Dominique Januel

Left superior temporal gyrus activation during sentence perception negatively correlates with auditory hallucination severity in schizophrenia patients

The left superior temporal cortex, which supports linguistic functions, has consistently been reported to activate during auditory-verbal hallucinations in schizophrenia patients. It has been suggested that auditory hallucinations and the processing of normal external speech compete for common neurophysiological resources. We tested the hypothesis of a negative relationship between the clinical severity of hallucinations and local brain activity in posterior linguistic regions while patients were listening to external speech. Fifteen right-handed patients with schizophrenia and daily auditory hallucinations for at least 3 months were studied with event-related fMRI while listening to sentences in French or to silence. Severity of hallucinations, assessed using the auditory hallucination subscales of the Psychotic Symptom Rating Scales (PSYRATS) and of the Scale for the Assessment of Positive Symptoms (SAPS-AH), negatively correlated with activation in the left temporal superior region in the French minus silence condition. This finding supports the hypothesis that auditory hallucinations compete with normal external speech for processing sites within the temporal cortex in schizophrenia.

Repetitive transcranial magnetic stimulation as an add-on therapy in the treatment of mania: a case series of eight patients

The aim of this study is to assess the efficacy of repetitive transcranial magnetic stimulation (rTMS) as an add-on therapy in the treatment of manic bipolar patients. Eight patients were enrolled in an open trial. They received fast rTMS (five trains of 15 s, 80% of the motor threshold, 10 Hz) over the right dorsolateral prefrontal cortex (DLPFC). They were evaluated using the Mania Assessment Scale (MAS) and the Clinical Global Impression (CGI) at baseline and at day 14. All patients were taking medication during the treatment trial. There was a significant improvement of manic symptoms at the end of the trial. No side effects were reported. The results show a significant improvement of mania when patients are treated with fast rTMS over the right DLPFC. However, these results have to be interpreted with caution since they derive from an open case series and all the subjects were taking psychotropic medication during rTMS treatment. Double-blind controlled studies with a sham comparison condition should be conducted to investigate the efficiency of this treatment in manic bipolar disorders.

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.

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

Neural correlates of cognitive improvements following cognitive remediation in schizophrenia: a systematic review of randomized trials

Background Cognitive impairments are a core feature in schizophrenia and are linked to poor social functioning. Numerous studies have shown that cognitive remediation can enhance cognitive and functional abilities in patients with this pathology. The underlying mechanism of these behavioral improvements seems to be related to structural and functional changes in the brain. However, studies on neural correlates of such enhancement remain scarce. Objectives We explored the neural correlates of cognitive enhancement following cognitive remediation interventions in schizophrenia and the differential effect between cognitive training and other therapeutic interventions or patients’ usual care. Method We searched MEDLINE, PsycInfo, and ScienceDirect databases for studies on cognitive remediation therapy in schizophrenia that used neuroimaging techniques and a randomized design. Search terms included randomized controlled trial, cognitive remediation, cognitive training, rehabilitation, magnetic resonance imaging, positron emission tomography, electroencephalography, magnetoencephalography, near infrared spectroscopy, and diffusion tensor imaging. We selected randomized controlled trials that proposed multiple sessions of cognitive training to adult patients with a schizophrenia spectrum disorder and assessed its efficacy with imaging techniques. Results In total, 15 reports involving 19 studies were included in the systematic review. They involved a total of 455 adult patients, 271 of whom received cognitive remediation. Cognitive remediation therapy seems to provide a neurobiological enhancing effect in schizophrenia. After therapy, increased activations are observed in various brain regions mainly in frontal – especially prefrontal – and also in occipital and anterior cingulate regions during working memory and executive tasks. Several studies provide evidence of an improved functional connectivity after cognitive training, suggesting a neuroplastic effect of therapy through mechanisms of functional reorganization. Neurocognitive and social-cognitive training may have a cumulative effect on neural networks involved in social cognition. The variety of proposed programs, imaging tasks, and techniques may explain the heterogeneity of observed neural improvements. Future studies would need to specify the effect of cognitive training depending on those variables.

