Jerome Brunelin

Slow transcranial magnetic stimulation can rapidly reduce resistant auditory hallucinations in schizophrenia

BACKGROUND Almost a quarter of patients with schizophrenia present with resistant auditory verbal hallucinations (AVH), a phenomenon that may relate to activation of brain areas underlying speech perception. Repetitive transcranial magnetic stimulation (rTMS) at 1 Hz reduces cortical activation, and recent results have shown that 1-Hz left temporoparietal rTMS may reduce AVH. The aim of this study was to replicate recent data and investigate whether low-frequency rTMS with a high total stimulation number delivered in a shorter 5-day block produces similar benefit. METHODS Ten right-handed schizophrenia patients with resistant AVH received 5 days of active rTMS and 5 days of sham rTMS (2,000 stimulations per day at 90% of motor threshold) over the left temporoparietal cortex in a double-blind crossover design. The two weeks of stimulation were separated by a 1-week washout period. RESULTS AVH were robustly improved (56%) by 5 days active rTMS, whereas no variation was observed after sham. Seven patients were responders to active treatment, five of whom maintained improvement for at least 2 months. CONCLUSIONS These data confirm the efficiency of low-frequency rTMS applied to the left temporoparietal cortex, compared with sham stimulation, in reducing resistant AVH. This improvement can be obtained in only 5 days without serious initial adverse events.

Efficacité de la stimulation magnétique transcrânienne (rTMS) dans le traitement de la dépression : revue de la littérature

Resume Depuis 10 ans, l’evaluation de l’interet therapeutique de la stimulation magnetique transcrânienne repetee (rTMS) fait l’objet d’un interet croissant. Basee sur le principe d’induction decouvert par Michael Faraday en 1831, la rTMS pourrait constituer une methode therapeutique antidepressive et, peut-etre, une alternative a l’electroconvulsivotherapie (ECT). Afin de faire le point des connaissances dans ce domaine, nous avons analyse les principaux travaux realisesa ce jour au travers de leur diversite methodologique par l’intermediaire d’une consultation de la banque de donnees informatisee Medline et d’une base de donnees disponible en ligne (ISTS), completee d’une recherche manuelle ; nous avons retenu 66 etudes qui font l’objet de cette revue. Malgre l’heterogeneite de ces publications en termes de methodologie et de parametres de traitements, les proprietes antidepressives de la rTMS semblent se dessiner (37 % de sujets repondeurs vs 20 % dans les groupes controles sur 30 etudes analysables) et ceci ouvre des perspectives interessantes, dans le traitement des depressions resistantes et peut-etre en tant que potentialisateur des antidepresseurs dans les autres formes de depression. Cependant, un grand nombre d’inconnues subsistent (methodologie du traitement et indications privilegiees), ce qui justifie le developpement de travaux d’evaluation structures sur de grands echantillons.

Can transcranial direct current stimulation (tDCS) alleviate symptoms and improve cognition in psychiatric disorders

Abstract Objectives. Since the discovery of psychopharmacological treatments in the early 1950s, followed by the development of second-generation antidepressants and antipsychotics, biological psychiatry has not achieved much progress. Recent technological advances in the field of non-invasive brain stimulation open new perspectives in the treatment of psychiatric disorders. Amongst them, transcranial direct current stimulation (tDCS) modulates cortical excitability and induces long-lasting effects. Here, we aimed at evaluating whether tDCS has potential to be developed as an innovative treatment in psychiatry. Methods. We conducted a systematic review of the current state of development and application of tDCS in psychiatric disorders, exploring clinical and cognitive effects, especially in major depressive disorder (MDD), schizophrenia and substance use disorder. Results. Systematic literature search yielded 40 publications: 22 in MDD, nine in schizophrenia, seven in substance use disorder, one in obsessive–compulsive disorder and one in mania. Our findings indicated beneficial clinical effects of tDCS for MDD and a promising literature in schizophrenia and substance use disorder. Conclusions. Despite methodological differences, the data published to date are promising and supports the use of tDCS as a treatment for psychiatric disorders. However, its place regarding other treatments still has to be determined before becoming a routine clinical treatment.

Are Hallucinations Due to an Imbalance Between Excitatory and Inhibitory Influences on the Brain

This review from the International Consortium on Hallucinations Research intends to question the pertinence of the excitatory-to-inhibitory (E/I) imbalance hypothesis as a model for hallucinations. A large number of studies suggest that subtle impairments of the E/I balance are involved in neurological and psychiatric conditions, such as schizophrenia. Emerging evidence also points to a role of the E/I balance in maintaining stable perceptual representations, suggesting it may be a plausible model for hallucinations. In support, hallucinations have been linked to inhibitory deficits as shown with impairment of gamma-aminobutyric acid transmission, N-methyl-d-aspartate receptor plasticity, reductions in gamma-frequency oscillations, hyperactivity in sensory cortices, and cognitive inhibition deficits. However, the mechanisms by which E/I dysfunctions at the cellular level might relate to clinical symptoms and cognitive deficits remain unclear. Given recent data advances in the field of clinical neuroscience, it is now possible to conduct a synthesis of available data specifically related to hallucinations. These findings are integrated with the latest computational frameworks of hallucinations, and recommendations for future research are provided.

