Altered functional connectivity of the subthalamus and the bed nucleus of the stria terminalis in obsessive-compulsive disorder

Background: the assessment of inter-regional functional connectivity (FC) has allowed for the description of the putative mechanism of action of treatments such as deep brain stimulation (DBS) of the nucleus accumbens in patients with obsessive-compulsive disorder (OCD). Nevertheless, the possible FC alterations of other clinically-effective DBS targets have not been explored. Here we evaluated the FC patterns of the subthalamic nucleus (STN) and the bed nucleus of the stria terminalis (BNST) in patients with OCD, as well as their association with symptom severity. Methods: eighty-six patients with OCD and 104 healthy participants were recruited. A resting-state image was acquired for each participant and a seed-based analysis focused on our two regions of interest was performed using statistical parametric mapping software (SPM8). Between-group differences in FC patterns were assessed with two-sample t test models, while the association between symptom severity and FC patterns was assessed with multiple regression analyses. Results: in comparison with controls, patients with OCD showed: (1) increased FC between the left STN and the right pre-motor cortex, (2) decreased FC between the right STN and the lenticular nuclei, and (3) increased FC between the left BNST and the right frontopolar cortex. Multiple regression analyses revealed a negative association between clinical severity and FC between the right STN and lenticular nucleus. Conclusions: this study provides a neurobiological framework to understand the mechanism of action of DBS on the STN and the BNST, which seems to involve brain circuits related with motor response inhibition and anxiety control, respectively

Emotion Regulation and Excess Weight: Impaired Affective Processing Characterized by Dysfunctional Insula Activation and Connectivity

Emotion-regulation strategies are understood to influence food intake. This study examined the neurophysiological underpinnings of negative emotion processing and emotion regulation in individuals with excess weight compared to normal-weight controls. Fifteen participants with excess-weight (body mass index >25) and sixteen normal-weight controls (body mass index 18-25) performed an emotion-regulation task during functional magnetic resonance imaging. Participants were exposed to 24 negative affective or neutral pictures that they were instructed to Observe (neutral pictures), Maintain (sustain the emotion elicited by negative pictures) or Regulate (down-regulate the emotion provoked by negative pictures through previously trained reappraisal techniques). When instructed to regulate negative emotions by means of cognitive reappraisal, participants with excess weight displayed persistently heightened activation in the right anterior insula. Decreased responsivity was also found in right anterior insula, the orbitofrontal cortex and cerebellum during negative emotion experience in participants with excess weight. Psycho-physiological interaction analyses showed that excess-weight participants had decreased negative functional coupling between the right anterior insula and the right dlPFC, and the bilateral dmPFC during cognitive reappraisal. Our findings support contentions that excess weight is linked to an abnormal pattern of neural activation and connectivity during the experience and regulation of negative emotions, with the insula playing a key role in these alterations. We posit that ineffective regulation of emotional states contributes to the acquisition and preservation of excess weight

Brain Volumetric Correlates of Right Unilateral Versus Bitemporal Electroconvulsive Therapy for Treatment-Resistant Depression.

Objective: The selection of a bitemporal (BT) or right unilateral (RUL) electrode placement affects the efficacy and side effects of ECT. Previous studies have not entirely described the neurobiological underpinnings of such differential effects. Recent neuroimaging research on gray matter volumes is contributing to our understanding of the mechanism of action of ECT and could clarify the differential mechanisms of BT and RUL ECT. Methods: To assess the whole-brain gray matter volumetric changes observed after treating patients with treatment-resistant depression with BT or RUL ECT, the authors used MRI to assess 24 study subjects with treatment-resistant depression (bifrontotemporal ECT, N=12; RUL ECT, N=12) at two time points (before the first ECT session and after ECT completion). Results: Study subjects receiving BT ECT showed gray matter volume increases in the bilateral limbic system, but subjects treated with RUL ECT showed gray matter volume increases limited to the right hemisphere. The authors observed significant differences between the two groups in midtemporal and subcortical limbic structures in the left hemisphere. Conclusions: These findings highlight that ECT-induced gray matter volume increases may be specifically observed in the stimulated hemispheres. The authors suggest that electrode placement may relevantly contribute to the development of personalized ECT protocols

Structural covariance of neostriatal and limbic regions in patients with obsessive-compulsive disorder

