Differentiating transcranial magnetic stimulation cortical and auditory responses via single pulse and paired pulse protocols: A TMS-EEG study

ObjectiveWe measured the neurophysiological responses of both active and sham transcranial magnetic stimulation (TMS) for both single pulse (SP) and paired pulse (PP; long interval cortical inhibition (LICI)) paradigms using TMS-EEG (electroencephalography).MethodsNineteen healthy subjects received active and sham (coil 90° tilted and touching the scalp) SP and PP TMS over the left dorsolateral prefrontal cortex (DLPFC). We measured excitability through SP TMS and inhibition (i.e., cortical inhibition (CI)) through PP TMS.ResultsCortical excitability indexed by area under the curve (AUC_(25-275ms)) was significantly higher in the active compared to sham stimulation (F(1,18) = 43.737, p < 0.001, η² = 0.708). Moreover, the amplitude of N100-P200 complex was significantly larger (F(1,18) = 9.118, p < 0.01, η² = 0.336) with active stimulation (10.38 ± 9.576 µV) compared to sham (4.295 ± 2.323 µV). Significant interaction effects were also observed between active and sham stimulation for both the SP and PP (i.e., LICI) cortical responses. Finally, only active stimulation (CI = 0.64 ± 0.23, p < 0.001) resulted in significant cortical inhibition.ConclusionThe significant differences between active and sham stimulation in both excitatory and inhibitory neurophysiological responses showed that active stimulation elicits responses from the cortex that are different from the non-specific effects of sham stimulation.SignificanceOur study reaffirms that TMS-EEG represents an effective tool to evaluate cortical neurophysiology with high fidelity.     

Unilateral and bilateral MRI-targeted repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled study

BackgroundSeveral factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) over sham rTMS in patients with treatment-resistant depression (TRD). These factors include unilateral stimulation (i.e., treatment of only the left dorsolateral prefrontal cortex [DLPFC]), suboptimal methods of targeting the DLPFC and insufficient stimulation intensity (based on coil-to-cortex distance).MethodsWe recruited patients with TRD between the ages of 18 and 85 years from a university hospital, and participants were randomized to receive sequential bilateral rTMS (600 pulses at 1 Hz followed by 1500 pulses at 10 Hz), unilateral high-frequency left (HFL)-rTMS (2100 pulses at 10 Hz) or sham rTMS for 3 or 6 weeks depending on treatment response. Stimulation was targeted with MRI localization over the junction of the middle and anterior thirds of the middle frontal gyrus, using 120% of the coil-to-cortex adjusted motor threshold. Our primary outcome of interest was the remission rate.ResultsA total of 121 patients participated in this study. The remission rate was significantly higher in the bilateral group than the sham group. The remission rate in the HFL-rTMS group was intermediate and did not differ statistically from the rate in the 2 other groups. There were no significant differences in reduction of depression scores among the 3 groups.LimitationsThe number of pulses used per session in the unilateral group was somewhat lower in our trial than in more recent trials, and the sham condition did not involve active stimulation.ConclusionOur findings suggest that sequential bilateral rTMS is superior to sham rTMS; however, adjusting for coil-to-cortex distance did not yield enhanced efficacy rates.     

The influence of endogenous estrogen on high-frequency prefrontal transcranial magnetic stimulation

BackgroundThe use of repetitive transcranial magnetic stimulation (rTMS) as both therapeutic and experimental tools has grown enormously over the past decade. However, variability in response to rTMS is one challenge that remains to be solved. Estrogen can impact neural plasticity and may also affect plastic changes following rTMS. The present study investigated whether estrogen levels influence the neurophysiological effects of high-frequency (HF) rTMS in the left dorsolateral prefrontal cortex (DLPFC).HypothesisIt was hypothesised that individuals with higher endogenous estrogen would demonstrate greater rTMS-induced changes in cortical reactivity.Methods29 healthy adults (15M/14F) received HF-rTMS over left DLPFC. Females attended two sessions, one during a high-estrogen (HE) phase of the menstrual cycle, another during a low-estrogen (LE) phase. Males attended one session. Estrogen level was verified via blood assay. TMS-EEG was used to probe changes in cortical plasticity and comparisons were made using cluster-based permutation statistics and Bayesian analysis.ResultsIn females, a significant increase in TMS-evoked P60 amplitude, and decrease in N45, N100 and P180 amplitudes was observed during HE. A less pervasive pattern of change was observed during LE. No significant changes in TEPs were seen in males. Between-condition comparisons revealed higher likelihood of the change in N100 and/or P180 being larger in females during HE compared to both females during LE and males.ConclusionsThese preliminary findings indicate that a greater neuroplastic response to prefrontal HF-rTMS is seen in women when estrogen is at its highest compared to men, suggesting that endogenous estrogen levels contribute to variability in response to HF-rTMS.     

