Session Of High Frequency Repetitive Transcranial Magnetic Stimulation Research Articles

High-frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex may reduce impulsivity in patients with methamphetamine use disorders: A pilot study.

BackgroundIndividuals who use methamphetamine (MA) for a long period of time may experience decreased inhibition and increased impulsivity. In order to reduce impulsivity or improve inhibitory control ability, high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has attracted much attention of researchers. Recent studies on addiction have shown that rTMS can stimulate different brain regions to produce different therapeutic effects. Recent work also suggests that HF-rTMS over right dorsolateral prefrontal cortex (DLPFC) does not affect the impulsivity of patients with alcohol use disorder; while HF-rTMS over left DLPFC could improve the impulsivity of patients with alcohol use disorder and cigarette smokers. However, it should be noted that empirical studies applying HF-rTMS over left DLPFC of patients with MA use disorders (MAUD) (to evaluate its effect on impulsivity) are still lacking.MethodsTwenty-nine patients with MAUD underwent five sessions of HF-rTMS on the left DLPFC per week for 4 consecutive weeks. The cue-induced craving and stop-signal and NoGo task were assessed pre-rTMS and post-rTMS (at the end of the 4-week rTMS treatment). In addition, 29 healthy controls were recruited. There was no rTMS intervention for the controls, the performance of the stop-signal and NoGo task was evaluated on them.ResultsIn total, HF-rTMS of the left DLPFC significantly decreased MA-dependent patients’ cue-induced craving and stop-signal reaction time (SSRT). For SSRT, the pre-test of experimental group was significantly higher than the score of control group. In the experimental group, the pre-test score was significantly higher than the post-test score. For Go and stop-signal delay (SSD), the pre-test scores of the experimental group was significantly lower than the scores of the control group. No significant difference was found between the pre-test and the post-test scores of the experimental group.ConclusionAdd-on HF-rTMS of left DLPFC may be an effective intervention for reducing impulsivity and cue-induced craving of patients with MAUD. Future research with a control group of MAUD that does not undergo the treatment is needed to confirm the effectiveness.

Use of high-frequency repetitive transcranial magnetic stimulation to probe the neural circuitry of food choice in anorexia nervosa: A proof-of-concept study.

Repetitive transcranial magnetic stimulation (rTMS) is used to modulate neural systems and provides the opportunity for experimental tests of hypotheses regarding mechanisms underlying anorexia nervosa (AN). The present pilot study has investigated whether high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) to a region of the right dorsolateral prefrontal cortex (DLPFC) might be associated with change in food selection among adult inpatients with AN. Ten women received one session of sham and one session of HF-rTMS targeting the right DLPFC while completing a computerized Food Choice Task. Compared to sham, HF-rTMS was associated with changes in food ratings and food choice: inpatients reported higher healthiness ratings of low- and high-fat foods and selected a significantly greater proportion of high-fat foods over a neutrally rated reference item while receiving HF-rTMS. Findings suggest that HF-rTMS to the right DLPFC was associated with a reduction of fat avoidance on a food choice task among inpatients with AN and provide additional support for the possibility that this region, and related neural circuits, may underlie restrictive food choice. Research using rTMS to experimentally test neural mechanisms is needed to elucidate the underpinnings of AN and supports the development of novel treatment targets.

A double-blind randomized clinical trial of high frequency rTMS over the DLPFC on nicotine dependence, anxiety and depression

High frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dorsolateral prefrontal cortex (L-DLPFC) is a widely applied treatment protocol for chronic smoking and major depressive disorder. However, no previous study has measured the effects of rTMS on both nicotine consumption and anxiety/depression in the same volunteers despite the relationship between them. The aim of this work was to evaluate the efficacy of 10 daily sessions of HF-rTMS over the L-DLPFC in chronic cigarette smokers’ addiction and investigate the possible beneficial effects of this treatment procedure on symptoms of depression and anxiety in the same subjects. The study included 40 treatment-seeking nicotine-dependent cigarette smokers. Onset/duration of smoking, number of cigarettes/day, Fagerstrom Test of Nicotine Dependence (FTND), Tobacco Craving Questionnaire-Short Form (TCQ-SF), Hamilton depression and anxiety scales (HAM-D and HAM-A) were recorded. Participants were randomly assigned to the active or the sham treatment group. Those in the active group received 10 trains of 20 Hz stimulation, at 80% of the resting motor threshold (rMT) for 10 consecutive working days over L-DLPFC. Participants were reassessed immediately after treatment, and then 3 months later using all rating scales. There were no differences between active and sham groups at baseline. The cigarette consumption/day, and scores on FTND, and TCQ decreased significantly in both groups (p = 0.0001 for each) immediately after treatment. However, improvement persisted to 3 months in the active group but not in the sham group. Moreover, there was a significant reduction in HAM-D and HAM-A scores immediately after treatment in the active but not the sham group. Subjects with a longer history of smoking had a lower percent improvement in FTND (p = 0.005). Our findings revealed that HF-rTMS over L-DLPCF for 10 days reduced cigarette consumption, craving, dependence, and improved associated symptoms of anxiety and depression.ClinicalTrials.gov Identifier: NCT03264755 registered at 29/08/2017.

Effects of High Frequency Repetitive Transcranial Magnetic Stimulation (HF-rTMS) on Delay Discounting in Major Depressive Disorder: An Open-Label Uncontrolled Pilot Study.

Background: Delay discounting (DD) refers to the decrease of a present subjective value of a future reward as the delay of its delivery increases. Major depressive disorder (MDD), besides core emotional and physical symptoms, involves difficulties in reward processing. Depressed patients often display greater temporal discounting rates than healthy subjects. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique applied in several countries to adult patients with treatment resistant depression. Studies suggest that this technique can be used to modulate DD, but no trial has assessed its effects on depressed patients. Methods: In this open-label uncontrolled trial, 20 patients diagnosed with MDD and at least stage II treatment resistance criteria underwent 20 HF-rTMS sessions over the dorsolateral prefrontal cortex (dlPFC; 10 Hz, 110% MT, 20 min). Pre-post treatment DD rates were compared. Effects on impulsivity, personality factors, and depressive symptoms were also evaluated. Results: No significant effect of HF-rTMS over the left dlPFC on DD of depressed individuals was observed, although rates seemed to increase after sessions. However, treatment resulted in significant improvement on cognitive impulsivity and depressive symptoms, and was well-tolerated. Conclusion: Despite the limitations involved, this pilot study allows preliminary evaluation of HF-rTMS effects on DD in MDD, providing substrate for further research.

Effects of High Frequency Repetitive Transcranial Magnetic Stimulation (HF-rTMS) on Delay Discounting in Major Depressive Disorder

Background Major depressive disorder (MDD) is marked by core depressive emotional and physical symptoms and is also accompanied by difficulties in reward processing. A reduction of reward anticipation, along with diminishment in anticipation predicting reduced motivation for rewards has been documented in the acute phase. Cognitive neuroscience studies suggest that non-invasive brain stimulation techniques can be used to modulate processes involved in decision making, especially when stimulation is applied over the dorsolateral prefrontal cortex (dlPFC). However, studies assessing its effects on intertemporal decision-making in clinical populations are scarce. Methods By using high frequency repetitive transcranial magnetic stimulation (HF-rTMS) we investigated the potential impact of one and 20 sessions on temporal impulsivity, severity of depressive symptoms, impulsivity and personality factors of depressed individuals. Twenty patients meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for unipolar depression and meeting at least stage II treatment resistant criteria underwent 20 HF-rTMS stimulation sessions. Results In odds with prior investigations, data analysis revealed a lack of significant (or even a deleterious) effect of HF-rTMS sessions over the left dlPFC on discounting rates of depressed individuals. Treatment was well-tolerated and resulted in significant improvement on cognitive impulsivity and depressive symptoms. Hypothesis concerning the results were discussed. Conclusion Despite limitations involved in this study, results allow preliminary evaluation of rTMS effect on temporal impulsivity in depressed individuals, providing substrate for further research.

