Pathological amygdala activation during working memory performance: Evidence for a pathophysiological trait marker in bipolar affective disorder

Abstract

Recent evidence suggests that deficits of working memory may be a promising neurocognitive endophenotype of bipolar affective disorder. However, little is known about the neurobiological correlates of these deficits. The aim of this study was to determine possible pathophysiological trait markers of bipolar disorder in neural circuits involved in working memory. Functional magnetic resonance imaging was performed in 18 euthymic bipolar patients and 18 matched healthy volunteers using two circuit-specific experimental tasks established by prior systematic neuroimaging studies of working memory. Both euthymic bipolar patients and healthy controls showed working memory-related brain activations that were highly consistent with findings from previous comparable neuroimaging studies in healthy subjects. While these patterns of brain activation were completely preserved in the bipolar patients, only the patients exhibited activation of the right amygdala during the articulatory rehearsal task. In the same task, functional activation in right frontal and intraparietal cortex and in the right cerebellum was significantly enhanced in the patients. These findings indicate that the right amygdala is pathologically activated in euthymic bipolar patients during performance of a circuit-specific working memory task (articulatory rehearsal). This pathophysiological abnormality appears to be a trait marker in bipolar disorders that can be observed even in the euthymic state and that seems to be largely independent of task performance and medication.

Sustained attention in psychosis: Neuroimaging findings

“…During emotional tasks, an altered functioning of the amygdala in BD has been extensively reported, especially in manic patients [100][101][102][103] , but also during depressive [104] and euthymic states [105,106] of the illness. An important finding highlighted by the current review is that an augmented activation of the amygdala was observed also during attention tasks without any emotional components, this results suggesting that emotional limbic areas may interfere with cognition in BD [107] . In our systematic review we reported that an altered functioning of the insula during sustained attention task was frequently found in both Schizophrenia and Bipolar Disorder.…”

Assessing Working Memory via N-Back Task in Euthymic Bipolar I Disorder Patients: A Review of Functional Magnetic Resonance Imaging Studies

“…Indeed, many of the aforementioned cognitive deficits were found to persist during euthymic phases [5,6,7,8], often being responsible for partial interepisodic functional recovery [9,10]. For such reasons, a growing body of evidence suggests that they may be considered as trait biomarkers, rather than as state variables of illness [11,12]. …”

Gender Differences in Verbal and Visuospatial Working Memory Performance and Networks

“…While, for instance, our own work group was able to consistently show a dissociation of the neural networks underlying the verbal and visuospatial component of WM [2,6,7,8,9,10] when using a Sternberg Item Recognition Task [11], other researchers did not confirm such a domain-specific organization when using the less process-specific N-back WM task [12,13]. The most comprehensive meta-analysis so far [14] included 189 WM functional magnetic resonance imaging (fMRI) experiments on healthy subjects trying to integrate the heterogeneous body of literature.…”

“…The investigation of this essential cognitive function not only promotes insight into basic functions of the healthy brain but also into the pathophysiological processes involved in multiple neurological [1] and psychiatric disorders [2,3,4]. …”