Administration Of rTMS Research Articles

Royal Australian and New Zealand College of Psychiatrists professional practice guidelines for the administration of repetitive transcranial magnetic stimulation.

To provide guidance for the optimal administration of repetitive transcranial magnetic stimulation, based on scientific evidence and supplemented by expert clinical consensus. Articles and information were sourced from existing guidelines and published literature. The findings were then formulated into consensus-based recommendations and guidance by the authors. The guidelines were subjected to rigorous successive consultation within the RANZCP, involving the Section of ECT and Neurostimulation (SEN) Committee, its broader membership and expert committees. The RANZCP professional practice guidelines (PPG) for the administration of rTMS provide up-to-date advice regarding the use of rTMS in clinical practice. The guidelines are intended for use by psychiatrists and non-psychiatrists engaged in the administration of rTMS to facilitate best practice to optimise outcomes for patients. The guidelines strive to find the appropriate balance between promoting best evidence-based practice and acknowledging that evidence for rTMS use is a continually evolving. The guidelines provide up-to-date advice for psychiatrists and non-psychiatrists to promote optimal standards of rTMS practice.

High-frequency repetitive transcranial magnetic stimulation protects against cerebral ischemia/reperfusion injury in rats: Involving the mitigation of ferroptosis and inflammation.

Repetitive transcranial magnetic stimulation (rTMS) has been found to attenuate cerebral ischemia/reperfusion (I/R) injury. However, its effects and mechanism of action have not yet been clarified. It has been reported that cerebral I/R injury is closely associated not only with ferroptosis but also with inflammation. Hence, the current study aimed to investigate whether high-frequency rTMS attenuates middle cerebral artery occlusion (MCAO)-induced cerebral I/R injury and further to elucidate the mediatory role of ferroptosis and inflammation. The protective effects of rTMS on experimental cerebral I/R injury were investigated using transient MCAO model rats. Neurological scores and pathological changes of cerebral ischemic cortex were assessed to evaluate the effects of rTMS on cerebral I/R injury. The involvement of ferroptosis and that of inflammation were examined to investigate the mechanism underlying the effects of rTMS. High-frequency rTMS remarkably rescued the MCAO-induced neurological deficits and morphological damage. rTMS treatment also increased the mRNA and protein expression of glutathione-dependent peroxidase 4, decreased the mRNA and protein levels of acyl-CoA synthetase long-chain family member 4 and transferrin receptor in the cortex. Moreover, rTMS administration reduced the cerebrospinal fluid IL-1β, IL-6, and TNF-α concentrations. These findings implicated that high-frequency rTMS alleviates MCAO-induced cerebral I/R injury, and the underlying mechanism could involve the inhibition of ferroptosis and inflammation. Our study identifies rTMS as a promising therapeutic agent for the treatment of cerebral I/R injury. Moreover, the mechanistic insights into ferroptosis and inflammation advance our understanding of it as a potential therapeutic target for diseases beyond cerebral ischemia stroke.

Neuronavigated Repetitive Transcranial Stimulation Improves Neurocognitive Functioning in Veterans with Schizophrenia: A Possible Role of BDNF Polymorphism.

It has been reported in the previous literatures that high-frequency (HF) neuronavigated repetitive transcranial magnetic stimulation (rTMS) may improve neurocognitive functioning in patients with schizophrenia. Nonetheless, the heterogeneity of the research findings with regards to the effectiveness of HF-rTMS on the neurocognitive functioning in patients with schizophrenia greatly hinders its clinical application. The current study was designed to determine the predictive role of BDNF variants for neurocognitive improvements after rTMS administration in veterans with schizophrenia. 109 hospitalized veterans with schizophrenia were randomly allocated to active HF-rTMS (n=63) or sham stimulation (n=46) over left DLPFC for 4 consecutive weeks. Neurocognitive functions were assessed by using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at baseline and at the end of week 4. BDNF polymorphism was genotyped by the technicians. Compared with sham stimulation sessions, the immediate memory performance was significantly increased in active sessions after neuronavigated HF-rTMS administration. In addition, patients with the CC homozygotes demonstrated greater improvement of immediate memory after rTMS treatment, while T allele carriers showed no significant improvement in immediate memory domain relative to baseline performance of immediate memory. Our findings suggest that add-on neuronavigated HF-rTMS is beneficial on immediate memory only in patients with CC homozygotes, but not in T allele carriers. This pilot study provides further evidence for BDNF as a promise biomarker in predicting the clinical response to rTMS stimulation.

