The priming effect of repetitive transcranial magnetic stimulation on clinical response to electroconvulsive therapy in treatment-resistant depression: a randomized, double-blind, sham-controlled study.

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression (TRD). However, due to response delay and cognitive impairment, ECT remains an imperfect treatment. Compared to ECT, repetitive transcranial magnetic stimulation (rTMS) is less effective at treating severe depression, but has the advantage of being quick, easy to use, and producing almost no side effects. In this study, our objective was to assess the priming effect of rTMS sessions before ECT on clinical response in patients with TRD. METHODS: In this multicenter, randomized, double-blind, sham-controlled trial, 56 patients with TRD were assigned to active or sham rTMS before ECT treatment. Five sessions of active/sham neuronavigated rTMS were administered over the left dorsolateral prefrontal cortex (20 Hz, 90% resting motor threshold, 20 2 s trains with 60-s intervals, 800 pulses/session) before ECT (which was active for all patients) started. Any relative improvements were then compared between both groups after five ECT sessions, in order to assess the early response to treatment. RESULTS: After ECT, the active rTMS group exhibited a significantly greater relative improvement than the sham group [43.4% (28.6%) v. 25.4% (17.2%)]. The responder rate in the active group was at least three times higher. Cognitive complaints, which were assessed using the Cognitive Failures Questionnaire, were higher in the sham rTMS group compared to the active rTMS group, but this difference was not corroborated by cognitive tests. CONCLUSIONS: rTMS could be used to enhance the efficacy of ECT in patients with TRD. ClinicalTrials.gov: NCT02830399.

Repetitive transcranial magnetic stimulation for patients with functional paralysis: a randomized controlled study.

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat functional neurological disorders. Here, the aim was to assess the efficacy of rTMS to treat functional paralysis in a controlled randomized trial. METHODS: Patients received two sessions of active or sham 0.25 Hz rTMS (60 stimuli each), with a 1-day interval, applied over the motor cortex contralateral to the paralysis. The primary outcome was the number of patients with an increase in motor score between baseline and after the second rTMS session, rated by two investigators blinded to the treatment allocation. Secondary outcomes were changes in global and fine motor scores between groups after rTMS, and the occurrence of adverse events. RESULTS: Sixty-two patients (46 female; mean [SD] age, 35.2 [13.9] years) were enrolled and randomized. Thirteen out of 32 (41%) and 11/30 (37%) patients had increased motor strength after active or sham rTMS, respectively (p = 0.80). Changes in both global and fine motor scores after rTMS relative to baseline were also not significantly different between treatment groups (median difference in the global motor score 0.62 [0.83] and 0.37 [0.61], and in the fine motor scores 0.12 [0.18] and 0.08 [0.11], in active and sham rTMS groups, respectively; p = 0.14). Six serious adverse events, consisting of three cephalalgia in the active group and two cephalalgia and one asthenia in the sham group, were observed. CONCLUSIONS: Two sessions of sham or active low frequency rTMS were effective to improve functional paralysis, suggesting a placebo effect of this non-invasive brain stimulation technique.

Effects of repetitive transcranial magnetic stimulation of the right inferior parietal lobe on the body image perception in anorexia nervosa: A pilot randomized controlled study.

INTRODUCTION: Restrictive anorexia nervosa (AN) is associated with distorted perception of body shape, previously linked to hypoactivity and reduced excitability of the right inferior parietal lobe (rIPL). Here, we investigated the impact of high-frequency repetitive transcranial magnetic stimulation (HF rTMS) of the rIPL on body shape perception in patients with AN. METHODS: Seventeen patients with AN (median [Q1_Q3] age, 35 [27_39] years; disease duration, 12 [6_18] years) were randomly assigned to receive real or sham HF (10 Hz) rTMS of the rIPL over a period of 2 weeks, comprising 10 sessions. The primary outcome measure was the Body Shape Questionnaire (BSQ). Secondary outcomes included eating disorder symptoms, body mass index, mood, anxiety, and safety. Data collection were done at baseline, post-rTMS, and at 2 weeks and 3 months post-rTMS. RESULTS: Following both real and sham rTMS of the rIPL, no significant differences were observed in body shape perception or other parameters. Both real and sham rTMS interventions were deemed safe and well tolerated. Notably, serious adverse events were associated with the underlying eating and mood disorders, resulting in hospitalization for undernutrition (five patients) or suicidal attempts (two patients). CONCLUSION: This pilot study does not support the use of rTMS of the rIPL as an effective method for improving body shape perception in individuals with the restrictive form of AN. Further research is warranted to comprehensively explore both the clinical and neurophysiological effects of HF rTMS in this population.

Cardiorespiratory changes associated with micro-arousals during naps.

