Jean-Arthur Micoulaud-Franchi

EEG neurofeedback treatments in children with ADHD: an updated meta-analysis of randomized controlled trials

Objective: We undertook a meta-analysis of published Randomized Controlled Trials (RCT) with semi-active control and sham-NF groups to determine whether Electroencephalogram-neurofeedback (EEG-NF) significantly improves the overall symptoms, inattention and hyperactivity/impulsivity dimensions for probably unblinded assessment (parent assessment) and probably blinded assessment (teacher assessment) in children with Attention Deficit Hyperactivity Disorder (ADHD). Data sources: A systematic review identified independent studies that were eligible for inclusion in a random effects meta-analysis. Data extraction: Effect sizes for ADHD symptoms were expressed as standardized mean differences (SMD) with 95% confidence intervals. Results: Five identified studies met eligibility criteria, 263 patients with ADHD were included, 146 patients were trained with EEG-NF. On parent assessment (probably unblinded assessment), the overall ADHD score (SMD = −0.49 [−0.74, −0.24]), the inattention score (SMD = −0.46 [−0.76, −0.15]) and the hyperactivity/impulsivity score (SMD = −0.34 [−0.59, −0.09]) were significantly improved in patients receiving EEG-NF compared to controls. On teacher assessment (probably blinded assessment), only the inattention score was significantly improved in patients receiving EEG-NF compared to controls (SMD = −0.30 [−0.58, −0.03]). Conclusions: This meta-analysis of EEG-NF in children with ADHD highlights improvement in the inattention dimension of ADHD symptoms. Future investigations should pay greater attention to adequately blinded studies and EEG-NF protocols that carefully control the implementation and embedding of training.

Resting cortical PET metabolic changes in psychogenic non-epileptic seizures (PNES)

Background The pathophysiology of psychogenic non-epileptic seizures (PNES) is poorly understood. Functional neuroimaging data in various functional neurological disorders increasingly support specific neurobiological dysfunction. However, to date, no studies have been reported of positron emission tomography (PET) in patients presenting with PNES. Methods Sixteen patients being evaluated in a specialist epilepsy centre underwent PET with 2-deoxy-2-[fluorine-18]fluoro-d-glucose (18FDG-PET) because of suspected intractable epileptic seizures. However, in all patients, the diagnosis was subsequently confirmed to be PNES with no coexisting epilepsy. 18FDG-PET was also performed in 16 healthy controls. A voxel by voxel intergroup analysis was performed to look for significant differences in interictal (resting state) cerebral metabolism. In addition, metabolic connectivity was studied using voxel-wise inter-regional correlation analysis. Results In comparison to group analysis of healthy participants, the group analysis of patients with PNES exhibited significant PET hypometabolism within the right inferior parietal and central region, and within the bilateral anterior cingulate cortex. A significant increase in metabolic correlation was found in patients with PNES, in comparison to healthy participants, between the right inferior parietal/central region and the bilateral cerebellum, and between the bilateral anterior cingulate cortex and the left parahippocampal gyrus. Conclusions To the best of our knowledge, this is the first study describing FDG-PET alterations in patients with PNES. Although we cannot exclude that our data reflect changes due to comorbidities, they may indicate a dysfunction of neural systems in patients with PNES. Hypometabolism regions might relate to two of the pathophysiological mechanisms that may be involved in PNES, that is, emotional dysregulation (anterior cingulate hypometabolism) and dysfunctional processes underlying the consciousness of the self and the environment (right parietal hypometabolism). Trial registration number NCT00484523.

One step closer to a global tool for rapid screening of major depression in epilepsy: Validation of the French NDDI-E