Administration of rTMS Alleviates Stroke-Induced Cognitive Deficits by Modulating miR-409-3p/CTRP3/AMPK/Sirt1 Axis.

Cognitive deficit is a typical complication induced by stroke injuries. Repetitive transcranial magnetic stimulation (rTMS) is a technique that can both attenuate neuropsychiatric disorders and influence miR levels. We attempted to assess effects of rTMS on post-stroke cognitive deficit (PSCD) by focusing on the activity of miR-409-3p/CTRP3/AMPK/Sirt1 axis. PSCD was induced in rats using middle cerebral artery occlusion (MCAO) method and handled with rTMS. MiRs responding to rTMS administration were determined using microarray method. Changes in cognitive function, brain histological feature, neuron apoptosis, and activity of miR-409-3p/CTR3/AMPK/Sirt1 axis were detected. The interaction between of miR-409-3p and rTMS was verified by inducing its level in MCAO rats. rTMS influenced levels of miRs in MCAO rats, with 104 miRs being upregulated and 249s miR being downregulated, contributing to the function changes in multiple biological processes. Moreover, the technique improved brain function and structure in model rats. At the molecular level, rTMS inhibited miR-409-3p and activated CTRP3/AMPK/Sirt1 pathway. After the induction of miR-409-3p, effects of rTMS were counteracted, which were represented by the impaired cognitive function and neuron viability in model rats. Collectively, rTMS could protect against stroke-induced cognitive deficits, which depended on the inhibition of miR-409-3p level.

Repetitive Transcranial Magnetic Stimulation Improves Mild Cognitive Impairment Associated with Alzheimer's Disease in Mice by Modulating the miR-567/NEUROD2/PSD95 Axis.

BackgroundMild cognitive impairment (MCI) is a typical symptom of early Alzheimer’s disease (AD) and is driven by the dysfunction of microRNAs (miRs). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique for handling neuropsychiatric disorders and has universally effects on the functions of miRs. In the current study, the improvement effects of rTMS on MCI associated with AD were explored by focusing on miR-567/NEUROD2/PSD95 axis.MethodsMCI was induced in mice using scopolamine and was treated with rTMS of two frequencies (1 Hz and 10 Hz). The changes in cognitive function, brain structure, neurotrophic factor levels, and activity of miR-567/NEUROD2/PSD95 axis were assessed. The interaction between rTMS and miR-567 was further verified by inducing the level of miR-567 in AD mice.ResultsThe administrations of rTMS improved the cognitive function of AD mice and attenuated brain tissue destruction, which were associated with the restored production of BDNF and NGF. Additionally, rTMS administrations suppressed the expression of miR-567 and up-regulated the expressions of NEUROD2 and PSD95, which contributed to the improved condition in central nerve system. With the induced level of miR-567, the effects of rTMS were counteracted: the learning and memorizing abilities of mice were impaired, the brain neuron viability was suppressed, and the production of neurotrophic factors was suppressed even under the administration of rTMS. The changes in brain function and tissues were associated with the inhibited expressions of NEUROD2 and PSD95.ConclusionThe findings outlined in the current study demonstrated that rTMS treatment could protect brain against AD-induced MCI without significant side effects, and the function depended on the inhibition of miR-567.

Assessment of multiple salivary biomarkers during repetitive transcranial magnetic stimulation (rTMS) treatment for major depression

Steroid hormones may serve as potential biomarkers of treatment response for major depressive disorder (MDD). Here, we assessed salivary levels of cortisol, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S), as well as α-amylase activity, across 30 sessions of bilateral repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex in MDD patients. While rTMS significantly improved symptoms as measured by three different symptom scales, salivary biomarker levels and their ratios showed no significant changes across sessions. These results do not support the routine clinical use of these biomarkers as reliable indicators of treatment outcome during rTMS administration for MDD.