Personalized repetitive transcranial magnetic stimulation temporarily alters default mode network in healthy subjects

High frequency repetitive transcranial magnetic stimulation (HF-rTMS) delivered to the left dorsolateral prefrontal cortex (DLPFC) is an effective treatment option for treatment resistant depression. However, the underlying mechanisms of a full session of HF-rTMS in healthy volunteers have not yet been described. Here we investigated, with a personalized selection of DLPFC stimulation sites, the effects driven by HF-rTMS in healthy volunteers (n = 23) over the default mode network (DMN) in multiple time windows. After a complete 10 Hz rTMS (3000 pulses) session, we observe a decrease of functional connectivity between the DMN and the subgenual Anterior Cingulate Cortex (sgACC), as well as the ventral striatum (vStr). A negative correlation between the magnitude of this decrease in the right sgACC and the harm avoidance domain measure from the Temperament and Character Inventory was observed. Moreover, we identify that coupling strength of right vStr with the DMN post-stimulation was proportional to a decrease in self-reports of negative mood from the Positive and Negative Affect Schedule. This shows HF-rTMS attenuates perception of negative mood in healthy recipients in agreement with the expected effects in patients. Our study, by using a personalized selection of DLPFC stimulation sites, contributes understanding the effects of a full session of rTMS approved for clinical use in depression over related brain regions in healthy volunteers.

ENHANCING COGNITIVE-BEHAVIORAL THERAPY FOR OBSESSIVE-COMPULSIVE DISORDER WITH TRANSCRANIC MAGNETIC STIMULATION: A PROOF OF CONCEPT

Cognitive behavioral therapy (CBT) is a well established first line treatment for obsessive compulsive disorder (OCD). It consists of a cognitive and a behavioral treatment (exposure and response prevention therapy (ERP)) [1]. The goal of the cognitive treatment is the cognitive restructuring of meta-cognitions while the goal of exposure therapy is enhancing and facilitating patients’ fear extinction processes in front of the feared object, situation or thought/obsession. Several studies have tried to enhance fear extinction through pharmacological agents with mixed results [2]. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS), through its capacity to induce long-term potentiation, is able to modulate learning processes and hippocampal plasticity [3]. Moreover, several studies showed that HF-rTMS over the dosrsolateral prefrontal cortex (DLPFC) is able to induce better working memory performance after active stimulation [4]. Thus, rTMS could represent a promising tool to enhance cognitive restructuring and fear extinction learning processes during the cognitive-behavioral treatment sessions. Recently, we published a case report of a patient treated with HF-rTMS over the left DLPFC before each ERP session [5]. Here we adopted a new protocol in order to potentiate both the cognitive and the behavioral part of the treatment. The aim of this study was to evaluate the potential CBT enhancing effect of HF-rTMS over the left DLPFC in OCD patients who failed to respond to a previous CBT trial. Each patient underwent a 16 sessions CBT trial (1 session per week, 50/60 minutes per session). The first six sessions were dedicated to establishing an individual hierarchy of obsessions and compulsions and to a cognitive restructuring of meta-cognitions. The following 10 sessions focused on in vivo ERP exercises. For the first six sessions patients underwent a HF-rTMS session over the left DLPFC immediately before the session in order to enhance working memory processes during cognitive restructuring of metacognitions (6 stimulation sessions). Subsequently, each exposure session was immediately followed by an HF-rTMS session over the left DLPFC (10 stimulation sessions). During the treatment, 32 trains of 5 seconds has been applied at 10 Hz and at 110% of the left motor trheshold over the left DLPFC, with a 25 seconds inter-train interval (a total of 1600 stimuli per session). No pharmacological treatment changes were allowed during the CBT trail and patients were stable on their undergoing medications since 4 weeks before starting the CBT sessions. We enrolled two OCD patients (with prominent checking and symmetry/ordering symptoms respectively) who failed a previous CBT trial and showed only slight depressive symptoms. At the end of the 16 CBT sessions patients showed a 35% and 30% symptoms reduction on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) respectively. HF-rTMS was well tolerated. rTMS could represent e tolerable tool in order to enhance the effect of CBT with exposure and response prevention techniques in patients with obsessive-compulsive disorder.

