to undergo an invasive procedure. Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) using a figure-8 coil can relieve NP noninvasively, but its ability to relieve lower limb pain is still limited. Deep rTMS using an H-coil can effectively stimulate deep brain regions and has been widely used for the treatment of various neurological diseases; however, there have been no clinical studies comparing the effectiveness of figure-8 coils and H-coils. This study assessed the clinical effectiveness of 5 once-daily stimulations with H-coils and figure-8 coils in patients with NP. METHODS This randomized, double-blind, 3-way crossover trial examined 18 patients with NP who sequentially received 3 types of stimulations in the M1 for 5 consecutive days; each 5-day stimulation period was followed by a 17-day follow-up period before crossing over to the next type of stimulation. During each rTMS session, patients received a 5-Hz rTMS to the M1 region corresponding to the painful lower limb. The visual analog scale (VAS) and the Japanese version of the short-form McGill Pain Questionnaire 2 (SF-MPQ2-J) were used to measure pain intensity. The primary outcome was VAS score reduction immediately after and 1 hour after intervention. RESULTS Both the VAS and SF-MPQ2-J showed significant pain improvement immediately after deep rTMS with an H-coil as compared with the sham group (p < 0.001 and p = 0.049, respectively). However, neither outcome measure showed significant pain improvement when using a figure-8 coil. The VAS also showed significant pain improvement 1 hour after deep rTMS with an H-coil (p = 0.004) but not 1 hour after rTMS using a figure-8 coil. None of the patients exhibited any serious adverse events. CONCLUSIONS The current findings suggest that the use of deep rTMS with an H-coil in the lower limb region of the M1 in

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

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

Clinical improvement in patients with borderline personality disorder after treatment with repetitive transcranial magnetic stimulation: preliminary results.

PubMed

Reyes-López, Julian; Ricardo-Garcell, Josefina; Armas-Castañeda, Gabriela; García-Anaya, María; Arango-De Montis, Iván; González-Olvera, Jorge J; Pellicer, Francisco

2018-01-01

Current treatment of borderline personality disorder (BPD) consists of psychotherapy and pharmacological interventions. However, the use of repetitive transcranial magnetic stimulation (rTMS) could be beneficial to improve some BPD symptoms. The objective of this study was to evaluate clinical improvement in patients with BPD after application of rTMS over the right or left dorsolateral prefrontal cortex (DLPFC). Twenty-nine patients with BPD from the National Institute of Psychiatry, Mexico, were randomized in two groups to receive 15 sessions of rTMS applied over the right (1 Hz, n=15) or left (5 Hz, n=14) DLPFC. Improvement was measured by the Clinical Global Impression Scale for BPD (CGI-BPD), Borderline Evaluation of Severity Over Time (BEST), Beck Depression Inventory (BDI), Hamilton Anxiety Rating Scale (HAM-A), and Barratt Impulsiveness Scale (BIS). Intragroup comparison showed significant (p < 0.05) reductions in every psychopathologic domain of the CGI-BPD and in the total scores of all scales in both groups. Both protocols produced global improvement in severity and symptoms of BPD, particularly in impulsiveness, affective instability, and anger. Further studies are warranted to explore the therapeutic effect of rTMS in BPD. NCT02273674

The effect of rTMS over the inferior parietal lobule on EEG sensorimotor reactivity differs according to self-reported traits of autism in typically developing individuals.

PubMed

Puzzo, Ignazio; Cooper, Nicholas R; Cantarella, Simona; Fitzgerald, Paul B; Russo, Riccardo

2013-12-06

Previous research suggested that EEG markers of mirror neuron system activation may differ, in the normal population as a function of different levels of the autistic spectrum quotient; (AQ). The present study aimed at modulating the EEG sensorimotor reactivity induced by hand movement observation by means of repetitive transcranial magnetic stimulation (rTMS) applied to the inferior parietal lobule. We examined how the resulting rTMS modulation differed in relation to the self-reported autistic traits in the typically developing population. Results showed that during sham stimulation, all participants had significantly greater sensorimotor alpha reactivity (motor cortex-C electrodes) when observing hand movements compared to static hands. This sensorimotor alpha reactivity difference was reduced during active rTMS stimulation. Results also revealed that in the average AQ group at sham there was a significant increase in low beta during hand movement than static hand observation (pre-motor areas-FC electrodes) and that (like alpha over the C electrodes) this difference is abolished when active rTMS is delivered. Participants with high AQ scores showed no significant difference in low beta sensorimotor reactivity between active and sham rTMS during static hand or hand movement observation. These findings suggest that unlike sham, active rTMS over the IPL modulates the oscillatory activity of the low beta frequency of a distal area, namely the anterior sector of the sensorimotor cortex, when participants observe videos of static hand. Importantly, this modulation differs according to the degree of self-reported traits of autism in a typically developing population. © 2013 Elsevier B.V. All rights reserved.

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.

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

High-frequency repetitive transcranial magnetic stimulation over the left DLPFC for major depression: Session-dependent efficacy: A meta-analysis.

PubMed

Teng, S; Guo, Z; Peng, H; Xing, G; Chen, H; He, B; McClure, M A; Mu, Q

2017-03-01

Depression is a major debilitating psychiatric disorder. Current antidepressant drugs are often associated with side effects or treatment resistance. The aim of this meta-analysis was to evaluate therapeutic effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) in major depression (MD). The medical data bases of PubMed, Medline, Embase and Cochrane Central Register were searched for randomized controlled trials (RCTs) reporting the therapeutic effects of high-frequency rTMS for depression, which were published in English between January 1990 and June 2016. The index terms were "depress*", "depression" and "transcranial magnetic stimulation". Depression outcome data of different sessions (5, 10, 15, and 20 sessions of rTMS treatment) were extracted and synthesized by calculating standardized mean difference (SMD) with 95% confidence intervals (CI) by using a random-effect model. Within each session group, the subgroup analyses based on the number of pulses (≤1000, 1200-1500, 1600-1800, and 2000-3000) were also conducted. Thirty RCTs with a total of 1754 subjects including 1136 in the rTMS group and 618 in the sham group were included in this meta-analysis. rTMS had a significant overall therapeutic effect on depression severity scores (SMD=-0.73, P<0.00001). The five, 10, 15, 20 sessions of rTMS treatments yielded the significant mean effect sizes of -0.43, -0.60, -1.13, and -2.74, respectively. In the four groups (5, 10, 15, 20 sessions), the maximal mean effect size was all obtained in the subgroup of 1200-1500 pulses per day (-0.97, -1.14, -1.91, -5.47; P<0.05). The increasing of HF-rTMS sessions is associated with the increased efficacy of HF-rTMS in reducing depressed patients' symptom severity. A total number of pulses of 1200-1500 per day appear to deliver the best antidepressant effects of HF-rTMS. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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.

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.

Lateralized Contribution of Prefrontal Cortex in Controlling Task-Irrelevant Information during Verbal and Spatial Working Memory Tasks: rTMS Evidence

ERIC Educational Resources Information Center

Sandrini, Marco; Rossini, Paolo Maria; Miniussi, Carlo

2008-01-01

The functional organization of working memory (WM) in the human prefrontal cortex remains unclear. The present study used repetitive transcranial magnetic stimulation (rTMS) to clarify the role of the dorsolateral prefrontal cortex (dlPFC) both in the types of information (verbal vs. spatial), and the types of processes (maintenance vs.…

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.

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

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

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.

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.

Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders

PubMed Central

2014-01-01

Background Repetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood. Results Here we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically. Conclusions Deep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models. PMID:24512669

Role of the dorsal premotor cortex in rhythmic auditory-motor entrainment: a perturbational approach by rTMS.

PubMed

Giovannelli, Fabio; Innocenti, Iglis; Rossi, Simone; Borgheresi, Alessandra; Ragazzoni, Aldo; Zaccara, Gaetano; Viggiano, Maria Pia; Cincotta, Massimo

2014-04-01

Synchronization of body movements to an external beat is a universal human ability, which has also been recently documented in nonhuman species. The neural substrates of this rhythmic motor entrainment are still under investigation. Correlational neuroimaging data suggest an involvement of the dorsal premotor cortex (dPMC) and the supplementary motor area (SMA). In 14 healthy volunteers, we more specifically investigated the neural network underlying this phenomenon using a causal approach by an established 1-Hz repetitive transcranial magnetic stimulation (rTMS) protocol, which produces a focal suppression of cortical excitability outlasting the stimulation period. Synchronization accuracy between rhythmic cues and right index finger tapping, as measured by the mean time lag (asynchrony) between motor and auditory events, was significantly affected when the right dPMC function was transiently perturbed by "off-line" focal rTMS, whereas the reproduction of the rhythmic sequence per se (inter-tap-interval) was spared. This approach affected metrical rhythms of different complexity, but not non-metrical or isochronous sequences. Conversely, no change in auditory-motor synchronization was observed with rTMS of the SMA, of the left dPMC or over a control site (midline occipital area). Our data strongly support the view that the right dPMC is crucial for rhythmic auditory-motor synchronization in humans.

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.

Focal hand dystonia: individualized intervention with repeated application of repetitive transcranial magnetic stimulation

PubMed Central

Kimberley, Teresa Jacobson; Borich, Michael R.; Schmidt, Rebekah; Carey, James R.; Gillick, Bernadette

2016-01-01

Objective Examine for individual factors that may predict response to inhibitory repetitive transcranial magnetic stimulation (rTMS) in focal hand dystonia (FHD); present method for determining the optimal stimulation to increase inhibition in a given patient; and examine individual responses to prolonged intervention. Design A single-subject design to determine optimal parameters to increase inhibition for a given subject and to employ the selected parameters 1/wk for 6 weeks, with 1 wk follow up, to determine response. Setting Clinical research laboratory Participants A volunteer sample of 2 subjects with FHD. One participant had TMS responses indicating impaired inhibition, the other had responses within normal limits. Interventions 1200 pulses of 1 Hz rTMS delivered using 4 different stimulation site/intensity combinations: primary motor cortex (M1) at 90% or 110% resting motor threshold (RMT); dorsal premotor cortex (PMd) at 90% or 110% of RMT. The parameters producing the greatest within-session increase in cortical silent period (CSP) duration were then used as intervention. Main outcome measures Response variables included handwriting pressure and velocity, subjective symptom rating, CSP, and short-latency intracortical inhibition and facilitation. Results The individual with baseline TMS responses indicating impaired inhibition responded favorably to the repeated intervention, with reduced handwriting force, increase in CSP and subjective report of “moderate” symptom improvement at 1-wk follow-up. The individual with normal baseline responses failed to respond to the intervention. In both subjects, 90% RMT to PMd produced greatest lengthening of CSP and was used as intervention. Conclusions An individualized understanding of neurophysiologic measures may be indicators of responsiveness to inhibitory rTMS in focal dystonia, with further work needed to determine 3 likely responders vs. non-responders. PMID:25256555

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.

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.

Brain stimulation to treat Internet addiction: A commentary.

PubMed

Trojak, Benoit; Zullino, Daniele; Achab, Sophia

2017-01-01

In February, 2015, French television screened a report on Internet addiction (IA) in which an individual, identifying himself as cyberdependent, was offered treatment with repetitive Transcranial Magnetic Stimulation (rTMS), a Non-Invasive Brain Stimulation (NIBS) technique. Two issues deserve to be emphasized. Firstly, the concept of IA is not unanimously recognized by scientists and has raised a number of questions. Secondly, although the first results suggest that brain stimulation techniques could be a potential therapy for Substance Use Disorders (SUDs), no data are available on the therapeutic effects of rTMS on IA or even excessive Internet use. Currently, we cannot promote the use of rTMS for Internet detoxification because there is no evidence to prove its efficacy. Nevertheless, the similarities between SUDs and IA, and the results of NIBS on SUDs suggest that research can be done to examine the efficacy of NIBS techniques to treat Internet gaming disorder and other forms of IA. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Accelerometer-based automatic voice onset detection in speech mapping with navigated repetitive transcranial magnetic stimulation.

PubMed

Vitikainen, Anne-Mari; Mäkelä, Elina; Lioumis, Pantelis; Jousmäki, Veikko; Mäkelä, Jyrki P

2015-09-30

The use of navigated repetitive transcranial magnetic stimulation (rTMS) in mapping of speech-related brain areas has recently shown to be useful in preoperative workflow of epilepsy and tumor patients. However, substantial inter- and intraobserver variability and non-optimal replicability of the rTMS results have been reported, and a need for additional development of the methodology is recognized. In TMS motor cortex mappings the evoked responses can be quantitatively monitored by electromyographic recordings; however, no such easily available setup exists for speech mappings. We present an accelerometer-based setup for detection of vocalization-related larynx vibrations combined with an automatic routine for voice onset detection for rTMS speech mapping applying naming. The results produced by the automatic routine were compared with the manually reviewed video-recordings. The new method was applied in the routine navigated rTMS speech mapping for 12 consecutive patients during preoperative workup for epilepsy or tumor surgery. The automatic routine correctly detected 96% of the voice onsets, resulting in 96% sensitivity and 71% specificity. Majority (63%) of the misdetections were related to visible throat movements, extra voices before the response, or delayed naming of the previous stimuli. The no-response errors were correctly detected in 88% of events. The proposed setup for automatic detection of voice onsets provides quantitative additional data for analysis of the rTMS-induced speech response modifications. The objectively defined speech response latencies increase the repeatability, reliability and stratification of the rTMS results. Copyright © 2015 Elsevier B.V. All rights reserved.

Improvements in emotion regulation following repetitive transcranial magnetic stimulation for generalized anxiety disorder.

PubMed

Diefenbach, Gretchen J; Assaf, Michal; Goethe, John W; Gueorguieva, Ralitza; Tolin, David F

2016-10-01

Generalized anxiety disorder (GAD) is characterized by emotion regulation difficulties, which are associated with abnormalities in neural circuits encompassing fronto-limbic regions including the dorsolateral prefrontal cortex (DLPFC). The aim of this study was to determine whether DLPFC neuromodulation improves emotion regulation in patients with GAD. This is a secondary analysis from a randomized-controlled trial comparing 30 sessions of low-frequency right-sided active (n=13) versus sham (n=12, sham coil) repetitive transcranial magnetic stimulation (rTMS) at the right DLPFC in patients with GAD. Results indicated statistically significant improvements in self-reported emotion regulation difficulties at posttreatment and 3-month follow-up in the active group only. Improvements were found primarily in the domains of goal-directed behaviors and impulse control and were significantly associated with a global clinician rating of improvement. These preliminary results support rTMS as a treatment for GAD and suggest improved emotion regulation as a possible mechanism of change. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

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

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 for treatment of major depressive disorder with comorbid generalized anxiety disorder.

PubMed

White, Daniela; Tavakoli, Sason

2015-08-01

Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in treating individuals with behavioral disorders such as major depressive disorder (MDD), posttraumatic stress disorder, obsessive-compulsive disorder, and social anxiety disorder. A number of applications of rTMS to different regions of the left and right prefrontal cortex have been used to treat these disorders, but no study of treatment for MDD with generalized anxiety disorder (GAD) has been conducted with application of rTMS to both the left and right prefrontal cortex. We hypothesized that applying low-frequency rTMS to the right dorsolateral prefrontal cortex (DLPFC) before applying it to the left DLPFC for the treatment of depression would be anxiolytic in patients with MDD with GAD. Thirteen adult patients with comorbid MDD and GAD received treatment with rTMS in an outpatient setting. The number of treatments ranged from 24 to 36 over 5 to 6 weeks. Response was defined as a ≥ 50% reduction in symptoms from baseline, and remission was defined as a score of < 5 for anxiety symptoms on the 7-item Generalized Anxiety Disorder (GAD-7) scale and < 8 for depressive symptoms on the 21-item Hamilton Rating Scale for Depression (HAM-D-21). At the end of the treatment period, for the GAD-7 scale, 11 out of 13 (84.6%) patients' anxiety symptoms were in remission, achieving a score of < 5 on the GAD-7, and 10 out of 13 patients (76.9%) achieved a HAM-D-21 score of < 8 for depressive symptoms. In this small pilot study of 13 patients with comorbid MDD and GAD, significant improvement in anxiety symptoms along with depressive symptoms was achieved in a majority of patients after bilateral rTMS application.

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.