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

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. 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 4 additional weeks. The final outcome measure was remission, defined as a HAM‐D score of <3 or 2 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). Twenty‐six percent 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. Depression and Anxiety, 2011. © 2011 Wiley Periodicals, Inc.     

Antidepressant effects of high and low frequency repetitive transcranial magnetic stimulation to the dorsolateral prefrontal cortex: a double-blind, randomized, placebo-controlled trial

Repetitive transcranial magnetic stimulation (rTMS) has antidepressant effects in patients with major depressive disorder. The mechanisms of action and optimal stimulation parameters remain unclear. To test the hypothesis that rTMS exerts antidepressant effects either by enhancing left dorsolateral prefrontal cortex (DLPFC) excitability or by decreasing right DLPFC excitability, the authors studied 45 patients with unipolar recurrent major depressive disorder in a double-blind, randomized, parallel group, sham-controlled trial. Patients were randomized to receive 1 Hz or 10 Hz rTMS to the left DLPFC, 1 Hz to the right DLPFC or sham TMS. Left 10 Hz and right 1 Hz rTMS showed similar significant antidepressant effects. Other parameters led to no significant antidepressant effects.     

Functional connectivity of the anterior cingulate cortex predicts treatment outcome for rTMS in treatment-resistant depression at 3-month follow-up

Background and objectiveRepetitive transcranial magnetic stimulation (rTMS) is a first-line treatment for treatment-resistant depression (TRD). The mechanisms of action of rTMS are not fully understood, and no biomarkers are available to assist in clinical practice to predict response to rTMS. This study aimed to demonstrate that after-rTMS clinical improvement is associated with functional connectivity (FC) changes of the subgenual cingulate cortex (sgACC) and rostral anterior cingulate (rACC), and FC of sgACC and rACC might serve as potential predictors for treatment response.MethodsResting-state functional magnetic resonance imaging (rs-fMRI) data were collected within 1 week before rTMS initiation in 50 TRD patients to predict subsequent response to rTMS on the left dorsolateral prefrontal cortex (DLPFC). Follow-up rs-fMRI was obtained 12 weeks after completion of rTMS and neural correlates of rTMS in sgACC- and rACC-related FC patterns were compared to before rTMS data and with rs-fMRI from healthy participants.ResultsTreatment response was associated with lower FC of sgACC to right DLPFC and higher FC of rACC to left lateral parietal cortex (IPL) measured at baseline. Using sgACC-DLPFC and rACC-IPL connectivity as features, responder-nonresponder classification accuracies of 84% and 76% (end-of-treatment), 88% and 81% (3-month follow-up), respectively were achieved. Longitudinal rs-fMRI data analyses revealed that the hyperconnectivity between sgACC and visual cortex was normalized to a level which was comparable to that of healthy participants.ConclusionsBrain activity patterns in depression are predictive of treatment response to rTMS, and longitudinal change of brain activity in relevant brain circuits after rTMS is associated with treatment response in depression. Target engagement paradigms may offer opportunities to increase the efficacy of rTMS in TRD by optimal selection of patients for treatment.Trial registrationClinicalTrials.gov Identifiers: NCT01887782 and NCT02800226.     

