Impaired Modulation of Corticospinal Excitability in Drug-Free Patients With Major Depressive Disorder: A Theta-Burst Stimulation Study

Impaired neural plasticity may be an important mechanism in the pathophysiology of major depressive disorder (MDD). Coupled with electromyography (EMG), repetitive transcranial magnetic stimulation (rTMS) is a useful tool to evaluate corticospinal excitability and cortical neuroplasticity in living humans. The goal of this study was to compare rTMS-induced cortical plasticity changes in patients with MDD and in healthy volunteers. In this single-blind controlled study, 11 drug-free patients with MDD and 11 matched healthy controls were analyzed. Cortical excitability, measured by the amplitude of motor evoked potentials (MEPs) evoked by single-pulse TMS, was assessed before and repeatedly after (for 30 min) participants received a single session of intermittent theta-burst stimulation (iTBS) and continuous TBS (cTBS). rTMS was applied over the left motor cortex using a neuronavigation system. Intensity was set at 80% of the active motor threshold (AMT). A large interindividual variability was observed after both iTBS and cTBS in the two groups. At the group level, we observed impaired iTBS-induced neuroplasticity in patients with MDD compared to that in controls. No differences were observed between the groups regarding cTBS-induced neuroplasticity. Our results suggest impaired long-term potentiation (LTP)-like mechanisms in MDD.Clinical Trial Registration: www.Clinicaltrials.gov, identifier #NCT02438163

TREATMENT OF SHIZOPHRENIC PATIENTS AND rTMS

Introduction: Schizophrenia (SCH) is a heterogeneous syndrome characterized by positive and negative symptoms. Despite appropriate medication, about 1/4 of patients suffer for refractory positive and/or negative symptoms, which are associated with functional handicap, increase of duration and of the number of hospitalizations. Numerous studies have suggested that the pathophysiology of auditory hallucinations (AH) is related to a hyper activity of the left temporoparietal cortex (TPC). On the other hand, negative symptoms are associated with a prefrontal hypoactivity and the efficiency of pharmacological treatments is frequently partial. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool with excellent tolerability and safety. Given its hypothesized mechanisms of action and the clinical beneficial effects obtained in several types of pathology (Aleman et al. 2007), the efficacy of rTMS has been investigated for drug-resistant SCH symptoms. Objective: Our objective is to expose the knowledge concerning the rTMS use in the treatment of these symptoms and to purpose a critical analysis of these data. Method: a systematic review of the literature has been conducted using NIH Pubmed. The following search terms were used: TMS - rTMS - Schizophrenia - negative symptoms - hallucinations. Results: Concerning the treatment of AH, 16 publications and 4 meta analyses were selected. For the negative symptoms, we retained 16 studies and 3 meta analyses. The most extensively investigated application for rTMS in SCH is the use of low-frequency stimulation to the left TPC with the aim to improve AH symptomatology. When compared to sham, this type of acute course of rTMS has been proven to induce a substantial and significant reduction in AH. But this effect does not seem long-lasting and maintenance protocols must be developed. Concerning negative symptoms, the results are less solid but we find some works which demonstrate an improvement of these symptoms while various stimulation parameters were used. Recently, new parameters of stimulation in particular the theta burst stimulation have permitted us to obtain larger effects with longer duration. The interest of these new parameters will be discussed here. Conclusion: Overall, rTMS studies have demonstrated some promise in the treatment of SCH. However, more research is required to enhance rTMS efficacy and increase its beneficial effect duration and to test new therapeutic strategies in this topic