Are there clinical and neurophysiologic predictive factors for a positive response to HF-rTMS in patients with treatment-resistant depression?

Better selection of patients with treatment-resistant depression for high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) would make the procedure more efficient. The objective of this study was to search for clinical and neurophysiologic predictors of therapeutic response with a special focus on the bipolar population.Forty patients (30 bipolar) underwent 20 daily sessions of HF-rTMS. Clinical outcome measures included the 21-item Hamilton Depression Rating Scale, the Beck Depression Inventory, the Clinical Global Impression, and the Patient Global Impression. Neurophysiologic measurements included repeated estimation of the motor threshold and cortical silent period.Improvement was obtained in all psychometric scales, with no difference between unipolar and bipolar patients. Longer duration of the illness, higher number of prior hospitalizations, and more disturbed activity were associated with a worse response to rTMS, and somatic anxiety, sleep disorders, and health worries were positive predictors. In bipolar patients, longer disease duration and therapy with mirtazapine, mianserin, trazodone, hydroxyzine, and promethazine were associated with a worse response. Sleep disturbances, higher baseline motor threshold, and longer cortical silent period predicted a better response.In this study, we found several clinical and neurophysiologic predictors of better/worse responses to the standard HF-rTMS protocol. Our preliminary data need to be reproduced.

P.3.017 - Differential effects of left and right prefrontal magnetic stimulation on resting state connectivity in healthy individuals

Introduction High frequency repetitive transcranial magnetic stimulation (HF-rTMS) has gained great interest in multiple clinical and research fields. With HF-rTMS a coil – wherein an alternating current is running – is placed on top of the skull, creating a magnetic field that influences the perpendicular neural tissue, thereby stimulating the neuronal activity of the targeted cortical area [1]. Although it is believed that HF-rTMS accomplishes its effect by influencing entire neuronal networks [2]. One cortical area frequently chosen as stimulation target is the dorsolateral prefrontal cortex (dlPFC), as it is part of the control network. However, despite its popularity and frequent use, very little is known about the differential effect of HF-rTMS over the left and right dlPFC on intrinsic functional connectivity networks in healthy individuals. Therefore the current study will address this issue. Methods The current study assessed the differential effects of left or right dlPFC HF-rTMS (corrected for sham) on intrinsic functional connectivity networks in a sample of 45 healthy individuals. The study was a randomized, single-blind trial with two sessions. During the first session demographic data were obtained and a baseline resting state functional magnetic resonance imaging (rsfMRI) scan was performed. During the second session subjects were randomized to either sham dlPFC HF-rTMS (n=15), left active dlPFC HF-rTMS (n=15) or right active dlPFC HF-rTMS (n=15) directly followed by a second rsfMRI scan. A HF-rTMS session consisted of sixty trains of 5 seconds at a frequency of 10Hz. During the sham condition the coil was tilted 90 degrees relative to the skull. This condition was used in order to correct for time and placebo effects. Independent Component Analysis (ICA) were performed to assess baseline differences and stimulation effects on within and between network functional connectivity. The five components of interest were the left frontal parietal network, right frontal parietal network, default mode network, salience network and reward network. Results The three stimulation groups did not differ on within as well as between functional connectivity of the five components of interest at baseline. Regarding the stimulation effects on within network connectivity, stimulation of the left dlPFC resulted in decreased functional connectivity in the salience network whereas right dlPFC stimulation resulted in increased functional connectivity within this network. Regarding the stimulation effects on between network connectivity, no differences between left or right dlPFC stimulation were found. Discussion Stimulation of either the left or the right dlPFC (compared to sham stimulation) thus seems to lead to opposite effects within the salience network. Since the role of this network in directing attention between internal and external processes [3], and decreased functional connectivity is associated with worsened cognitive functioning in aging [4], the results of this study might have implications for the clinical effects of HF-rTMS over the dlPFC. Therefore future (clinical) studies should implement questionnaires and/ or neurocognitive tasks in order to be able to relate changes in functional connectivity to changes in cognitive functioning.