Test-retest assessment of cortical activation induced by repetitive transcranial magnetic stimulation with brain atlas-guided optical topography

NASA Astrophysics Data System (ADS)

Tian, Fenghua; Kozel, F. Andrew; Yennu, Amarnath; Croarkin, Paul E.; McClintock, Shawn M.; Mapes, Kimberly S.; Husain, Mustafa M.; Liu, Hanli

2012-11-01

Repetitive transcranial magnetic stimulation (rTMS) is a technology that stimulates neurons with rapidly changing magnetic pulses with demonstrated therapeutic applications for various neuropsychiatric disorders. Functional near-infrared spectroscopy (fNIRS) is a suitable tool to assess rTMS-evoked brain responses without interference from the magnetic or electric fields generated by the TMS coil. We have previously reported a channel-wise study of combined rTMS/fNIRS on the motor and prefrontal cortices, showing a robust decrease of oxygenated hemoglobin concentration (Δ[HbO2]) at the sites of 1-Hz rTMS and the contralateral brain regions. However, the reliability of this putative clinical tool is unknown. In this study, we develop a rapid optical topography approach to spatially characterize the rTMS-evoked hemodynamic responses on a standard brain atlas. A hemispherical approximation of the brain is employed to convert the three-dimensional topography on the complex brain surface to a two-dimensional topography in the spherical coordinate system. The test-retest reliability of the combined rTMS/fNIRS is assessed using repeated measurements performed two to three days apart. The results demonstrate that the Δ[HbO2] amplitudes have moderate-to-high reliability at the group level; and the spatial patterns of the topographic images have high reproducibility in size and a moderate degree of overlap at the individual level.

Efficacy of repetitive transcranial magnetic stimulation with quetiapine in treating bipolar II depression: a randomized, double-blinded, control study.

PubMed

Hu, Shao-Hua; Lai, Jian-Bo; Xu, Dong-Rong; Qi, Hong-Li; Peterson, Bradley S; Bao, Ai-Min; Hu, Chan-Chan; Huang, Man-Li; Chen, Jing-Kai; Wei, Ning; Hu, Jian-Bo; Li, Shu-Lan; Zhou, Wei-Hua; Xu, Wei-Juan; Xu, Yi

2016-07-27

The clinical and cognitive responses to repetitive transcranial magnetic stimulation (rTMS) in bipolar II depressed patients remain unclear. In this study, thirty-eight bipolar II depressed patients were randomly assigned into three groups: (i) left high-frequency (n = 12), (ii) right low-frequency (n = 13), (iii) sham stimulation (n = 13), and underwent four-week rTMS with quetiapine concomitantly. Clinical efficacy was evaluated at baseline and weekly intervals using the 17-item Hamilton Depression Rating Scale (HDRS-17) and Montgomery-Asberg Depression Rating Scale (MADRS). Cognitive functioning was assessed before and after the study with the Wisconsin Card Sorting Test (WCST), Stroop Word-Color Interference Test (Stroop), and Trail Making Test (TMT). Thirty-five patients were included in the final analysis. Overall, the mean scores of both the HDRS-17 and the MADRS significantly decreased over the 4-week trial, which did not differ among the three groups. Exploratory analyses revealed no differences in factor scores of HDRS-17s, or in response or remission rates. Scores of WCST, Stroop, or TMT did not differ across the three groups. These findings indicated active rTMS combined with quetiapine was not superior to quetiapine monotherapy in improving depressive symptoms or cognitive performance in patients with bipolar II depression.

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

Effect of Low-Frequency rTMS on Aphasia in Stroke Patients: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

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

Background 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. Methods 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. Results 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. Conclusions 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

Evaluating the roles of the inferior frontal gyrus and superior parietal lobule in deductive reasoning: an rTMS study.

PubMed

Tsujii, Takeo; Sakatani, Kaoru; Masuda, Sayako; Akiyama, Takekazu; Watanabe, Shigeru

2011-09-15

This study used off-line repetitive transcranial magnetic stimulation (rTMS) to examine the roles of the superior parietal lobule (SPL) and inferior frontal gyrus (IFG) in a deductive reasoning task. Subjects performed a categorical syllogistic reasoning task involving congruent, incongruent, and abstract trials. Twenty four subjects received magnetic stimulation to the SPL region prior to the task. In the other 24 subjects, TMS was administered to the IFG region before the task. Stimulation lasted for 10min, with an inter-pulse frequency of 1Hz. We found that bilateral SPL (Brodmann area (BA) 7) stimulation disrupted performance on abstract and incongruent reasoning. Left IFG (BA 45) stimulation impaired congruent reasoning performance while paradoxically facilitating incongruent reasoning performance. This resulted in the elimination of the belief-bias. In contrast, right IFG stimulation only impaired incongruent reasoning performance, thus enhancing the belief-bias effect. These findings are largely consistent with the dual-process theory of reasoning, which proposes the existence of two different human reasoning systems: a belief-based heuristic system; and a logic-based analytic system. The present findings suggest that the left language-related IFG (BA 45) may correspond to the heuristic system, while bilateral SPL may underlie the analytic system. The right IFG may play a role in blocking the belief-based heuristic system for solving incongruent reasoning trials. This study could offer an insight about functional roles of distributed brain systems in human deductive reasoning by utilizing the rTMS approach. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Combining functional neuroimaging with off-line brain stimulation: modulation of task-related activity in language areas.

PubMed

Andoh, Jamila; Paus, Tomás

2011-02-01

Repetitive TMS (rTMS) provides a noninvasive tool for modulating neural activity in the human brain. In healthy participants, rTMS applied over the language-related areas in the left hemisphere, including the left posterior temporal area of Wernicke (LTMP) and inferior frontal area of Broca, have been shown to affect performance on word recognition tasks. To investigate the neural substrate of these behavioral effects, off-line rTMS was combined with fMRI acquired during the performance of a word recognition task. Twenty right-handed healthy men underwent fMRI scans before and after a session of 10-Hz rTMS applied outside the magnetic resonance scanner. Functional magnetic resonance images were acquired during the performance of a word recognition task that used English or foreign-language words. rTMS was applied over the LTMP in one group of 10 participants (LTMP group), whereas the homologue region in the right hemisphere was stimulated in another group of 10 participants (RTMP group). Changes in task-related fMRI response (English minus foreign languages) and task performances (response time and accuracy) were measured in both groups and compared between pre-rTMS and post-rTMS. Our results showed that rTMS increased task-related fMRI response in the homologue areas contralateral to the stimulated sites. We also found an effect of rTMS on response time for the LTMP group only. These findings provide insights into changes in neural activity in cortical regions connected to the stimulated site and are consistent with a hypothesis raised in a previous review about the role of the homologue areas in the contralateral hemisphere for preserving behavior after neural interference.

Low-Frequency Repetitive Transcranial Magnetic Stimulation and Intensive Occupational Therapy for Poststroke Patients with Upper Limb Hemiparesis: Preliminary Study of a 15-Day Protocol

ERIC Educational Resources Information Center

Kakuda, Wataru; Abo, Masahiro; Kobayashi, Kazushige; Momosaki, Ryo; Yokoi, Aki; Fukuda, Akiko; Ishikawa, Atsushi; Ito, Hiroshi; Tominaga, Ayumi

2010-01-01

The purpose of the study was to determine the safety and feasibility of a 15-day protocol of low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with intensive occupational therapy (OT) on motor function and spasticity in hemiparetic upper limbs in poststroke patients. Fifteen poststroke patients (age at study entry 55 [plus…

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.

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

New modalities of brain stimulation for stroke rehabilitation

PubMed Central

Lucas, T. H.; Carey, J. R.; Fetz, E. E.

2014-01-01

Stroke is a leading cause of disability, and the number of stroke survivors continues to rise. Traditional neurorehabilitation strategies aimed at restoring function to weakened limbs provide only modest benefit. New brain stimulation techniques designed to augment traditional neurorehabilitation hold promise for reducing the burden of stroke-related disability. Investigators discovered that repetitive transcranial magnetic stimulation (rTMS), trans-cranial direct current stimulation (tDCS), and epidural cortical stimulation (ECS) can enhance neural plasticity in the motor cortex post-stroke. Improved outcomes may be obtained with activity-dependent stimulation, in which brain stimulation is contingent on neural or muscular activity during normal behavior. We review the evidence for improved motor function in stroke patients treated with rTMS, tDCS, and ECS and discuss the mediating physiological mechanisms. We compare these techniques to activity-dependent stimulation, discuss the advantages of this newer strategy for stroke rehabilitation, and suggest future applications for activity-dependent brain stimulation. PMID:23192336

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.

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.

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

Cortical regions involved in semantic processing investigated by repetitive navigated transcranial magnetic stimulation and object naming.

PubMed

Sollmann, Nico; Tanigawa, Noriko; Tussis, Lorena; Hauck, Theresa; Ille, Sebastian; Maurer, Stefanie; Negwer, Chiara; Zimmer, Claus; Ringel, Florian; Meyer, Bernhard; Krieg, Sandro M

2015-04-01

Knowledge about the cortical representation of semantic processing is mainly derived from functional magnetic resonance imaging (fMRI) or direct cortical stimulation (DCS) studies. Because DCS is regarded as the gold standard in terms of language mapping but can only be used during awake surgery due to its invasive character, repetitive navigated transcranial magnetic stimulation (rTMS)—a non-invasive modality that uses a similar technique as DCS—seems highly feasible for use in the investigation of semantic processing in the healthy human brain. A total number of 100 (50 left-hemispheric and 50 right-hemispheric) rTMS-based language mappings were performed in 50 purely right-handed, healthy volunteers during an object-naming task. All rTMS-induced semantic naming errors were then counted and evaluated systematically. Furthermore, since the distribution of stimulations within both hemispheres varied between individuals and cortical regions stimulated, all elicited errors were standardized and subsequently related to their cortical sites by projecting the mapping results into the cortical parcellation system (CPS). Overall, the most left-hemispheric semantic errors were observed after targeting the rTMS to the posterior middle frontal gyrus (pMFG; standardized error rate: 7.3‰), anterior supramarginal gyrus (aSMG; 5.6‰), and ventral postcentral gyrus (vPoG; 5.0‰). In contrast to that, the highest right-hemispheric error rates occurred after stimulation of the posterior superior temporal gyrus (pSTG; 12.4‰), middle superior temporal gyrus (mSTG; 6.2‰), and anterior supramarginal gyrus (aSMG; 6.2‰). Although error rates were low, the rTMS-based approach of investigating semantic processing during object naming shows convincing results compared to the current literature. Therefore, rTMS seems a valuable, safe, and reliable tool for the investigation of semantic processing within the healthy human brain. Copyright © 2015 Elsevier Ltd. All rights

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

PubMed

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

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

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.

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 Repetitive Transcranial Magnetic Stimulation in the Rehabilitation of Communication and Deglutition Disorders: Systematic Review of Randomized Controlled Trials.

PubMed

Gadenz, Camila Dalbosco; Moreira, Tais de Campos; Capobianco, Dirce Maria; Cassol, Mauriceia

2015-01-01

To systematically review randomized controlled trials that evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on rehabilitation aspects related to communication and swallowing functions. A search was conducted on PubMed, Clinical Trials, Cochrane Library, and ASHA electronic databases. Studies were judged according to the eligibility criteria and analyzed by 2 independent and blinded researchers. We analyzed 9 studies: 4 about aphasia, 3 about dysphagia, 1 about dysarthria in Parkinson's disease and 1 about linguistic deficits in Alzheimer's disease. All aphasia studies used low-frequency rTMS to stimulate Broca's homologous area. High-frequency rTMS was applied over the pharyngoesophageal cortex from the left and/or right hemisphere in the dysphagia studies and over the left dorsolateral prefrontal cortex in the Parkinson's and Alzheimer's studies. Two aphasia and all dysphagia studies showed a significant improvement of the disorder, compared to the sham group. The other 2 studies related to aphasia found a benefit restricted to subgroups with a severe case or injury on the anterior portion of the language cortical area, respectively, whereas the Alzheimer's study demonstrated positive effects specific to auditory comprehension. There were no changes for vocal function in the Parkinson's study. The benefits of the technique and its applicability in neurogenic disorders related to communication and deglutition are still uncertain. Therefore, other randomized controlled trials are needed to clarify the optimal stimulation protocol for each disorder studied and its real effects. © 2015 S. Karger AG, Basel.

Short and Long Term Effects of Left and Bilateral Repetitive Transcranial Magnetic Stimulation in Schizophrenia Patients with Auditory Verbal Hallucinations: A Randomized Controlled Trial

PubMed Central

Bais, Leonie; Vercammen, Ans; Stewart, Roy; van Es, Frank; Visser, Bert; Aleman, André; Knegtering, Henderikus

2014-01-01

Background Repetitive transcranial magnetic stimulation of the left temporo-parietal junction area has been studied as a treatment option for auditory verbal hallucinations. Although the right temporo-parietal junction area has also shown involvement in the genesis of auditory verbal hallucinations, no studies have used bilateral stimulation. Moreover, little is known about durability effects. We studied the short and long term effects of 1 Hz treatment of the left temporo-parietal junction area in schizophrenia patients with persistent auditory verbal hallucinations, compared to sham stimulation, and added an extra treatment arm of bilateral TPJ area stimulation. Methods In this randomized controlled trial, 51 patients diagnosed with schizophrenia and persistent auditory verbal hallucinations were randomly allocated to treatment of the left or bilateral temporo-parietal junction area or sham treatment. Patients were treated for six days, twice daily for 20 minutes. Short term efficacy was measured with the Positive and Negative Syndrome Scale (PANSS), the Auditory Hallucinations Rating Scale (AHRS), and the Positive and Negative Affect Scale (PANAS). We included follow-up measures with the AHRS and PANAS at four weeks and three months. Results The interaction between time and treatment for Hallucination item P3 of the PANSS showed a trend for significance, caused by a small reduction of scores in the left group. Although self-reported hallucination scores, as measured with the AHRS and PANAS, decreased significantly during the trial period, there were no differences between the three treatment groups. Conclusion We did not find convincing evidence for the efficacy of left-sided rTMS, compared to sham rTMS. Moreover, bilateral rTMS was not superior over left rTMS or sham in improving AVH. Optimizing treatment parameters may result in stronger evidence for the efficacy of rTMS treatment of AVH. Moreover, future research should consider investigating factors

[Noninvasive cerebral stimulation for treatment of ADHD: A review of the literature].

PubMed

Brandejsky, L; Micoulaud Franchi, J-A; Lopez, R; Bioulac, S; Da Fonseca, D; Daudet, C; Boyer, L; Richieri, R; Lançon, C

2017-10-01

The aim of this review is to summarize the available data in the literature about the therapeutic applications of transcranial magnetic stimulation and transcranial direct current stimulation in attention-deficit hyperactivity disorder (ADHD). The scientific literature search of international articles was performed in February 2016 using the PubMed electronic database. The following MeSH terms were employed: "attention-deficit disorder with hyperactivity" AND "transcranial magnetic stimulation", "attention-deficit disorder with hyperactivity" AND "transcranial direct current stimulation". Five studies were retained by the literature search and were included in the review about rTMS and ADHD. Except for one study, they all showed significant positive effects of rTMS on ADHD. Four studies were retained by the literature search and were included in the review about tDCS and ADHD. Three of them showed significant positive effects of tDCS on ADHD. Two of them used tDCS during sleep at a frequency<1Hz. Only low-level evidences are available to support treatment with rTMS or tDCS in patients with ADHD. Indeed, randomized controlled trials are rare in this field of research. Additional studies are needed to confirm the efficacy of rTMS and tDCS in ADHD. rTMS could be used as an alternative therapy when methylphenidate is not well tolerated or shows an insufficient efficacy. Nevertheless, the optimal target, frequency and duration remain to be determined. tDCS can modulate attention in healthy subjects but data are insufficient in ADHD to conclude. It could be interesting to study its use in association with cognitive remediation to enhance its cognitive efficacy. Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Efficacy of twice-daily vs once-daily sessions of repetitive transcranial magnetic stimulation in the treatment of major depressive disorder: a retrospective study

PubMed Central

Modirrousta, Mandana; Meek, Benjamin P; Wikstrom, Sara L

2018-01-01

Purpose There is no clinical consensus on the optimal protocol for the treatment of major depressive disorder (MDD) using repetitive transcranial magnetic stimulation (rTMS). Accelerated protocols using more than a single session of treatment per day have been suggested as a means to reduce the overall length of time required for rTMS therapy. The objective of this study is to compare the treatment outcomes of patients with MDD who received two sessions of rTMS per day vs those who received one session per day, keeping the overall number of delivered pulses constant. Patients and methods In a retrospective study, we compared treatment outcomes of 36 patients with MDD who received 30 sessions of high-frequency (10 Hz) rTMS over the left dorsolateral prefrontal cortex. Patients received 3,000 pulses per session (5 s trains, 25 s intertrain interval) at 110% of resting motor threshold using a figure-eight coil. Patients received either two rTMS sessions per day (n=17) or one session per day (n=19). Depression symptoms were assessed by a psychiatrist using the Hamilton Rating Scale for Depression at baseline and after every 10 sessions of rTMS. Results The majority of patients in both groups responded to treatment, and there was a trend toward greater response rate in the twice-daily (TD) group (82.4%) compared to the once-daily (OD) group (52.6%). TD stimulation was tolerable for patients and produced no adverse side effects. Patients in the TD group experienced an improvement in symptoms faster than the OD group due to the accelerated therapy period. Conclusion Administration of two rTMS treatment sessions per day is tolerable for patients and does not seem to be inferior in efficacy to a OD protocol. TD administration has the benefit of producing symptom improvement over a shorter time span and requires fewer visits to the clinic. PMID:29398915

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.