Effect of Two Weeks of rTMS on Brain Activity in Healthy Subjects During an n-Back Task: A Randomized Double Blind Study

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has shown significant efficiency in the treatment of several psychiatric disorders. In depressive disorders, the dorsolateral prefrontal cortex (DLPFC) is the main target for rTMS, but the effects of this stimulation on cognitive functions and their neural correlates are not well known. Previous works have established that the left DLPFC is reliably activated during the n-back working memory task.ObjectiveThe aim of this randomized double-blind study was to determine the impact of rTMS applied to the DLPFC on brain activity during an n-back task in healthy subjects.MethodsAfter randomization, twenty subjects received either active treatment (10 sessions; 1 session a day; frequency = 10 Hz; intensity = 110% of motor threshold) or placebo treatment (sham coil). Subjects performed an n-back task during two functional magnetic resonance imaging sessions (one before stimulation, and one after 10 active or sham rTMS sessions).ResultsNo significant changes, neither in mood nor in performance in the n-back task, were shown. A significant group-by-time interaction effect was found in the bilateral middle frontal gyrus and in the left caudate nucleus.ConclusionsThese results show that rTMS applied on the left DLPFC had close and remote effects on brain areas involved in working memory.     

Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer’s dementia

The aim of the study was to compare the long-term efficacy of high versus low frequency repetitive transcranial magnetic stimulation (rTMS), applied bilaterally over the dorsolateral prefrontal cortex (DLPFC), on cognitive function and cortical excitability of patients with Alzheimer's disease (AD). Forty-five AD patients were randomly classified into three groups. The first two groups received real rTMS over the DLPFC (20 and 1 Hz, respectively) while the third group received sham stimulation. All patients received one session daily for five consecutive days. In each session, rTMS was applied first over the right DLPFC, immediately followed by rTMS over the left DLPFC. Mini Mental State Examination (MMSE), Instrumental Daily Living Activity (IADL) scale and the Geriatric Depression Scale (GDS) were assessed before, after the last (fifth) session, and then followed up at 1 and 3 months. Neurophysiological evaluations included resting and active motor threshold (rMT and aMT), and the duration of transcallosal inhibition (TI) before and after the end of the treatment sessions. At base line assessment there were no significant differences between groups in any of the rating scales. The high frequency rTMS group improved significantly more than the low frequency and sham groups in all rating scales (MMSE, IADL, and GDS) and at all time points after treatment. Measures of cortical excitability immediately after the last treatment session showed that treatment with 20 Hz rTMS reduced TI duration. These results confirm that five daily sessions of high frequency rTMS over the left and then the right DLPFC improves cognitive function in patients with mild to moderate degree of AD. This improvement was maintained for 3 months. High frequency rTMS may be a useful addition to therapy for the treatment of AD.     

Predictive value of dorso-lateral prefrontal connectivity for rTMS response in treatment-resistant depression: A brain perfusion SPECT study

Background

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.

Investigating the Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Cortical Excitability in Healthy Males

ObjectivesAs a potential treatment for epilepsy, transcutaneous auricular vagus nerve stimulation (taVNS) has yielded inconsistent results. Combining transcranial magnetic stimulation with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) can be used to investigate the effect of interventions on cortical excitability by evaluating changes in motor evoked potentials (MEPs) and TMS-evoked potentials (TEPs). The goal of this study is to objectively evaluate the effect of taVNS on cortical excitability with TMS-EMG and TMS-EEG. These findings are expected to provide insight in the mechanism of action and help identify more optimal stimulation paradigms.Materials and MethodsIn this prospective single-blind cross-over study, 15 healthy male subjects underwent active and sham taVNS for 60 min, using a maximum tolerated stimulation current. Single and paired pulse TMS was delivered over the right-sided motor hotspot to evaluate MEPs and TEPs before and after the intervention. MEP statistical analysis was conducted with a two-way repeated measures ANOVA. TEPs were analyzed with a cluster-based permutation analysis. Linear regression analysis was implemented to investigate an association with stimulation current.ResultsMEP and TEP measurements were not affected by taVNS in this study. An association was found between taVNS stimulation current and MEP outcome measures indicating a decrease in cortical excitability in participants who tolerated higher taVNS currents. A subanalysis of participants (n = 8) who tolerated a taVNS current ≥2.5 mA showed a significant increase in the resting motor threshold, decrease in MEP amplitude and modulation of the P60 and P180 TEP components.ConclusionstaVNS did not affect cortical excitability measurements in the overall population in this study. However, taVNS has the potential to modulate specific markers of cortical excitability in participants who tolerate higher stimulation levels. These findings indicate the need for adequate stimulation protocols based on the recording of objective outcome parameters.     