Protective effects of repetitive transcranial magnetic stimulation against 6-OHDA-induced Parkinson’s symptoms in a mice model: the key role of miR-409-3p/PDHB axis

Aim Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique showing improvement effects on Parkinson’s disease (PD). Multiple microRNAs (miRs) are dys-expressed during the progression of PD. In the current study, the potential involvement of miRs in the anti-PD effects of rTMS was explored. Methods PD symptoms were induced in mice with 6-OHDA. The expression profile of miRs influenced by rTMS in PD mice was detected by microarray technique and validated by RT-qPCR detection. The PD mice were treated with rTMS and the changes in cognitive behaviors, substantia nigra neuron number, brain histology, and Aβ1-42 level were detected. The activity of miR-409-3p/PDHB axis was also detected to preliminarily explain the interaction between miRs and rTMS. Results The detection of microarray showed that 266 miRs were dys-expressed in PD mice after the administration of rTMS, including 101 up-regulated ones and 146 down-regulated ones. With validation by RT-qPCR detection, miR-409-3p was selected for subsequent assays. Administrations of rTMS improved cognitive behaviors of mice, increased neuron number, and attenuated brain injuries induced by 6-OHDA. The cerebrospinal fluid (CSF) level of Aβ1-42 was induced, while the brain level of Aβ1-42 was suppressed by rTMS. Regarding miR-409-3p/PDHB axis, rTMS administrations suppressed miR-409-3p level and increased the expression of PDHB. Conclusion Administrations of rTMS showed considerable protective effects on brain tissues against PD-induced injuries, which was associated with the changes in miR levels. The current study demonstrated that the inhibition of miR-409-3p by rTMS contributed to the attenuation of PD by inducing PDHB.

Repetitive transcranial magnetic stimulation for the treatment of postpartum depression

BackgroundPostpartum depression (PPD) is a common and gravely disabling health concern. Repetitive transcranial magnetic stimulation (rTMS) is an FDA approved treatment for major depression and may be a valuable tool in the treatment of PPD. The treatment effect of rTMS is rapid, generally well tolerated, without systemic effects, and without medication exposure to a fetus and/or breastfed infant. MethodsSix women with PPD received 20 sessions of 10 Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) over a 4 week period. Psychiatric rating scales (BDI, EPDS, STATI), cognitive assessments (MMSE, Trails B, List Generation) and breastfeeding practices were surveyed at baseline and post rTMS treatment. BDI and EPDS were obtained weekly, as well as 3 months and 6 months post study conclusion. ResultsAverage BDI, EPDS, and STAI scores declined over the 4-week duration of rTMS treatment. Of the six patients, four achieved remission as assessed by EPDS and one achieved remission and two responded as assessed by BDI. Mean BDI and EPDS scores at 3 and 6 months follow-up remained below levels at study entry. No evidence of cognitive changes or breastfeeding disruptions. LimitationsThis was an exploratory study with small sample size with no sham control arm. Daily administration of rTMS provides potential for confounding of behavioral activation in the otherwise often isolative postpartum period. ConclusionsrTMS was safe and well tolerated among participants with evidence of sustained improvements in depression and anxiety scores. This study supports rTMS as a promising non-pharmacologic treatment modality for perinatal depression.

Repetitive transcranial magnetic stimulation protects mice against 6-OHDA-induced Parkinson's disease symptoms by regulating brain amyloid β1-42 level.