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

CONTEXT The 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). METHOD In 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. RESULTS We 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). CONCLUSION Low 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.

A comparison of facial emotion processing in neurological and psychiatric conditions

Patients suffering from various neurological and psychiatric disorders show different levels of facial emotion recognition (FER) impairment, sometimes from the early phases of the disease. Investigating the relative severity of deficits in FER across different clinical and high-risk populations has potential implications for the diagnosis and treatment of these diseases, and could also allow us to understand the neurobiological mechanisms of emotion perception itself. To investigate the role of the dopaminergic system and of the frontotemporal network in FER, we reanalyzed and compared data from four of our previous studies investigating FER performance in patients with frontotemporal dysfunctions and/or dopaminergic system abnormalities at different stages. The performance of patients was compared to the performance obtained by a specific group of matched healthy controls using Cohen’s d effect size. We thus compared emotion and gender recognition in patients with frontotemporal dementia (FTD), amnestic mild cognitive impairment (aMCI), Alzheimer’s disease (AD) at the mild dementia stage, major depressive disorder, Parkinson’s disease treated by l-DOPA (PD-ON) or not (PD-OFF), remitted schizophrenia (SCZ-rem), first-episode schizophrenia treated by antipsychotic medication (SCZ-ON), and drug-naïve first-episode schizophrenia (SCZ-OFF), as well as in unaffected siblings of patients with schizophrenia (SIB). The analyses revealed a pattern of differential impairment of emotion (but not gender) recognition across pathological conditions. On the one hand, dopaminergic medication seems not to modify the moderate deficits observed in SCZ and PD groups (ON vs. OFF), suggesting that the deficit is independent from the dopaminergic system. On the other hand, the observed increase in effect size of the deficit among the aMCI, AD, and FTD groups (and also among the SIB and SCZ-rem groups) suggests that the deficit is dependent on neurodegeneration of the frontotemporal neural networks. Our transnosographic approach combining clinical and high-risk populations with the impact of medication provides new information on the trajectory of impaired emotion perception in neuropsychiatric conditions, and on the role of the dopaminergic system and the frontotemporal network in emotion perception.

Transcranial direct current stimulation in treatment-resistant obsessive–compulsive disorder: An open-label pilot study

BACKGROUND Obsessive-compulsive disorder (OCD) is a severe mental illness. OCD symptoms are often resistant to available treatments. Abnormalities within the orbitofronto-striato-pallido-thalamic circuitry, especially orbitofrontal cortex (OFC) hyperactivity and cerebellar hypoactivity have been observed in patients. Non-invasive brain stimulation studies have indicated that transcranial direct current stimulation (tDCS) may be a useful alternative to alleviate treatment-resistant symptoms in various neuropsychiatric conditions. METHODS In an open-label pilot study, 8 patients with treatment-resistant OCD received 10 sessions (twice a day) of 2mA tDCS applied with the cathode over the left OFC and the anode over the right cerebellum. OCD (Y-BOCS and OCD-VAS) as well as depressive (MADRS) symptoms were measured 4 times: one time before tDCS and 3 times after (immediately after, 1 and 3months after the 10th tDCS session). RESULTS We reported a significant 26.4% (±15.8) decrease of Y-BOCS score (p=0.002). The beneficial effect lasted during the 3month follow-up. No effect of tDCS was observed on depressive symptoms. At end point, 5 out of 8 patients had a decrease of ≥25%; and 3 out of 8 patients had a decrease of ≥35% in Y-BOCS score. tDCS was well tolerated. CONCLUSION tDCS with the cathode placed over the left OFC combined with the anode placed over the right cerebellum is a suitable and safe approach to decrease OCD symptoms in patients with treatment-resistant OCD. Large scale randomized controlled studies are needed to confirm this promising result.

Non-invasive brain stimulation can induce paradoxical facilitation. Are these neuroenhancements transferable and meaningful to security services?

