Impact of network-targeted multichannel transcranial direct current stimulation on intrinsic and network-to-network functional connectivity

Dynamics within and between functional resting-state networks have a crucial role in determining both healthy and pathological brain functioning in humans. The possibility to noninvasively interact and selectively modulate the activity of networks would open to relevant applications in neuroscience. Here we tested a novel approach for multichannel, network-targeted transcranial direct current stimulation (net-tDCS), optimized to increase excitability of the sensorimotor network (SMN) while inducing cathodal inhibitory modulation over prefrontal and parietal brain regions negatively correlated with the SMN. Using an MRI-compatible multichannel transcranial electrical stimulation (tES) device, 20 healthy participants underwent real and sham tDCS while at rest in the MRI scanner. Changes in functional connectivity (FC) during and after stimulation were evaluated, looking at the intrinsic FC of the SMN and the strength of the negative connectivity between SMN and the rest of the brain. Standard, bifocal tDCS targeting left motor cortex (electrode ~C3) and right frontopolar (~Fp2) regions was tested as a control condition in a separate sample of healthy subjects to investigate network specificity of multichannel stimulation effects. Net-tDCS induced greater FC increase over the SMN compared to bifocal tDCS, during and after stimulation. Moreover, exploratory analysis of the impact of net-tDCS on negatively correlated networks showed an increase in the negative connectivity between SMN and prefrontal/parietal areas targeted by cathodal stimulation both during and after real net-tDCS. Results suggest preliminary evidence of the possibility of manipulating distributed network connectivity patterns through net-tDCS, with potential relevance for the development of cognitive enhancement and therapeutic tES solutions.     

Modulating cortico-striatal and thalamo-cortical functional connectivity with transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that has been shown to alter cortical excitability and activity via application of weak direct currents. Beyond intracortical effects, functional imaging as well as behavioral studies are suggesting additional tDCS-driven alterations of subcortical areas, however, direct evidence for such effects is scarce. We aimed to investigate the impact of tDCS on cortico-subcortical functional networks by seed functional connectivity analysis of different striatal and thalamic regions to prove tDCS-induced alterations of the cortico-striato-thalamic circuit. fMRI resting state data sets were acquired immediately before and after 10 min of bipolar tDCS during rest, with the anode/cathode placed over the left primary motor cortex (M1) and the cathode/anode over the contralateral frontopolar cortex. To control for possible placebo effects, an additional sham stimulation session was carried out. Functional coupling between the left thalamus and the ipsilateral primary motor cortex (M1) significantly increased following anodal stimulation over M1. Additionally, functional connectivity between the left caudate nucleus and parietal association cortices was significantly strengthened. In contrast, cathodal tDCS over M1 decreased functional coupling between left M1 and contralateral putamen. In summary, in this study, we show for the first time that tDCS modulates functional connectivity of cortico-striatal and thalamo-cortical circuits. Here we highlight that anodal tDCS over M1 is capable of modulating elements of the cortico-striato-thalamo-cortical functional motor circuit.     

Improved isometric force endurance after transcranial direct current stimulation over the human motor cortical areas

Neuromuscular fatigue is the exercise-dependent decrease in the ability of muscle fibres to generate force. To investigate whether manipulation of brain excitability by transcranial direct current stimulation (tDCS; 1.5 mA, 10 min, 0.026 C/cm(2)) modulates neuromuscular fatigue, we evaluated the effect of brain polarization over the right motor areas of the cerebral cortex of healthy subjects on the endurance time for a submaximal isometric contraction of left elbow flexors. In 24 healthy volunteers the study protocol comprised an assessment of the maximum voluntary contraction (MVC) for the left elbow flexors and a fatiguing isometric contraction (35% of MVC), before and immediately after brain polarization. One hour elapsed between baseline (T0) and postconditioning (T1) evaluation. After tDCS, MVC remained unchanged from baseline (mean +/- SEM; anodal tDCS: T0, 154.4 +/- 18.07; T1, 142.8 +/- 16.62 N; cathodal tDCS: T0, 156 +/- 18.75; T1, 141.86 +/- 17.53 N; controls: T0, 148.8 +/- 6.64; T1, 137.6 +/- 7.36 N; P > 0.1). Conversely, endurance time decreased significantly less after anodal than after cathodal tDCS or no stimulation (-21.1 +/- 5.5%, -35.7 +/- 3.3% and -39.3 +/- 3.3%, respectively; P < 0.05). None of the evaluated electromyographic variables changed after tDCS. Anodal tDCS could improve endurance time by directly modulating motor cortical excitability, modulating premotor areas, decreasing fatigue-related muscle pain, increasing motivation and improving synergist muscle coupling. Our findings, showing that anodal tDCS over the motor areas of the cerebral cortex improves muscle endurance, open the way to increasing muscle endurance and decreasing muscle fatigue in normal (i.e. sports medicine) and pathological conditions.     