Background: Frontostriatal and frontoamygdalar connectivity alterations in patients with obsessive-compulsive disorder (OCD) have been typically described in functional neuroimaging studies. However, structural covariance, or volumetric correlations across distant brain regions, also provides network-level information. Altered structural covariance has been described in patients with different psychiatric disorders, including OCD, but to our knowledge, alterations within frontostriatal and frontoamygdalar circuits have not been explored. Methods: We performed a mega-analysis pooling structural MRI scans from the Obsessive-compulsive Brain Imaging Consortium and assessed whole-brain voxel-wise structural covariance of 4 striatal regions (dorsal and ventral caudate nucleus, and dorsal-caudal and ventral-rostral putamen) and 2 amygdalar nuclei (basolateral and centromedial-superficial). Images were preprocessed with the standard pipeline of voxel-based morphometry studies using Statistical Parametric Mapping software. Results: Our analyses involved 329 patients with OCD and 316 healthy controls. Patients showed increased structural covariance between the left ventral-rostral putamen and the left inferior frontal gyrus/frontal operculum region. This finding had a significant interaction with age; the association held only in the subgroup of older participants. Patients with OCD also showed increased structural covariance between the right centromedial-superficial amygdala and the ventromedial prefrontal cortex. Limitations: This was a cross-sectional study. Because this is a multisite data set analysis, participant recruitment and image acquisition were performed in different centres. Most patients were taking medication, and treatment protocols differed across centres. Conclusion: Our results provide evidence for structural network-level alterations in patients with OCD involving 2 frontosubcortical circuits of relevance for the disorder and indicate that structural covariance contributes to fully characterizing brain alterations in patients with psychiatric disorders

Correlatos neurobiológicos de la Terapia Electroconvulsiva en pacientes con Trastorno Depresivo Mayor: estudio de neuroimagen multimodal

[spa] La depresión se caracteriza por la persistencia de pensamientos y emociones negativas que perturban el estado de ánimo, la cognición, la motivación y la conducta del paciente. La Organización Mundial de la Salud ha apuntado que la depresión es uno de los trastornos psiquiátricos más comunes y una de las principales causas de discapacidad en el mundo. En ausencia de una intervención terapéutica exitosa puede convertirse en una enfermedad de curso crónico causando una alteración severa en las actividades diarias de las personas que la padecen. Y, en el peor de los casos, incrementa el riesgo de mortalidad. En este contexto, a pesar de los avances en la comprensión de su fisiopatología, los tratamientos antidepresivos de segunda generación y/o la terapia cognitivo- conductual son solo parcialmente efectivos. Llegado a este nivel de resistencia terapéutica, la terapia electroconvulsiva (TEC) se convierte en un tratamiento alternativo para los pacientes que sufren de depresión resistente al tratamiento (DRT). La TEC es un tratamiento somático consistente en inducir una convulsión tónico-clónica generalizada mediante la administración de un estímulo eléctrico mientras el paciente se encuentra bajo anestesia general. Y, aunque la TEC es una alternativa eficaz bien establecida para los pacientes que sufren de DRT, su mecanismo de acción aún no se conoce por completo lo que limita la optimización y personalización de los programas de intervención. Con el objetivo de aportar una mejor comprensión de las bases neurobiológicas de la TEC en pacientes con DRT la presente tesis incluye (1) un análisis de conectividad funcional (CF) en estado de reposo, (2) un análisis de trayectoria o path analysis, (3) un análisis de morfometría cerebral longitudinal, (4) un análisis de covarianza estructural y (5) un análisis de espectroscopia por resonancia magnética. Los resultados de la presente tesis indican que una disminución temprana de la CF intralímbica da paso a un aumento posterior en la CF límbico-prefrontal, que a su vez se asocia con la mejoría clínica de los pacientes con DRT al final de un ciclo de TEC. Estos resultados sugieren que la respuesta a la TEC implica cambios secuenciales en la CF límbico-prefrontal. Asimismo, la disminución de la CF intralímbica podría constituir un biomarcador temprano de respuesta al tratamiento con TEC. Por otra parte, un aumento del volumen de sustancia gris (SG) en el lóbulo temporal medial (LTM) se asoció con un aumento del volumen de SG en la corteza cingulada anterior rostral, una disminución de la concentración de N-acetil-aspartato (NAA) hipocampal, un aumento de la concentración de Glutamato/Glutamina (Glu/Gln) hipocampal y una mejoría clínica significativa. En este sentido, diferentes cambios neuroplásticos y neuroinflamatorios pueden ser inducidos por la TEC y explicar su mecanismo de acción. Por último, los incrementos del volumen de SG asociados con la TEC se observan específicamente de manera ipsilateral al(a los) hemisferio(s) estimulado(s) (TEC bilateral versus TEC unilateral derecha). Por tanto, los hallazgos neurovolumétricos de la presente tesis parecen relacionarse con la distribución de la densidad de corriente subyacente a la disposición de los electrodos. Además, la TEC bilateral fue más efectiva que la TEC unilateral derecha (89,26% versus 33,41%). En este sentido, la mayor dispersión de la respuesta neuronal tras la estimulación eléctrica parece dar lugar a mayores efectos clínicos antidepresivos.[eng] Despite advances in the understanding of the depression pathophysiology, first- line antidepressant treatments are only partially effective. In this context, electroconvulsive therapy (ECT) has become an effective alternative treatment for patients with treatment-resistant depression (TRD). In order to provide a better understanding of the neurobiological bases of ECT in patients with TRD, the present thesis includes the following longitudinal analyses: resting-state functional connectivity (FC), path analysis, brain morphometry, structural covariance and magnetic resonance spectroscopy. The results indicated that an incipient intralimbic FC decrease gave way to a subsequent limbic-prefrontal FC increase, which in turn, was associated with clinical improvement observed in patients with TRD after the completion of the ECT course. These results suggest that ECT action involves sequential limbic-prefrontal FC changes. Likewise, intralimbic FC decreases could constitute a potential early biomarker of ECT treatment response. On the other hand, increases in gray matter (GM) volume in the medial temporal lobe were associated with a GM volume increase in the perigenual anterior cingulate cortex, a hippocampal N-acetylaspartate concentration decrease, a hippocampal Glutamate+Glutamine concentration increase and significant clinical improvement. In this sense, different neuroplastic and neuroinflammatory changes may be induced by ECT and explain its mechanism of action. Finally, the GM volume increases associated with ECT are specifically observed ipsilateral to the stimulated hemispheres (bilateral ECT versus right unilateral ECT). Accordingly, the brain volumetric findings of the present thesis appear to be related to the current density distribution underlying the specific placement of the electrodes. In addition, bilateral ECT was more effective than right unilateral ECT. In this sense, greater neuronal response dispersion after electrical stimulation seems to lead to greater clinical antidepressant effects