OBJECTIVE Depression in people with epilepsy (PWE) is underdiagnosed and undertreated. The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a screening questionnaire used for detecting major depressive episode (MDE) in PWE, and is already validated in 10 languages. However a version in French, one of the worlds widely spoken languages, was, until now, lacking. We aimed to translate and validate the French NDDI-E. METHODS This study was performed under the auspices of the ILAE. People with epilepsy >18years of age were recruited from 2 specialist epilepsy units in Marseille, France. Two native French speakers and 2 native English speakers performed a forward-backward translation. The Mini International Neuropsychiatric Interview (MINI) was performed as the gold standard, and the Center for Epidemiological Studies Depression symptoms index (CES-D) was performed for external validity. Data were compared between PWE with MDE and PWE without MDE using the chi-square test and Students t-test. Internal structural validity, external validity, and receiver operator characteristics were analyzed. RESULTS Testing was performed on 116 PWE: mean age=40.39years (SD=13.83, range: [18-81]years old); 58.6% (68) were women; 87.1% had focal epilepsy. Using the MINI, we found that 33 (28.4%) patients had current MDE and that 15 (12.9%) patients had dysthymia; also, we found that 37 (31.9%) patients presented suicidal ideation and/or behavior. Cronbachs alpha coefficient was 0.838, indicating satisfactory internal consistency. Correlation between the NDDI-E and the CES-D scores was high (r(116)=0.817, p<0.0001), indicating good external validity. Receiver operator characteristic analysis showed an area under the curve of 0.958 (95% CI=0.904-0.986), (p<0.0001), indicating good capacity of the NDDI-E to detect MDE (defined by MINI). The cutoff for maximal sensitivity and specificity was 15. The mean NDDI-E score in PWE with MDE was 18.27 (SD=2.28), and the mean NDDI-E score in PWE without MDE was 10.61 (SD=3.63). SIGNIFICANCE This study validated the French NDDI-E, with a cutoff score of 15/24 for MDE, similar to previous studies, and reinforces the NDDI-E as a global tool for detection of MDE.

Skin conductance biofeedback training in adults with drug-resistant temporal lobe epilepsy and stress-triggered seizures: A proof-of-concept study

The present proof-of-concept study investigated the feasibility of skin conductance biofeedback training in reducing seizures in adults with drug-resistant temporal lobe epilepsy (TLE), whose seizures are triggered by stress. Skin conductance biofeedback aims to increase levels of peripheral sympathetic arousal in order to reduce cortical excitability. This might seem somewhat counterintuitive, since such autonomic arousal may also be associated with increased stress and anxiety. Thus, this sought to verify that patients with TLE and stress-triggered seizures are not worsened in terms of stress, anxiety, and negative emotional response to this nonpharmacological treatment. Eleven patients with drug-resistant TLE with seizures triggered by stress were treated with 12 sessions of biofeedback. Patients did not worsen on cognitive evaluation of attentional biases towards negative emotional stimuli (P>.05) or on psychometric evaluation with state anxiety inventory (P = .059); in addition, a significant improvement was found in the Negative Affect Schedule (P = .014) and in the Beck Depression Inventory (P = .009). Biofeedback training significantly reduced seizure frequency with a mean reduction of -48.61% (SD = 27.79) (P = .005). There was a correlation between the mean change in skin conductance activity over the biofeedback treatment and the reduction of seizure frequency (r(11) = .62, P = .042). Thus, the skin conductance biofeedback used in the present study, which teaches patients to achieve an increased level of peripheral sympathetic arousal, was a well-tolerated nonpharmacological treatment. Further, well-controlled studies are needed to confirm the therapeutic value of this nonpharmacological treatment in reducing seizures in adults with drug-resistant TLE with seizures triggered by stress.

Rapid detection of generalized anxiety disorder and major depression in epilepsy: Validation of the GAD-7 as a complementary tool to the NDDI-E in a French sample

OBJECTIVE Generalized anxiety disorder (GAD) in people with epilepsy (PWE) is underdiagnosed and undertreated. The GAD-7 is a screening questionnaire to detect GAD. However, the usefulness of the GAD-7 as a screening tool in PWE remains to be validated. Thus, we aimed to: (1) validate the GAD-7 in French PWE and (2) assess its complementarity with regard to the previously validated screening tool for depression, the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). METHODS This study was performed under the auspices of the ILAE Commission on Neuropsychiatry. People with epilepsy >18 years of age were recruited from the specialist epilepsy unit in Marseille, France. The Mini-International Neuropsychiatric Interview (MINI) was performed as gold standard, and the Penn State Worry Questionnaire (PSWQ) and the NDDI-E were performed for external validity. Data were compared between PWE with/without GAD using Chi(2) test and Students t-test. Internal structural validity, external validity, and receiver operator characteristics were analyzed. A principal component factor analysis with Varimax rotation was performed on the 13 items of the GAD-7 (7 items) plus the NDDI-E (6 items). RESULTS Testing was performed on 145 PWE: mean age = 39.38 years old (SD=14.01, range: 18-75); 63.4% (92) women; 75.9% with focal epilepsy. Using the MINI, 49 (33.8%) patients had current GAD. Cronbachs alpha coefficient was 0.898, indicating satisfactory internal consistency. Correlation between GAD-7 and the PSQW scores was high (r (145)=.549, P<.0001), indicating good external validity. Factor analysis shows that the anxiety investigated with the GAD-7 and depression investigated with the NDDI-E reflect distinct factors. Receiver operator characteristic analysis showed area under the curve of 0.899 (95% CI 0.838-0.943, P < 0.0001) indicating good capacity of the GAD-7 to detect GAD (defined by MINI). Cutoff for maximal sensitivity and specificity was 7. Mean GAD-7 score in PWE with GAD was 13.22 (SD = 3.99), and that without GAD was 5.17 (SD = 4.66). SIGNIFICANCE This study validates the French language version of the GAD-7 screening tool for generalized anxiety in PWE, with a cutoff score of 7/21 for GAD, and also confirms that the GAD-7 is a short and easily administered test. Factor analysis shows that the GAD-7 (screening for generalized anxiety disorder) and the NDDI-E (screening for major depression) provide complementary information. The routine use of both GAD-7 and NDDI-E should be considered in clinical evaluation of patients with epilepsy.