Corticospinal excitability measurements using transcranial magnetic stimulation are valid with intramuscular electromyography

PubMed Central

2017-01-01

Objectives Muscular targets that are deep or inaccessible to surface electromyography (sEMG) require intrinsic recording using fine-wire electromyography (fEMG). It is unknown if fEMG validly record cortically evoked muscle responses compared to sEMG. The purpose of this investigation was to establish the validity and agreement of fEMG compared to sEMG to quantify typical transcranial magnetic stimulation (TMS) measures pre and post repetitive TMS (rTMS). The hypotheses were that fEMG would demonstrate excellent validity and agreement compared with sEMG. Materials and methods In ten healthy volunteers, paired pulse and cortical silent period (CSP) TMS measures were collected before and after 1200 pulses of 1Hz rTMS to the motor cortex. Data were simultaneously recorded with sEMG and fEMG in the first dorsal interosseous. Concurrent validity (r and rho) and agreement (Tukey mean-difference) were calculated. Results fEMG quantified corticospinal excitability with good to excellent validity compared to sEMG data at both pretest (r = 0.77–0.97) and posttest (r = 0.83–0.92). Pairwise comparisons indicated no difference between sEMG and fEMG for all outcomes; however, Tukey mean-difference plots display increased variance and questionable agreement for paired pulse outcomes. CSP displayed the highest estimates of validity and agreement. Paired pulse MEP responses recorded with fEMG displayed reduced validity, agreement and less sensitivity to changes in MEP amplitude compared to sEMG. Change scores following rTMS were not significantly different between sEMG and fEMG. Conclusion fEMG electrodes are a valid means to measure CSP and paired pulse MEP responses. CSP displays the highest validity estimates, while caution is warranted when assessing paired pulse responses with fEMG. Corticospinal excitability and neuromodulatory aftereffects from rTMS may be assessed using fEMG. PMID:28231250

Corticospinal excitability measurements using transcranial magnetic stimulation are valid with intramuscular electromyography.

PubMed

Summers, Rebekah L S; Chen, Mo; Kimberley, Teresa J

2017-01-01

Muscular targets that are deep or inaccessible to surface electromyography (sEMG) require intrinsic recording using fine-wire electromyography (fEMG). It is unknown if fEMG validly record cortically evoked muscle responses compared to sEMG. The purpose of this investigation was to establish the validity and agreement of fEMG compared to sEMG to quantify typical transcranial magnetic stimulation (TMS) measures pre and post repetitive TMS (rTMS). The hypotheses were that fEMG would demonstrate excellent validity and agreement compared with sEMG. In ten healthy volunteers, paired pulse and cortical silent period (CSP) TMS measures were collected before and after 1200 pulses of 1Hz rTMS to the motor cortex. Data were simultaneously recorded with sEMG and fEMG in the first dorsal interosseous. Concurrent validity (r and rho) and agreement (Tukey mean-difference) were calculated. fEMG quantified corticospinal excitability with good to excellent validity compared to sEMG data at both pretest (r = 0.77-0.97) and posttest (r = 0.83-0.92). Pairwise comparisons indicated no difference between sEMG and fEMG for all outcomes; however, Tukey mean-difference plots display increased variance and questionable agreement for paired pulse outcomes. CSP displayed the highest estimates of validity and agreement. Paired pulse MEP responses recorded with fEMG displayed reduced validity, agreement and less sensitivity to changes in MEP amplitude compared to sEMG. Change scores following rTMS were not significantly different between sEMG and fEMG. fEMG electrodes are a valid means to measure CSP and paired pulse MEP responses. CSP displays the highest validity estimates, while caution is warranted when assessing paired pulse responses with fEMG. Corticospinal excitability and neuromodulatory aftereffects from rTMS may be assessed using fEMG.

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 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.

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

Effects of antidepressant treatment with rTMS and fluoxetine on brain perfusion in PD.

PubMed

Fregni, F; Ono, C R; Santos, C M; Bermpohl, F; Buchpiguel, C; Barbosa, E R; Marcolin, M A; Pascual-Leone, A; Valente, K D

2006-06-13

Although depression is highly prevalent in Parkinson disease (PD), little is known about the neural correlates associated with depression and antidepressant treatment in PD. To examine the effects of fluoxetine and repetitive transcranial magnetic stimulation (rTMS) on regional cerebral blood flow (rCBF) using SPECT in patients with PD and depression. Twenty-six patients were enrolled into two groups: One received active rTMS and placebo medication and the other sham rTMS and fluoxetine 20 mg/day. Brain SPECT was performed at baseline and after 2 and 8 weeks. Changes in rCBF were compared across timepoints and correlated with clinical scores. In addition, baseline rCBF of these patients was compared with that of 29 healthy, age-matched subjects. At baseline, patients with PD and depression showed significantly lower rCBF in the left prefrontal cortex, posterior cingulate gyrus, left insula, and right parietal cortex when compared with healthy controls. Both treatments induced significant clinical improvement and increases in rCBF in the posterior cingulate gyrus and decreases in rCBF in the right medial frontal gyrus. These changes were significantly correlated to the clinical outcome. Furthermore, the comparison between these two treatments revealed that whereas rTMS treatment was associated with an increased perfusion in the right and left prefrontal cortex, fluoxetine treatment was associated with a relative rCBF increase in the occipital lobe. Depression in patients with Parkinson disease is correlated with a dysfunction of the frontal-limbic network that can be modulated by two different antidepressant therapies.

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

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".

Effects of 10 Hz Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex in Disorders of Consciousness.

PubMed

Xia, Xiaoyu; Bai, Yang; Zhou, Yangzhong; Yang, Yi; Xu, Ruxiang; Gao, Xiaorong; Li, Xiaoli; He, Jianghong

2017-01-01

While repetitive transcranial magnetic stimulation (rTMS) has been applied in treatment of patients with disorders of consciousness (DOC), a standardized stimulation protocol has not been proposed, and its therapeutic effects are inconsistently documented. To assess the efficacy of rTMS in improving consciousness in patients with persistent minimally conscious state (MCS) or unresponsive wakefulness syndrome (UWS), previously known as vegetative state (VS). A prospective single-blinded study, with selected subjects, was carried out. In total, 16 patients (5 MCS and 11 VS/UWS) with chronic DOC were included. All patients received active 10 Hz rTMS at the left dorsolateral prefrontal cortex (DLPFC), at one session per day, for 20 consecutive days. A single daily session of stimulation consisted of 1,000 pulses (10 s of 10 Hz trains; repeated 10 times with an inter-train interval of 60 s; and 11 min and 40 s for total session). The main outcome measures were changes in the total score on the JFK Coma Recovery Scale-Revised (CRS-R) scale. Additional measures were the impressions of caregivers after the conclusion of the interventions, which were assessed using the Clinical Global Impression-Improvement (CGI-I) scale. The CRS-R scores were increased in all 5 MCS patients and 4 of 11 VS/UWS patients, while a significant enhancement of CRS-R scores was observed compared to the baseline in all participants ( p  = 0.007). However, the improvement was more notable in MCS patients ( p  = 0.042) than their VS/UWS counterparts ( p  = 0.066). Based on the CGI-I scores, two patients improved considerably, two improved, six minimally improved, six experienced no change, and none deteriorated. Good concordance was seen between the CGI-I result and the increases in CRS-R scores. Treatment of 10 Hz multisession rTMS applied to the left DLPFC is promising for the rehabilitation of DOC patients, especially those in MCS. Further validation with a cohort of a

Transcranial magnetic stimulation in brain injury.

PubMed

Castel-Lacanal, E; Tarri, M; Loubinoux, I; Gasq, D; de Boissezon, X; Marque, P; Simonetta-Moreau, M

2014-02-01

Transcranial magnetic stimulations (TMS) have been used for many years as a diagnostic tool to explore changes in cortical excitability, and more recently as a tool for therapeutic neuromodulation. We are interested in their applications following brain injury: stroke, traumatic and anoxic brain injury. Following brain injury, there is decreased cortical excitability and changes in interhemispheric interactions depending on the type, the severity, and the time-lapse between the injury and the treatment implemented. rTMS (repetitive TMS) is a therapeutic neuromodulation tool which restores the interhemispheric interactions following stroke by inhibiting the healthy cortex with frequencies ≤1Hz, or by exciting the lesioned cortex with frequencies between 3 and 50Hz. Results in motor recovery are promising and those in improving aphasia or visuospatial neglect are also encouraging. Finally, the use of TMS is mainly limited by the risk of seizure, and is therefore contraindicated for many patients. TMS is a useful non-invasive brain stimulation tool to diagnose the effects of brain injury, to study the mechanisms of recovery and a non-invasive neuromodulation promising tool to influence the post-lesional recovery. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Local Immediate versus Long-Range Delayed Changes in Functional Connectivity Following rTMS on the Visual Attention Network.

PubMed

Battelli, Lorella; Grossman, Emily D; Plow, Ela B

The interhemispheric competition hypothesis attributes the distribution of selective attention to a balance of mutual inhibition between homotopic, interhemispheric connections in parietal cortex (Kinsbourne 1977; Battelli et al., 2009). In support of this hypothesis, repetitive inhibitory TMS over right parietal cortex in healthy individuals rapidly induces interhemispheric imbalance in cortical activity that spreads beyond the site of stimulation (Plow et al., 2014). Behaviorally, the impacts of inhibitory rTMS may be long delayed from the onset of stimulation, as much as 30 minutes (Agosta et al., 2014; Hubl et al., 2008). In this study, we examine the temporal dynamics of inhibitory rTMS on cortical network integrity that supports sustained visual attention. Healthy individuals received 15 min of 1 Hz offline, inhibitory rTMS (or sham) over left parietal cortex, and then immediately engaged in a bilateral visual tracking task while we recorded brain activity with fMRI. We computed functional connectivity (FC) between three nodes of the attention network engaged by visual tracking: the intraparietal sulcus (IPS), frontal eye fields (FEF) and human MT+ (hMT+). FC immediately and significantly decreased between the stimulation site (left IPS) and all other regions, then recovered to normal levels within 30 minutes. rTMS increased FC between left and right FEF at approximately 36 min following stimulation, and between sites in the unstimulated hemisphere approximately 48 min after stimulation. These findings demonstrate large-scale changes in cortical organization following inhibitory rTMS. The immediate impact of rTMS on connectivity to the stimulation site dovetails with the putative role of interhemispheric balance for bilateral visual sustained attention. The delayed, compensatory increases in functional connectivity have implications for models of dynamic reorganization in networks supporting spatial and nonspatial selective attention, and

Electromagnetic characteristics of eccentric figure-eight coils for transcranial magnetic stimulation: A numerical study

NASA Astrophysics Data System (ADS)

Kato, Takuya; Sekino, Masaki; Matsuzaki, Taiga; Nishikawa, Atsushi; Saitoh, Youichi; Ohsaki, Hiroyuki

2012-04-01

Repetitive transcranial magnetic stimulation (rTMS) is effective for treatment of several neurological and psychiatric diseases. We proposed an eccentric figure-eight coil, which induces strong eddy currents in the target brain tissue. In this study, numerical analyses were carried out to obtain magnetic field distribution of the eccentric figure-eight coil and eddy current in the brain. The analyses were performed with various coil design parameters, such as the outer and inner diameters and number of turns, to investigate the influence of these parameters on the coil characteristics. Increases in the inner diameter, outer diameter, and number of turns caused increases in the maximum eddy current densities. Coil inductance, working voltage, and heat generation also became higher with the increases in these design parameters. In order to develop a compact stimulator system for use at home, we need to obtain strong eddy current density, keeping the working voltage as low as possible. Our results show that it is effective to enlarge the outer diameter.

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.

Transient functional suppression and facilitation of Japanese ideogram writing induced by repetitive transcranial magnetic stimulation of posterior inferior temporal cortex.

PubMed

Ueki, Yoshino; Mima, Tatsuya; Nakamura, Kimihiro; Oga, Tatsuhide; Shibasaki, Hiroshi; Nagamine, Takashi; Fukuyama, Hidenao

2006-08-16

The Japanese writing system is unique in that it is composed of two different orthographies: kanji (morphograms) and kana (syllabograms). The retrieval of the visual orthographic representations of Japanese kanji is crucial to the process of writing in Japanese. We used low-frequency repetitive transcranial magnetic stimulation (rTMS) to clarify the functional relevance of the left and right posterior inferior temporal cortex (PITC) to this process in native Japanese speakers. The experimental paradigms included the mental recall of kanji, kana-to-kanji transcription, semantic judgment, oral reading, and copying of kana and kanji. The first two tasks require the visualization of the kanji image of the word. We applied 0.9 Hz rTMS (600 total pulses) over individually determined left or right PITC to suppress cortical activity and measured subsequent task performance. In the mental recall of kanji and kana-to-kanji transcription, rTMS over the left PITC prolonged reaction times (RTs), whereas rTMS over the right PITC reduced RTs. In the other tasks, which do not involve the mental visualization of kanji, rTMS over the left or right PITC had no effect on performance. These results suggest that the left PITC is crucial for the retrieval of the visual graphic representation of kanji. Furthermore, the right PITC may work to suppress the dominant left PITC in the neural network for kanji writing, which involves visual word recognition.

Repetitive transcranial magnetic stimulation of the supplementary motor area in treatment-resistant obsessive-compulsive disorder: An open-label pilot study.

PubMed

Lee, Young-Ji; Koo, Bon-Hoon; Seo, Wan-Seok; Kim, Hye-Geum; Kim, Ji-Yean; Cheon, Eun-Jin

2017-10-01

Obsessive-compulsive disorder (OCD) is a severely distressing disorder represented by obsessions and compulsions. A significant proportion of OCD patients fail to improve with conventional treatment methods. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as an alternative for OCD treatment. Functional neuroimaging studies indicate that OCD is associated with increased activity in the supplementary motor area (SMA), a region that plays an important role in the pathophysiology of this disorder. In this study, we assessed the efficacy of augmentation with 1Hz rTMS over the SMA in treatment-resistant OCD patients. The participants received 1Hz rTMS over the SMA in 20 daily sessions for 4weeks. We observed significant reduction in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score at the 4th week of the treatment. Reduction in compulsion contributed to the reduction of global Y-BOCS whereas there was no significant reduction in obsession. Clinical global impression-global improvement also showed significant change at the 2nd and 4th week of the treatment. No additional significant changes or significant adverse effects were seen. These findings suggest that 1Hz rTMS over the SMA can be an efficient and safe add-on therapeutic method in treatment-resistant patients with OCD. Further controlled studies in larger samples are required to confirm the effect of 1Hz rTMS over the SMA in OCD. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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 (magnetic stimulation (rTMS) diminishes treatment-resistant auditory hallucinations. A neuroimaging study elucidating the effect of rTMS in auditory hallucinations has yet to be published. To evaluate the distribution of neuronal electrical activity and the brain metabolism changes after low-frequency rTMS in patients with auditory hallucinations. Low-frequency rTMS (0.9 Hz, 100% of motor threshold, 20 min) applied to the left temporoparietal cortex was used for 10 days in the treatment of medication-resistant auditory hallucinations in schizophrenia (n = 12). The effect of rTMS on the low-resolution brain electromagnetic tomography (LORETA) and brain metabolism ((18)FDG PET) was measured before and after 2 weeks of treatment. We found a significant improvement in the total and positive symptoms (PANSS), and on the hallucination scales (HCS, AHRS). The rTMS decreased the brain metabolism in the left superior temporal gyrus and in interconnected regions, and effected increases in the contralateral cortex and in the frontal lobes. We detected a decrease in current densities (LORETA) for the beta-1 and beta-3 bands in the left temporal lobe whereas an increase was found for beta-2 band contralaterally. Our findings implicate that the effect is connected with decreased metabolism in the cortex underlying the rTMS site, while facilitation of metabolism is propagated by transcallosal and intrahemispheric connections. The LORETA indicates that the neuroplastic changes affect the functional laterality and provide the substrate for a metabolic effect. (c) 2007 S. Karger AG, Basel.

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.

Low-frequency rTMS with language therapy over a 3-month period for sensory-dominant aphasia: case series of two post-stroke Japanese patients.

PubMed

Kakuda, Wataru; Abo, Masahiro; Uruma, Go; Kaito, Nobuyoshi; Watanabe, Motoi

2010-01-01

To examine the safety and feasibility of therapeutic application of low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with language therapy for post-stroke patients with sensory-dominant aphasia. Two post-stroke Japanese patients with sensory-dominant aphasia were studied. In both patients, 10 sessions of 20-minute low-frequency rTMS with 1 Hz to the Wernicke's area were provided throughout 6-day hospitalization, followed by weekly outpatient rTMS treatment for 3 months. The language therapy was also provided through the period of in- and out-patient treatment. Language function was evaluated using the Token test and the Standard Language Test of Aphasia (SLTA) at the start and end of the in-patient treatment and the end of the outpatient treatment. The therapeutic protocol was well tolerated throughout the in- and out-patient treatments, without any adverse effects. The scores of the Token test and certain sub-categories of SLTA increased in both patients after the in-patient rTMS treatment. Persistent improvement of the score was noted over the 3-month post-discharge period. The proposed protocol of long-term application of low-frequency rTMS to the Wernicke's area and language therapy is considered a safe and feasible therapeutic approach for post-stroke patients with sensory-dominant aphasia.