The autonomic nervous system (ANS) and the central nervous system (CNS) interplay during sleep, particularly during phasic events such as micro-arousals, has been the subject of several studies. The underlying mechanisms of such relationship which remain unclear, specifically during daytime sleep, were partly investigated in this study. Napping polysomnography was performed on two occasions at least one week apart in 15 healthy subjects. The following cardiorespiratory variables were extracted from the recordings: tachogram, pulse transit time (PTT), pulse wave amplitude, respiratory cycle amplitude, and frequency. Two experts first detected micro-arousal events, then, cardiorespiratory variables were averaged by 30-s epochs over 2 min centered on the onset of the micro-arousals. We found that in the 30 s preceding the arousal events as detected on the electroencephalogram (EEG) recordings, there was a decrease in tachogram, pulse wave amplitude, and PTT values while the respiratory amplitude increased. These changes were more prominent in stage N2 and N3 sleep than in stage N1. The present findings provide new insights into the autonomic changes during the pre-arousal period in daytime naps, as all the variables investigated suggest a sympathetic physiological origin for the changes.

Auditory verbal hallucinations in schizophrenia: current perspectives in brain stimulation treatments.

PURPOSE: This review reports the current perspectives of brain stimulation techniques in the treatment of auditory verbal hallucinations (AVH) in schizophrenia. METHODS: A systematic search of the literature in the PubMed database revealed that the most studied techniques are noninvasive techniques (NIBS), including electroconvulsive therapy (ECT), transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS). RESULTS: The results showed that ECT could have great clinical efficacy but is currently underused in practice perhaps due to the costs associated with its limited implementation and potential associated risks. tDCS is still poorly studied and does not demonstrate sufficiently homogeneous or conclusive results yet to prove its efficacy in the treatment of AVH. However, its safe and simple implementation allows us to recommend it to patients who are refractory to other stimulation techniques. Finally, rTMS seems to be the most efficacious NIBS to offer patients with persistent AVH as an add-on therapeutic strategy. Its implementation has a non negligible cost but can be performed by a single practitioner. Great evolution in these techniques with technological progress, robotics and computer science are currently being tested and will undoubtedly improve the clinical efficacy of these procedures, particularly towards more personalized treatments such as individual rTMS targets and intensities. There are also new techniques for deep brain stimulation based on focused ultrasound that could provide much insight into the treatment of AVH in schizophrenia. CONCLUSION: This review suggests that add-on brain stimulation treatments could play a key role among the therapeutic strategies for auditory hallucinations reduction in schizophrenia.

[Mood disorders: When should we use repetitive transcranial magnetic stimulation?] / Troubles de l'humeur : quand recourir à la stimulation magnétique transcrânienne ?

Repeated transcranial magnetic stimulation (rTMS) is still a recent treatment in psychiatry. This article aims at updating the clinicians'knowledge about rTMS in the treatment of mood disorders (uni and bipolar depressive disorders, manic/mixed states, suicidal risk, catatonia). It is intended for clinicians who are required to indicate and/or use rTMS in their current practice. rTMShas the highest level of evidence for the treatment of unipolar depression, provided that effective parameters are used, that is to say, for classical high frequency protocols: 20 to 30 sessions, 1000 pulses/session, 5 to 20Hz, and 110 % of the motor threshold. Low frequency protocol are also efficient and well tolerated. The duration of the efficacy varies with relapses rates around 50 % at one year. Pharmacological treatment generally remains associated. With regard to manic states, and mixed states the results are preliminary and limited to a possible reduction in symptoms. In the suicidal risk associated with mood disorders, the interest of rTMS is still to demonstrate, as well as in catatonia. The current place of the rTMS is no longer disputed in the curative treatment of major depressive disorder, preferentially used after one or two lines of antidepressants upstream. Further studies are needed to confirm preliminary positive findings in other aspects of mood disorders.

Effects of low- and high-frequency repetitive transcranial magnetic stimulation on long-latency auditory evoked potentials.

Long-latency auditory event potentials (LLAEPs) involving local and global auditory processes have been investigated to examine the impact of low-frequency (LF) and high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) on the cortical excitability of the temporal cortex. We hypothesized that both stimulation frequencies have the same modulation effect, in accordance with clinical data showing a reduction in auditory verbal hallucinations (AVHs) after LF and HF temporal rTMS in patients with schizophrenia. With 30 right-handed healthy volunteer participants enrolled in a crossover trial, we analyzed LLAEPs before and after LF- and HF-rTMS of the left temporal cortex. While we observed no changes in latencies, we did observe a similar inhibitory action of both rTMS frequencies on LLAEP amplitudes. Analysis of surface potential maps and cortical generators revealed some differences regarding auditory processes: HF-rTMS produced earlier, more diffuse, and more right-lateralized effects than LF-rTMS. Beyond a local impact, rTMS exerted a remote modulation influence on the frontal cortex that might be involved in attentional processes. This association could explain the therapeutic effect of temporal HF-rTMS on AVH.

High-Frequency Neuronavigated rTMS in Auditory Verbal Hallucinations: A Pilot Double-Blind Controlled Study in Patients With Schizophrenia.