Parieto-temporal alpha EEG band power at baseline as a predictor of antidepressant treatment response with repetitive Transcranial Magnetic Stimulation: A preliminary study

BACKGROUND The aim of this preliminary study was to determine the predictive value of absolute alpha band power measured during the rest EEG eyes closed task for responses to 20 sessions of high frequency repetitive transcranial stimulation (rTMS) in the left dorsolateral prefrontal cortex in patients with pharmacoresistant major depressive episode. METHODS 13 major depressive disorders (8 males) and 8 bipolar disorders (6 males) were included (mean age 58years). Spearman correlations between pretreatment alpha band power in height regions of analysis and absolute improvement in Beck Depression Inventory Short Form (ΔBDI-SF) were analyzed. The predictive value of alpha band power for classifying patients as responders and non-responders to rTMS was determined using Receiver Operating Characteristic (ROC) curve. RESULTS Spearman correlation analysis revealed that ΔBDI-SF correlated significantly and negatively with alpha band power on the right (r=-.673, p=.001) and left parieto-temporal regions (r=-.638, p=.002). The area under the ROC curve for the right parieto-temporal was .815, p=.0037. The cut-off point that maximized both sensitivity and specificity was 1.49μV. Sensitivity, specificity, positive and negative predictive values were 100, 66, 80, 100% respectively. LIMITATIONS The population was small and lacked homogeneity concerning affective disorders (unipolar and bipolar disorder). The use of a self-rating subjective scale (BDI-SF) to measure the severity of depression could be criticized. CONCLUSIONS Pretreatment alpha band power on parieto-temporal regions could be a predictor for response to rTMS in patients with homogenous demographic/clinical features. The association between electrical activity and the perfusion under each electrode need to be examined.

D2 and D3 dopamine receptor affinity predicts effectiveness of antipsychotic drugs in obsessive-compulsive disorders: a metaregression analysis

Rationale and objectiveThe relationship between clinically effective antipsychotic drugs in obsessive–compulsive disorders (OCD) and binding affinities to cloned dopamine and serotonin receptor subtypes was analyzed in an effort to clarify the contribution of individual receptor subtypes to medication response.MethodsMeta-analysis was used to update previous meta-analyses of effectiveness data of add-on antipsychotic drugs to selective serotonin reuptake inhibitors (SSRIs) in OCD. Twelve previously analyzed randomized controlled trials (RCTs) and one new RCT were included. We performed a metaregression using a mixed-effect model to examine the association between antipsychotic’s effectiveness and receptor affinity.ResultsA total of 5 treatment arms obtained from 13 RCTs (431 patients) were included in our study. The results of our metaregression showed a significant association between D2 and D3 dopamine receptor affinities and effectiveness in OCD (respectively, slope = −0.36, p = 0.01; and slope = −0.50, p = 0.01) whereas other dopamine receptors and serotonin receptors were not significantly associated.ConclusionsThese observations suggest that increasing D2 and D3 dopamine receptor binding affinities enhances antipsychotics’ effectiveness in obsessive–compulsive disorders.