Emotion Regulation and Excess Weight: Impaired Affective Processing Characterized by Dysfunctional Insula Activation and Connectivity

Emotion-regulation strategies are understood to influence food intake. This study examined the neurophysiological underpinnings of negative emotion processing and emotion regulation in individuals with excess weight compared to normal-weight controls. Fifteen participants with excess-weight (body mass index >25) and sixteen normal-weight controls (body mass index 18-25) performed an emotion-regulation task during functional magnetic resonance imaging. Participants were exposed to 24 negative affective or neutral pictures that they were instructed to Observe (neutral pictures), Maintain (sustain the emotion elicited by negative pictures) or Regulate (down-regulate the emotion provoked by negative pictures through previously trained reappraisal techniques). When instructed to regulate negative emotions by means of cognitive reappraisal, participants with excess weight displayed persistently heightened activation in the right anterior insula. Decreased responsivity was also found in right anterior insula, the orbitofrontal cortex and cerebellum during negative emotion experience in participants with excess weight. Psycho-physiological interaction analyses showed that excess-weight participants had decreased negative functional coupling between the right anterior insula and the right dlPFC, and the bilateral dmPFC during cognitive reappraisal. Our findings support contentions that excess weight is linked to an abnormal pattern of neural activation and connectivity during the experience and regulation of negative emotions, with the insula playing a key role in these alterations. We posit that ineffective regulation of emotional states contributes to the acquisition and preservation of excess weight

Emotion Regulation and Excess Weight: Impaired Affective Processing Characterized by Dysfunctional Insula Activation and Connectivity

Emotion-regulation strategies are understood to influence food intake. This study examined the neurophysiological underpinnings of negative emotion processing and emotion regulation in individuals with excess weight compared to normal-weight controls. Fifteen participants with excess-weight (body mass index >25) and sixteen normal-weight controls (body mass index 18-25) performed an emotion-regulation task during functional magnetic resonance imaging. Participants were exposed to 24 negative affective or neutral pictures that they were instructed to Observe (neutral pictures), Maintain (sustain the emotion elicited by negative pictures) or Regulate (down-regulate the emotion provoked by negative pictures through previously trained reappraisal techniques). When instructed to regulate negative emotions by means of cognitive reappraisal, participants with excess weight displayed persistently heightened activation in the right anterior insula. Decreased responsivity was also found in right anterior insula, the orbitofrontal cortex and cerebellum during negative emotion experience in participants with excess weight. Psycho-physiological interaction analyses showed that excess-weight participants had decreased negative functional coupling between the right anterior insula and the right dlPFC, and the bilateral dmPFC during cognitive reappraisal. Our findings support contentions that excess weight is linked to an abnormal pattern of neural activation and connectivity during the experience and regulation of negative emotions, with the insula playing a key role in these alterations. We posit that ineffective regulation of emotional states contributes to the acquisition and preservation of excess weight