For ages, we have been looking for ways to enhance our physical and cognitive capacities in order to augment our security. One potential way to enhance our capacities may be to externally stimulate the brain. Methods of non-invasive brain stimulation (NIBS), such as repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), have been recently developed to modulate brain activity. Both techniques are relatively safe and can transiently modify motor and cognitive functions outlasting the stimulation period. The purpose of this paper is to review data suggesting that NIBS can enhance motor and cognitive performance in healthy volunteers. We frame these findings in the context of whether they may serve security purposes. Specifically, we review studies reporting that NIBS induces paradoxical facilitation in motor (precision, speed, strength, acceleration endurance, and execution of daily motor task) and cognitive functions (attention, impulsive behavior, risk-taking, working memory, planning, and deceptive capacities). Although transferability and meaningfulness of these NIBS-induced paradoxical facilitations into real-life situations are not clear yet, NIBS may contribute at improving training of motor and cognitive functions relevant for military, civil, and forensic security services. This is an enthusiastic perspective that also calls for fair and open debates on the ethics of using NIBS in healthy individuals to enhance normal functions.

Evaluation of the therapeutic effect of theta burst stimulation on drug-resistant auditory hallucinations in a schizophrenic patient and its impact on cognitive function and neuronal excitability: A case study

Resistant auditory hallucinations are reported in 25% of schizophrenia cases (Shergill et al., 1998). Recent meta-analyses (Aleman et al., 2007; Freitas et al., 2009) have shown that low-frequency repetitive transcranial magnetic stimulation (rTMS at 61 Hz) applied to the left temporoparietal cortex (LTPC) half way between T3 and P3 using the 10–20 EEG system is an effective treatment for drug-resistant auditory hallucinations. Neuronal plasticity manifests as a change in cortical excitability and the effect of rTMS on synaptic plasticity varies considerably between individuals (Huang et al., 2005). Theta burst stimulation (TBS) is a powerful stimulation technique (at a frequency of 50 Hz) generating a persistent modulatory effect 30 min after a session of 190 s (Huang et al., 2005) but also stimulation parameters such as the site, frequency and the pathology, which must be confirmed by future studies. We describe here a 52-year-old right-handed schizophrenic patient (diagnosed on the basis of DSM IV-TR criteria), on olanzapine (30 mg/day), treated by TBS (20 sessions in four weeks) for hallucinations resistant (Wahlbeck et al., 2000) to various treatments administered over a period of more than 5 years. The stimulation parameters were as previously described in a protocol for cTBS (continuous theta burst stimulation) by Huang et al. (2005): 600 pulses per session, in continuous trains of 40 s (3 pulses per burst, at a frequency of 50 Hz), administered to the LTPC determined by the 10–20 EEG system, at 80% of the motor threshold (MT), by a Magstim Super Rapid stimulator, with a figure-of-eight coil. Clinical evaluation on the day before treatment (D0) and after one (M1) and two (M2) months involved a self-assessment of auditory hallucinations (Hoffman et al., 2000) with a visual analogue scale (VAS), and a heteroevaluation with the PANSS (Positive and Negative Syndrome Scale; Stanley Kay et al., 1988) and the PSRS (Psychotic Symptom Rating Scale; Haddok et al., 1999). Neuropsychological assessment at D0 and M1 involved amnestic and executive function tests and a source memory task (Brunelin et al., 2008). Clinical observations showed a 54% decrease between D0 and M1 in hallucination scores based on Hoffman ratings, and a decrease of more than 70% in the intensity of anxiety (79%), sadness (75%) and hallucinations (90%) as assessed with the VAS. These improvements persisted for at least two months. A decrease of 24% in PSRS score was also observed. By contrast, PANSS score remained unchanged, at 34.5 during the four weeks of treatment. The potential importance of placebo effect cannot be discounted. However, the persistence of improvement after rTMS in patient with long-term persistence of auditory hallucinations suggests, but does not prove, that observed clinical changes were an effect of stimulation. The results of the neuropsychological tests demonstrate an overall improvement between D0 and M1: a 50% increase in WSCT 802 Letters to the Editor / Clinical Neu

Disrupting Pre-SMA Activity Impairs Facial Happiness Recognition: An Event-Related TMS Study

It has been suggested that the left pre-supplementary motor area (pre-SMA) could be implicated in facial emotion expression and recognition, especially for laughter/happiness. To test this hypothesis, in a single-blind, randomized crossover study, we investigated the impact of transcranial magnetic stimulation (TMS) on performances of 18 healthy participants during a facial emotion recognition task. Using a neuronavigation system based on T1-weighted magnetic resonance imaging of each participant, TMS (5 pulses, 10 Hz) was delivered over the pre-SMA or the vertex (control condition) in an event-related fashion after the presentation of happy, fear, and angry faces. Compared with performances during vertex stimulation, we observed that TMS applied over the left pre-SMA specifically disrupted facial happiness recognition (FHR). No difference was observed between the 2 conditions neither for fear and anger recognition nor for reaction times (RT). Thus, interfering with pre-SMA activity with event-related TMS after stimulus presentation produced a selective impairment in the recognition of happy faces. These findings provide new insights into the functional implication of the pre-SMA in FHR, which may rely on the mirror properties of pre-SMA neurons.