Stimulation magnétique transcrânienne et fonctions cognitives

Resume La stimulation magnetique transcrânienne (TMS) semble donner des espoirs prometteurs en ce qui concerne la recherche en neuropsychologie. La TMS est une methode non invasive de stimulation du systeme nerveux central qui utilise le principe de l’inductance pour transmettre un courant electrique au travers de la boite crânienne, permettant ainsi d’interferer directement avec l’activite neuronale. La TMS peut interrompre transitoirement l’activation d’une region precise et creer ce que l’on appelle des « lesions virtuelles », fonctionnelles, grâce a des stimulations repetees et tres proches dans le temps. L’interet est de mettre en evidence les zones cerebrales concernees par l’accomplissement de certaines tâches cognitives. L’objectif de notre travail est de presenter de maniere non exhaustive quelques travaux qui se sont penches sur la TMS en rapport avec le fonctionnement cognitif (processus visuels, langage, memoire, fonctions executives, reconnaissance des emotions…) principalement chez le sujet sain. D’autre part, la TMS est testee comme traitement de troubles psychiatriques tels que la depression et de plus en plus dans la schizophrenie ou les troubles anxieux. Certains auteurs rapportent des effets antidepresseurs de la TMS sans consequence nefaste sur les fonctions cognitives des patients.

Repetitive Transcranial Magnetic Stimulation to Supplementary Motor Area in Refractory Obsessive-Compulsive Disorder Treatment: a Sham-Controlled Trial

Background: Repetitive transcranial magnetic stimulation has been explored in patients with obsessive-compulsive disorder, but with negative or conflicting results. This randomized double-blind study was designed to assess the efficacy of 1-Hz repetitive transcranial magnetic stimulation over the presupplementary area. Methods: Forty medication-resistant patients were assigned to 4 weeks of either active or sham repetitive transcranial magnetic stimulation targeting the presupplementary area with the help of a neuronavigation system. Results: According to the Yale-Brown obsessive-compulsive scale, the baseline-week 4 evolution showed no significant differences between groups. Responder rates at week 4 were not different between groups (repetitive transcranial magnetic stimulation 10.5% vs sham 20%; P=.63). Conclusion: Low-frequency repetitive transcranial magnetic stimulation applied to the presupplementary area seems ineffective for the treatment of obsessive-compulsive disorder patients, at least in severe and drug-refractory cases such as those included in this study. Further research is required to determine profiles of responder patients and appropriate repetitive transcranial magnetic stimulation parameters for obsessive-compulsive disorder.

Annonce du diagnostic de schizophrénie au sein d’un service de psychiatrie de secteur