The comparative effects of unilateral and bilateral transcranial direct current stimulation on motor learning and motor performance: A systematic review of literature and meta-analysis

Application of unilateral tDCS (Uni-tDCS) vs. bilateral tDCS (Bi-tDCS) is another important factor that can affect the physiological results of tDCS intervention on motor learning and motor performance. According to the evidence, some studies indicated that motor performance or motor learning are facilitated in healthy individuals by application of the Bi-tDCS more than the Uni-tDCS. On the other hand, some studies showed that there was no significant differences between Uni-tDCS and Bi-tDCS; and both techniques were more effective than sham stimulation. In contrast, the other studies have shown more significant effectiveness of Uni-tDCS than Bi-tDCS on motor performance and motor learning. The aim of this study was to systematically review the studies which investigated the effectiveness of Uni-tDCS and Bi-tDCS intervention on the motor learning and motor performance. The search was performed from databases in the Google Scholar, PubMed, Elsevier, Medline, Ovid and Science Direct with the keywords of motor behavior, motor performance, motor learning, Bi-tDCS or bilateral tDCS, dual tDCS, Uni-tDCS or unilateral tDCS, anodal tDCS and cathodal tDCS from 2000 to 2019. The results indicated that the study population was a key factor in determining study’s findings. Data meta-analysis showed that Uni-tDCS was more effective than Bi-tDCS in patients with stroke, while, Bi-tDCS was more effective than Uni-tDCS to improve motor learning and motor performance in healthy individuals.     

Bifrontal transcranial direct current stimulation modulates tinnitus intensity and tinnitus-distress-related brain activity

Bifrontal transcranial direct current stimulation (tDCS), with the anodal electrode overlying the right and the cathodal electrode overlying the left dorsolateral prefrontal cortex, has been shown to suppress tinnitus significantly in 30% of patients. The source localized resting‐state electrical activity is recorded before and after bifrontal tDCS in patients who respond to tDCS to unravel the mechanism by which tDCS suppresses tinnitus. The present electroencephalography study (N = 12) provides support for the ability of bifrontal tDCS to suppress tinnitus intensity and tinnitus‐related distress by modulation of the pregenual anterior cingulate cortex, parahippocampal area and right primary auditory cortex in resting‐state spontaneous brain activity. These findings provide direct support for tDCS having an impact not only directly on the underlying dorsolateral prefrontal cortex but also indirectly on functionally connected brain areas relevant for tinnitus distress and tinnitus intensity, respectively.     

Prefrontal transcranial direct current stimulation alters activation and connectivity in cortical and subcortical reward systems: A tDCS‐fMRI study

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique used both experimentally and therapeutically to modulate regional brain function. However, few studies have directly measured the aftereffects of tDCS on brain activity or examined changes in task‐related brain activity consequent to prefrontal tDCS. To investigate the neural effects of tDCS, we collected fMRI data from 22 human subjects, both at rest and while performing the Balloon Analog Risk Task (BART), before and after true or sham transcranial direct current stimulation. TDCS decreased resting blood perfusion in orbitofrontal cortex and the right caudate and increased task‐related activity in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in response to losses but not wins or increasing risk. Network analysis showed that whole‐brain connectivity of the right ACC correlated positively with the number of pumps subjects were willing to make on the BART, and that tDCS reduced connectivity between the right ACC and the rest of the brain. Whole‐brain connectivity of the right DLPFC also correlated negatively with pumps on the BART, as prior literature would suggest. Our results suggest that tDCS can alter activation and connectivity in regions distal to the electrodes. Hum Brain Mapp 35:3673–3686, 2014. © 2014 Wiley Periodicals, Inc .     

