Alteraciones neurales persistentes en trastorno bipolar: Estudio de neuroimagen con pacientes eutímicos

Abstract

Introduction: The bipolar disorder is a severe mental disorder with a tendency to chronicity characterized by pathologic mood fluctuations between major depressive episodes and episodes of mania and/or hypomania, interspersed with periods of euthymia. Together with these affective symptomatology, bipolar patients also present cognitive deficits that persist even when they are in clinical remission. Even though the use of neuroimaging techniques has provided us with a way to study the alterations related with this disorder, the neurobiological mechanisms of this pathology are not yet clearly defined. A better understanding of the brain characteristics of bipolar patients during euthymia would allow us to define what alterations are related with cognitive symptoms and the susceptibility to relapse into new affective episodes. Objectives: Expand the existing knowledge of structural and functional brain alterations in patients with bipolar depression in clinic remission and assess its relationship with cognitive impairment. Methods: 27 patients with bipolar disorder in clinical remission and 25 healthy participants were included in the study. As components of a multimodal neuroimaging study, participants underwent sequences of structural (T1) magnetic resonance imaging (MRI), diffusion weighted imaging (DWI) and functional MRI (BOLD) during paradigms of working memory (n-back) and self-processing (Self). Participants were assessed with a neuropsychological battery to evaluate the cognitive domains of attention and working memory, processing speed, verbal memory, visual memory and executive function. Group comparisons (ANCOVA) were performed for the grey matter volumes of cortical and subcortical regions defined with FreeSurfer software. Similarly, group differences (t-test) were assessed for diffusion metrics within white matter tracts defined with tractography software TRACULA. Regarding brain function, we performed group comparisons (t-test) exploring for differences in brain activation patterns related to working memory load (2-back > 1-back) and self-processing (Self condition > Control condition). Finally, correlations (Pearson) were explored between structural alterations detected in bipolar disorder and the cognitive performance of patients within the 5 cognitive domains assessed. Results: At a functional level, patients with bipolar disorder, in comparison to healthy participants, presented an increased activation of the ventromedial prefrontal cortex (vmPFC) during a working memory task and an increased activation of the dorsal prefrontal cortex (dlPFC-dmPFC) during a task of self-processing. Regarding structural differences, patients showed higher values of grey matter volumes of the left fusiform gyrus and the bilateral parahippocampal gyrus as well as increased ventricular volumes in comparison to healthy participants. On the other hand, no significative differences were found in diffusion metrics. Grey matter volumes of the left fusiform and parahippocampal gyri were correlated with a better executive function. Limitations: Small sample size. Conclusions: We replicated previous findings of a lack of deactivation within the default mode network in euthymic patients with bipolar disorder during tasks of working memory. Our research is the first to find an increased activation of the central executive network in a self-processing task, which represents the complementary result. We suggest both results might be reflecting a common endophenotype of a disrupted sincronization/anticorrelation between these two networks. The values of grey matter volume within the medial temporal lobe, increased in patients, suggest an adaptive mechanism that might promote the conservation of executive functions in bipolar disorder.

Date of Award	13 Dec 2023
Original language	Spanish
Supervisor	Narcis Cardoner Alvarez (Director), Marta Subira Coromina (Director) & Marta Cano Català (Director)