Repetitive transcranial magnetic stimulation (rTMS) is a technique protecting neurons against diverse neurodegenerative disorders by delivering magnetic stimuli into the brain through the intact scalp. In the current study, the protection effect of rTMS on Parkinson's disease (PD) and the associated mechanism driving the treatment were explored. The PD symptoms were induced using 6-OHDA in mice, and the effect of rTMS of two frequencies (1Hz and 10Hz) on the cognitive behaviors and neuron viability was detected. Afterwards, the level of Aβ1-42 and activity of MKK7-ERK-Fos-APP axis under the administration of rTMS were recorded as well. The intracranial injection of 6-OHDA impaired the cognitive behaviors of the mice in the test of Morris water maze as well as reducing the viability and number of neurons in PD mice. After the treatment of rTMS of both frequencies, the cognitive function of mice was improved and the neuron viability and number were restored in mice brain tissues. The administration of rTMS also increased the cerebrospinal fluid (CSF) level of Aβ1-42 in PD mice, which was accompanied by the suppressed levels of p-MKK7, p-ERK1/2, p-c-Fos, and APP. Moreover, the effect of rTMS on mice nerve system was all exerted in a frequency-dependent manner. In conclusion, the findings outlined in the current study affirmed the protection effect of rTMS against PD. The anti-PD function of rTMS was associated with the suppression of MKK7-ERK-Fos-APP axis, which subsequently resulted in the increased CSF Aβ1-42 level and decreased brain Aβ1-42 level.

Cortical Hemodynamic Response and Connectivity Modulated by Sub-threshold High-Frequency Repetitive Transcranial Magnetic Stimulation.

Repetitive transcranial magnetic stimulation (rTMS) at sub-threshold intensity is a viable clinical strategy to enhance the sensory and motor functions of extremities by increasing or decreasing motor cortical excitability. Despite this, it remains unclear how sub-threshold rTMS modulates brain cortical excitability and connectivity. In this study, we applied functional near-infrared spectroscopy (fNIRS) to investigate the alterations in hemodynamic responses and cortical connectivity patterns that are induced by high-frequency rTMS at a sub-threshold intensity. Forty high-frequency (10 Hz) trains of rTMS at 90% resting motor threshold (RMT) were delivered through a TMS coil placed over 1–2 cm lateral from the vertex. fNIRS signals were acquired from the frontal and bilateral motor areas in healthy volunteers (n = 20) during rTMS administration and at rest. A significant reduction in oxygenated hemoglobin (HbO) concentration was observed in most defined regions of interest (ROIs) during the stimulation period (p < 0.05). Decreased functional connectivity within prefrontal areas as well as between symmetrical ROI-pairs was also observed in most participants during the stimulation (p < 0.05). Results suggest that fNIRS imaging is able to provide a reliable measure of regional cortical brain activation that advances our understanding of the manner in which sub-threshold rTMS affects cortical excitability and brain connectivity.

Repetitive Transcranial Magnetic Stimulation for Upper Extremity Motor Recovery: Does It Help?

Repetitive transcranial magnetic stimulation (rTMS) noninvasively modulates brain excitability in humans and influences mediators of plasticity in animals. When applied in humans in the months to years after stroke, potentiation of motor recovery has been limited. Recently, investigators have shifted rTMS administration into the early weeks following stroke, when injury-induced plasticity could be maximally engaged. This article provides an overview of basic mechanisms of rTMS, consideration of its interaction with various forms of neuroplasticity, and a summary of the highest quality clinical evidence for rTMS given early after stroke. Studies of repetitive magnetic stimulation in vitro and in vivo have found modulation of excitatory and inhibitory neurotransmission and induction of cellular mechanisms supporting plasticity. A handful of clinical studies have shown sustained improvements in grip strength and UE motor impairment when rTMS is delivered in the first weeks after stroke. Though in its infancy, recent research suggests a plasticity-enhancing influence and modest motor recovery potentiation when rTMS is delivered early after stroke.