Vers une nouvelle déclinaison de la neurophysiologie clinique en psychiatrie : le neurofeedback par imagerie par résonance magnétique fonctionnelle appliqué aux dysfonctions des processus émotionnels

Emotions color in a singular way our everyday life and constitute important determinants of human cognition and behavior. Emotional regulation is an essential process involved in neuropathophysiology and therapeutic efficacy in many psychiatric disorders. Yet, traditional psychiatric therapeutic has focused on symptomatic rather than neurophysiological criteria. Therefore, it was proposed to teach patients to modify their own brain activity directly, in order to obtain a therapeutic effect. These techniques, which are named neurofeedback, were originally developed using electroencephalography. Recent technical advances in fMRI enable real-time acquisition, and open opportunities to its utilization in neurofeedback. This seems particularly interesting in emotion regulation, which, at a neurofunctional level, lies on cortico-limbic pathways that, in great parts, were previously identified by traditional fMRI paradigms. This emotion regulation plays a central role in the etiopathogeny psychiatric, especially depressive and anxious, disorders. It is possible to devise new therapeutic strategies and research approach for addressing directly the neurophysiological processes of emotion regulation by integrating the neurofunctional activities of a subject. These prospects seem to be in line with the neurophenomenology project, which proposes to establish a link between subjective experiences and objective neurophysiological measures.Emotions color in a singular way our everyday life and constitute important determinants of human cognition and behavior. Emotional regulation is an essential process involved in neuropathophysiology and therapeutic efficacy in many psychiatric disorders. Yet, traditional psychiatric therapeutic has focused on symptomatic rather than neurophysiological criteria. Therefore, it was proposed to teach patients to modify their own brain activity directly, in order to obtain a therapeutic effect. These techniques, which are named neurofeedback, were originally developed using electroencephalography. Recent technical advances in fMRI enable real-time acquisition, and open opportunities to its utilization in neurofeedback. This seems particularly interesting in emotion regulation, which, at a neurofunctional level, lies on cortico-limbic pathways that, in great parts, were previously identified by traditional fMRI paradigms. This emotion regulation plays a central role in the etiopathogeny psychiatric, especially depressive and anxious, disorders. It is possible to devise new therapeutic strategies and research approach for addressing directly the neurophysiological processes of emotion regulation by integrating the neurofunctional activities of a subject. These prospects seem to be in line with the neurophenomenology project, which proposes to establish a link between subjective experiences and objective neurophysiological measures.

Quality of life is associated with chronic inflammation in schizophrenia: a cross-sectional study

Inflammation may play a crucial role in the pathogenesis of schizophrenia. However, the association between chronic inflammation and health outcomes in schizophrenia remains unclear, particularly for patient-reported outcomes. The aim of this study was to investigate the relationship between quality of life (QoL) and chronic inflammation assessed using C -Reactive Protein (CRP) in patients with schizophrenia. Two hundred and fifty six patients with schizophrenia were enrolled in this study. After adjusting for key socio-demographic and clinical confounding factors, patients with high levels of CRP (>3.0 mg/l) had a lower QoL than patients with normal CRP levels (OR = 0.97, 95% CI = 0.94–0.99). An investigation of the dimensions of QoL revealed that psychological well-being, physical well-being and sentimental life were the most salient features of QoL associated with CRP. Significant associations were found between lower educational level (OR = 4.15, 95% CI = 1.55–11.07), higher body mass index (OR = 1.16, 95% CI = 1.06–1.28), higher Fagerström score (OR = 1.22, 95% CI = 1.01–1.47) and high levels of CRP. After replications with longitudinal approaches, the association between QoL and chronic inflammation may offer interesting interventional prospects to act both on inflammation and QoL in patients with schizophrenia.

(Mis)use of Prescribed Stimulants in the Medical Student Community: Motives and Behaviors: A Population-Based Cross-Sectional Study

AbstractThe aim of this study was to estimate the prevalence of psychostimulant use in the French medical community and their motives.A population-based cross-sectional study using a self-administered online survey was done.A total of 1718 French students and physicians (mean age, 26.84±7.19 years, 37.1% men) were included. Self-reported lifetime use, motives, socio-demographic and academic features for over the counter (OTC), medically prescribed (MPP), and illicit (IP) psychostimulant users were reported. Lifetime prevalence of psychostimulant use was 33% (29.7% for OTC, 6.7% for MPP, and 5.2% for IP). OTC consumption mainly aimed at increasing academic performance and wakefulness during competitive exams preparation. OTC consumption started early and was predictive of later MPP use. Corticoids were the most frequently consumed MPP (4.5%) before methylphenidate and modafinil. Motives for MPP consumption were increased academic performance, concentration, memory, and wakefulness.Psychostimulant use is common among French medical community. Our results suggest that restrictions on methylphenidate and modafinil prescriptions are effective at limiting their use. However, these restrictions may explain the observed rates of corticoids consumption, which raise a new public health problem, given that corticoids may have severe side effects.