Meta-analysis of the effects of transcranial direct current stimulation on inhibitory control

BackgroundInhibitory control refers to a central cognitive capacity involved in the interruption and correction of actions. Dysfunctions in these cognitive control processes have been identified as major maintaining mechanisms in a range of mental disorders such as ADHD, binge eating disorder, obesity, and addiction. Improving inhibitory control by transcranial direct current stimulation (tDCS) could ameliorate symptoms in a broad range of mental disorders.ObjectiveThe primary aim of this pre-registered meta-analysis was to investigate whether inhibitory control can be improved by tDCS in healthy and clinical samples. Additionally, several moderator variables were investigated.MethodsA comprehensive literature search was performed on PubMed/MEDLINE database, Web of Science, and Scopus. To achieve a homogenous sample, only studies that assessed inhibitory control in the go-/no-go (GNG) or stop-signal task (SST) were included, yielding a total of 75 effect sizes from 45 studies.ResultsResults of the meta-analysis indicate a small but significant overall effect of tDCS on inhibitory control (g = 0.21) which was moderated by target and return electrode placement as well as by the task. The small effect size was further reduced after correction for publication bias.ConclusionBased on the studies included, our meta-analytic approach substantiates previously observed differences between brain regions, i.e., involvement of the right inferior frontal gyrus (rIFG) vs. the right dorsolateral prefrontal cortex (rDLPFC) in inhibitory control. Results indicate a small moderating effect of tDCS on inhibitory control in single-session studies and highlight the relevance of technical and behavioral parameters.     

Modulating functional connectivity patterns and topological functional organization of the human brain with transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that alters cortical excitability and activity in a polarity‐dependent way. Stimulation for few minutes has been shown to induce plastic alterations of cortical excitability and to improve cognitive performance. These effects might be caused by stimulation‐induced alterations of functional cortical network connectivity. We aimed to investigate the impact of tDCS on cortical network function through functional connectivity and graph theoretical analysis. Single recordings in healthy volunteers with 62 electroencephalography channels were acquired before and after 10 min of facilitatory anodal tDCS over the primary motor cortex (M1), combined with inhibitory cathodal tDCS of the contralateral frontopolar cortex, in resting state and during voluntary hand movements. Correlation matrices containing all 62 pairwise electrode combinations were calculated with the synchronization likelihood (SL) method and thresholded to construct undirected graphs for the θ, α, β, low‐γ and high‐γ frequency bands. SL matrices and undirected graphs were compared before and after tDCS. Functional connectivity patterns significantly increased within premotor, motor, and sensorimotor areas of the stimulated hemisphere during motor activity in the 60–90 Hz frequency range. Additionally, tDCS‐induced significant intrahemispheric and interhemispheric connectivity changes in all the studied frequency bands. In summary, we show for the first time evidence for tDCS‐induced changes in brain synchronization and topological functional organization. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Transcranial direct current stimulation preconditioning modulates the effect of high-frequency repetitive transcranial magnetic stimulation in the human motor cortex

Experimental studies emphasize the importance of homeostatic plasticity as a mean of stabilizing the properties of neural circuits. In the present work we combined two techniques able to produce short-term (5-Hz repetitive transcranial magnetic stimulation, rTMS) and long-term (transcranial direct current stimulation, tDCS) effects on corticospinal excitability to evaluate whether and how the effects of 5-Hz rTMS can be tuned by tDCS preconditioning. Twelve healthy subjects participated in the study. Brief trains of 5-Hz rTMS were applied to the primary motor cortex at an intensity of 120% of the resting motor threshold, with recording of the electromyograph traces evoked by each stimulus of the train from the contralateral abductor pollicis brevis muscle. This interventional protocol was preconditioned by 15 min of anodal or cathodal tDCS delivered at 1.5 mA intensity. Our results showed that motor-evoked potentials (MEPs) increased significantly in size during trains of 5-Hz rTMS in the absence of tDCS preconditioning. After facilitatory preconditioning with anodal tDCS, 5-Hz rTMS failed to produce progressive MEP facilitation. Conversely, when 5-Hz rTMS was preceded by inhibitory cathodal tDCS, MEP facilitation was not abolished. These findings may give insight into the mechanisms of homeostatic plasticity in the human cerebral cortex, suggesting also more suitable applications of tDCS in a clinical setting.     