INTRODUCTION: Despite extensive testing, the efficacy of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of temporo-parietal targets for the treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia is still controversial, but promising results have been reported with both high-frequency and neuronavigated rTMS. Here, we report a double-blind sham-controlled study to assess the efficacy of high-frequency (20 Hz) rTMS applied over a precise anatomical site in the left temporal region using neuronavigation. METHODS: Fifty-nine of 74 randomized patients with schizophrenia or schizoaffective disorders (DSM-IV R) were treated with rTMS or sham treatment and fully evaluated over 4 weeks. The rTMS target was determined by morphological MRI at the crossing between the projection of the ascending branch of the left lateral sulcus and the superior temporal sulcus (STS). RESULTS: The primary outcome was response to treatment, defined as a 30% decrease of the Auditory Hallucinations Rating Scale (AHRS) frequency item, observed at 2 successive evaluations. While there was no difference in primary outcome between the treatment groups, the percentages of patients showing a decrease of more than 30% of AHRS score (secondary outcome) did differ between the active (34.6%) and sham groups (9.1%) (P = .016) at day 14. DISCUSSION: This controlled study reports negative results on the primary outcome but demonstrates a transient effect of 20 Hz rTMS guided by neuronavigation and targeted on an accurate anatomical site for the treatment of AVHs in schizophrenia patients.

Is it relevant to screen young women hospitalized in psychiatric department for neuropsychiatric systemic lupus erythematosus (NPSLE)?: A prospective study of 100 psychiatric inpatients.

On the basis that diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) is sometimes difficult and systemic lupus erythematosus (SLE) can present with isolated psychiatric symptoms, we initiated a survey in a psychiatric department to screen for NPSLE in young female inpatients.We prospectively studied consecutive young female patients referred to the department of psychiatry. Antinuclear antibodies (ANA), anti-deoxyribonucleic acid (DNA), and antiextractable soluble nuclear antigens (ENA) in the serum of patients were screened. In case of positive anti-DNA or anti-ENA, the patient was referred to the department of internal medicine.One hundred patients were enrolled, mean age 33.1 ±â€Š8.4 years. Most patients presented underlying psychiatric disorders: depression (46%), schizophrenia (13%), anxiety disorder (6%), and personality disorder (10%). A quarter of the cohort did not display underlying psychiatric disorders before hospitalization. Positive ANA ≥1:160 were found in 32 of the 100 patients tested (32%). No patients presented anti-DNA antibodies. One patient had positive anti-sjogrën's syndrome related antigen A (SSA), but did not present any features of SLE or Sjögren syndrome.Thus, systematic screening of SLE is not relevant in young women hospitalized in psychiatric department. However, clinicians should keep in mind that SLE can present with pure psychiatric symptoms.

Cortical Anatomical Variations and Efficacy of rTMS in the Treatment of Auditory Hallucinations.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) shows high inter-subject variability in its efficacy for treating resistant auditory verbal hallucinations in schizophrenia. Currently, the response of an individual patient to rTMS treatment cannot be predicted. It is possible that cortical anatomical characteristics could affect the therapeutic response. OBJECTIVE: We hypothesized that rTMS efficacy is related to anatomical variations underlying the stimulation target in the left temporal cortex. We investigated two regions of interest (ROIs) that have been implicated in rTMS: the left temporal cortex, where the stimulation is delivered, and the primary hand motor cortex, where the stimulation strength is determined by the resting motor threshold (rMT). METHODS: Fifteen patients with schizophrenia (DSM IV) underwent rTMS and magnetic resonance imaging. The scalp-to-cortex distance (SCD) and the grey matter density (GMD) were measured in both ROIs. Linear regression models were used to investigate the relationships between these measures and the clinical efficacy of rTMS. RESULTS: Treatment efficacy was highly predicted by the temporal SCD and the GMD in the temporal and primary hand motor cortex regions. In contrast, the rMT was not predicted by the primary hand motor cortex SCD or GMD. CONCLUSION: These results suggest that rTMS treatment efficacy could be related to the depth of the temporal target. The data raise the question of whether rMT is the best measure for assessing the stimulation intensity in treating patients with schizophrenia.

How do high- and low-frequency repetitive transcranial magnetic stimulations modulate the temporal cortex.

Few studies have examined the impact of repetitive transcranial magnetic stimulation (rTMS) on the cortical excitability of nonmotor cortices; current treatments often target the temporal or prefrontal cortex. We used auditory evoked potentials recorded in 24 healthy subjects to evaluate the neuromodulatory effects of low- and high-frequency rTMS in the temporal lobe. Both auditory evoked potential P50 amplitude, a marker of cortical excitability, and P50 ratio, a marker of sensory gating known to be impaired in patients with auditory verbal hallucinations, were compared before and after rTMS. We observed a similar effect after both stimulation frequencies, with a decrease in P50 amplitude and no significant effect on P50 ratio. Low- and high-frequency rTMS applied to the temporal lobe seemed to exert the same cortical neuromodulation effect, while auditory sensory gating may not be modulated by temporal rTMS.