Effects of short-term, high-frequency repetitive transcranial magnetic stimulation to bilateral dorsolateral prefrontal cortex on smoking behavior and cognition in patients with schizophrenia and non-psychiatric controls

BackgroundHigh rates of tobacco smoking and smoking cessation failure in schizophrenia may be related to prefrontal cortical dysfunction. Novel treatment options for tobacco use disorder are needed given the limited efficacy of current pharmacotherapies. Preliminary evidence suggests high-frequency repetitive transcranial magnetic stimulation (rTMS) to bilateral dorsolateral prefrontal cortex (DLPFC) may suppress tobacco craving in smokers with schizophrenia. The goal of this study was to determine effects of rTMS for tobacco craving and cognition using a short-term (3-day) human laboratory paradigm. MethodsBilateral active (20Hz) versus sham rTMS stimulation was administered in a counterbalanced, double-blind, cross-over design to thirteen smokers with schizophrenia and n=14 non-psychiatric smoking controls. Participants were studied at baseline (smoking satiated), after 16h of smoking abstinence, and after smoking reinstatement. Primary outcome measures included tobacco craving, withdrawal and cognition. ResultsOvernight abstinence produced a significant increase in tobacco craving and withdrawal, and impaired verbal memory and visuospatial working memory in both diagnostic groups; these effects were reversed with smoking reinstatement. However, active rTMS did not modify this pattern of results. Moreover, active versus sham rTMS had no significant effects on cognitive outcomes, and was not associated with significant adverse events. ConclusionsOur preliminary findings suggest that short-term rTMS administration may not be sufficient enough to modify cognition, craving, and withdrawal outcomes in smokers with schizophrenia (NCT00736710). Longer-term, controlled treatment studies examining effects of rTMS on smoking behaviors and cognition in schizophrenia are warranted.

P223 Adaptability and reproducibility of a memory disruption rTMS protocol in the PharmaCog IMI European project

Introduction The capacity of repetitive TMS to transiently interfere with cognitive processes in humans may offer an experimental platform for pharmacological studies. Developing compounds could then be tested to reverse artificially generated cognitive dysfunction, providing first hints of efficacy. In the FP7-IMI European ’Pharmacog’ Project, an rTMS protocol previously published in the literature, was adapted and validated as a ’cognitive challenge model’ to mimic episodic memory dysfunction occurring in early Alzheimer’s disease. However, it would be desirable to test whether the effects of TMS are comparable and reproducible across different centres and time-point assessments. Objectives Our main aims were, (1) to find out if visual memory interference through rTMS administration could be replicated using our specific experimental settings and task adaptations (Fig. 1), (2) to test if results are comparable in two centres and (3) to investigate if the effects obtained are reproducible when subjects are re-tested 15 days later. Methods 68 healthy young male subjects were included. Neuronavigated (Fig. 1) repetitive TMS was applied over the left dorsolateral prefrontal cortex (LDLPFC) or the Vertex area (control condition) during encoding of pictures, for latter memory recognition. Subjects attended one of two research centres in three main occasions: On visit 1, rTMS was applied using a sham coil and served as a baseline measure. On visit 2, real rTMS was administered. On visit 3, 15 days later, a subsample (N = 21) performed the same protocol to test for reproducibility of effects. Results A time (visit 1 vs visit 2) × TMS type (LDLPFC vs Vertex) ANOVA and posterior pairwise comparisons revealed that only rTMS delivered over the LDLPFC and during visit 2 day resulted in a significant decrease in subsequent memory recognition (F = 8.95, p = 0.004; Fig. 2a). No centre effect observed (F = 0.03, p = 0.96). Initial rTMS effects could not be replicated in the subsample (Fig. 2b). Conclusions Our findings offers positive evidence regarding the feasibility of adapting a rTMS cognitive interference protocol, to conduct new experimental research in separate independent institutions. The factors underlying the lack of test–retest reproducibility of the interference should be further investigated. Download : Download high-res image (345KB) Download : Download full-size image Download : Download high-res image (400KB) Download : Download full-size image

Comprehensive Guide for the Safe Administration of rTMS While Providing for Patient Comfort

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive somatic treatment with promising therapeutic potential for a variety of neuropsychiatric conditions (George & Belmaker, 2007). A...

