Transcranial Direct Current Stimulation as an Add-on Treatment to Cognitive-Behavior Therapy in First Episode Drug-Naïve Major Depression Patients: The ESAP Study Protocol.

Background: Major Depressive Disorder (MDD) affects more than 264 million people worldwide. Current treatments include the use of psychotherapy and/or drugs, however ~30% of patients either do not respond to these treatments, or do not tolerate the side effects associated to the use of pharmacological interventions. Thus, it is important to study non-pharmacological interventions targeting mechanisms not directly involved with the regulation of neurotransmitters. Several studies demonstrated that transcranial Direct Current Stimulation (tDCS) can be effective for symptoms relief in MDD. However, tDCS seems to have a better effect when used as an add-on treatment to other interventions. Methods/Design: This is a study protocol for a parallel, randomized, triple-blind, sham-controlled clinical trial in which a total of 90 drug-naïve, first-episode MDD patients (45 per arm) will be randomized to one of two groups to receive a 6-weeks of CBT combined with either active or sham tDCS to the dorsolateral prefrontal cortex (DLPFC). The primary outcome will depressive symptoms improvement as assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) at 6-weeks. The secondary aim is to test whether CBT combined with tDCS can engage the proposed mechanistic target of restoring the prefrontal imbalance and connectivity through the bilateral modulation of the DLPFC, as assessed by changes over resting-state and emotional task eliciting EEG. Discussion: This study evaluates the synergetic clinical effects of CBT and tDCS in the first episode, drug-naïve, patients with MDD. First episode MDD patients provide an interesting opportunity, as their brains were not changed by the pharmacological treatments, by the time course, or by the recurrence of MDD episodes (and other comorbidities). Trial Registration: This study is registered with the United States National Library of Medicine Clinical Trials Registry (NCT03548545). Registered June 7, 2018, clinicaltrials.gov/ct2/show/NCT03548545. Protocol Version 1.

Patterns of Default Mode Network Deactivation in Obsessive Compulsive Disorder.

The objective of the present study was to research the patterns of Default Mode Network (DMN) deactivation in Obsessive Compulsive Disorder (OCD) in the transition between a resting and a non-rest emotional condition. Twenty-seven participants, 15 diagnosed with OCD and 12 healthy controls (HC), underwent a functional neuroimaging paradigm in which DMN brain activation in a resting condition was contrasted with activity during a non-rest condition consisting in the presentation of emotionally pleasant and unpleasant images. Results showed that HC, when compared with OCD, had a significant deactivation in two anterior nodes of the DMN (medial frontal and superior frontal) in the non-rest pleasant stimuli condition. Additional analysis for the whole brain, contrasting the resting condition with all the non-rest conditions grouped together, showed that, compared with OCD, HC had a significantly deactivation of a widespread brain network (superior frontal, insula, middle and superior temporal, putamen, lingual, cuneus, and cerebellum). Concluding, the present study found that OCD patients had difficulties with the deactivation of DMN even when the non-rest condition includes the presentation of emotional provoking stimuli, particularly evident for images with pleasant content.

Alterations of gray and white matter morphology in obsessive compulsive disorder / Las alteraciones de morfología de la sustancia blanca y gris en el trastorno obsesivo compulsivo

BACKGROUND: While the ethio-pathogenesis of Obsessive-Compulsive disorder (OCD) remains unknown, there is increased evidence of widespread structural alterations in both white and gray matter in OCD patients that include, but are not restricted, to abnormalities in corticostriatal-thalamo-cortical (CSTC) regions. The objective of this study was to test the existence of structural alterations in both white and gray matter in a sample of OCD patients when compared with a group of non-clinical matched controls (NCC), using voxel-based morphometry (VBM). METHOD: Fifteen patients with OCD and 15 NCC underwent MRI structural scanning. RESULTS: Frontal (increased gray matter in the middle frontal gyrus) and subcortical regions (increased white matter in the pallidum) were found to be affected in patients. Additionally, temporalparietal regions were also found to be affected and highly correlated with OCD symptom severity (decrease of gray matter in the superior parietal lobe and white matter in the angular and superior temporal gyri). CONCLUSIONS: These alterations may be associated with prominent OCD symptoms, such as diffi culties with inhibitory control (pallidum, angular gyrus), executive functioning (middle frontal gyris), compulsive checking (superior temporal gyrus) and visual-spatial defi cits (superior parietal lobe)

ANTECEDENTES: mientras que la etiopatogenia del trastorno obsesivo-compulsivo (TOC) sigue siendo desconocida, hay una mayor evidencia en las personas que sufren este trastorno de alteraciones estructurales que incluyen, pero no se limitan, a anormalidades en regiones cortico-estriado-tálamo-corticales (CSTC). El objetivo de este estudio fue comprobar la existencia de alteraciones estructurales tanto en la materia blanca como en la materia gris en una muestra de pacientes con TOC en comparación con un grupo de controles no clínicos (NCC), utilizándose para ello análisis morfométricos basados en «voxel» (VBM). MÉTODO: quince pacientes con TOC y quince NCC fueron estudiados mediante resonancia magnética estructural. RESULTADOS: se encontraron alteraciones en los pacientes en regiones frontales (aumento de la materia gris en la circunvolución frontal media) y subcorticales (aumento de la materia blanca en el pallidum). Además, también se encontraron afectadas regiones témporo-parietales con una alta correlación con la gravedad de los síntomas del TOC (disminución de la materia gris en el lóbulo parietal superior y de la materia blanca en las circunvoluciones temporales angular y superior). CONCLUSIONES: las alteraciones encontradas pueden estar asociados con síntomas predominantes en el TOC, como dificultades en el control inhibitorio (pallidum, giro angular), función ejecutiva (circunvolución frontal media), verificaciones compulsivas (circunvolución temporal superior) y déficit visual-espacial (lóbulo parietal superior)

Alterations of gray and white matter morphology in obsessive compulsive disorder.