Visceral Adiposity and Insular networks: Associations with Food Craving

Background/objectives: Accumulation of visceral adiposity can disrupt the brain’s sensitivity to interoceptive feedback, which is coded in the insula. This study aimed to test the link between visceral fat and the functional connectivity of two insulae regions relevant for eating behavior: the middle-dorsal insula (mIns), which codes homeostatic changes, and the rostral insula (rIns), which codes stable representations of food properties. We also assessed the impact of visceral adiposity-associated insulae networks on food craving. Subjects/methods: Seventy-five adults ranging in weight status (normal and excess weight) underwent resting-state functional magnetic resonance imaging (fMRI) and subjective food craving measures. We examined the association between visceral fat and seed-based functional connectivity of the mIns and the rIns, controlling for BMI, age, and sex, using multiple regressions in SPM8. We also tested if visceral fat mediated the association between insulae connectivity and food craving. Results: Higher visceral adiposity was associated with decreased connectivity between the mIns and a cluster involving the hypothalamus and the bed nucleus of the stria terminalis. Decreased connectivity in this network was associated with greater food craving, a relation mediated by visceral adiposity. Visceral adiposity was also associated with increased connectivity between the mIns and the middle frontal gyri and the right intraparietal cortex, and between the rIns and the right amygdala. Conclusions: Accumulation of visceral adiposity is linked to disrupted functional connectivity within the mIns and rIns networks. Furthermore, the link between the mIns network and food craving is mediated by visceral fat. Findings suggest that visceral fat disrupts insula coding of bodily homeostatic signals, which may boost externally driven food cravings

Competències transversals a la Universitat de Barcelona (Grup de Treball)

El present document és el resultat d’un grup de treball sobre competències transversals constituït des del vicerectorat de política docent de la Universitat de Barcelona. A partir de constatar el repte que l’enfocament de l’aprenentatge per competències suposa per a la UB, es va procedir a la constitució d’un grup de treball composat per persones seleccionades des del PMID pel fet d’haver desenvolupat projectes vinculats al desenvolupament i l’avaluació de competències. Els membre del grup són, per ordre alfabètic, els professors i professores següents: Manuela Alcañiz Zanón, Conxita Amat Miralles, Montserrat Cruells Cadevall, Jaime López Sánchez, Margarita Mauri Álvarez, José Luís Menéndez Varela, Carme Riera i Prunera, Magdalena Rivero García, Pilar Sabater Mateu, Marta Sancho i Planas, Marina Solé Català, Maite Fernández Ferrer (secretària del grup de treball) i Elena Cano García (coordinadora del grup de treball). Aquest equip va debatre sobre el sentit i les implicacions de les competències a diverses reunions de treball, va dissenyar les passes que cal seguir per implementar dissenys curriculars per competències en sessions de treball col·legiat i autònom i va aportar els exemples que cadascú d’ells/es havien creat en el marc dels grups d’innovació docent als què pertanyen. Com a conseqüència de tota aquesta feina s’ha generat aquest document que vol ser un exemple de pràctiques que es poden dur a terme per afavorir el treball de les competències transversals, contribuint així al traspàs cap els dissenys curriculars per competències per a tot el professorat universitari de la UB

Competències transversals a la Universitat de Barcelona (Grup de Treball)

El present document és el resultat d’un grup de treball sobre competències transversals constituït des del vicerectorat de política docent de la Universitat de Barcelona. A partir de constatar el repte que l’enfocament de l’aprenentatge per competències suposa per a la UB, es va procedir a la constitució d’un grup de treball composat per persones seleccionades des del PMID pel fet d’haver desenvolupat projectes vinculats al desenvolupament i l’avaluació de competències. Els membre del grup són, per ordre alfabètic, els professors i professores següents: Manuela Alcañiz Zanón, Conxita Amat Miralles, Montserrat Cruells Cadevall, Jaime López Sánchez, Margarita Mauri Álvarez, José Luís Menéndez Varela, Carme Riera i Prunera, Magdalena Rivero García, Pilar Sabater Mateu, Marta Sancho i Planas, Marina Solé Català, Maite Fernández Ferrer (secretària del grup de treball) i Elena Cano García (coordinadora del grup de treball). Aquest equip va debatre sobre el sentit i les implicacions de les competències a diverses reunions de treball, va dissenyar les passes que cal seguir per implementar dissenys curriculars per competències en sessions de treball col·legiat i autònom i va aportar els exemples que cadascú d’ells/es havien creat en el marc dels grups d’innovació docent als què pertanyen. Com a conseqüència de tota aquesta feina s’ha generat aquest document que vol ser un exemple de pràctiques que es poden dur a terme per afavorir el treball de les competències transversals, contribuint així al traspàs cap els dissenys curriculars per competències per a tot el professorat universitari de la UB