Brain SPECT guided repetitive transcranial magnetic stimulation (rTMS) in treatment resistant major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) has emerged as a potential treatment in treatment resistant major depressive disorder (MDD). However, there is no consensus about the exact site of stimulation for rTMS. Single-photon emission computed tomography (SPECT) offers a potential technique in deciding the site of stimulation. The present study was conducted to assess the difference in outcome of brain SPECT assisted rTMS versus standard protocol of twenty sessions of high frequency rTMS as add on treatment in 20 patients with treatment resistant MDD, given over a period of 4 weeks. Thirteen subjects (group I) received high frequency rTMS over an area of hypoperfusion in the prefrontal cortex, as identified on SPECT, whereas 7 subjects (group II) were administered rTMS in the left dorsoslateral prefrontal cortex (DLPFC) area. Improvement was monitored using standardized instruments. Patients in the group I showed a significantly better response compared to those in the group II. In group I, 46% of the subjects were responders on MADRS, 38% on BDI and 77% on CGI. The parallel figures of responders in Group II were 0% on MADRS, 14% on BDI and 43% on CGI. There were no remitters in the study. No significant untoward side effects were noticed. The study had limitations of a small sample size and non-controlled design, and all the subjects were also receiving the standard antidepressant therapy. Administration of rTMS over brain SPECT specified area of hypoperfusion may have a better clinical outcome compared to the standard protocol.

RTMS in the management of auditory hallucinations in patients with schizophrenia.

rTMS in the management of auditory hallucinations in patients with schizophrenia.

P 65. The effect of controlled behavior during 10 Hz rTMS administration on subsequent offline performance in a visual attention task

Repetitive transcranial magnetic stimulation (rTMS) in ‘offline’ experiments is commonly administered to participants that are in a relaxed ’resting state’. Clearly, this approach leads to an ill controlled baseline state of the participants’ brain, in face of evidence that the mental baseline influences how the brain is affected by TMS (e.g., Silvanto and Pascual-Leone (2008) Brain Topography 21). The aim of the present study was to assess the effect of uncontrolled vs. controlled behavior during rTMS administration on participants’ performance in a subsequent visual localization task. We compared the offline effects of 10 Hz rTMS for standard TMS administration (uncontrolled ‘resting’ behavior without task) to 10 Hz rTMS administered while the participants were performing a visual localization task (controlled behavior with task). Tasks during the online and offline period were identical, testing the participants’ ability to allocate attention to the detection of peripheral unilateral (left or right) or bilateral (left and right) peri-threshold visual stimuli. rTMS or sham stimulation (by vertically tilted coil) were applied to the 10–20 coordinate P4, located in the right posterior parietal cortex. Performance after rTMS in the ‘resting’ condition appeared similar to the performance in the ‘with task’ condition. Importantly, however, when compared to sham stimulation conditions, rTMS induced a deterioration of offline performance relative to sham stimulation in the ‘resting’ condition, whereas it led to better performance relative to sham in the ‘with task’ condition ( Fig. 1 ). We conclude that in the present paradigm, the manipulation ‘with task’ versus ‘resting’ during the administration of rTMS might be too weak to induce brain states that are distinct enough to induce different levels of performance in the subsequent task. From this perspective, controlling the participants’ behavior during rTMS administration does not appear to matter for their offline behavior after rTMS. However, the results of the study also demonstrate that whether rTMS leads to a deterioration or improvement of performance critically depends on the baseline to which the offline performance is compared. Offline performance after rTMS or sham stimulation applied to participants during a behavioral task or at rest. Performance was evaluated as inverse efficiency, computed as reaction time/ proportion of correct trials. Shown are the results for bilateral visual stimuli. Within-subject error bars were created using the method of Cousineau (2005).

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

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.