Resume L’annonce du diagnostic de schizophrenie aux patients atteints de cette maladie est en France un sujet d’actualite. L’evolution des pratiques cliniques, une meilleure efficacite des moyens therapeutiques et un droit a l’information plus exigeant des patients en sont les principaux facteurs. En effet, si cette annonce est de pratique courante dans les pays anglo-saxons, et notamment aux Etats-Unis ou la legislation influence de facon predominante l’information faite au malade, les medecins francais se montrent reticents sur l’interet d’une telle annonce. La schizophrenie demeure une pathologie heterogene marquee par un polymorphisme clinique. Le pronostic reste neanmoins classiquement reserve, avec une evolution le plus souvent synonyme de chronicite. Le caractere potentiellement deficitaire de l’evolution classe cette affection parmi les troubles psychiatriques les plus invalidants. La revue de la litterature a ce sujet est pauvre concernant les etudes methodologiques et peu de donnees ont jusqu’ici ete publiees en France sur le niveau d’information des patients schizophrenes et leurs besoins en ce domaine, a l’exception de l’enquete de Bayle et al. La litterature est essentiellement constituee de reflexions sur les aspects medico-legaux et legislatifs ainsi que d’enquetes aupres de confreres medecins sur l’annonce diagnostique. En se basant sur ces donnees et notre experience clinique, nous avons institue dans notre service un protocole d’information au sujet de la schizophrenie. Cette procedure se deroule en 3 phases sur une periode d’un mois, en accord avec le desir du patient d’etre informe sur sa maladie. Les aspects cliniques, etiologiques et therapeutiques de la maladie sont abordes au cours de cette procedure. L’amelioration clinique constatee notamment aux scores des echelles d’evaluation (BPRS et CGI et les scores aux echelles EVA infirmiers) ne peut bien entendu etre imputee a la procedure d’information du diagnostic, les patients ayant beneficie d’un traitement antipsychotique pendant leur hospitalisation. L’observance aux traitements sur la duree de 2 ans est egalement assez satisfaisante. Cette procedure, elaboree sous forme d’entretiens semi-structures regroupes en un cahier « d’annonce diagnostique » mis a la disposition des medecins et de l’equipe, a probablement aide les soignants a donner l’information dans un cadre preetabli. De plus, il a ete propose aux patients ayant beneficie de l’annonce diagnostique de participer a 2 groupes de psychoeducation sur la maladie et les medicaments. Les familles des patients ayant connaissance du diagnostic, pouvaient participer a un groupe specifique dont le but est la connaissance de la maladie et d’ameliorer les communications entre la famille et le malade. Bien que ces premieres observations constatees au cours de cette procedure d’annonce soient encourageantes, elles necessitent d’etre confirmees par l’elargissement du nombre de patients concernes et au long cours. La plupart des auteurs soulignent l’interet d’une annonce diagnostique au cours des 2 premieres annees de la maladie, afin d’ameliorer le pronostic et en raison de meilleures capacites d’insight. Aussi a-t-il ete mis en place dans notre service un suivi sur 2 ans des patients ayant beneficie de cette annonce pour evaluer a long terme le benefice ou non de l’annonce diagnostique sur la compliance et la qualite de vie de ces patients. Cette demarche presente plusieurs interets : elle repond a une ethique de l’information, elle permet une comprehension de la maladie. L’annonce diagnostique s’inscrit sur le mode du partenariat, dans un processus dynamique et psychoeducatif ou le patient et son entourage sont des partenaires eclaires.

Effect of repetitive transcranial magnetic stimulation on mood in healthy subjects

Background High frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) has shown significant efficiency in the treatment of resistant depression. However in healthy subjects, the effects of rTMS remain unclear. Objective Our aim was to determine the impact of 10 sessions of rTMS applied to the DLPFC on mood and emotion recognition in healthy subjects. Design In a randomised double-blind study, 20 subjects received 10 daily sessions of active (10 Hz frequency) or sham rTMS. The TMS coil was positioned on the left DLPFC through neuronavigation. Several dimensions of mood and emotion processing were assessed at baseline and after rTMS with clinical scales, visual analogue scales (VASs), and the Ekman 60 faces test. Results The 10 rTMS sessions targeting the DLPFC were well tolerated. No significant difference was found between the active group and the control group for clinical scales and the Ekman 60 faces test. Compared to the control group, the active rTMS group presented a significant improvement in their adaptation to daily life, which was assessed through VAS. Conclusion This study did not show any deleterious effect on mood and emotion recognition of 10 sessions of rTMS applied on the DLPFC in healthy subjects. This study also suggested a positive effect of rTMS on quality of life.

Humour et théorie de l’esprit dans la schizophrénie, revue de la littérature

Humour is a universal phenomenon, a daily fact holding positive aspects valued in society. The sense of humour is subjective, inherent in each and everyone and difficult to assess. We could qualify it as an indefinable sense set by an absence of norms. This intangible notion occupies a primordial social role of communication, confidence, shared by all with both therapeutic and physical benefit. Scientists started researching this theme in schizophrenic patients from 1950. Studies show a net deficit of humour capabilities between healthy subjects and patients. The hypothesis of a deficit of the theory of mind in the evaluation of humour in schizophrenics is currently the object of several experiments. Nowadays, cognitive functions are also taken into account in humour perception studies. However the little or few studies relevant to this subject are a definite obstacle to the understanding of this complex phenomenon.