Differential Effects of Left and Right Prefrontal High-Frequency Repetitive Transcranial Magnetic Stimulation on Resting-State Functional Magnetic Resonance Imaging in Healthy Individuals.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has gained great interest in multiple clinical and research fields and is believed to accomplish its effect by influencing neuronal networks. The dorsolateral prefrontal cortex (dlPFC) is frequently chosen as the cortical target for HF-rTMS. However, very little is known about the differential effect of HF-rTMS over the left and right dlPFC on intrinsic functional connectivity networks in patients or in healthy individuals. The current study assessed the differential effects of left or right HF-rTMS (corrected for sham) on intrinsic independent component analysis (ICA)-defined functional connectivity networks in a sample of 45 healthy individuals. All subjects had a first scanning session in which baseline functional connectivity was assessed. During the second session, individuals received one session of left, right, or sham dlPFC HF-rTMS (60 5-sec trains of 10 Hz at 110% motor threshold). The sham condition was used to correct for time and placebo effects. ICAs were performed to assess baseline differences and stimulation effects on within- and between-network functional connectivity. Stimulation of the left dlPFC resulted in decreased functional connectivity in the salience network, whereas right dlPFC stimulation resulted in increased functional connectivity within this network. No differences between left or right dlPFC stimulation were found in between-network connectivity. These results suggest that left and right HF-rTMS may have differential effects, and more research is needed on the clinical consequences.

Two Versus One High-Frequency Repetitive Transcranial Magnetic Stimulation Session per Day for Treatment-Resistant Depression: A Randomized Sham-Controlled Trial.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has proven antidepressant effects, but the optimal frequency of sessions remains unclear. We conducted a 3-week, sham-controlled trial to assess the antidepressant efficacy of 1 active HF-rTMS session per day (A1 group) compared with 2 per day (A2 group) and equivalent sham sessions (once a day, S1 group; twice a day, S2 group) in patients with treatment-resistant major depression with a subsequent 2-week follow-up period. One hundred seventy-seven patients were screened, of whom 105 met eligibility criteria and 98 consented and were randomized. The HF-rTMS (20 Hz) was targeted to the left prefrontal cortex in sessions of approximately 40 trains (2 seconds each) at 100% resting motor threshold with an intertrain interval of 1 minute. Treatment response was defined as a 50% or greater decrease in the Hamilton Depression Rating Scale (HDRS) score and/or Clinician Global Impressions-Severity of Illness (CGI-S) score of 3 or less. Remission was defined as HDRS score less than 8 and/or CGI-S score of 2 or less. Practically none of the subjects in either sham groups achieved remission. Increased odds of remission were present for CGI-S by stimulating twice rather than once per day (odds ratio [OR] = 1.5, P = 0.018), whereas there was a marginal result for HDRS (OR = 3.9, P = 0.066). Patients who had lower baseline HDRS (OR = 0.75, P = 0.014) and CGI-S scores (OR = 0.18, P = 0.001) were more likely to achieve remission. Twice per day active HF-rTMS might be more effective than once per day active HF-rTMS or sham stimulation.