A multimodal approach using TMS and EEG reveals neurophysiological changes in Parkinson's disease

IntroductionAlterations in large scale neural networks leading to neurophysiological changes have been described in Parkinson's disease (PD). The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been suggested as a promising tool to identify and quantify neurophysiological mechanisms. The aim of this study was to investigate specific changes in electrical brain activity in response to stimulation of four brain areas in patients with PD.Methods21 healthy controls and 32 patients with PD underwent a combined TMS-EEG assessment that included stimulation of four brain areas: left M1, right M1, left dorso-lateral prefrontal cortex (DLPFC), and right DLPFC. Six measures were calculated to characterize the TMS evoked potentials (TEP) using EEG: (1) wave form adherence (WFA), (2) late phase deflection (LPD), (3) early phase deflection (EPD), (4) short-term plasticity (STP), (5) inter-trial adherence, and (6) connectivity between right and left M1 and DLPFC. A Linear mixed-model was used to compare these measures between groups and areas stimulated.ResultsPatients with PD showed lower WFA (p = 0.052), lower EPD (p = 0.009), lower inter-trial adherence (p < 0.001), and lower connectivity between homologs areas (p = 0.050), compared to healthy controls. LPD and STP measures were not different between the groups. In addition, lower inter-trial adherence correlated with longer disease duration (r = −0.355, p = 0.050).ConclusionsOur findings provide evidence to various alterations in neurophysiological measures in patients with PD. The higher cortical excitability along with increased variability and lower widespread of the evoked potentials in PD can elucidate different aspects related to the pathophysiology of the disease.     

Dorsomedial prefrontal cortex repetitive transcranial magnetic stimulation for treatment-refractory major depressive disorder: A three-arm,blinded, randomized controlled trial

BackgroundDorsomedial prefrontal cortex (DMPFC) repetitive transcranial magnetic stimulation (rTMS) is a novel intervention for treatment-refractory depression (TRD). To date, many open-label case series and one randomized controlled trial of modest sample size have provided preliminary evidence that DMPFC-rTMS is an effective treatment for TRD. Here, we report the results of a large, double-blinded, sham-controlled trial of DMPFC-rTMS for TRD.ObjectiveThe primary aim of this study was to determine the efficacy of DMPFC-rTMS for TRD under sham-controlled conditions.Methods120 TRD patients were randomized to receive 30 twice-daily sessions of either active high-frequency, active low-frequency, or sham DMPFC-rTMS using a novel bent active/sham double-cone coil. Placebo stimulation also involved the use of surface electrodes placed above the eyebrows. The 17-item Hamilton Rating Scale for Depression served as the primary outcome measure.ResultsAlthough there was a significant main effect of treatment across all arms, active DMPFC-rTMS was not superior to sham. Both participants and assessors were unable to accuracy determine whether patients received active or placebo stimulation. However, technicians’ treatment arm guesses were significantly above chance.ConclusionDMPFC rTMS did not result in improvement of depressive symptoms greater than sham stimulation. We cannot rule out that the sham apparatus may also have elicited an antidepressant effect via electrical trigeminal stimulation; future DMPFC-rTMS trials are therefore warranted.     