High frequency heart rate variability evoked by repetitive transcranial magnetic stimulation over the medial prefrontal cortex: A preliminary investigation on brain processing of acute stressor-evoked cardiovascular reactivity

Introduction: Transcranial Magnetic Stimulation (TMS) is a non-invasive technique for brain stimulation. Repetitive TMS (rTMS) over the medial Prefrontal Cortex (mPFC), Broadman Area 10 (BA10) may stimulate transynaptically perigenual Anterior Cingulate Cortex (pACC, BA 33), insula, amigdala, hypothalamus and connected branches of the Autonomic Nervous System (ANS) involved in stressorevoked cardiovascular reactivity. Stressors are associated with an increase in sympathetic cardiac control, a decrease in parasympathetic control, or both, and, consequently, an increase in systolic/stroke volume, total vascular impedance/resistance and heart rate, a decrease of baroreflex sensitivity, i.e., an increase in blood pressure/arterial tension. Objectives and Aims: The present work aims, using TMS and accordingly to Gianaros modeling, based on functional neuroimaging studies and previous neuroanatomical data from animal models, to probe the connectivity of brain systems involved in stressor-evoked cardiovascular reactivity and to explore TMS potential as a tool for detection and stratification of individual differences concerning this reactivity and hemorreological risk factors correlated with the development of Coronary Heart Disease (CHD). Methods: Both subjects, a 52 years old male and a 40 years old female with previous increased Low Frequency (LF)/High Frequency (HF) Heart Rate Variability (HRV) ratios (respectively, 4.209/3.028) without decompensated cardiorespiratory symptoms, gave informed consent, and ethico-legal issues have been observed. Electroencephalographic (EEG) monitoring has been performed for safety purposes. Immediately after administration, over the mPFC, of 15 pulses of rTMS, during 60 second, with an inductive electrical current, at the stimulating coil, of 85.9 Ampère per μsecond and 66 Ampère per μsecond, respectively, for male and female subjects (a “figure-of-eight” coil and magnetic stimulator MagLite, Dantec/Medtronic, have been used), HRV spectrum analysis (cStress software) has been performed (during 5 minutes, in supine position). Results: In both subjects, LF power, HF power and LF/HF ratio results, before and after rTMS administration, pointed towards sympathetic attenuation and parasympathetic augmentation (respectively, in male/female subject: decreased LF power—65.1 nu/69.3 nu, before rTMS; 56.1 nu/41.6 nu, after rTMS; increased HF power—15.5 nu/22.9 nu, before rTMS; 30.9 nu/45.5 nu, after rTMS). Conclusions: In this preliminary investigation, the existence of a link between “mind” and heart’s function has been put in evidence, through a reversible “virtual” lesion, of brain systems involved in cardiovascular control, caused by TMS. Repetitive TMS over mPFC decreased brain function involved in stressorevoked cardiovascular reactivity, suggesting the importance of TMS in the management of stress-related cardiovascular disorders.

The relationship between brain oscillatory activity and therapeutic effectiveness of transcranial magnetic stimulation in the treatment of major depressive disorder

Major depressive disorder (MDD) is marked by disturbances in brain functional connectivity. This connectivity is modulated by rhythmic oscillations of brain electrical activity, which enable coordinated functions across brain regions. Oscillatory activity plays a central role in regulating thinking and memory, mood, cerebral blood flow, and neurotransmitter levels, and restoration of normal oscillatory patterns is associated with effective treatment of MDD. Repetitive transcranial magnetic stimulation (rTMS) is a robust treatment for MDD, but the mechanism of action (MOA) of its benefits for mood disorders remains incompletely understood. Benefits of rTMS have been tied to enhanced neuroplasticity in specific brain pathways. We summarize here the evidence that rTMS entrains and resets thalamocortical oscillators, normalizes regulation and facilitates reemergence of intrinsic cerebral rhythms, and through this mechanism restores normal brain function. This entrainment and resetting may be a critical step in engendering neuroplastic changes and the antidepressant effects of rTMS. It may be possible to modify the method of rTMS administration to enhance this MOA and achieve better antidepressant effectiveness. We propose that rTMS can be administered: (1) synchronized to a patient's individual alpha frequency (IAF), or synchronized rTMS (sTMS); (2) as a low magnetic field strength sinusoidal waveform; and, (3) broadly to multiple brain areas simultaneously. We present here the theory and evidence indicating that these modifications could enhance the therapeutic effectiveness of rTMS for the treatment of MDD.