A novel approach for monitoring writing interferences during navigated transcranial magnetic stimulation mappings of writing related cortical areas.

PubMed

Rogić Vidaković, Maja; Gabelica, Dragan; Vujović, Igor; Šoda, Joško; Batarelo, Nikolina; Džimbeg, Andrija; Zmajević Schönwald, Marina; Rotim, Krešimir; Đogaš, Zoran

2015-11-30

It has recently been shown that navigated repetitive transcranial magnetic stimulation (nTMS) is useful in preoperative neurosurgical mapping of motor and language brain areas. In TMS mapping of motor cortices the evoked responses can be quantitatively monitored by electromyographic (EMG) recordings. No such setup exists for monitoring of writing during nTMS mappings of writing related cortical areas. We present a novel approach for monitoring writing during nTMS mappings of motor writing related cortical areas. To our best knowledge, this is the first demonstration of quantitative monitoring of motor evoked responses from hand by EMG, and of pen related activity during writing with our custom made pen, together with the application of chronometric TMS design and patterned protocol of rTMS. The method was applied in four healthy subjects participating in writing during nTMS mapping of the premotor cortical area corresponding to BA 6 and close to the superior frontal sulcus. The results showed that stimulation impaired writing in all subjects. The corresponding spectra of measured signal related to writing movements was observed in the frequency band 0-20 Hz. Magnetic stimulation affected writing by suppressing normal writing frequency band. The proposed setup for monitoring of writing provides additional quantitative data for monitoring and the analysis of rTMS induced writing response modifications. The setup can be useful for investigation of neurophysiologic mechanisms of writing, for therapeutic effects of nTMS, and in preoperative mapping of language cortical areas in patients undergoing brain surgery. Copyright © 2015 Elsevier B.V. All rights reserved.

Using non-invasive transcranial stimulation to improve motor and cognitive function in Parkinson's disease: a systematic review and meta-analysis.

PubMed

Goodwill, Alicia M; Lum, Jarrad A G; Hendy, Ashlee M; Muthalib, Makii; Johnson, Liam; Albein-Urios, Natalia; Teo, Wei-Peng

2017-11-01

Parkinson's disease (PD) is a neurodegenerative disorder affecting motor and cognitive abilities. There is no cure for PD, therefore identifying safe therapies to alleviate symptoms remains a priority. This meta-analysis quantified the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (TES) to improve motor and cognitive dysfunction in PD. PubMed, EMBASE, Web of Science, Google Scholar, Scopus, Library of Congress and Cochrane library were searched. 24 rTMS and 9 TES studies (n = 33) with a sham control group were included for analyses. The Physiotherapy Evidence Database and Cochrane Risk of Bias showed high quality (7.5/10) and low bias with included studies respectively. Our results showed an overall positive effect in favour of rTMS (SMD = 0.394, CI [0.106-0.683], p = 0.007) and TES (SMD = 0.611, CI [0.188-1.035], p = 0.005) compared with sham stimulation on motor function, with no significant differences detected between rTMS and TES (Q [1] = 0.69, p = 0.406). Neither rTMS nor TES improved cognition. No effects for stimulation parameters on motor or cognitive function were observed. To enhance the clinical utility of non-invasive brain stimulation (NBS), individual prescription of stimulation parameters based upon symptomology and resting excitability state should be a priority of future research.

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

Safety of primed repetitive transcranial magnetic stimulation and modified constraint-induced movement therapy in a randomized controlled trial in pediatric hemiparesis.

PubMed

Gillick, Bernadette T; Krach, Linda E; Feyma, Tim; Rich, Tonya L; Moberg, Kelli; Menk, Jeremiah; Cassidy, Jessica; Kimberley, Teresa; Carey, James R

2015-04-01

To investigate the safety of combining a 6-Hz primed low-frequency repetitive transcranial magnetic stimulation (rTMS) intervention in the contralesional hemisphere with a modified constraint-induced movement therapy (mCIMT) program in children with congenital hemiparesis. Phase 1 randomized, double-blinded, placebo-controlled pretest/posttest trial. University academic facility and pediatric specialty hospital. Subjects (N = 19; age range, 8-17 y) with congenital hemiparesis caused by ischemic stroke or periventricular leukomalacia. No subject withdrew because of adverse events. All subjects included completed the study. Subjects were randomized to 1 of 2 groups: either real rTMS plus mCIMT (n = 10) or sham rTMS plus mCIMT (n = 9). Adverse events, physician assessment, ipsilateral hand function, stereognosis, cognitive function, subject report of symptoms assessment, and subject questionnaire. No major adverse events occurred. Minor adverse events were found in both groups. The most common events were headaches (real: 50%, sham: 89%; P = .14) and cast irritation (real: 30%, sham: 44%; P = .65). No differences between groups in secondary cognitive and unaffected hand motor measures were found. Primed rTMS can be used safely with mCIMT in congenital hemiparesis. We provide new information on the use of rTMS in combination with mCIMT in children. These findings could be useful in research and future clinical applications in advancing function in congenital hemiparesis. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Factor Analysis of Low-Frequency Repetitive Transcranial Magnetic Stimulation to the Temporoparietal Junction for Tinnitus

PubMed Central

Li, Bei; Wang, Meiye; Li, Ming; Yin, Shankai

2016-01-01

Objectives. We investigated factors that contribute to suppression of tinnitus after repetitive transcranial magnetic stimulation (rTMS). Methods. A total of 289 patients with tinnitus underwent active 1 Hz rTMS in the left temporoparietal region. A visual analog scale (VAS) was used to assess tinnitus loudness. All participants were interviewed regarding age, gender, tinnitus duration, laterality and pitch, audiometric parameters, sleep, and so forth. The resting motor thresholds (RMTs) were measured in all patients and 30 age- and gender-matched volunteers. Results. With respect to different factors that contribute to tinnitus suppression, we found improvement in the following domains: shorter duration, normal hearing (OR: 3.25, 95%CI: 2.01–5.27, p = 0.001), and without sleep disturbance (OR: 2.51, 95%CI: 1.56–4.1, p = 0.005) adjusted for age and gender. The patients with tinnitus lasting less than 1 year were more likely to show suppression of tinnitus (OR: 2.77, 95%CI: 1.48–5.19, p = 0.002) compared to those with tinnitus lasting more than 5 years. Tinnitus patients had significantly lower RMTs compared with healthy volunteers. Conclusion. Active low-frequency rTMS results in a significant reduction in the loudness of tinnitus. Significant tinnitus suppression was shown in subjects with shorter tinnitus duration, with normal hearing, and without sleep disturbance. PMID:27847647

The Dorsolateral Prefrontal Cortex Plays a Role in Self-Initiated Elaborative Cognitive Processing during Episodic Memory Encoding: rTMS Evidence

PubMed Central

Hawco, Colin; Berlim, Marcelo T.; Lepage, Martin

2013-01-01

During episodic memory encoding, elaborative cognitive processing can improve later recall or recognition. While multiple studies examined the neural correlates of encoding strategies, few studies have explicitly focused on the self-initiation of elaborative encoding. Repetitive transcranial magnetic stimulation (rTMS), a method which can transiently disrupt neural activity, was administered during an associative encoding task. rTMS was either applied to the left dorsolateral prefrontal cortex (DLPFC) or to the vertex (a control region not involved in memory encoding) during presentation of pairs of words. Pairs could be semantically related or not related. Two encoding instructions were given, either cueing participants to analyze semantic relationships (cued condition), or to memorize the pair without any specific strategy cues (the self-initiated condition). Participants filled out a questionnaire regarding their use of memory strategies and performed a cued-recall task. We hypothesized that if the DLPFC plays a role in the self-initiation of elaborative encoding we would observe a reduction in memory performance in the self-initiated condition, particularly for related. We found a significant correlation between the effects of rTMS and strategy use, only in the self-initiated condition with related pairs. High strategy users showed reduced performance following DLPFC stimulation, while low strategy users tended to show increased recall following DLPFC stimulation during encoding. These results suggest the left DLPFC may be involved in the self-initiation of memory strategy use, and individuals may utilize different neural networks depending on their use of encoding strategies. PMID:24040072

Event-related rTMS at encoding affects differently deep and shallow memory traces.

PubMed

Innocenti, Iglis; Giovannelli, Fabio; Cincotta, Massimo; Feurra, Matteo; Polizzotto, Nicola R; Bianco, Giovanni; Cappa, Stefano F; Rossi, Simone

2010-10-15

The "level of processing" effect is a classical finding of the experimental psychology of memory. Actually, the depth of information processing at encoding predicts the accuracy of the subsequent episodic memory performance. When the incoming stimuli are analyzed in terms of their meaning (semantic, or deep, encoding), the memory performance is superior with respect to the case in which the same stimuli are analyzed in terms of their perceptual features (shallow encoding). As suggested by previous neuroimaging studies and by some preliminary findings with transcranial magnetic stimulation (TMS), the left prefrontal cortex may play a role in semantic processing requiring the allocation of working memory resources. However, it still remains unclear whether deep and shallow encoding share or not the same cortical networks, as well as how these networks contribute to the "level of processing" effect. To investigate the brain areas casually involved in this phenomenon, we applied event-related repetitive TMS (rTMS) during deep (semantic) and shallow (perceptual) encoding of words. Retrieval was subsequently tested without rTMS interference. RTMS applied to the left dorsolateral prefrontal cortex (DLPFC) abolished the beneficial effect of deep encoding on memory performance, both in terms of accuracy (decrease) and reaction times (increase). Neither accuracy nor reaction times were instead affected by rTMS to the right DLPFC or to an additional control site excluded by the memory process (vertex). The fact that online measures of semantic processing at encoding were unaffected suggests that the detrimental effect on memory performance for semantically encoded items took place in the subsequent consolidation phase. These results highlight the specific causal role of the left DLPFC among the wide left-lateralized cortical network engaged by long-term memory, suggesting that it probably represents a crucial node responsible for the improved memory performance induced by

[The Problems with Domestic Introduction of rTMS from the Three Viewpoints of Scientific Evidence, Specialty and Social Responsibility].

PubMed

Shinosaki, Kazuhiro

2015-01-01

The domestic introduction of rTMS is expected as a new treatment option for treatment-resistant depression. I discussed some problems with the introduction from three viewpoints : scientific evidence, specialty, and social responsibility. I surveyed scientific evidence for rTMS regarding the action mechanism, effectiveness, side effects, and its positioning in the treatment guidelines. To secure the quality of rTMS treatment, I proposed rTMS guidelines, nurturing of the specialists, and a center hospital plan, and pointed out some medium-term problems after its introduction and the consistency of rTMS treatment and standard depression treatment. From the viewpoint of social responsibility, rTMS treatment should be a medical service covered by health insurance to avoid its misuse. We should prepare to overcome the public suspicion of brain stimulation treatment for mental disease.

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.

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

High-frequency rTMS on DLPFC increases prosocial attitude in case of decision to support people.

PubMed

Balconi, Michela; Canavesio, Ylenia

2014-02-01

Engaging in prosocial behavior was explored in the present research, by investigating the role of dorsolateral prefrontal cortex (DLPFC) in modulation of intention to support other people and of emotional attuning as it was expressed by facial feedback (electromiography, EMG). High-frequency rTMS was applied on DLPFC to 25 subjects when they were required to choose to directly intervene or not to support other people in emotionally valenced social situations (cooperative, noncooperative, conflictual, neutral contexts). Two control conditions were included in the experimental design to control the simple stimulation effect (sham condition with absence of TMS stimulation) and the location effect (control site condition with Pz stimulation). In comparison with sham and control condition, rTMS stimulation induced increased prosocial behavior in all the emotional situations. Moreover, as a function of valence, zygomatic (for positive situations) and corrugators (for negative situations) muscle activity was increased, with significant effect by DLPFC stimulation which induced a "facilitation effect". In addition, negative situations showed a higher rTMS impact for both behavioral and EMG responsiveness. Finally, prosocial behavior was found to be predicted (regression analysis) by EMG variations, as a function of the negative versus positive valence. The prefrontal circuit was suggested to support emotional responsiveness and facial feedback in order to facilitate the prosocial behavior.

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.

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

A comparison of 15 Hz sine on-line and off-line magnetic stimulation affecting the voltage-gated sodium channel currents of prefrontal cortex pyramidal neurons

NASA Astrophysics Data System (ADS)

Zheng, Yu; Dong, Lei; Gao, Yang; Dou, Jun-Rong; Li, Ze-yan

2016-10-01

Combined with the use of patch-clamp techniques, repetitive transcranial magnetic stimulation (rTMS) has proven to be a noninvasive neuromodulation tool that can inhibit or facilitate excitability of neurons after extensive research. The studies generally focused on the method: the neurons are first stimulated in an external standard magnetic exposure device, and then moved to the patch-clamp to record electrophysiological characteristics (off-line magnetic exposure). Despite its universality, real-time observation of the effects of magnetic stimulation on the neurons is more effective (on-line magnetic stimulation). In this study, we selected a standard exposure device for magnetic fields acting on mouse prefrontal cortex pyramidal neurons, and described a new method that a patch-clamp setup was modified to allow on-line magnetic stimulation. By comparing the off-line exposure and on-line stimulation of the same magnetic field intensity and frequency affecting the voltage-gated sodium channel currents, we succeeded in proving the feasibility of the new on-line stimulation device. We also demonstrated that the sodium channel currents of prefrontal cortex pyramidal neurons increased significantly under the 15 Hz sine 1 mT, and 2 mT off-line magnetic field exposure and under the 1 mT and 2 mT on-line magnetic stimulation, and the rate of acceleration was most significant on 2 mT on-line magnetic stimulation. This study described the development of a new on-line magnetic stimulator and successfully demonstrated its practicability for scientific stimulation of neurons.

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.

High-frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex restores attention bias to negative information in methamphetamine addicts.

PubMed

Zhang, Ling; Cao, Xinyu; Liang, Qiongdan; Li, Xiang; Yang, Jiemin; Yuan, Jiajin

2018-07-01

Methamphetamine (hereafter, meth) addiction results in various emotional problems linked to structural impairments in the prefrontal cortex (PFC). In this paper, we investigated whether high-frequency (10 Hz) repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral PFC (DLPFC) can improve emotional attention. Thirty-one meth addicts were randomly assigned to a 10 Hz or sham rTMS group; additionally, 31 healthy participants were enrolled, who were required to respond as correctly and quickly as possible to a yellow arrow embedded in an image depicting emotional content (neutral, fear, sadness, or disgust). Results showed that the healthy participants responded more rapidly to negative compared to neutral stimuli, while meth addicts responded indiscriminately to stimuli representing disgust, fear, and neutral content. The randomization check showed no significant differences in the pretest of emotional attention measures between the 10 Hz and sham groups. However, 10 Hz rTMS yielded faster response to negative pictures than to neutral pictures, which was similar to the performance of healthy participants but Sham not. However, this attention bias effect persisted in the 10 Hz group 2 weeks later. These results demonstrate that high-frequency rTMS of the left DLPFC can improve the emotional attention of meth addicts. Copyright © 2018 Elsevier B.V. All rights reserved.

Primary motor cortex functionally contributes to language comprehension: An online rTMS study.

PubMed

Vukovic, Nikola; Feurra, Matteo; Shpektor, Anna; Myachykov, Andriy; Shtyrov, Yury

2017-02-01

Among various questions pertinent to grounding human cognitive functions in a neurobiological substrate, the association between language and motor brain structures is a particularly debated one in neuroscience and psychology. While many studies support a broadly distributed model of language and semantics grounded, among other things, in the general modality-specific systems, theories disagree as to whether motor and sensory cortex activity observed during language processing is functional or epiphenomenal. Here, we assessed the role of motor areas in linguistic processing by investigating the responses of 28 healthy volunteers to different word types in semantic and lexical decision tasks, following repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex. We found that early rTMS (delivered within 200ms of word onset) produces a left-lateralised and meaning-specific change in reaction speed, slowing down behavioural responses to action-related words, and facilitating abstract words - an effect present only during semantic, but not lexical, decision. We interpret these data in light of action-perception theory of language, bolstering the claim that motor cortical areas play a functional role in language comprehension. Copyright © 2017 Elsevier Ltd. All rights reserved.

The neural basis of form and form-motion integration from static and dynamic translational Glass patterns: A rTMS investigation.