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

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

P.4.d.004 - Enhancing cognitive-behavioral therapy for obsessive-compulsive disorder with transcranial magnetic stimulation: a proof of concept

Background Cognitive behavioral therapy (CBT) is a well established first line treatment for obsessive compulsive disorder (OCD). It consists of a cognitive and a behavioral treatment (exposure and response prevention therapy (ERP)) [1]. The goal of the cognitive treatment is the cognitive restructuring of meta-cognitions while the goal of exposure therapy is enhancing and facilitating patients’ fear extinction processes in front of the feared object, situation or thought/obsession. Several studies have tried to enhance fear extinction through pharmacological agents with mixed results [2]. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS), through its capacity to induce long-term potentiation, is able to modulate learning processes and hippocampal plasticity [3]. Moreover, several studies showed that HF-rTMS over the dosrsolateral prefrontal cortex (DLPFC) is able to induce better working memory performance after active stimulation [4]. Thus, rTMS could represent a promising tool to enhance cognitive restructuring and fear extinction learning processes during the cognitive-behavioral treatment sessions. Recently, we published a case report of a patient treated with HF-rTMS over the left DLPFC before each ERP session [5]. Here we adopted a new protocol in order to potentiate both the cognitive and the behavioral part of the treatment. Aims The aim of this study was to evaluate the potential CBT enhancing effect of HF-rTMS over the left DLPFC in OCD patients who failed to respond to a previous CBT trial. Methods Each patient underwent a 16 sessions CBT trial (1 session per week, 50/60 minutes per session). The first six sessions were dedicated to establishing an individual hierarchy of obsessions and compulsions and to a cognitive restructuring of meta-cognitions. The following 10 sessions focused on in vivo ERP exercises. For the first six sessions patients underwent a HF-rTMS session over the left DLPFC immediately before the session in order to enhance working memory processes during cognitive restructuring of metacognitions (6 stimulation sessions). Subsequently, each exposure session was immediately followed by an HF-rTMS session over the left DLPFC (10 stimulation sessions). During the treatment, 32 trains of 5 seconds has been applied at 10 Hz and at 110% of the left motor trheshold over the left DLPFC, with a 25 seconds inter-train interval (a total of 1600 stimuli per session). No pharmacological treatment changes were allowed during the CBT trail and patients were stable on their undergoing medications since 4 weeks before starting the CBT sessions. Results We enrolled two OCD patients (with prominent checking and symmetry/ordering symptoms respectively) who failed a previous CBT trial and showed only slight depressive symptoms. At the end of the 16 CBT sessions patients showed a 35% and 30% symptoms reduction on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) respectively. HF-rTMS was well tolerated. Conclusion rTMS could represent e tolerable tool in order to enhance the effect of CBT with exposure and response prevention techniques in patients with obsessive-compulsive disorder.

Neurophysiological, psychological and behavioural correlates of rTMS treatment in alcohol dependence

BackgroundAddiction is associated with dorso-lateral prefrontal cortex (DLPFC) dysfunction and altered brain-oscillations. High frequency repetitive transcranial magnetic stimulation (HFrTMS) over DLPFC reportedly reduces drug craving. Its effects on neuropsychological, behavioural and neurophysiological are unclear. MethodsWe assessed psychological, behavioural and neurophysiological effects of 4 sessions of 10-min adjunctive HFrTMS over the left DLPFC during two weeks during a residential programme for alcohol detoxification. Participants were randomized to active HFrTMS (10Hz, 100% motor threshold) or sham. Immediately before the first and after the last session, 32-channels EEG was recorded and alcohol craving Visual Analogue Scale, Symptom Check List-90-R, Numeric Stroop task and Go/No-go task administered. Tests were repeated at 1-month follow-up. Results17 subjects (mean age 44.7 years, 4 F) were assessed. Active rTMS subjects performed better at Stroop test at end of treatment (p=0.036) and follow up (p=0.004) and at Go-NoGo at end of treatment (p=0.05) and follow up (p=0.015). Depressive symptoms decreased at end of active treatment (p=0.036). Active-TMS showed an overall decrease of fast EEG frequencies after treatment compared to sham (p=0.026). No significant modifications over time or group emerged for craving and number of drinks at follow up. Conclusion4 HFrTMS sessions over two weeks on the left DLPFC can improve inhibitory control task and selective attention and reduce depressive symptoms. An overall reduction of faster EEG frequencies was observed. Nonetheless, this schedule is ineffective in reducing craving and alcohol intake.