BACKGROUND: While the ethio-pathogenesis of Obsessive-Compulsive disorder (OCD) remains unknown, there is increased evidence of widespread structural alterations in both white and gray matter in OCD patients that include, but are not restricted, to abnormalities in cortico-striatal-thalamo-cortical (CSTC) regions. The objective of this study was to test the existence of structural alterations in both white and gray matter in a sample of OCD patients when compared with a group of non-clinical matched controls (NCC), using voxel-based morphometry (VBM). METHOD: Fifteen patients with OCD and 15 NCC underwent MRI structural scanning. RESULTS: Frontal (increased gray matter in the middle frontal gyrus) and subcortical regions (increased white matter in the pallidum) were found to be affected in patients. Additionally, temporal-parietal regions were also found to be affected and highly correlated with OCD symptom severity (decrease of gray matter in the superior parietal lobe and white matter in the angular and superior temporal gyri). CONCLUSIONS: These alterations may be associated with prominent OCD symptoms, such as difficulties with inhibitory control (pallidum, angular gyrus), executive functioning (middle frontal gyris), compulsive checking (superior temporal gyrus) and visual-spatial deficits (superior parietal lobe).

Cognitive and emotional impairments in obsessive-compulsive disorder: Evidence from functional brain alterations.

There is a common agreement on the existence of dysfunctional cortico-striatal-thalamus-cortical pathways in OCD. Despite this consensus, recent studies showed that brain regions other than the CSTC loops are needed to understand the complexity and diversity of cognitive and emotional deficits in OCD. This review presents examples of research using functional neuroimaging, reporting abnormal brain processes in OCD that may underlie specific cognitive/executive (inhibitory control, cognitive flexibility, working memory), and emotional impairments (fear/defensive, disgust, guilt, shame). Studies during resting state conditions show that OCD patients have alterations in connectivity not only within the CSTC pathways but also in more extended resting state networks, particularly the default mode network and the fronto-parietal network. Additionally, abnormalities in brain functioning have been found in several cognitive and emotionally task conditions, namely: inhibitory control (e.g., CSTC loops, fronto-parietal networks, anterior cingulate); cognitive flexibility (e.g., CSTC loops, extended temporal, parietal, and occipital regions); working memory (e.g., CSTC loops, frontal parietal networks, dorsal anterior cingulate); fear/defensive (e.g., amygdala, additional brain regions associated with perceptual - parietal, occipital - and higher level cognitive processing - prefrontal, temporal); disgust (e.g., insula); shame (e.g., decrease activity in middle frontal gyrus and increase in frontal, limbic, temporal regions); and guilt (e.g., decrease activity anterior cingulate and increase in frontal, limbic, temporal regions). These findings may contribute to the understanding of OCD as both an emotional (i.e., anxiety) and cognitive (i.e., executive control) disorder.

Inferior frontal gyrus white matter abnormalities in obsessive-compulsive disorder.

The aim of the present study is to explore obsessive-compulsive disorder (OCD)-related abnormalities in white matter connectivity in OCD for a core region associated with inhibitory control [i.e. inferior frontal gyrus (IFG)]. Fifteen patients with OCD (11 men) and 15 healthy controls (nine men) underwent diffusion tensor imaging scanning to study four diffusivity indexes of white matter integrity [fractional anisotropy, mean diffusivity (MD), axial diffusivity and radial diffusivity (RD)]. The results showed that persons with OCD manifested significantly lower fractional anisotropy levels in the bilateral IFG as well as its parcellations in the pars opercularis, pars triangularis, and pars orbitalis. Significantly higher levels of MD, RD were evident for the OCD group in the IFG as a whole as well as in the bilateral subregions of the pars triangularis and pars opercularis (for MD and RD), the right side of the pars orbitalis (for RD), and the left side of the pars triangularis and right side pars opercularis (for axial diffusivity). Overall, the results suggest significant alterations in structural connectivity, probably associated with myelination and axonal abnormalities in the IFG of OCD patients.

Brain activation of the defensive and appetitive survival systems in obsessive compulsive disorder.

Several studies have shown that basic emotions are responsible for a significant enhancement of early visual processes and increased activation in visual processing brain regions. It may be possible that the cognitive uncertainty and repeated behavioral checking evident in Obsessive Compulsive Disorder (OCD) is due to the existence of abnormalities in basic survival circuits, particularly those associated with the visual processing of the physical characteristics of emotional-laden stimuli. The objective of the present study was to test if patients with OCD show evidence of altered basic survival circuits, particularly those associated with the visual processing of the physical characteristics of emotional stimuli. Fifteen patients with OCD and 12 healthy controls underwent functional magnetic resonance imaging acquisition while being exposed to emotional pictures, with different levels of arousal, intended to trigger the defensive and appetitive basic survival circuits. Overall, the present results seem to indicate dissociation in the activity of the defense and appetitive survival systems in OCD. Results suggest that the clinical group reacts to basic threat with a strong activation of the defensive system mobilizing widespread brain networks (i.e., frontal, temporal, occipital-parietal, and subcortical nucleus) and blocking the activation of the appetitive system when facing positive emotional triggers from the initial stages of visual processing (i.e., superior occipital gyrus).