PubMed

Pavan, Andrea; Ghin, Filippo; Donato, Rita; Campana, Gianluca; Mather, George

2017-08-15

A long-held view of the visual system is that form and motion are independently analysed. However, there is physiological and psychophysical evidence of early interaction in the processing of form and motion. In this study, we used a combination of Glass patterns (GPs) and repetitive Transcranial Magnetic Stimulation (rTMS) to investigate in human observers the neural mechanisms underlying form-motion integration. GPs consist of randomly distributed dot pairs (dipoles) that induce the percept of an oriented stimulus. GPs can be either static or dynamic. Dynamic GPs have both a form component (i.e., orientation) and a non-directional motion component along the orientation axis. GPs were presented in two temporal intervals and observers were asked to discriminate the temporal interval containing the most coherent GP. rTMS was delivered over early visual area (V1/V2) and over area V5/MT shortly after the presentation of the GP in each interval. The results showed that rTMS applied over early visual areas affected the perception of static GPs, but the stimulation of area V5/MT did not affect observers' performance. On the other hand, rTMS was delivered over either V1/V2 or V5/MT strongly impaired the perception of dynamic GPs. These results suggest that early visual areas seem to be involved in the processing of the spatial structure of GPs, and interfering with the extraction of the global spatial structure also affects the extraction of the motion component, possibly interfering with early form-motion integration. However, visual area V5/MT is likely to be involved only in the processing of the motion component of dynamic GPs. These results suggest that motion and form cues may interact as early as V1/V2. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2018-04-28

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

Targeted transcranial theta-burst stimulation alters fronto-insular network and prefrontal GABA.

PubMed

Iwabuchi, Sarina J; Raschke, Felix; Auer, Dorothee P; Liddle, Peter F; Lankappa, Sudheer T; Palaniyappan, Lena

2017-02-01

Repetitive transcranial magnetic stimulation (rTMS) has been used worldwide to treat depression. However, the exact physiological effects are not well understood. Pathophysiology of depression involves crucial limbic structures (e.g. insula), and it is still not clear if these structures can be modulated through neurostimulation of surface regions (e.g. dorsolateral prefrontal cortex, DLPFC), and whether rTMS-induced excitatory/inhibitory transmission alterations relate to fronto-limbic connectivity changes. Therefore, we sought proof-of-concept for neuromodulation of insula via prefrontal intermittent theta-burst stimulation (iTBS), and how these effects relate to GABAergic and glutamatergic systems. In 27 healthy controls, we employed a single-blind crossover randomised-controlled trial comparing placebo and real iTBS using resting-state functional MRI and magnetic resonance spectroscopy. Granger causal analysis was seeded from right anterior insula (rAI) to locate individualized left DLPFC rTMS targets. Effective connectivity coefficients within rAI and DLPFC were calculated, and levels of GABA/Glx, GABA/Cr and Glx/Cr in DLPFC and anterior cingulate voxels were also measured. ITBS significantly dampened fronto-insular connectivity and reduced GABA/Glx in both voxels. GABA/Glx had a significant mediating effect on iTBS-induced changes in DLPFC-to-rAI connectivity. We demonstrate modulation of the rAI using targeted iTBS through alterations of excitatory/inhibitory interactions, which may underlie therapeutic effects of rTMS, offering promise for rTMS treatment optimization. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain plasticity in the adult: modulation of function in amblyopia with rTMS.

PubMed

Thompson, Benjamin; Mansouri, Behzad; Koski, Lisa; Hess, Robert F

2008-07-22

Amblyopia is a cortically based visual disorder caused by disruption of vision during a critical early developmental period. It is often thought to be a largely intractable problem in adult patients because of a lack of neuronal plasticity after this critical period [1]; however, recent advances have suggested that plasticity is still present in the adult amblyopic visual cortex [2-6]. Here, we present data showing that repetitive transcranial magnetic stimulation (rTMS) of the visual cortex can temporarily improve contrast sensitivity in the amblyopic visual cortex. The results indicate continued plasticity of the amblyopic visual system in adulthood and open the way for a potential new therapeutic approach to the treatment of amblyopia.

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.

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.

Cost effectiveness analysis comparing repetitive transcranial magnetic stimulation to antidepressant medications after a first treatment failure for major depressive disorder in newly diagnosed patients - A lifetime analysis.

PubMed

Voigt, Jeffrey; Carpenter, Linda; Leuchter, Andrew

2017-01-01

Repetitive Transcranial Magnetic Stimulation (rTMS) commonly is used for the treatment of Major Depressive Disorder (MDD) after patients have failed to benefit from trials of multiple antidepressant medications. No analysis to date has examined the cost-effectiveness of rTMS used earlier in the course of treatment and over a patients' lifetime. We used lifetime Markov simulation modeling to compare the direct costs and quality adjusted life years (QALYs) of rTMS and medication therapy in patients with newly diagnosed MDD (ages 20-59) who had failed to benefit from one pharmacotherapy trial. Patients' life expectancies, rates of response and remission, and quality of life outcomes were derived from the literature, and treatment costs were based upon published Medicare reimbursement data. Baseline costs, aggregate per year quality of life assessments (QALYs), Monte Carlo simulation, tornado analysis, assessment of dominance, and one way sensitivity analysis were also performed. The discount rate applied was 3%. Lifetime direct treatment costs, and QALYs identified rTMS as the dominant therapy compared to antidepressant medications (i.e., lower costs with better outcomes) in all age ranges, with costs/improved QALYs ranging from $2,952/0.32 (older patients) to $11,140/0.43 (younger patients). One-way sensitivity analysis demonstrated that the model was most sensitive to the input variables of cost per rTMS session, monthly prescription drug cost, and the number of rTMS sessions per year. rTMS was identified as the dominant therapy compared to antidepressant medication trials over the life of the patient across the lifespan of adults with MDD, given current costs of treatment. These models support the use of rTMS after a single failed antidepressant medication trial versus further attempts at medication treatment in adults with MDD.

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.

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

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.

Repetitive transcranial magnetic stimulation for depression after basal ganglia ischaemic stroke: protocol for a multicentre randomised double-blind placebo-controlled trial.

PubMed

Tang, Ying; Chen, Aimin; Zhu, Shuzhen; Yang, Li; Zhou, Jiyuan; Pan, Suyue; Shao, Min; Zhao, Lianxu

2018-02-03

Studies suggest that repetitive transcranial magnetic stimulation (rTMS) is effective for the treatment of depression and promotes the repair of white matter. This study aims to assess the effectiveness of rTMS in treating depression after basal ganglia ischaemic stroke and to examine whether such effects are related to restoration of white matter integrity. Sixty-six participants will be recruited from Zhujiang Hospital, Nanfang Hospital and Sichuan Bayi Rehabilitation Hospital and randomised in a 1:1 ratio to receive active rTMS treatment or sham rTMS treatment in addition to routine supportive treatments. The data will be collected at 0, 2 and 4 weeks after the commencement of treatment. The primary outcome is the measurement of 24-item Hamilton Depression Rating Scale scores, and the secondary outcomes include diffusion tensor imaging results and the results of neuropsychological tests including the National Institutes of Health Stroke Scale, Activities of Daily Living Scale, Montreal Cognitive Assessment, Clinical Global Impressions scales, Aphasia Battery in Chinese, Social Support Revalued Scale and Medical Coping Modes Questionnaire. This study has been approved by the Ethics Committee of Zhujiang Hospital of Southern Medical University. The findings will be disseminated by publication in a peer-reviewed journal and by presentation at international conferences. NCT03159351. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cost effectiveness analysis comparing repetitive transcranial magnetic stimulation to antidepressant medications after a first treatment failure for major depressive disorder in newly diagnosed patients – A lifetime analysis

PubMed Central

2017-01-01

Objective Repetitive Transcranial Magnetic Stimulation (rTMS) commonly is used for the treatment of Major Depressive Disorder (MDD) after patients have failed to benefit from trials of multiple antidepressant medications. No analysis to date has examined the cost-effectiveness of rTMS used earlier in the course of treatment and over a patients’ lifetime. Methods We used lifetime Markov simulation modeling to compare the direct costs and quality adjusted life years (QALYs) of rTMS and medication therapy in patients with newly diagnosed MDD (ages 20–59) who had failed to benefit from one pharmacotherapy trial. Patients’ life expectancies, rates of response and remission, and quality of life outcomes were derived from the literature, and treatment costs were based upon published Medicare reimbursement data. Baseline costs, aggregate per year quality of life assessments (QALYs), Monte Carlo simulation, tornado analysis, assessment of dominance, and one way sensitivity analysis were also performed. The discount rate applied was 3%. Results Lifetime direct treatment costs, and QALYs identified rTMS as the dominant therapy compared to antidepressant medications (i.e., lower costs with better outcomes) in all age ranges, with costs/improved QALYs ranging from $2,952/0.32 (older patients) to $11,140/0.43 (younger patients). One-way sensitivity analysis demonstrated that the model was most sensitive to the input variables of cost per rTMS session, monthly prescription drug cost, and the number of rTMS sessions per year. Conclusion rTMS was identified as the dominant therapy compared to antidepressant medication trials over the life of the patient across the lifespan of adults with MDD, given current costs of treatment. These models support the use of rTMS after a single failed antidepressant medication trial versus further attempts at medication treatment in adults with MDD. PMID:29073256

Non-invasive brain stimulation of the right inferior frontal gyrus may improve attention in early Alzheimer's disease: a pilot study.

PubMed

Eliasova, Ilona; Anderkova, Lubomira; Marecek, Radek; Rektorova, Irena

2014-11-15

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool for modulating cortical activity. In this pilot study, we evaluated the effects of high frequency rTMS applied over the right inferior frontal gyrus (IFG) on cognitive functions in patients with amnestic mild cognitive impairment (MCI) or incipient dementia due to Alzheimer's disease (AD). Ten patients (6 men; 4 women, mean age of 72 ± 8 years; MMSE 23 ± 3.56) were enrolled in a randomized, placebo-controlled study with a crossover design. All participants received 2 sessions of 10 Hz rTMS over the non-dominant right hemisphere in random order: IFG (active stimulation site) and vertex (control stimulation site). Intensities were adjusted to 90% of resting motor threshold. A total of 2250 pulses were applied in a session. The Trail Making Test (TMT), the Stroop test, and the complex visual scene encoding task (CVSET) were administered before and immediately after each session. The Wilcoxon paired test was used for data analysis. Stimulation applied over the IFG induced improvement in the TMT parts A (p = 0.037) and B (p = 0.049). No significant changes were found in the Stroop test or the CVSET after the IFG stimulation. We observed no significant cognitive aftereffects of rTMS applied over the vertex. High frequency rTMS of the right IFG induced significant improvement of attention and psychomotor speed in patients with MCI/mild dementia due to AD. This pilot study is part of a more complex protocol and ongoing research. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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

Variation in the dopamine D2 receptor gene plays a key role in human pain and its modulation by transcranial magnetic stimulation.

PubMed

Jääskeläinen, Satu K; Lindholm, Pauliina; Valmunen, Tanja; Pesonen, Ullamari; Taiminen, Tero; Virtanen, Arja; Lamusuo, Salla; Forssell, Heli; Hagelberg, Nora; Hietala, Jarmo; Pertovaara, Antti

2014-10-01

We tested whether variation of the dopamine D2 receptor (DRD2) gene contributes to individual differences in thermal pain sensitivity and analgesic efficacy of repetitive transcranial magnetic stimulation (rTMS) in healthy subjects (n=29) or susceptibility to neuropathic pain in patients with neurophysiologically confirmed diagnosis (n=16). Thermal sensitivity of healthy subjects was assessed before and after navigated rTMS provided to the S1/M1 cortex. All subjects were genotyped for the DRD2 gene 957C>T and catechol-O-methyltransferase (COMT) protein Val158Met polymorphisms. In healthy subjects, 957C>T influenced both innocuous and noxious thermal detection thresholds that were lowest in 957TT homozygotes (P values from .0277 to .0462). rTMS to S1 cortex had analgesic effect only in 957TT homozygote genotype (P=.0086). In patients, prevalence of 957TT homozygote genotype was higher than in a healthy Finnish population (50% vs 27%; P=.0191). Patients with 957TT genotype reported more severe pain than patients with other genotypes (P=.0351). COMT Val158Met polymorphism was not independently associated with the studied variables. Genetic regulation of DRD2 function by 957C>T polymorphism thus seems to influence thermal and pain sensitivity, its modulation by rTMS, and susceptibility to neuropathic pain. This indicates a central role for the dopamine system and DRD2 in pain and analgesia. This may have clinical implications regarding individualized selection of patients for rTMS treatment and assessment of risks for neuropathic pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Transcranial magnetic stimulation in mild to severe hemiparesis early after stroke: a proof of principle and novel approach to improve motor function

PubMed Central

Anjos, Sarah M.; Saposnik, Gustavo; Mello, Eduardo A.; Nagaya, Erina M.; Santos, Waldyr; Ferreiro, Karina N.; Melo, Eduardo S.; Reis, Felipe I.; Scaff, Milberto; Cohen, Leonardo G.

2016-01-01

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere can enhance function of the paretic hand in patients with mild motor impairment. Effects of low-frequency rTMS to the contralesional motor cortex at an early stage of mild to severe hemiparesis after stroke are unknown. In this pilot, randomized, double-blind clinical trial we compared the effects of low-frequency rTMS or sham rTMS as add-on therapies to outpatient customary rehabilitation, in 30 patients within 5–45 days after ischemic stroke, and mild to severe hand paresis. The primary feasibility outcome was compliance with the interventions. The primary safety outcome was the proportion of intervention-related adverse events. Performance of the paretic hand in the Jebsen–Taylor test and pinch strength were secondary outcomes. Outcomes were assessed at baseline, after ten sessions of treatment administered over 2 weeks and at 1 month after end of treatment. Baseline clinical features were comparable across groups. For the primary feasibility outcome, compliance with treatment was 100% in the active group and 94% in the sham group. There were no serious intervention-related adverse events. There were significant improvements in performance in the Jebsen–Taylor test (mean, 12.3% 1 month after treatment) and pinch force (mean, 0.5 Newtons) in the active group, but not in the sham group. Low-frequency rTMS to the contralesional motor cortex early after stroke is feasible, safe and potentially effective to improve function of the paretic hand, in patients with mild to severe hemiparesis. These promising results will be valuable to design larger randomized clinical trials. PMID:22173953

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.

The influence of rTMS over prefrontal and motor areas in a morphological task: grammatical vs. semantic effects.

PubMed

Gerfo, Emanuele Lo; Oliveri, Massimiliano; Torriero, Sara; Salerno, Silvia; Koch, Giacomo; Caltagirone, Carlo

2008-01-31

We investigated the differential role of two frontal regions in the processing of grammatical and semantic knowledge. Given the documented specificity of the prefrontal cortex for the grammatical class of verbs, and of the primary motor cortex for the semantic class of action words, we sought to investigate whether the prefrontal cortex is also sensitive to semantic effects, and whether the motor cortex is also sensitive to grammatical class effects. We used repetitive transcranial magnetic stimulation (rTMS) to suppress the excitability of a portion of left prefontal cortex (first experiment) and of the motor area (second experiment). In the first experiment we found that rTMS applied to the left prefrontal cortex delays the processing of action verbs' retrieval, but is not critical for retrieval of state verbs and state nouns. In the second experiment we found that rTMS applied to the left motor cortex delays the processing of action words, both name and verbs, while it is not critical for the processing of state words. These results support the notion that left prefrontal and motor cortex are involved in the process of action word retrieval. Left prefrontal cortex subserves processing of both grammatical and semantic information, whereas motor cortex contributes to the processing of semantic representation of action words without any involvement in the representation of grammatical categories.

Modulation of Effects of Intermittent Theta Burst Stimulation Applied Over Primary Motor Cortex (M1) by Conditioning Stimulation of the Opposite M1

PubMed Central

Ragert, Patrick; Camus, Mickael; Vandermeeren, Yves; Dimyan, Michael A.; Cohen, Leonardo G.

2009-01-01

The excitability of the human primary motor cortex (M1) as tested with transcranial magnetic stimulation (TMS) depends on its previous history of neural activity. Homeostatic plasticity might be one important physiological mechanism for the regulation of corticospinal excitability and synaptic plasticity. Although homeostatic plasticity has been demonstrated locally within M1, it is not known whether priming M1 could result in similar homeostatic effects in the homologous M1 of the opposite hemisphere. Here, we sought to determine whether down-regulating excitability (priming) in the right (R) M1 with 1-Hz repetitive transcranial magnetic stimulation (rTMS) changes the excitability-enhancing effect of intermittent theta burst stimulation (iTBS) applied over the homologous left (L) M1. Subjects were randomly allocated to one of four experimental groups in a sham-controlled parallel design with real or sham R M1 1-Hz TMS stimulation always preceding L M1 iTBS or sham by about 10 min. The primary outcome measure was corticospinal excitability in the L M1, as measured by recruitment curves (RCs). Secondary outcome measures included pinch force, simple reaction time, and tapping speed assessed in the right hand. The main finding of this study was that preconditioning R M1 with 1-Hz rTMS significantly decreased the excitability-enhancing effects of subsequent L M1 iTBS on RCs. Application of 1-Hz rTMS over R M1 alone and iTBS over L M1 alone resulted in increased RC in L M1 relative to sham interventions. The present findings are consistent with the hypothesis that homeostatic mechanisms operating across hemispheric boundaries contribute to regulate motor cortical function in the primary motor cortex. PMID:19474173

The theta burst transcranial magnetic stimulation over the right PFC affects electroencephalogram oscillation during emotional processing.