Noninvasive remote activation of the ventral midbrain by transcranial direct current stimulation of prefrontal cortex

The midbrain lies deep within the brain and has an important role in reward, motivation, movement and the pathophysiology of various neuropsychiatric disorders such as Parkinson''s disease, schizophrenia, depression and addiction. To date, the primary means of acting on this region has been with pharmacological interventions or implanted electrodes. Here we introduce a new noninvasive brain stimulation technique that exploits the highly interconnected nature of the midbrain and prefrontal cortex to stimulate deep brain regions. Using transcranial direct current stimulation (tDCS) of the prefrontal cortex, we were able to remotely activate the interconnected midbrain and cause increases in participants'' appraisals of facial attractiveness. Participants with more enhanced prefrontal/midbrain connectivity following stimulation exhibited greater increases in attractiveness ratings. These results illustrate that noninvasive direct stimulation of prefrontal cortex can induce neural activity in the distally connected midbrain, which directly effects behavior. Furthermore, these results suggest that this tDCS protocol could provide a promising approach to modulate midbrain functions that are disrupted in neuropsychiatric disorders.     

Unihemispheric concurrent dual‐site cathodal transcranial direct current stimulation: the effects on corticospinal excitability

We aimed to assess the effects of concurrent cathodal transcranial direct current stimulation (c‐tDCS) of two targets in a hemisphere, termed unihemispheric concurrent dual‐site cathodal tDCS (c‐tDCS_UHCDS), on the size of M1 corticospinal excitability and its lasting effect. Secondary aims were to identify the mechanisms behind the efficacy of c‐tDCS_UHCDS and to evaluate the side effects of this new technique. Twelve healthy volunteers received 20 min c‐tDCS under five conditions in a random order: M1 c‐tDCS, c‐tDCS_UHCDS of M1–dorsolateral prefrontal cortex (DLPFC), M1–primary sensory cortex (S1), M1–primary visual cortex (V1) and sham. The M1 corticospinal excitability of the first dorsal interossei muscle was assessed before, immediately after, and 30 min, 60 min and 24 h after the interventions. Short‐interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were also assessed, using a paired‐pulse paradigm. Compared to conventional M1 c‐tDCS, corticospinal excitability significantly increased following c‐tDCS_UHCDS of M1‐DLPFC and M1‐V1 for up to 24 h (P = 0.001). Significant increases in ICF were observed following c‐tDCS_UHCDS of M1‐DLPFC (P = 0.005) and M1‐V1 (P = 0.002). Compared to baseline values, ICF and SICI increased significantly at T₆₀ (P < 0.001) and T_24 h (P < 0.001) following the concurrent c‐tDCS of M1 and V1. Sham c‐tDCS_UHCDS did not induce any significant alteration. The corticospinal excitability increase was mainly accompanied by ICF increase, which indirectly indicates the activity of glutamergic mechanisms. The findings may help us to more fully understand the brain function and develop future motor learning studies. No significant excitability change induced by sham c‐tDCS_UHCDS suggests that there is no placebo effect associated with this new tDCS technique.     

Assessing neurophysiological changes associated with combined transcranial direct current stimulation and cognitive‐emotional training for treatment‐resistant depression

Transcranial direct current stimulation (tDCS), a form of non‐invasive brain stimulation, is a promising treatment for depression. Recent research suggests that tDCS efficacy can be augmented using concurrent cognitive‐emotional training (CET). However, the neurophysiological changes associated with this combined intervention remain to be elucidated. We therefore examined the effects of tDCS combined with CET using electroencephalography (EEG). A total of 20 participants with treatment‐resistant depression took part in this open‐label study and received 18 sessions over 6 weeks of tDCS and concurrent CET. Resting‐state and task‐related EEG during a 3‐back working memory task were acquired at baseline and immediately following the treatment course. Results showed an improvement in mood and working memory accuracy, but not response time, following the intervention. We did not find significant effects of the intervention on resting‐state power spectral density (frontal theta and alpha asymmetry), time–frequency power (alpha event‐related desynchronisation and theta event‐related synchronisation) or event‐related potentials (P2 and P3 components). We therefore identified little evidence of neurophysiological changes associated with treatment using tDCS and concurrent CET, despite significant improvements in mood and near‐transfer effects of cognitive training to working memory accuracy. Further research incorporating a sham‐controlled group may be necessary to identify the neurophysiological effects of the intervention.     