TREATMENT OF SHIZOPHRENIC PATIENTS AND rTMS

Introduction: Schizophrenia (SCH) is a heterogeneous syndrome characterized by positive and negative symptoms. Despite appropriate medication, about 1/4 of patients suffer for refractory positive and/or negative symptoms, which are associated with functional handicap, increase of duration and of the number of hospitalizations. Numerous studies have suggested that the pathophysiology of auditory hallucinations (AH) is related to a hyper activity of the left temporoparietal cortex (TPC). On the other hand, negative symptoms are associated with a prefrontal hypoactivity and the efficiency of pharmacological treatments is frequently partial. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool with excellent tolerability and safety. Given its hypothesized mechanisms of action and the clinical beneficial effects obtained in several types of pathology (Aleman et al. 2007), the efficacy of rTMS has been investigated for drug-resistant SCH symptoms. Objective: Our objective is to expose the knowledge concerning the rTMS use in the treatment of these symptoms and to purpose a critical analysis of these data. Method: a systematic review of the literature has been conducted using NIH Pubmed. The following search terms were used: TMS - rTMS - Schizophrenia - negative symptoms - hallucinations. Results: Concerning the treatment of AH, 16 publications and 4 meta analyses were selected. For the negative symptoms, we retained 16 studies and 3 meta analyses. The most extensively investigated application for rTMS in SCH is the use of low-frequency stimulation to the left TPC with the aim to improve AH symptomatology. When compared to sham, this type of acute course of rTMS has been proven to induce a substantial and significant reduction in AH. But this effect does not seem long-lasting and maintenance protocols must be developed. Concerning negative symptoms, the results are less solid but we find some works which demonstrate an improvement of these symptoms while various stimulation parameters were used. Recently, new parameters of stimulation in particular the theta burst stimulation have permitted us to obtain larger effects with longer duration. The interest of these new parameters will be discussed here. Conclusion: Overall, rTMS studies have demonstrated some promise in the treatment of SCH. However, more research is required to enhance rTMS efficacy and increase its beneficial effect duration and to test new therapeutic strategies in this topic

Low- vs High-Frequency Repetitive Transcranial Magnetic Stimulation as an Add-On Treatment for Refractory Depression

Objectives: Repetitive transcranial magnetic stimulation (rTMS) seems to be effective as an antidepressant, however, some confusion remains about the best parameters to apply and the efficacy of its association with pharmacological antidepressant treatments. Method: In a single blind randomized study 14 patients with unipolar resistant depression to one antidepressant treatment were enrolled to receive, in combination with venlafaxine (150 mg), either 20 sessions of 10 Hz rTMS (2000 pulses per session) applied over the left dorsolateral prefrontal cortex (DLPFC) or 20 sessions of 1 Hz rTMS (120 stimulations per sessions) applied over the right DLPFC. Results: A similar antidepressant effect was observed in both groups with a comparable antidepressant delay of action (2 weeks) and a comparable number of responders (MADRS < 15) after 4 weeks of daily rTMS sessions (66 vs 50%). Conclusion: Low- and high- frequency rTMS seems to be effective as an add-on treatment to venlafaxine as monotherapy in pharmacological refractory major depression (stage 1). Due to its short duration (one session of 1 Hz rTMS lasts 4 min vs 16 for 10 Hz rTMS) and its safety, low frequency rTMS may be a useful alternative treatment for patients with refractory depression

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 neuron

Learning Riemannian metric for disease progression modeling

International audienceLinear mixed-effect models provide a natural baseline for estimating disease progression using longitudinal data. They provide interpretable models at the cost of modeling assumptions on the progression profiles and their variability across subjects. A significant improvement is to embed the data in a Riemannian manifold and learn patient-specific trajectories distributed around a central geodesic. A few interpretable parameters characterize subject trajectories at the cost of a prior choice of the metric, which determines the shape of the trajectories. We extend this approach by learning the metric from the data allowing more flexibility while keeping the interpretability. Specifically, we learn the metric as the push-forward of the Euclidean metric by a diffeomorphism. This diffeomorphism is estimated iteratively as the composition of radial basis functions belonging to a reproducible kernel Hilbert space. The metric update allows us to improve the forecasting of imaging and clinical biomarkers in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Our results compare favorably to the 56 methods benchmarked in the TADPOLE challenge

Transcranial Direct Current Stimulation for Obsessive-Compulsive Disorder: A Systematic Review

Despite the advances in psychopharmacology and established psychotherapeutic interventions, more than 40% of patients with obsessive-compulsive disorder (OCD) do not respond to conventional treatment approaches. Transcranial direct current stimulation (tDCS) has been recently proposed as a therapeutic tool to alleviate treatment-resistant symptoms in patients with OCD. The aim of this review was to provide a comprehensive overview of the current state of the art and future clinical applications of tDCS in patients with OCD. A literature search conducted on the PubMed database following PRISMA guidelines and completed by a manual search yielded 12 results: eight case reports, three open-label studies (with 5, 8, and 42 participants), and one randomized trial with two active conditions (12 patients). There was no sham-controlled study. A total of 77 patients received active tDCS with a large diversity of electrode montages mainly targeting the dorsolateral prefrontal cortex, the orbitofrontal cortex or the (pre-) supplementary motor area. Despite methodological limitations and the heterogeneity of stimulation parameters, tDCS appears to be a promising tool to decrease obsessive-compulsive symptoms as well as comorbid depression and anxiety in patients with treatment-resistant OCD. Further sham-controlled studies are needed to confirm these preliminary results