PubMed

Cao, Dan; Li, Yingjie; Niznikiewicz, Margaret A; Tang, Yingying; Wang, Jijun

2018-03-02

Prefrontal cortex (PFC) plays an important role in emotional processing and therefore is one of the most frequently targeted regions for non-invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS) in clinical trials, especially in the treatment of emotional disorders. As an approach to enhance the effectiveness of rTMS, continuous theta burst stimulation (cTBS) has been demonstrated to be efficient and safe. However, it is unclear how cTBS affects brain processes related to emotion. In particular, psychophysiological studies on the underlying neural mechanisms are sparse. In the current study, we investigated how the cTBS influences emotional processing when applied over the right PFC. Participants performed an emotion recognition Go/NoGo task, which asked them to select a GO response to either happy or fearful faces after the cTBS or after sham stimulation, while 64-channel electroencephalogram (EEG) was recorded. EEG oscillation was examined using event-related spectral perturbation (ERSP) in a time-interval between 170 and 310ms after face stimuli onset. In the sham group, we found a significant difference in the alpha band between response to happy and fearful stimuli but that effect did not exist in the cTBS group. The alpha band activity at the scalp was reduced suggesting the excitatory effect at the brain level. The beta and gamma band activity was not sensitive to cTBS intervention. The results of the current study demonstrate that cTBS does affect emotion processing and the effect is reflected in changes in EEG oscillations in the alpha band specifically. The results confirm the role of prefrontal cortex in emotion processing. We also suggest that this pattern of cTBS results elucidates mechanisms by which mood improvement in depressive disorders is achieved using cTBS intervention. Copyright © 2017 Elsevier Inc. All rights reserved.

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

ERIC Educational Resources Information Center

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

2012-01-01

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

Use of low frequency repetitive transcranial magnetic stimulation to reduce context-dependent learning in people with Parkinson's disease.

PubMed

Lee, Ya-Yun; Fisher, Beth E

2017-05-22

Compared with age-matched non-disabled adults, people with Parkinson's disease (PD) demonstrated greater context-dependent learning, a phenomenon in which an individual shows inferior motor performance when the testing environmental context is different from the original practice context. Additionally, enhanced context- dependency has been shown to be associated with an increased activation of the dorsolateral prefrontal cortex (DLPFC). This study aimed to determine whether context-dependent learning in people with PD could be reduced by decreasing DLPFC activation with low frequency repetitive transcranial magnetic stimulation (rTMS). Quasi-experimental pre-post test controlled study. University laboratory. Twenty-seven participants (18 individuals with PD and 9 age-matched non- disabled adults) were recruited into the PD, PD_rTMS (PD participants who received low frequency rTMS), and Control groups. All participants practiced a finger sequence task containing 3 sequences embedded within specific contexts (colored circles and spatial location on a computer screen) on the first day. On day 2, the participants were tested under the SWITCH and SAME conditions. In the SWITCH condition, the sequence-context association changed from that of practice; in the SAME condition, the sequence-context association remained the same as practice. The PD_rTMS group received 1 Hz rTMS applied over the left DLPFC on the second day before the testing conditions. Switch cost, the performance difference between the SWITCH and SAME conditions, was calculated to indicate context-dependency. All participants improved throughout practice on the first day. Analysis of the switch cost revealed a significant group main effect (p = 0.050). Post-hoc analysis revealed that the PD_rTMS group had significantly smaller switch cost than the PD group (p = 0.031) but not the Control group. Low frequency rTMS applied over DLPFC reduced context-dependency in people with PD. The findings provide a

Effects of low-frequency repetitive transcranial magnetic stimulation and neuromuscular electrical stimulation on upper extremity motor recovery in the early period after stroke: a preliminary study.

PubMed

Tosun, Aliye; Türe, Sabiha; Askin, Ayhan; Yardimci, Engin Ugur; Demirdal, Secil Umit; Kurt Incesu, Tülay; Tosun, Ozgur; Kocyigit, Hikmet; Akhan, Galip; Gelal, Fazıl Mustafa

2017-07-01

To assess the efficacy of inhibitory repetitive transcranial magnetic stimulation (rTMS) and neuromuscular electrical stimulation (NMES) on upper extremity motor function in patients with acute/subacute ischemic stroke. Twenty-five ischemic acute/subacute stroke subjects were enrolled in this randomized controlled trial. Experimental group 1 received low frequency (LF) rTMS to the primary motor cortex of the unaffected side + physical therapy (PT) including activities to improve strength, flexibility, transfers, posture, balance, coordination, and activities of daily living, mainly focusing on upper limb movements; experimental group 2 received the same protocol combined with NMES to hand extensor muscles; and the control group received only PT. Functional magnetic resonance imaging (fMRI) scan was used to evaluate the activation or inhibition of the affected and unaffected primary motor cortex. No adverse effect was reported. Most of the clinical outcome scores improved significantly in all groups, however no statistically significant difference was found between groups due to the small sample sizes. The highest percent improvement scores were observed in TMS + NMES group (varying between 48 and 99.3%) and the lowest scores in control group (varying between 13.1 and 28.1%). Hand motor recovery was significant in both experimental groups while it did not change in control group. Some motor cortex excitability changes were also observed in fMRI. LF-rTMS with or without NMES seems to facilitate the motor recovery in the paretic hand of patients with acute/subacute ischemic stroke. TMS or the combination of TMS + NMES may be a promising additional therapy in upper limb motor training. Further studies with larger numbers of patients are needed to establish their effectiveness in upper limb motor rehabilitation of stroke.

Treatment-Resistant Depression

MedlinePlus

... provide significant relief of severe depression. Repetitive transcranial magnetic stimulation (rTMS). Generally only used when ECT isn't effective, rTMS uses magnetic fields to stimulate nerve cells in the brain ...

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.

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

rTMS on left prefrontal cortex contributes to memories for positive emotional cues: a comparison between pictures and words.

PubMed

Balconi, M; Cobelli, C

2015-02-26

The present research explored the cortical correlates of emotional memories in response to words and pictures. Subjects' performance (Accuracy Index, AI; response times, RTs; RTs/AI) was considered when a repetitive Transcranial Magnetic Stimulation (rTMS) was applied on the left dorsolateral prefrontal cortex (LDLPFC). Specifically, the role of LDLPFC was tested by performing a memory task, in which old (previously encoded targets) and new (previously not encoded distractors) emotional pictures/words had to be recognized. Valence (positive vs. negative) and arousing power (high vs. low) of stimuli were also modulated. Moreover, subjective evaluation of emotional stimuli in terms of valence/arousal was explored. We found significant performance improving (higher AI, reduced RTs, improved general performance) in response to rTMS. This "better recognition effect" was only related to specific emotional features, that is positive high arousal pictures or words. Moreover no significant differences were found between stimulus categories. A direct relationship was also observed between subjective evaluation of emotional cues and memory performance when rTMS was applied to LDLPFC. Supported by valence and approach model of emotions, we supposed that a left lateralized prefrontal system may induce a better recognition of positive high arousal words, and that evaluation of emotional cue is related to prefrontal activation, affecting the recognition memories of emotions. Copyright © 2014 IBRO. Published by Elsevier Ltd. 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.

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.

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.

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

[Feasibility of auditory cortical stimulation for the treatment of tinnitus. Three case reports].

PubMed

Litré, C-F; Giersky, F; Theret, E; Leveque, M; Peruzzi, P; Rousseaux, P

2010-08-01

Tinnitus is a public health issue in France. Around 1 % of the population is affected and 30,000 people are handicapped in their daily life. The treatments available for disabling tinnitus have until now been disappointing. We report our experience on the treatment of these patients in neurosurgery. Between 2006 and 2008, transcranial magnetic stimulation (rTMS) was performed following several supraliminal and subliminal protocols in 16 patients whose mean age was 47 years (range, 35-71). All patients underwent anatomical and functional MRI of the auditory cortex before and 18 h after rTMS, to straddle the primary and secondary auditory cortices. All patients underwent audiometric testing by an ENT physician. Nine patients responded with rTMS. After these investigations, two quadrapolar electrodes (Resume), connected to a stimulating device implanted under the skin (Synergy, from Medtronic), were extradurally implanted in three patients. The electrodes were placed between the primary and secondary auditory cortices. The mean follow-up was 25 months and significant improvement was found in these patients. The feasibility of cortical stimulation in symptomatic treatment of tinnitus was demonstrated by this preparatory work. The intermediate- and long-term therapeutic effects remain to be evaluated. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

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.

Repetitive transcranial magnetic stimulation reveals a role for the left inferior parietal lobule in matching observed kinematics during imitation.

PubMed

Reader, Arran T; Royce, Ben P; Marsh, Jade E; Chivers, Katy-Jayne; Holmes, Nicholas P

2018-04-01

Apraxia (a disorder of complex movement) suggests that the left inferior parietal lobule (IPL) plays a role in kinematic or spatial aspects of imitation, which may be particularly important for meaningless (i.e. unfamiliar intransitive) actions. Mirror neuron theories indicate that the IPL is part of a frontoparietal system that can support imitation by linking observed and stored actions through visuomotor matching, and have less to say about different subregions of the left IPL, or how different types of action (i.e. meaningful or meaningless) are processed for imitation. We used repetitive transcranial magnetic stimulation (rTMS) to bridge this gap and better understand the roles of the left supramarginal gyrus (SMG) and left angular gyrus (AG) in imitation. We also examined whether these areas are differentially involved in meaningful and meaningless action imitation. We applied rTMS over the left SMG, over the left AG or during a no-rTMS baseline condition, and then asked participants to imitate a confederate's actions whilst the arm and hand movements of both individuals were motion-tracked. rTMS over both the left SMG and the left AG reduced the velocity of participants' finger movements relative to the actor during imitation of finger gestures, regardless of action meaning. Our results support recent claims in apraxia and confirm a role for the left IPL in kinematic processing during gesture imitation, regardless of action meaning. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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

PubMed

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

2010-11-01

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

Role of the right inferior parietal cortex in auditory selective attention: An rTMS study.

PubMed

Bareham, Corinne A; Georgieva, Stanimira D; Kamke, Marc R; Lloyd, David; Bekinschtein, Tristan A; Mattingley, Jason B

2018-02-01

Selective attention is the process of directing limited capacity resources to behaviourally relevant stimuli while ignoring competing stimuli that are currently irrelevant. Studies in healthy human participants and in individuals with focal brain lesions have suggested that the right parietal cortex is crucial for resolving competition for attention. Following right-hemisphere damage, for example, patients may have difficulty reporting a brief, left-sided stimulus if it occurs with a competitor on the right, even though the same left stimulus is reported normally when it occurs alone. Such "extinction" of contralesional stimuli has been documented for all the major sense modalities, but it remains unclear whether its occurrence reflects involvement of one or more specific subregions of the temporo-parietal cortex. Here we employed repetitive transcranial magnetic stimulation (rTMS) over the right hemisphere to examine the effect of disruption of two candidate regions - the supramarginal gyrus (SMG) and the superior temporal gyrus (STG) - on auditory selective attention. Eighteen neurologically normal, right-handed participants performed an auditory task, in which they had to detect target digits presented within simultaneous dichotic streams of spoken distractor letters in the left and right channels, both before and after 20 min of 1 Hz rTMS over the SMG, STG or a somatosensory control site (S1). Across blocks, participants were asked to report on auditory streams in the left, right, or both channels, which yielded focused and divided attention conditions. Performance was unchanged for the two focused attention conditions, regardless of stimulation site, but was selectively impaired for contralateral left-sided targets in the divided attention condition following stimulation of the right SMG, but not the STG or S1. Our findings suggest a causal role for the right inferior parietal cortex in auditory selective attention. Copyright © 2017 Elsevier Ltd. All rights

Primed low-frequency repetitive transcranial magnetic stimulation and constraint-induced movement therapy in pediatric hemiparesis: a randomized controlled trial.

PubMed

Gillick, Bernadette T; Krach, Linda E; Feyma, Tim; Rich, Tonya L; Moberg, Kelli; Thomas, William; Cassidy, Jessica M; Menk, Jeremiah; Carey, James R

2014-01-01

The aim of this study was to determine the feasibility and efficacy of five treatments of 6 Hz primed, low-frequency, repetitive transcranial magnetic stimulation (rTMS) combined with constraint-induced movement therapy (CIMT) to promote recovery of the paretic hand in children with congenital hemiparesis. Nineteen children with congenital hemiparesis aged between 8 and 17 years (10 males, nine females; mean age 10 years 10 months, SD 2 years 10 months; Manual Ability Classification Scale levels I-III) underwent five sessions of either real rTMS (n=10) or sham rTMS (n=9) alternated daily with CIMT. CIMT consisted of 13 days of continuous long-arm casting with five skin-check sessions. Each child received a total of 10 hours of one-to-one therapy. The primary outcome measure was the Assisting Hand Assessment (AHA) and the secondary outcome variables were the Canadian Occupational Performance Measure (COPM) and stereognosis. A Wilcoxon signed-rank sum test was used to analyze differences between pre- and post-test scores within the groups. Analysis of covariance was used to compute mean differences between groups adjusting for baseline. Fisher's exact test was used to compare individual change in AHA raw scores with the smallest detectable difference (SDD) of 4 points. All participants receiving treatment finished the study. Improvement in AHA differed significantly between groups (p=0.007). No significant differences in the secondary outcome measures were found. Eight out of 10 participants in the rTMS/CIMT group showed improvement greater than the SDD, but only two out of nine in the sham rTMS/CIMT group showed such improvement (p=0.023). No serious adverse events occurred. Primed, low-frequency rTMS combined with CIMT appears to be safe, feasible, and efficacious in pediatric hemiparesis. Larger clinical trials are now indicated. © 2013 Mac Keith Press.

Non-invasive brain stimulation in Parkinson's disease: Exploiting crossroads of cognition and mood.

PubMed

Dinkelbach, Lars; Brambilla, Michela; Manenti, Rosa; Brem, Anna-Katharine

2017-04-01

Cognitive impairments and depression are common non-motor manifestations in Parkinson's disease (PD). Recent evidence suggests that both partially arise via the same frontostriatal network, opening the opportunity for concomitant treatment with non-invasive brain stimulation (NIBS) techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). In this systematic review, we evaluate the effects of NIBS on cognition and/or mood in 19 placebo-controlled studies involving 561 PD patients. Outcomes depended on the area stimulated and the technique used. rTMS over the dorsolateral-prefrontal cortex (DLPFC) resulted in significant reductions in scores of depressive symptoms with moderate to large effect sizes along with increased performance in several tests of cognitive functions. tDCS over the DLPFC improved performance in several cognitive measures, including executive functions with large effect sizes. Additional effects of tDCS on mood were not detectable; however, only non-depressed patients were assessed. Further confirmatory research is needed to clarify the contribution that NIBS could make in the care of PD patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Brain stimulation and constraint for perinatal stroke hemiparesis

PubMed Central

Andersen, John; Herrero, Mia; Nettel-Aguirre, Alberto; Carsolio, Lisa; Damji, Omar; Keess, Jamie; Mineyko, Aleksandra; Hodge, Jacquie; Hill, Michael D.

2016-01-01

Objective: To determine whether the addition of repetitive transcranial magnetic stimulation (rTMS) and/or constraint-induced movement therapy (CIMT) to intensive therapy increases motor function in children with perinatal stroke and hemiparesis. Methods: A factorial-design, blinded, randomized controlled trial (clinicaltrials.gov/NCT01189058) assessed rTMS and CIMT effects in hemiparetic children (aged 6–19 years) with MRI-confirmed perinatal stroke. All completed a 2-week, goal-directed, peer-supported motor learning camp randomized to daily rTMS, CIMT, both, or neither. Primary outcomes were the Assisting Hand Assessment and the Canadian Occupational Performance Measure at baseline, and 1 week, 2 and 6 months postintervention. Outcome assessors were blinded to treatment. Interim safety analyses occurred after 12 and 24 participants. Intention-to-treat analysis examined treatment effects over time (linear mixed effects model). Results: All 45 participants completed the trial. Addition of rTMS, CIMT, or both doubled the chances of clinically significant improvement. Assisting Hand Assessment gains at 6 months were additive and largest with rTMS + CIMT (β coefficient = 5.54 [2.57–8.51], p = 0.0004). The camp alone produced large improvements in Canadian Occupational Performance Measure scores, maximal at 6 months (Cohen d = 1.6, p = 0.002). Quality-of-life scores improved. Interventions were well tolerated and safe with no decrease in function of either hand. Conclusions: Hemiparetic children participating in intensive, psychosocial rehabilitation programs can achieve sustained functional gains. Addition of CIMT and rTMS increases the chances of improvement. Classification of evidence: This study provides Class II evidence that combined rTMS and CIMT enhance therapy-induced functional motor gains in children with stroke-induced hemiparetic cerebral palsy. PMID:27029628

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

Design of a placebo-controlled, randomized study of the efficacy of repetitive transcranial magnetic stimulation for the treatment of chronic tinnitus.