Effect of 5 Hz repetitive transcranial magnetic stimulation on cognition during a Go/NoGo task

Repetitive transcranial magnetic stimulation (rTMS) has been developed as a novel tool for modulating cognition by delivering stimulation in the brain. However, the effects of rTMS on cognition are still controversial. This randomized, sham-controlled, crossover study was designed to determine whether rTMS of the left dorsolateral prefrontal cortex (DLPFC) interferes with the Go/NoGo task and whether personal parameters such as age affect rTMS. A total of 24 healthy subjects (12 male and 12 female, aged 20-37 years) underwent one session of active rTMS followed by sham rTMS (total of 1600 pulses, 100% of motor threshold, 5 Hz, 8 s), or vice versa. The results did not show any differences between active and sham rTMS stimulation in terms of performance accuracy, response speed, or choice reaction time (cRT) implicating that short-term rTMS will not enhance or deteriorate cognition. However, percentage cRT shortening induced by active rTMS was negatively correlated with age (r = -0.57, P = 0.005), whereas that induced by sham rTMS was not (r = -0.23, P > 0.05), suggesting that cognition of younger subjects might have greater modulation by active stimulation than older ones. This finding may help explain some of the controversies or paradoxical results observed in studies of the effect of left DLPFC rTMS on cognition.     

Bifrontal active and sham rTMS in treatment-resistant unipolar major depression

Abstract

Background and aim: Prevention of the recurrence of major depression and its residual symptoms requires effective treatment. Our aim was to study the effects of bifrontal active rTMS controlled by sham rTMS in treatment-resistant unipolar major depressive disorder (MDD).

Methods: Thirty-seven patients with treatment-resistant MDD were randomized into two groups. One group received a total of 30 sessions of active bifrontal rTMS (10?Hz rTMS on left dorsolateral prefrontal cortex (DLPFC) and 1?Hz rTMS on right DLPFC) and the other group received bilateral sham rTMS on five days a week for six weeks.

Results: Depressive symptoms significantly improved in both the groups, but without a significant group difference. Furthermore, patients with psychotic depression improved similarly to those with moderate or severe depression.

Conclusions: The results of present study indicate a large sham effect of stimulation treatment. The intensive structured treatment protocol may explain the positive outcome in both the groups. It is important to recognize, appreciate, and utilize placebo effects as a significant means of rehabilitation in psychiatric care.     

A randomized,double blind,sham-controlled trial of repetitive transcranial magnetic stimulation (rTMS) in the treatment of negative symptoms in schizophrenia

BackgroundResearch has implicated hypofrontality in the pathogenesis of Negative symptoms of schizophrenia.These symptoms are often resistant to treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) has been shown to reverse this hypofrontality. Higher frequency rTMS has shown better promise, but so far there has been very little research in this area.ObjectiveWe aimed to evaluate the efficacy of high-frequency (20 Hz) unilateral rTMS over the left Dorso-Lateral Pre-frontal Cortex (DLPFC) in the improvement of Negative symptoms in Schizophrenia. Methods:100 patients of schizophrenia with predominantly negative symptoms, were enrolled for this randomized, sham-controlled, double-blind trial.Each participant received 20 sessions of rTMS at 20 Hz frequency and 100% motor threshold, via either the active or the sham coil, over 4 weeks. A total of 2000 pulses were imparted in 10 trains per session. Negative symptoms were assessed with the SANS and PANSS. CDSS was used to rule out depressive symptoms. Assessments were carried out at baseline, post-intervention, and 1-month, 2-months, 3-months and 4-months follow ups.ResultsThe improvement in the negative symptoms (Anhedonia, Alogia, Avolition, Attention impairment) in active group was statistically significant at 0.01 and 0.05 (p-value) as compared to sham group.ConclusionsThese results suggest that high-frequency rTMS may lead to improvement in negative symptoms of schizophrenia. It may be worth considering its use as an adjunct to pharmacological treatment of negative symptoms.     

Determining optimal rTMS parameters through changes in cortical inhibition

ObjectivesEvidence shows that repetitive transcranial magnetic stimulation (rTMS) changes cortical inhibition (CI) and excitability and that these changes may relate to its therapeutic effects. This study aimed to investigate the effects of differing durations or ‘doses’ of rTMS on cortical inhibition and excitability in healthy subjects.MethodsFour different experiments were conducted: 1 session of 1200 pulses of 1 or 20 Hz active or sham rTMS; 10 sessions of 1 or 20 Hz active or sham rTMS, 1200 pulses/session; 1 session of 3600 pulses of 1 or 20 Hz active or sham rTMS; 1 session of 6000 pulses of 20 Hz active or sham rTMS. Measures of cortical inhibition and excitability included short-interval intracortical inhibition, long interval cortical inhibition, cortical silent period (CSP), motor evoked potential amplitude, resting motor threshold and intracortical facilitation.ResultsOnly 6000 pulses of 20 Hz rTMS lead to a significant lengthening of the CSP and therefore potentiation of CI. There were no changes to excitability measures.ConclusionOnly high frequency rTMS potentiated CI. Longer treatment durations are required to produce such changes.SignificanceStudies investigating the therapeutic effects of rTMS may benefit from extended dosing with increased number of pulses per session. CSP lengthening may be used to guide treatment response.     