Functional connectivity patterns during motor behaviour: the impact of past on present activity

Everyday behaviour often depends on the performance of multiple movements executed in a particular order. Here, the impact of task history on the neural activation patterns of motor behaviour is examined by evaluating unimanual and bimanual actions that are produced in a serial arrangement, such that switching between tasks is required. Cortical dynamics was assessed by means of EEG coherence in the beta frequency band (13-30 Hz). Results showed that although behavioural performance was not affected, switching trials induced increased coherence as compared to control (repeat) trials. This reorganization was dependent on task history and was more pronounced for unimanual than for bimanual tasks. Overall, the data illustrate that neural processing of motor behaviour within a serial arrangement integrates past and present activity, and accordingly impacts on neural efficiency.     

Effects of transcranial direct current stimulation coupled with repetitive electrical stimulation on cortical spreading depression

We have recently shown that two techniques of brain stimulation - repetitive electrical stimulation (ES) (that mimics transcranial magnetic stimulation) and transcranial direct current stimulation (tDCS) - modify the velocity of cortical spreading depression (CSD) significantly. Herein we aimed to study the effects of these two techniques combined on CSD. Thirty-two Wistar rats were divided into four groups according to the treatment: sham tDCS/sham ES, sham tDCS/1 Hz ES, anodal tDCS/1 Hz ES, cathodal tDCS/1 Hz ES. Our findings show that 1 Hz ES reduced CSD velocity, and this effect was modified by either anodal or cathodal tDCS. Anodal tDCS induced larger effects than cathodal tDCS. Hereby CSD velocity was actually increased significantly after anodal tDCS/1 Hz ES. Our results show that combining two techniques of brain stimulation can modify significantly the effects of ES alone on cortical excitability as measured by the neurophysiological parameter of cortical spreading depression and therefore provide important insights into the effects of this new approach of brain stimulation on cortical activity.     

Investigation into the effect of transcranial direct current stimulation on cardiac pacemakers

BackgroundStudies investigating the therapeutic applications of transcranial direct current stimulation (tDCS) in the treatment of age-related neurodegenerative disease have been promising. However, exclusion criteria for these studies invariably disqualify patients implanted with internal cardiac pacemakers, citing safety concerns. Because the majority of cardiac pacemaker implantees are over 65, this criterion may limit candidacy for tDCS based research and/or treatment of age-related neurodegenerative disease.Objective/HypothesisWe will test the hypothesis that tDCS impacts pacemaker function. Strong electrical potentials, such as those generated by external defibrillators (∼500 V, ∼10 A), are known to occasionally damage pacemaker circuitry and software, but it seems unlikely tDCS would damage a pacemaker because it involves about 1/200th the energy (∼12 V, ∼2 mA) of an external defibrillator.MethodsWe delivered tDCS to seven participants (ages 70–92) with bipolar non-dependent pacemakers and subsequently collected data from the internal memory of the pacemakers to assess the tDCS signal detection, as well as alterations in mode switches, impedance levels, and pacing. Subsequently, similar assessments were carried out in participants who were pacemaker-dependent (ages 89–91).ResultsAfter a review of the recordings, it was found that tDCS had no impact on the non-dependant, as well as the dependent, pacemakers. There were zero mode switches nor any impact on impedance levels.ConclusionResults in this small series of cases found no evidence that tDCS interferes with the function of the pacemakers and suggests tDCS can be delivered to patients equipped with a cardiac pacemaker. Further studies are needed to generalize these results to other pacemakers.     

Anodal transcranial direct current stimulation of the motor cortex increases cortical voluntary activation and neural plasticity

Introduction: We examined the cumulative effect of 4 consecutive bouts of noninvasive brain stimulation on corticospinal plasticity and motor performance, and whether these responses were influenced by the brain‐derived neurotrophic factor (BDNF) polymorphism. Methods: In a randomized double‐blinded cross‐over design, changes in strength and indices of corticospinal plasticity were analyzed in 14 adults who were exposed to 4 consecutive sessions of anodal and sham transcranial direct current stimulation (tDCS). Participants also undertook a blood sample for BDNF genotyping (N = 13). Results: We observed a significant increase in isometric wrist flexor strength with transcranial magnetic stimulation revealing increased corticospinal excitability, decreased silent period duration, and increased cortical voluntary activation compared with sham tDCS. Conclusions: The results show that 4 consecutive sessions of anodal tDCS increased cortical voluntary activation manifested as an improvement in strength. Induction of corticospinal plasticity appears to be influenced by the BDNF polymorphism. Muscle Nerve 54 : 903–913, 2016     

Polarity and timing-dependent effects of transcranial direct current stimulation in explicit motor learning