PubMed

Landgrebe, Michael; Binder, Harald; Koller, Michael; Eberl, Yvonne; Kleinjung, Tobias; Eichhammer, Peter; Graf, Erika; Hajak, Goeran; Langguth, Berthold

2008-04-15

Chronic tinnitus is a frequent condition, which can have enormous impact on patient's life and which is very difficult to treat. Accumulating data indicate that chronic tinnitus is related to dysfunctional neuronal activity in the central nervous system. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method which allows to focally modulate neuronal activity. An increasing amount of studies demonstrate reduction of tinnitus after repeated sessions of low-frequency rTMS and indicate that rTMS might represent a new promising approach for the treatment of tinnitus. However available studies have been mono-centric and are characterized by small sample sizes. Therefore, this multi-center trial will test the efficacy of rTMS treatment in a large sample of chronic tinnitus patients. This is a randomized, placebo-controlled, double-blind multi-center trial of two weeks 1 Hz rTMS-treatment in chronic tinnitus patients. Eligible patients will be randomized to either 2 weeks real or sham rTMS treatment. Main eligibility criteria: male or female individuals aged 18-70 years with chronic tinnitus (duration > 6 months), tinnitus-handicap-inventory-score > or = 38, age-adjusted normal sensorineural hearing (i.e. not more than 5 dB below the 10% percentile of the appropriate age and gender group (DIN EN ISO 7029), conductive hearing loss < or = 15dB. The primary endpoint is a change of tinnitus severity according to the tinnitus questionnaire of Goebel and Hiller (baseline vs. end of treatment period). A total of 138 patients are needed to detect a clinical relevant change of tinnitus severity (i.e. 5 points on the questionnaire of Goebel and Hiller; alpha = 0.05; 1-beta = 0.80). Assuming a drop-out rate of less than 5% until the primary endpoint, 150 patients have to be randomized to guarantee the target number of 138 evaluable patients. The study will be conducted by otorhinolaryngologists and psychiatrists of 7 university hospitals and 1 municipal hospital

Efficacy of single versus three sessions of high rate repetitive transcranial magnetic stimulation in chronic migraine and tension-type headache.

PubMed

Kalita, Jayantee; Laskar, Sanghamitra; Bhoi, Sanjeev Kumar; Misra, Usha Kant

2016-11-01

We report the efficacy of three versus single session of 10 Hz repetitive transcranial magnetic stimulation (rTMS) in chronic migraine (CM) and chronic tension-type headache (CTTH). Ninety-eight patients with CM or CTTH were included and their headache frequency, severity, functional disability and number of abortive medications were noted. Fifty-two patients were randomly assigned to group I (three true sessions) and 46 to group II (one true and two sham rTMS sessions) treatment. 10 Hz rTMS comprising 600 pulses was delivered in 412.4 s on the left frontal cortex. Outcomes were noted at 1, 2 and 3 months. The primary outcome was 50 % reduction in headache frequency, and secondary outcomes were improvement in severity, functional disability, abortive drugs and side effects. The baseline headache characteristics were similar between the two groups. Follow up at different time points revealed significant improvement in headache frequency, severity, functional disability and number of abortive drugs compared to baseline in both group I and group II patients, although these parameters were not different between the two groups. In group I, 31 (79.4 %) had reduction of headache frequency and 29 (74.4 %) converted to episodic headache. In group II, these were 24 (64.8 %) and 22 (59.2 %), respectively. In chronic migraine, the severity of headache at 2 months reduced in group I compared to group II (62.5 vs 35.3 %; P = 0.01). Both single and three sessions of 10 Hz rTMS were found to be equally effective in CM and CTTH, and resulted in conversion of chronic to episodic headache in 67.1 % patients.

Cognitive and Anatomical Underpinnings of the Conceptual Knowledge for Common Objects and Familiar People: A Repetitive Transcranial Magnetic Stimulation Study

PubMed Central

Campanella, Fabio; Fabbro, Franco; Urgesi, Cosimo

2013-01-01

Several studies have addressed the issue of how knowledge of common objects is organized in the brain, whereas the cognitive and anatomical underpinnings of familiar people knowledge have been less explored. Here we applied repetitive transcranial magnetic stimulation (rTMS) over the left and right temporal poles before asking healthy individuals to perform a speeded word-to-picture matching task using familiar people and common objects as stimuli. We manipulated two widely used semantic variables, namely the semantic distance and the familiarity of stimuli, to assess whether the semantic organization of familiar people knowledge is similar to that of common objects. For both objects and faces we reliably found semantic distance and familiarity effects, with less accurate and slower responses for stimulus pairs that were more closely related and less familiar. However, the effects of semantic variables differed across categories, with semantic distance effects larger for objects and familiarity effects larger for faces, suggesting that objects and faces might share a partially comparable organization of their semantic representations. The application of rTMS to the left temporal pole modulated, for both categories, semantic distance, but not familiarity effects, revealing that accessing object and face concepts might rely on overlapping processes within left anterior temporal regions. Crucially, rTMS of the left temporal pole affected only the recognition of pairs of stimuli that could be discriminated at specific levels of categorization (e.g., two kitchen tools or two famous persons), with no effect for discriminations at either superordinate or individual levels. Conversely, rTMS of the right temporal pole induced an overall slowing of reaction times that positively correlated with the visual similarity of the stimuli, suggesting a more perceptual rather than semantic role of the right anterior temporal regions. Results are discussed in the light of current

Anterior temporal lobes mediate semantic representation: Mimicking semantic dementia by using rTMS in normal participants

PubMed Central

Pobric, Gorana; Jefferies, Elizabeth; Ralph, Matthew A. Lambon

2007-01-01

Studies of semantic dementia and PET neuroimaging investigations suggest that the anterior temporal lobes (ATL) are a critical substrate for semantic representation. In stark contrast, classical neurological models of comprehension do not include ATL, and likewise functional MRI studies often fail to show activations in the ATL, reinforcing the classical view. Using a novel application of low-frequency, repetitive transcranial magnetic stimulation (rTMS) over the ATL, we demonstrate that the behavioral pattern of semantic dementia can be mirrored in neurologically intact participants: Specifically, we show that temporary disruption to neural processing in the ATL produces a selective semantic impairment leading to significant slowing in both picture naming and word comprehension but not to other equally demanding, nonsemantic cognitive tasks. PMID:18056637

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

PubMed

Poreisz, Csaba; Paulus, Walter; Moser, Tobias; Lang, Nicolas

2009-05-29

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

Low-frequency brain stimulation to the left dorsolateral prefrontal cortex increases the negative impact of social exclusion among those high in personal distress.

PubMed

Fitzgibbon, Bernadette Mary; Kirkovski, Melissa; Bailey, Neil Wayne; Thomson, Richard Hilton; Eisenberger, Naomi; Enticott, Peter Gregory; Fitzgerald, Paul Bernard

2017-06-01

The dorsolateral prefrontal cortex (DLPFC) is thought to play a key role in the cognitive control of emotion and has therefore, unsurprisingly, been implicated in the regulation of physical pain perception. This brain region may also influence the experience of social pain, which has been shown to activate similar neural networks as seen in response to physical pain. Here, we applied sham or active low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC, previously shown to exert bilateral effects in pain perception, in healthy participants. Following stimulation, participants played the "Cyberball Task"; an online ball-tossing game in which the subject participant is included or excluded. Compared to sham, rTMS did not modulate behavioural response to social exclusion. However, within the active rTMS group only, greater trait personal distress was related to enhanced negative outcomes to social exclusion. These results add further support to the notion that the effect of brain stimulation is not homogenous across individuals, and indicates the need to consider baseline individual differences when assessing response to brain stimulation. This seems particularly relevant in social neuroscience investigations, where trait factors may have a meaningful effect.

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.

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

Brain stimulation-induced neuroplasticity underlying therapeutic response in phantom sounds.

PubMed

Poeppl, Timm B; Langguth, Berthold; Lehner, Astrid; Frodl, Thomas; Rupprecht, Rainer; Kreuzer, Peter M; Landgrebe, Michael; Schecklmann, Martin

2018-01-01

Noninvasive brain stimulation can modify phantom sounds for longer periods by modulating neural activity and putatively inducing regional neuroplastic changes. However, treatment response is limited and there are no good demographic or clinical predictors for treatment outcome. We used state-of-the-art voxel-based morphometry (VBM) to investigate whether transcranial magnetic stimulation-induced neuroplasticity determines therapeutic outcome. Sixty subjects chronically experiencing phantom sounds (i.e., tinnitus) received repetitive transcranial magnetic stimulation (rTMS) of left dorsolateral prefrontal and temporal cortex according to a protocol that has been shown to yield a significantly higher number of treatment responders than sham stimulation and previous stimulation protocols. Structural magnetic resonance imaging was performed before and after rTMS. In VBM whole-brain analyses (P < 0.05, FWE corrected), we assessed longitudinal gray matter changes as well as structural connectivity between the ensuing regions. We observed longitudinal mesoscopic gray matter changes of left dorsolateral prefontal (DLPFC), left operculo-insular, and right inferior temporal cortex (ITC) in responders (N = 22) but not nonresponders (N = 38), as indicated by a group × time interaction and post-hoc tests. These results were neither influenced by age, sex, hearing loss nor by tinnitus laterality, duration, and severity at baseline. Furthermore, we found robust DLPFC-insula and insula-ITC connectivity in responders, while only relatively weak DLPFC-insula connectivity and no insula-ITC connectivity could be demonstrated in nonresponders. Our results reinforce the implication of nonauditory brain regions in phantom sounds and suggest the dependence of therapeutic response on their neuroplastic capabilities. The latter in turn may depend on (differences in) their individual structural connectivity. Hum Brain Mapp 39:554-562, 2018. © 2017 Wiley Periodicals, Inc. �

Safety of primed repetitive transcranial magnetic stimulation and modified constraint-induced movement therapy in a randomized controlled trial in pediatric hemiparesis

PubMed Central

Gillick, Bernadette; Krach, Linda E; Feyma, Tim; Rich, Tonya L; Moberg, Kelli; Menk, Jeremiah; Cassidy, Jessica; Kimberley, Teresa; Carey, James R

2014-01-01

Objective To investigate the safety of combining 6-Hz primed low-frequency repetitive transcranial magnetic stimulation (rTMS) intervention in the contralesional hemisphere with a modified constraint-induced movement therapy (mCIMT) program in children with congenital hemiparesis. Design Phase 1 randomized, double-blinded, placebo-controlled pretest/posttest trial. Setting University academic facility and a pediatric specialty hospital. Participants Nineteen subjects aged 8 to 17 years with congenital hemiparesis due to ischemic stroke or periventricular leukomalacia. No subject withdrew due to adverse events. All subjects included completed the study. Interventions Subjects were randomized to one of two groups: either rTMSreal with mCIMT (n = 10) or rTMSsham with mCIMT (n = 9). Main Outcome Measures Adverse events, physician assessment, ipsilateral hand function, stereognosis, cognitive function, subject report of symptoms assessment and subject questionnaire. Results No major adverse events occurred. Minor adverse events were found in both groups. The most common were headaches (real: 50%, sham: 89%, p=0.14) and cast irritation (real: 30%, sham: 44%, p = 0.65). No differences between groups in secondary cognitive and unaffected hand motor measures were found. Conclusions Primed rTMS can be used safely with mCIMT in congenital hemiparesis. We provide new information on the use of rTMS in combination with mCIMT in children. These findings could be useful in research and future clinical applications in advancing function in congenital hemiparesis. PMID:25283350

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

PubMed

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

2014-07-01

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

Language function distribution in left-handers: A navigated transcranial magnetic stimulation study.

PubMed

Tussis, Lorena; Sollmann, Nico; Boeckh-Behrens, Tobias; Meyer, Bernhard; Krieg, Sandro M

2016-02-01

Recent studies suggest that in left-handers, the right hemisphere (RH) is more involved in language function when compared to right-handed subjects. Since data on lesion-based approaches is lacking, we aimed to investigate language distribution of left-handers by repetitive navigated transcranial magnetic stimulation (rTMS). Thus, rTMS was applied to the left hemisphere (LH) and RH in 15 healthy left-handers during an object-naming task, and resulting naming errors were categorized. Then, we calculated error rates (ERs=number of errors per number of stimulations) for both hemispheres separately and defined a laterality score as the quotient of the LH ER - RH ER through the LH ER + RH ER (abbreviated as (L-R)/(L+R)). In this context, (L-R)/(L+R)>0 indicates that the LH is dominant, whereas (L-R)/(L+R)<0 shows that the RH is dominant. No significant difference in ERs was found between hemispheres (all errors: mean LH 18.0±11.7%, mean RH 18.1±12.2%, p=0.94; all errors without hesitation: mean LH 12.4±9.8%, mean RH 12.9±10.0%, p=0.65; no responses: mean LH 9.3±9.2%, mean RH 11.5±10.3%, p=0.84). However, a significant difference between the results of (L-R)/(L+R) of left-handers and right-handers (source data of another study) for all errors (mean 0.01±0.14 vs. 0.19±0.20, p=0.0019) and all errors without hesitation (mean -0.02±0.20 vs. 0.19±0.28, p=0.0051) was revealed, whereas the comparison for no responses did not show a significant difference (mean: -0.004±0.27 vs. 0.09±0.44, p=0.64). Accordingly, left-handers present a comparatively equal language distribution across both hemispheres with language dominance being nearly equally distributed between hemispheres in contrast to right-handers. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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.

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.

Non-invasive brain stimulation techniques for chronic pain.

PubMed

O'Connell, Neil E; Marston, Louise; Spencer, Sally; DeSouza, Lorraine H; Wand, Benedict M

2018-03-16

This is an updated version of the original Cochrane Review published in 2010, Issue 9, and last updated in 2014, Issue 4. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS) and reduced impedance non-invasive cortical electrostimulation (RINCE). To evaluate the efficacy of non-invasive cortical stimulation techniques in the treatment of chronic pain. For this update we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, LILACS and clinical trials registers from July 2013 to October 2017. Randomised and quasi-randomised studies of rTMS, CES, tDCS, RINCE and tRNS if they employed a sham stimulation control group, recruited patients over the age of 18 years with pain of three months' duration or more, and measured pain as an outcome. Outcomes of interest were pain intensity measured using visual analogue scales or numerical rating scales, disability, quality of life and adverse events. Two review authors independently extracted and verified data. Where possible we entered data into meta-analyses, excluding studies judged as high risk of bias. We used the GRADE system to assess the quality of evidence for core comparisons, and created three 'Summary of findings' tables. We included an additional 38 trials (involving 1225 randomised participants) in this update, making a total of 94 trials in the review (involving 2983 randomised participants). This update included a total of 42 rTMS studies, 11 CES, 36 tDCS, two RINCE and two tRNS. One study evaluated both rTMS and tDCS. We judged only four studies as low risk of bias across all key criteria. Using the GRADE criteria we judged the quality of evidence for each outcome, and for all comparisons as low or very

Non-invasive brain stimulation techniques for chronic pain.

PubMed

O'Connell, Neil E; Marston, Louise; Spencer, Sally; DeSouza, Lorraine H; Wand, Benedict M

2018-04-13

This is an updated version of the original Cochrane Review published in 2010, Issue 9, and last updated in 2014, Issue 4. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS) and reduced impedance non-invasive cortical electrostimulation (RINCE). To evaluate the efficacy of non-invasive cortical stimulation techniques in the treatment of chronic pain. For this update we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, LILACS and clinical trials registers from July 2013 to October 2017. Randomised and quasi-randomised studies of rTMS, CES, tDCS, RINCE and tRNS if they employed a sham stimulation control group, recruited patients over the age of 18 years with pain of three months' duration or more, and measured pain as an outcome. Outcomes of interest were pain intensity measured using visual analogue scales or numerical rating scales, disability, quality of life and adverse events. Two review authors independently extracted and verified data. Where possible we entered data into meta-analyses, excluding studies judged as high risk of bias. We used the GRADE system to assess the quality of evidence for core comparisons, and created three 'Summary of findings' tables. We included an additional 38 trials (involving 1225 randomised participants) in this update, making a total of 94 trials in the review (involving 2983 randomised participants). This update included a total of 42 rTMS studies, 11 CES, 36 tDCS, two RINCE and two tRNS. One study evaluated both rTMS and tDCS. We judged only four studies as low risk of bias across all key criteria. Using the GRADE criteria we judged the quality of evidence for each outcome, and for all comparisons as low or very

On the functional role of human parietal cortex in number processing: How gender mediates the impact of a 'virtual lesion' induced by rTMS.