The Efficacy and Safety of Low Frequency Repetitive Transcranial Magnetic Stimulation for Treatment-resistant Depression: The Results From a Large Multicenter French RCT

ContextThe 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).MethodIn 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.ResultsWe 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).ConclusionLow 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.     

Repetitive Transcranial Magnetic Stimulation Over the Dorsolateral Prefrontal Cortex for Treating Posttraumatic Stress Disorder: An Exploratory Meta-Analysis of Randomized,Double-Blind and Sham-Controlled Trials

Objective

Repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex (DLPFC) has yielded promising results as a treatment for posttraumatic stress disorder (PTSD). However, to date, no quantitative review of its clinical utility has been published.

Method:

We searched for randomized and sham-controlled trials from 1995 to March 2013 using MEDLINE, Embase, PsycINFO, CENTRAL, and SCOPUS. We then performed an exploratory random effects meta-analysis.

Results:

Studies on rTMS applied to the right DLPFC included 64 adults with PTSD. The pooled Hedges g effect size for pre and post changes in clinician-rated and self-reported PTSD symptoms were, respectively, 1.65 (P < 0.001) and 1.91 (P < 0.001), indicating significant and large-sized differences in outcome favouring active rTMS. Also, there were significant pre and post decreases with active rTMS in overall anxiety (Hedges g = 1.24; P = 0.02) and depressive (Hedges g = 0.85; P < 0.001) symptoms. Dropout rates at study end did not differ between active and sham rTMS groups. Regarding rTMS applied to the left DLPFC, there is only one study published to date (using a high frequency protocol), and its results showed that active rTMS seems to be superior overall to sham rTMS.

Conclusions:

Our exploratory meta-analysis shows that active rTMS applied to the DLPFC seems to be effective and acceptable for treating PTSD. However, the small number of subjects included in the analyses limits the generalizability of these findings. Future studies should include larger samples and deliver optimized stimulation parameters.     

Low-frequency rTMS stimulation over superior parietal cortex medially improves time reproduction and increases the right dorsolateral prefrontal cortex predominance

Aim of the study: Previous studies have shown that several cortical regions are involved in temporal tasks in multiple timescales. However, the hemispheric predominance of the dorsolateral prefrontal cortex (DLPFC) during time reproduction after repetitive low-frequency transcranial magnetic stimulation (rTMS) is relatively unexplored. Here, we study the effects of 1?Hz rTMS and sham stimulation applied medially over the superior parietal cortex (SPC) on the DLPFC alpha and beta band asymmetry and on time reproduction.

Materials and methods: For this purpose, we have combined rTMS with electroencephalography in 20 healthy subjects who performed the time reproduction task in two conditions (sham and 1?Hz).

Results: The worst performance was observed in sham and 1Hz conditions for longer time intervals (p?<?.05), with the 1Hz condition subjects sub-reproducing the time interval, closer to the target interval (p?<?.05). The right DLPFC hemispheric predominance was found in both conditions, but after low-frequency rTMS, the right hemisphere predominance increased in the 1Hz condition (p?<?.05).

Conclusions: Results of this study suggest that rTMS applied over the SPC influences time interval interpretation and the DLPFC functions. Future studies would explore the effects of the rTMS application to other cortical areas, and study how it influences time interval interpretation.     

Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex Decreases Cue-induced Nicotine Craving and EEG Delta Power

BackgroundTMS 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.ObjectiveThe 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.MethodsFourteen 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.ResultsBoth 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.ConclusionHf 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.