Transcranial direct current stimulation (tDCS) is attracting increasing interest as a therapeutic tool for neurorehabilitation, particularly after stroke, because of its potential to modulate local excitability and therefore promote functional plasticity. Previous studies suggest that timing is important in determining the behavioural effects of brain stimulation. Regulatory metaplastic mechanisms exist to modulate the effects of a stimulation intervention in a manner dependent on prior cortical excitability, thereby preventing destabilization of existing cortical networks. The importance of such timing dependence has not yet been fully explored for tDCS. Here, we describe the results of a series of behavioural experiments in healthy controls to determine the importance of the relative timing of tDCS for motor performance. Application of tDCS during an explicit sequence-learning task led to modulation of behaviour in a polarity specific manner: relative to sham stimulation, anodal tDCS was associated with faster learning and cathodal tDCS with slower learning. Application of tDCS prior to performance of the sequence-learning task led to slower learning after both anodal and cathodal tDCS. By contrast, regardless of the polarity of stimulation, tDCS had no significant effect on performance of a simple reaction time task. These results are consistent with the idea that anodal tDCS interacts with subsequent motor learning in a metaplastic manner and suggest that anodal stimulation modulates cortical excitability in a manner similar to motor learning.     

Delta oscillation underlies the interictal spike changes after repeated transcranial direct current stimulation in a rat model of chronic seizures

BackgroundTranscranial direct current stimulation (tDCS) provides a noninvasive polarity-specific constant current to treat epilepsy, through a mechanism possibly involving excitability modulation and neural oscillation.ObjectiveTo determine whether EEG oscillations underlie the interictal spike changes after tDCS in rats with chronic spontaneous seizures.MethodsRats with kainic acid-induced spontaneous seizures were subjected to cathodal tDCS or sham stimulation for 5 consecutive days. Video-EEG recordings were collected immediately pre- and post-stimulation and for the subsequent 2 weeks following stimulation. The acute pre-post stimulation and subacute follow-up changes of interictal spikes and EEG oscillations in tDCS-treated rats were compared with sham. Ictal EEG with seizure behaviors, hippocampal brain-derived neurotrophic factor (BDNF) protein expression, and mossy fiber sprouting were compared between tDCS and sham rats.ResultsInterictal spike counts were reduced immediately following tDCS with augmented delta and diminished beta and gamma oscillations compared with sham. Cathodal tDCS also enhanced delta oscillations in normal rats. However, increased numbers of interictal spikes with a decrease of delta and theta oscillations were observed in tDCS-treated rats compared with sham during the following 2 weeks after stimulation. Resuming tDCS suppressed the increase of interictal spike activity. In tDCS rats, hippocampal BDNF protein expression was decreased while mossy fiber sprouting did not change compared with sham.ConclusionsThe inverse relationship between the changes of delta oscillation and interictal spikes during tDCS on and off stimulation periods indicates that an enhanced endogenous delta oscillation underlies the tDCS inhibitory effect on epileptic excitability.     

Acute modulation of cortical oscillatory activities during short trains of high-frequency repetitive transcranial magnetic stimulation of the human motor cortex: a combined EEG and TMS study

In this study, a combined repetitive transcranial magnetic stimulation/electroencephalography (rTMS/EEG) method was used to explore the acute changes of cortical oscillatory activity induced by intermittent short trains of high-frequency (5-Hz) rTMS delivered over the left primary motor cortex (M1). We evaluated the electrophysiological reaction to magnetic stimulation during and 2-4 s after 20 trains of 20-pulses rTMS, using event-related power (ERPow) that reflects the regional oscillatory activity of neural assemblies, and event-related coherence (ERCoh) that reflects the interregional functional connectivity of oscillatory neural activity. These event-related transformations were for the upper alpha (10-12 Hz) and beta (18-22 Hz) frequency ranges, respectively. For the alpha band, threshold rTMS and subthreshold rTMS induced an ERPow increase during the trains of stimulation mainly in frontal and central regions ipsilateral to stimulation. For the beta band, a similar synchronization of cortical oscillations for both rTMS intensities was seen. Moreover, subthreshold rTMS affected alpha-band activity more than threshold rTMS, inducing a specific ERCoh decrease over the posterior regions during the trains of stimulation. For beta band, the decrease in functional coupling was observed mainly during threshold rTMS. These findings provide a better understanding of the cortical effects of high-frequency rTMS, whereby the induction of oscillations reflects the capacity of electromagnetic pulses to alter regional and interregional synaptic transmissions of neural populations.