PubMed

Knops, Andre; Nuerk, Hans-Christoph; Sparing, Roland; Foltys, Henrik; Willmes, Klaus

2006-01-01

Areas around the horizontal part of the intraparietal sulcus (hIPS) have repeatedly been reported to participate in processing numerical magnitude. Using transcranial magnetic stimulation (TMS), we investigated the functional role of the hIPS by examining two effects from the domain of numerical cognition: in magnitude comparison tasks response latencies are inversely related to the numerical distance between two numbers. This distance effect indexes access to the mental number representation. In magnitude comparison tasks responses are faster when decade and unit comparison would lead to the same decision (e.g. 42_57, 4 < 5 and 2 < 7) than when they would not (e.g. 47_62, 4 < 6 but 7 > 2). This compatibility effect reflects unit-decade integration processes. Differential susceptibility of (fe)male participants to TMS was examined. We applied repetitive TMS (rTMS; 1Hz for 10 min) over the left hIPS in 12 participants (6 female). No stimulation and vertex stimulation served as control conditions. The effect of rTMS was mediated by gender: in male participants, the distance effect decreased after TMS over hIPS. For female participants distance and compatibility effect both increased. This modulation of the compatibility effect was limited in duration to no more than 4 min. The hIPS seems to be functionally involved both in number magnitude processing and in integrating unit-decade magnitude information of two-digit numbers. Relative hemispheric specialization of the hIPS with respect to two-digit magnitude comparison is discussed.

Brain stimulation and constraint for perinatal stroke hemiparesis: The PLASTIC CHAMPS Trial.

PubMed

Kirton, Adam; Andersen, John; Herrero, Mia; Nettel-Aguirre, Alberto; Carsolio, Lisa; Damji, Omar; Keess, Jamie; Mineyko, Aleksandra; Hodge, Jacquie; Hill, Michael D

2016-05-03

To determine whether the addition of repetitive transcranial magnetic stimulation (rTMS) and/or constraint-induced movement therapy (CIMT) to intensive therapy increases motor function in children with perinatal stroke and hemiparesis. A factorial-design, blinded, randomized controlled trial (clinicaltrials.gov/NCT01189058) assessed rTMS and CIMT effects in hemiparetic children (aged 6-19 years) with MRI-confirmed perinatal stroke. All completed a 2-week, goal-directed, peer-supported motor learning camp randomized to daily rTMS, CIMT, both, or neither. Primary outcomes were the Assisting Hand Assessment and the Canadian Occupational Performance Measure at baseline, and 1 week, 2 and 6 months postintervention. Outcome assessors were blinded to treatment. Interim safety analyses occurred after 12 and 24 participants. Intention-to-treat analysis examined treatment effects over time (linear mixed effects model). All 45 participants completed the trial. Addition of rTMS, CIMT, or both doubled the chances of clinically significant improvement. Assisting Hand Assessment gains at 6 months were additive and largest with rTMS + CIMT (β coefficient = 5.54 [2.57-8.51], p = 0.0004). The camp alone produced large improvements in Canadian Occupational Performance Measure scores, maximal at 6 months (Cohen d = 1.6, p = 0.002). Quality-of-life scores improved. Interventions were well tolerated and safe with no decrease in function of either hand. Hemiparetic children participating in intensive, psychosocial rehabilitation programs can achieve sustained functional gains. Addition of CIMT and rTMS increases the chances of improvement. This study provides Class II evidence that combined rTMS and CIMT enhance therapy-induced functional motor gains in children with stroke-induced hemiparetic cerebral palsy. © 2016 American Academy of Neurology.

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

Interference with episodic memory retrieval following transcranial stimulation of the inferior but not the superior parietal lobule.

PubMed

Sestieri, Carlo; Capotosto, Paolo; Tosoni, Annalisa; Luca Romani, Gian; Corbetta, Maurizio

2013-04-01

Although posterior parietal cortex (PPC) has been traditionally associated with spatial attention and sensorimotor functions, recent neuroimaging evidence has suggested the involvement of regions of left PCC (LPPC) in memory retrieval. Yet, the role of the parietal lobe in memory-related functions is still controversial. Here we investigated the causal involvement of different LPPC regions in episodic memory retrieval using repetitive transcranial magnetic stimulation (rTMS) during a task that provided both objective and subjective measures of item recognition and source memory. Stimulation sites were identified on the basis of a recent fMRI study showing the involvement of regions of the default mode network (DMN), such as the angular gyrus (AG) in the inferior parietal lobule (IPL), during search for relevant information in episodic memory, and regions of the dorsal attention network (DAN), such as the superior parietal lobule (SPL), during perceptual search. We predicted a selective disruption of memory performance following rTMS stimulation of the left AG relative to a sham condition or stimulation of the left SPL. We found a modest but significant decrease of sensitivity for item recognition when AG was directly compared to SPL, but not to sham stimulation. A stronger effect was however observed for the criterion of source memory judgments when comparing AG with both SPL and sham stimulation, suggesting that the rTMS over AG affects subjective aspects of source monitoring associated with the weighing of relevant retrieved information for source attribution. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

[Health-related quality of life assessment in depression after low-frequency transcranial magnetic stimulation].

PubMed

Dumas, R; Boyer, L; Richieri, R; Guedj, E; Auquier, P; Lançon, C

2014-02-01

Major depressive disorder remains one of the leading causes of disability in developed countries despite pharmacological and psychological treatments. Patients with major depression have poorer health-related quality of life than persons of the general population, or patients with chronic somatic illness. Improvement of health-related quality of life in depression is thus a pertinent treatment objective. Both high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex and low-frequency rTMS over the right dorsolateral prefrontal cortex have shown their effectiveness in medication-resistant depression. However, the Health-related Quality of Life questionnaire remains under-utilized to assess the effectiveness of rTMS in research or in a routine clinical setting. Our study aims to investigate in an open label trial the efficacy of low-frequency rTMS over the right dorsolateral prefrontal cortex on health-related quality of life and clinical outcomes in medication-resistant depression. In a naturalistic trial, 33 unipolar and bipolar patients with medication-resistant depression were treated with daily low-frequency rTMS over the right dorsolateral prefrontal cortex for 4 weeks. Health-related quality of life was assessed using the SF-36 questionnaire. The SF-36 is a generic, self-administered, and worldwide-used questionnaire, consisting of 36 items describing eight health dimensions: physical functioning, social functioning, role-physical problems, role-emotional problems, mental health, vitality, bodily pain, and general health. Physical component summary and mental component summary scores were then obtained. Depression severity was assessed using the 21-item self-report Beck Depression Inventory. Anxiety severity was assessed using the State-Trait Anxiety Inventory. The SF-36, the Beck Depression Inventory and the State-Trait Anxiety Inventory were assessed before and after low-frequency rTMS. The effect of rTMS

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.

Left dorso-lateral repetitive transcranial magnetic stimulation affects cortical excitability and functional connectivity, but does not impair cognition in major depression.

PubMed

Shajahan, Polash M; Glabus, Mike F; Steele, J Douglas; Doris, Alan B; Anderson, Kay; Jenkins, Jenny A; Gooding, Patricia A; Ebmeier, Klaus P

2002-06-01

Transcranial magnetic stimulation (TMS) has been used for over a decade to investigate cortical function. More recently, it has been employed to treat conditions such as major depression. This study was designed to explore the effects of differential treatment parameters, such as stimulation frequency. In addition, the data were examined to determine whether a change in connectivity occurred following TMS. Fifteen patients with major depression were entered into a combined imaging and treatment experiment with single photon emission computed tomography (SPECT) and repetitive transcranial magnetic stimulation (rTMS) over left dorso-lateral prefrontal cortex (DLPFC). Brain perfusion during a verbal fluency task was compared between pre- and poststimulation conditions. Patients were then treated with 80% of motor threshold for a total of 10 days, using 5000 stimuli at 5, 10 or 20 Hz. Tests of cortical excitability and neuropsychological tests were done throughout the trial. Patients generally improved with treatment. There was no perceptible difference between stimulation frequencies, which may have reflected low study power. An increase in rostral anterior cingulate activation after the treatment day was associated with increased functional connectivity in the dorso-lateral frontal loop on the left and the limbic loop on both sides. No noticeable deterioration in neuropsychological function was observed. TMS at the stimulation frequencies used seems to be safe over a course of 5000 stimuli. It appears to have an activating effect in anterior limbic structures and increase functional connectivity in the neuroanatomical networks under the stimulation coil within an hour of stimulation.

Dexterity with numbers: rTMS over left angular gyrus disrupts finger gnosis and number processing.

PubMed

Rusconi, Elena; Walsh, Vincent; Butterworth, Brian

2005-01-01

Since the original description of Gerstmann's syndrome with its four cardinal symptoms, among which are finger agnosia and acalculia, the neuro-cognitive relationship between fingers and calculation has been debated. We asked our participants to perform four different tasks, two of which involved fingers and the other two involving numbers, during repetitive transcranial magnetic stimulation (rTMS) over the posterior parietal lobe of either hemisphere. In the finger tasks, they were required to transform a tactile stimulus randomly delivered on one of their fingers into a speeded key-press response either with the same or with the homologous finger on the opposite hand. In the numerical tasks, they were asked to perform a magnitude or a parity matching on pairs of single digits, in the context of arithmetically related or unrelated numerical primes. In accordance with the original anatomical hypothesis put forward by Gerstmann [Gerstmann, J. (1924). Fingeragnosie: eine umschriebene Stoerung der Orienterung am eigenen Koerper. Wiener clinische Wochenschrift, 37, 1010-12], we found that rTMS over the left angular gyrus disrupted tasks requiring access to the finger schema and number magnitude processing in the same group of participants. In addition to the numerous studies which have employed special populations such as neurological patients and children, our data confirm the presence of a relationship between numbers and body knowledge in skilled adults who no longer use their fingers for solving simple arithmetical tasks.

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

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.

Effect of High-Frequency Transcranial Magnetic Stimulation on Craving in Substance Use Disorder: A Meta-Analysis.

PubMed

Maiti, Rituparna; Mishra, Biswa Ranjan; Hota, Debasish

2017-01-01

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive, neuromodulatory tool, has been used to reduce craving in different substance use disorders. There are some studies that have reported conflicting and inconclusive results; therefore, this meta-analysis was conducted to evaluate the effect of high-frequency rTMS on craving in substance use disorder and to investigate the reasons behind the inconsistency across the studies. The authors searched clinical trials from MEDLINE, Cochrane databases, and International Clinical Trials Registry Platform. The PRISMA guidelines, as well as recommended meta-analysis practices, were followed in the selection process, analysis, and reporting of the findings. The effect estimate used was the standardized mean difference (Hedge's g), and heterogeneity across the considered studies was explored using subgroup analyses. The quality assessment was done using the Cochrane risk of bias tool, and sensitivity analysis was performed to check the influences on effect size by statistical models. After screening and assessment of eligibility, finally 10 studies were included for meta-analysis, which includes six studies on alcohol and four studies on nicotine use disorder. The random-model analysis revealed a pooled effect size of 0.75 (95% CI=0.29 to 1.21, p=0.001), whereas the fixed-model analysis showed a large effect size of 0.87 (95% CI=0.63 to 1.12, p<0.00001). Subgroup analysis for alcohol use disorder showed an effect size of -0.06 (95% CI=-0.89 to 0.77, p=0.88). In the case of nicotine use disorder, random-model analysis revealed an effect size of 1.00 (95% CI=0.48 to 1.55, p=0.0001), whereas fixed-model analysis also showed a large effect size of 0.96 (95% CI=0.71 to 1.22). The present meta-analysis identified a beneficial effect of high-frequency rTMS on craving associated with nicotine use disorder but not alcohol use disorder.

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.

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.

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.

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

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

Priming With 1-Hz Repetitive Transcranial Magnetic Stimulation Over Contralesional Leg Motor Cortex Does Not Increase the Rate of Regaining Ambulation Within 3 Months of Stroke: A Randomized Controlled Trial.

PubMed

Huang, Ying-Zu; Lin, Li-Fong; Chang, Kwang-Hwa; Hu, Chaur-Jong; Liou, Tsan-Hon; Lin, Yen-Nung

2018-05-01

The potential benefits of repetitive transcranial magnetic stimulation (rTMS), applied either alone or as a combination treatment, on recovery of lower limbs after stroke have been insufficiently studied. The aim of the study was to evaluate the effect of priming with 1-Hz repetitive transcranial magnetic stimulation over contralesional leg motor area with a double-cone coil before physical therapy on regaining ambulation. Thirty-eight subacute stroke patients with significant leg disabilities were randomly assigned into the experimental group or control group to receive a 15-min real or sham 1-Hz repetitive transcranial magnetic stimulation, respectively, over the contralesional motor cortex representing the quadriceps muscle followed by 45-min physical therapy for 15 sessions for 3 wks. Functional measures, motor evoked potentials, and quality of life were assessed. There was no significant difference between experimental group and control group regarding the recovery in ambulation, balance, motor functions, and activity of daily living. No significant difference was found in other functional measures and the quality of life. Only the control group displayed significantly increased cortical excitability of the contralesional hemisphere after the intervention. The present study found that insufficient evidence that contralesional priming with 1-Hz repetitive transcranial magnetic stimulation improves ambulatory and other motor functions among patients with a severe leg dysfunction in subacute stroke.

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

PubMed

Jazmati, Danny; Neubacher, Ute; Funke, Klaus

2018-02-24

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

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.

Moderate effects of noninvasive brain stimulation of the frontal cortex for improving negative symptoms in schizophrenia: Meta-analysis of controlled trials.

PubMed

Aleman, André; Enriquez-Geppert, Stefanie; Knegtering, Henderikus; Dlabac-de Lange, Jozarni J

2018-06-01

Negative symptoms in schizophrenia concern a clinically relevant reduction of goal-directed behavior that strongly and negatively impacts daily functioning. Existing treatments are of marginal effect and novel approaches are needed. Noninvasive neurostimulation by means of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are novel approaches that may hold promise. To provide a quantitative integration of the published evidence regarding effects of rTMS and tDCS over the frontal cortex on negative symptoms, including an analysis of effects of sham stimulation. Meta-analysis was applied, using a random effects model, to calculate mean weighted effect sizes (Cohen's d). Heterogeneity was assessed by using Cochrans Q and I 2 tests. For rTMS treatment, the mean weighted effect size compared to sham stimulation was 0.64 (0.32-0.96; k = 22, total N = 827). Studies with younger participants showed stronger effects as compared to studies with older participants. For tDCS studies a mean weighted effect size of 0.50 (-0.07 to 1.07; k = 5, total N = 134) was found. For all frontal noninvasive neurostimulation studies together (i.e., TMS and tDCS studies combined) active stimulation was superior to sham, the mean weighted effect size was 0.61 (24 studies, 27 comparisons, 95% confidence interval 0.33-0.89; total N = 961). Sham rTMS (baseline - posttreatment comparison) showed a significant improvement of negative symptoms, d = 0.31 (0.09-0.52; k = 16, total N = 333). Whereas previous meta-analyses were underpowered, our meta-analysis had a power of 0.87 to detect a small effect. The available evidence indicates that noninvasive prefrontal neurostimulation can improve negative symptoms. This finding suggests a causal role for the lateral frontal cortex in self-initiated goal-directed behavior. The evidence is stronger for rTMS than for tDCS, although this may be due to the small number of

Multiple blocks of intermittent and continuous theta-burst stimulation applied via transcranial magnetic stimulation differently affect sensory responses in rat barrel cortex

PubMed Central

Thimm, Andreas; Funke, Klaus

2015-01-01

Cortical sensory processing varies with cortical state and the balance of inhibition to excitation. Repetitive transcranial magnetic stimulation (rTMS) has been shown to modulate human cortical excitability. In a rat model, we recently showed that intermittent theta-burst stimulation (iTBS) applied to the corpus callosum, to activate primarily supragranular cortical pyramidal cells but fewer subcortical neurons, strongly reduced the cortical expression of parvalbumin (PV), indicating reduced activity of fast-spiking interneurons. Here, we used the well-studied rodent barrel cortex system to test how iTBS and continuous TBS (cTBS) modulate sensory responses evoked by either single or double stimuli applied to the principal (PW) and/or adjacent whisker (AW) in urethane-anaesthetized rats. Compared to sham stimulation, iTBS but not cTBS particularly enhanced late (>18 ms) response components of multi-unit spiking and local field potential responses in layer 4 but not the very early response (<18 ms). Similarly, only iTBS diminished the suppression of the second response evoked by paired PW or AW–PW stimulation at 20 ms intervals. The effects increased with each of the five iTBS blocks applied. With cTBS a mild effect similar to that of iTBS was first evident after 4–5 stimulation blocks. Enhanced cortical c-Fos and zif268 expression but reduced PV and GAD67 expression was found only after iTBS, indicating increased cortical activity due to lowered inhibition. We conclude that iTBS but less cTBS may primarily weaken a late recurrent-type cortical inhibition mediated via a subset of PV+ interneurons, enabling stronger late response components believed to contribute to the perception of sensory events. PMID:25504571

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