Effectiveness and acceptability of accelerated repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depressive disorder: An open label trial

BackgroundMajor depressive disorder (MDD) is a significant cause of worldwide disability and treatment resistance is common. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has emerged as a treatment for MDD, and while efficacious, the daily commitment for typical 4–6 weeks of treatment poses a significant challenge. We aimed to determine the effectiveness and acceptability of an accelerated rTMS protocol for MDD. MethodsIn this naturalistic trial, 27 patients with moderate to severe chronic and treatment-resistant MDD were treated with twice-daily HF-rTMS (10Hz) applied over the left dorsolateral prefrontal cortex for 2 consecutive weeks (60,000 pulses). The primary outcomes were rates of clinical remission and response (16-item Quick Inventory of Depressive Symptomatology post-treatment score ≤6, and≥50% reduction, respectively). Secondary outcomes were self-reported anxious symptoms, depressive symptoms and quality of life, and dropout rates as a proxy for acceptability. ResultsTen (37.0%) patients met criteria for clinical remission and 15 (55.6%) were classified as responders, with comparable outcomes for both moderate and severe MDD. Clinician-rated improvements in depressive symptoms were paralleled in self-reported depressive and anxious symptoms, as well as quality of life. No patient discontinued treatment. LimitationsThis study is limited by short treatment duration that might be lengthened with corresponding improvements in effectiveness, limited duration of follow-up, small sample size, and an open-label design requiring randomized controlled replication. ConclusionAn accelerated protocol involving twice-daily sessions of HF-rTMS over the left DLPFC for 2 weeks was effective in treatment-resistant MDD, and had excellent acceptability. Additional research is required to optimize accelerated rTMS treatment protocols and determine efficacy using sham-controlled trials.

The Impact of High-Frequency Repetitive Transcranial Magnetic Stimulation on Fine Motor Functions in Medication-Resistant Major Depression

Objectives: Although high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been reported to improve mood symptoms in major depressive disorder (MDD), research on its impact on psychomotor symptoms is scarce. This study assessed the psychomotor effects of 1 and 10 sessions, respectively, of HF-rTMS over the left DLPFC. Methods: Ten HF-rTMS sessions were applied in 21 medication-free MDD patients over a 2-week period. At the beginning, one placebo (sham)-controlled rTMS session was also applied in a cross-over, single-blind design. Psychomotor variables were digitally recorded during completion of a Fitts’ task, at baseline, after the first and second real/sham session and at the end point. Results: The total 10-session treatment period resulted in a decrease of depression severity. One HF-rTMS session resulted in improvements on the Fitts’ task, without a difference between active and sham stimulation, however. No further improvements occurred from session 2 to session 10. Conclusions: No evidence was provided to link the observed psychomotor improvements to HF-rTMS stimulation, as a practice effect could have impacted the significant psychomotor outcomes.

