Sequential multi-locus transcranial magnetic stimulation for treatment of obsessive-compulsive disorder with comorbid major depression: A case series

Obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) are highly comorbid [1], with depressive symptoms amplifying the chronicity and severity of OCD symptoms. Comorbid illness decreases quality of life and daily functioning [2] and is associated with greater suicidality and more frequent inpatient hospitalizations [3]. Furthermore, comorbid OCD/depression is associated with poorer response to OCD-focused psychological and pharmacological treatments [4]. Epidemiologic studies have shown that OCD symptoms generally precedes the occurrence of depression, suggesting a causal interacting model in which OCD predisposes to development of depressive symptoms [5]. In line with that causal model, Tadayonnejad et al. showed aberrant effective (directional) connectivity between OCD and MDD circuits may be a potential network mechanism of depressive symptom genesis or worsening in OCD-MDD [6]. The challenging nature of this comorbidity necessitates the development of novel, more effective treatments

Sequential multi-locus transcranial magnetic stimulation for treatment of obsessive-compulsive disorder with comorbid major depression: A case series

Obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) are highly comorbid [1], with depressive symptoms amplifying the chronicity and severity of OCD symptoms. Comorbid illness decreases quality of life and daily functioning [2] and is associated with greater suicidality and more frequent inpatient hospitalizations [3]. Furthermore, comorbid OCD/depression is associated with poorer response to OCD-focused psychological and pharmacological treatments [4]. Epidemiologic studies have shown that OCD symptoms generally precedes the occurrence of depression, suggesting a causal interacting model in which OCD predisposes to development of depressive symptoms [5]. In line with that causal model, Tadayonnejad et al. showed aberrant effective (directional) connectivity between OCD and MDD circuits may be a potential network mechanism of depressive symptom genesis or worsening in OCD-MDD [6]. The challenging nature of this comorbidity necessitates the development of novel, more effective treatments

Subthreshold stimulation intensity is associated with greater clinical efficacy of intermittent theta-burst stimulation priming for Major Depressive Disorder

Background: Intermittent theta-burst stimulation priming (iTBS-P) can improve clinical outcome of patients with Major Depressive Disorder (MDD) who do not show early benefit from 10 Hz stimulation of left dorsolateral prefrontal cortex (DLPFC), also known as high-frequency left-sided (HFL) stimulation. The intensity and pulse number for iTBS-P needed to induce clinical benefit have not been systematically examined. Objective: To study the effect of intensity and pulse number on the clinical efficacy of iTBS-P. Methods: We conducted a retrospective review of 71 participants who received at least five sessions of HFL with limited clinical benefit and received iTBS-P augmentation for between 5 and 25 sessions. Intensity of iTBS-P priming stimuli ranged from 75 to 120% of motor threshold (MT) and pulse number ranged from 600 to 1800. Associations among intensity, pulse number, and clinical outcome were analyzed using a mixed methods linear model with change in IDS-SR as the primary outcome variable, priming stimulation intensity (subthreshold or suprathreshold), pulse number (1200 pulses), and gender as fixed factors, and number of iTBS-P treatments and age as continuous covariates. Results: Subjects who received subthreshold intensity iTBS-P experienced greater reduction in depressive symptoms than those who received suprathreshold iTBS-P (p = 0.011) with no effect of pulse number after controlling for stimulus intensity. Conclusions: Subthreshold intensity iTBS-P was associated with greater clinical improvement than suprathreshold stimulation. This finding is consistent with iTBS-P acting through homeostatic plasticity mechanisms

Design concepts for the Cherenkov Telescope Array CTA: an advanced facility for ground-based high-energy gamma-ray astronomy

Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA

Rapport III-5. Détermination expérimentale du coefficient de dispersion longitudinale dans une rivière à l’aide d’un traceur radioactif

Are presented herein the results of four dispersion measurement campaigns, carried out with the use of a radio-active tracer in Sambre River (Meuse tributary at Namur) water, in the frame of C.I.P.S. programm which aim is to establish a "Mathematical model of Sambre River water pollution" .On présente les résultats de quatre campagnes de mesures de dispersion réalisées à l’aide d’un traceur radioactif dans la Sambre, affluent de la Meuse à Namur, dans le cadre du Programme C.I.P.S. pour l’établissement d’un «Modèle Mathématique de la pollution de la Sambre » .Sine L., Corlier F., Gaspar S. Rapport III-5. Détermination expérimentale du coefficient de dispersion longitudinale dans une rivière à l’aide d’un traceur radioactif. In: La mécanique des fluides et l'environnement. Prévision et maîtrise de la qualité de l'eau et de l'air. Compte rendu des quatorzièmes journées de l'hydraulique. Paris, 7-9 septembre 1976. Tome 1, 1977

Novel method for identification of individualized resonant frequencies for treatment of Major Depressive Disorder (MDD) using repetitive Transcranial Magnetic Stimulation (rTMS): A proof-of-concept study.

BackgroundRepetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD), but therapeutic benefit is highly variable. Clinical improvement is related to changes in brain circuits, which have preferred resonant frequencies (RFs) and vary across individuals.ObjectiveWe developed a novel rTMS-electroencephalography (rTMS-EEG) interrogation paradigm to identify RFs using the association of power/connectivity measures with symptom severity and treatment outcome.Methods35 subjects underwent rTMS interrogation at 71 frequencies ranging from 3 to 17 Hz administered to left dorsolateral prefrontal cortex (DLPFC). rTMS-EEG was used to assess resonance in oscillatory power/connectivity changes (phase coherence [PC], envelope correlation [EC], and spectral correlation coefficient [SCC]) after each frequency. Multiple regression was used to detect relationships between 10 Hz resonance and baseline symptoms as well as clinical improvement after 10 sessions of 10 Hz rTMS treatment.ResultsBaseline symptom severity was significantly associated with SCC resonance in left sensorimotor (SM; p < 0.0004), PC resonance in fronto-parietal (p = 0.001), and EC resonance in centro-posterior channels (p = 0.002). Subjects significantly improved with 10 sessions of rTMS treatment. Only decreased SCC SM resonance was significantly associated with clinical improvement (r = 0.35, p = 0.04). Subjects for whom 10 Hz SM SCC was highly ranked as an RF among all stimulation frequencies had better outcomes from 10 Hz treatment.ConclusionsResonance of 10 Hz stimulation measured using SCC correlated with both symptom severity and improvement with 10 Hz rTMS treatment. Research should determine whether this interrogation paradigm can identify individualized rTMS treatment frequencies

Rumination symptoms in treatment-resistant major depressive disorder, and outcomes of repetitive Transcranial Magnetic Stimulation (rTMS) treatment

Abstract Rumination is a maladaptive style of regulating thoughts and emotions. It is a common symptom of Major Depressive Disorder (MDD), and more severe rumination is associated with poorer medication and psychotherapy treatment outcomes, particularly among women. It is unclear to what extent rumination may influence the outcomes of, or be responsive to, repetitive Transcranial Magnetic Stimulation (rTMS) treatment of MDD. We retrospectively examined data collected during rTMS treatment of 155 patients (age 42.52 ± 14.22, 79 female) with moderately severe treatment-resistant MDD. The severity of rumination and depression was assessed before and during a course of 30 sessions of measurement-based rTMS treatment using the Ruminative Responses Scale (RSS) and the Patient Health Questionnaire (PHQ-9), respectively. Relationships among baseline levels of rumination, depression, and treatment outcome were assessed using a series of repeated measures linear mixed effects models. Both depression and rumination symptoms significantly improved after treatment, but improvement in depression was not a significant mediator of rumination improvement. Higher baseline rumination (but not depression severity) was associated with poorer depression outcomes independently of depression severity. Female gender was a significant predictor of worse outcomes for all RRS subscales. Both depressive and ruminative symptoms in MDD improved following rTMS treatment. These improvements were correlated, but improvement in rumination was not fully explained by reduction in depressive symptoms. These findings suggest that while improvement in rumination and depression severity during rTMS treatment are correlated, they are partly independent processes. Future studies should examine whether rumination symptoms should be specifically targeted with different rTMS treatment parameters

Effect of repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD) on cognitive control.

BackgroundMajor Depressive Disorder (MDD) is commonly accompanied by cognitive control dysfunction that may persist after remission of clinical symptoms with antidepressant medication treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment alternative for medication-resistant MDD. In this study, we investigated whether rTMS treatment had a beneficial effect not only on depressive symptoms, but on also cognitive control dysfunction.Methods77 subjects with MDD received a 30-session treatment course of 10 Hz rTMS administered at the left dorsolateral prefrontal cortex (DLPFC). Treatment efficacy was assessed using the Inventory of Depressive Symptomatology Self-Rated (IDS-SR) before and after treatment, with clinical response defined as 50% or greater decrease in the IDS-SR score at treatment 30. Cognitive control function was assessed before and after treatment using the Stroop word-color interference task. We examined changes in Stroop accuracy and reaction time for congruent and incongruent trials, as well as in relation to changes in depressive symptoms.ResultsPerformance accuracy improved particularly for the rTMS responders in the incongruent condition, with older subjects benefitting most from the rTMS treatment. Improvement in reaction times was positively associated with clinical improvement, especially in the incongruent condition.LimitationsWe used a single cognitive task in a naturalistic setting without control for individual rTMS treatment parameters or concomitant medication.ConclusionsOverall, these results indicate that rTMS treatment for MDD has beneficial effects on psychomotor speed and cognitive control. Future studies should extend these findings to larger patient populations and other cognitive domains

Psychostimulant use and clinical outcome of repetitive transcranial magnetic stimulation treatment of major depressive disorder

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD). Psychostimulant medication use may be associated with improved rTMS outcomes, but a detailed understanding of these relationships is lacking.MethodsWe compared MDD subjects taking psychostimulants (n = 37) with those not taking one of these medications (n = 53) during a course of 30 rTMS treatments. Changes in the 30-item Inventory of Depressive Symptomatology Self Report (IDS-SR30) subscale scores were examined at treatment 30. We also subdivided subjects into three categories based on drug mechanism and looked at IDS-SR30 total score after treatments 10, 20, and 30.ResultsSubjects taking psychostimulants had a significantly greater overall clinical improvement than those not taking these medications at treatment 30. The psychostimulant group also improved significantly more than the control group in "sleep" and "mood/cognition," but not "anxiety/arousal" IDS-SR30 subscales. No differences were detected among individual drug categories, which may reflect the limited sample size for individual medications. There was a negative dose-response relationship for the lisdexamfetamine/dextroamphetamine group, in which lower doses were associated with better clinical outcome.ConclusionsPsychostimulant medications may enhance clinical efficacy of rTMS for MDD by preferentially impacting specific symptom domains. For some psychostimulants, these effects may be dose-dependent. Prospective clinical trials are needed to guide psychostimulant augmentation of brain stimulation therapies