HF-rTMS Treatment in Medication-Resistant Melancholic Depression:Results from18FDG-PET Brain Imaging

High frequency repetitive transcranial magnetic stimulation (HF-rTMS) of the left dorsolateral prefrontal cortex (DLPFC) might be a promising strategy to treat depression, but not all patients show a positive outcome. In this open study, we evaluate whether a favorable HF-rTMS treatment outcome could be predicted by baseline prefrontal brain glucose metabolism (CMRglc), measured by 18fluorodeoxyglucose positron emission tomography (18FDG-PET). A sample of 21 antidepressant-free, treatment-resistant depression (TRD) patients of the melancholic subtype received 10 sessions of HF-rTMS delivered on the left DLPFC. Patients underwent a static 18FDG-PET before and after HF-rTMS treatment. Forty-three percent of the patients showed a reduction of at least 50% on their Hamilton Rating Scale for Depression scores. Higher baseline metabolic activities in the DLPFC and the anterior cingulate cortex (ACC) were associated with better clinical outcome. Successful HF-rTMS treatment was related to metabolic changes in subdivisions of the ACC (Brodmann areas 24 and 32). This biological impact of HF-rTMS on regional brain CMRglc explains to some extent how HF-rTMS may improve moods in TRD patients. Larger sham-controlled HF-rTMS treatment studies are needed to confirm these results.

The impact of one session of HF-rTMS on salivary cortisol in healthy female subjects

Previous studies in healthy volunteers reported a possible impact of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) on stress hormones, like cortisol. In this sham-controlled, “single blind”, crossover study, we examined whether HF-rTMS had an effect on the hypothalamic-pituitary-adrenal (HPA) axis, by analysing salivary cortisol levels. Two studies were conducted. First, HF-rTMS on the left dorsolateral prefrontal cortex (DLPFC) was performed in 28 young healthy female volunteers. Second, in a comparable, but different group of 26 healthy females, HF-rTMS was performed on the right DLPFC. Salivary cortisol levels were assessed before, immediately after and 30 min after real and sham HF-rTMS. We found no support for the hypothesis that one single session of HF-rTMS on the left or the right DLPFC has an immediate or delayed impact on the HPA–axis, as measured by salivary cortisol. Although we controlled for several methodological problems in HF-rTMS research, the hypothesis that one single session of HF-rTMS on the left or on the right DLPFC can influence the HPA-axis in healthy volunteers was not supported.

P02-86 The influence of HF-rTMS treatment on psychomotor symptoms in medication-resistant depressed patients of the melancholic subtype

Aims:Current evidence suggests that high frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) of the left dorsolateral prefrontal cortex (DLPFC) might be a promising treatment strategy for depression. However, due to rather modest clinical results, the efficacy of rTMS in depressed patients is still under debate. As melancholic depression seems to affect psychomotor activity, in this study, we wanted to evaluate whether HF-rTMS treatment affects psychomotor activity. We also wanted to examine whether the severity of psychomotor retardation could predict clinical outcome.Method:Our group consisted of twenty antidepressant-free unipolar depressed patients of the melancholic subtype. All were considered at least stage II treatment resistant. Depression severity was assessed with the Hamilton Depression Rating Scale (HDRS) and psychomotor symptoms with the Depressive Retardation Rating Scale (DRRS). All received 10 sessions of HF-rTMS delivered on the left DLPFC.Results:Forty percent of the patients showed a reduction of at least 50% on their initial HDRS score and were defined as HF-rTMS responders.The severity of psychomotor retardation, as measured with the DDRS, did not predict clinical outcome. HF-rTMS treatment resulted in significant decreases in DDRS scores for responders as well as for non-responders. However: the better the clinical outcome, the higher the observed level of psychomotor improvement.Conclusion:Our results suggest that HF-rTMS might act on the ‘psychomotor’ level and this might add some further information as to why this kind of treatment can be beneficial for severely depressed patients of the melancholic subtype.

The influence of High Frequency rTMS session on the Hypothalamic-Pituitary-Adrenal system

Previous studies in depressed patients, as well as in healthy volunteers, have reported a possible impact of High Frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) on the hypothalamic-pituitary-adrenal (HPA) axis. We wanted to evaluate the emotional and neurobiological impact of one session of HF-rTMS applied on the left DLPFC in a sample of unipolar treatment resistant depressed patients of the melancholic subtype.