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Prefrontal cortical activation during working memory task anticipation contributes to discrimination between bipolar and unipolar depression.

ABSTRACT: Distinguishing bipolar disorder (BD) from major depressive disorder (MDD) is clinically challenging, especially during depressive episodes. While both groups are characterized by aberrant working memory and anticipatory processing, the role of these processes in discriminating BD from MDD remains unexplored. In this study, we examine how brain activation corresponding to anticipation of and performance on easy vs. difficult working memory tasks with emotional stimuli contributes to discrimination among BD, MDD, and healthy controls (HC). Depressed individuals with BD (n = 18), MDD (n = 23), and HC (n = 23) were scanned while performing a working memory task in which they had to first anticipate performance on 1-back (easy) or 2-back (difficult) tasks with happy, fearful, or neutral faces, and then, perform the task. Anticipation-related and task-related brain activation was measured in the whole brain using functional magnetic resonance imagining. We used an elastic-net regression for variable selection, and a random forest classifier for BD vs. MDD classification. The former selected the activation differences (1-back minus 2-back) in the lateral and medial prefrontal cortices (PFC) during task anticipation and performance on the working memory tasks with fearful and neutral faces as variables relevant for BD vs. MDD classification. BD vs. MDD were classified with 70.7% accuracy (p < 0.01) based on the neuroimaging measures alone, with 80.5% accuracy (p = 0.001) based on clinical measures alone, and with 85.4% accuracy (p < 0.001) based on clinical and neuroimaging measures together. These findings suggest that PFC activation during working memory task anticipation and performance may be an important biological marker distinguishing BD from MDD.

SUBMITTER: Manelis A

PROVIDER: S-EPMC7162920 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Bipolar disorder is often misdiagnosed as major depressive disorder, which leads to inadequate treatment. Depressed individuals versus healthy control subjects, show increased expectation of negative outcomes. Due to increased impulsivity and risk for mania, however, depressed individuals with bipolar disorder may differ from those with major depressive disorder in neural mechanisms underlying anticipation processes. Graph theory methods for neuroimaging data analysis allow the identification of connectivity between multiple brain regions without prior model specification, and may help to identify neurobiological markers differentiating these disorders, thereby facilitating development of better therapeutic interventions. This study aimed to compare brain connectivity among regions involved in win/loss anticipation in depressed individuals with bipolar disorder (BDD) versus depressed individuals with major depressive disorder (MDD) versus healthy control subjects using graph theory methods. The study was conducted at the University of Pittsburgh Medical Center and included 31 BDD, 39 MDD, and 36 healthy control subjects. Participants were scanned while performing a number guessing reward task that included the periods of win and loss anticipation. We first identified the anticipatory network across all 106 participants by contrasting brain activation during all anticipation periods (win anticipation + loss anticipation) versus baseline, and win anticipation versus loss anticipation. Brain connectivity within the identified network was determined using the Independent Multiple sample Greedy Equivalence Search (IMaGES) and Linear non-Gaussian Orientation, Fixed Structure (LOFS) algorithms. Density of connections (the number of connections in the network), path length, and the global connectivity direction ('top-down' versus 'bottom-up') were compared across groups (BDD/MDD/healthy control subjects) and conditions (win/loss anticipation). These analyses showed that loss anticipation was characterized by denser top-down fronto-striatal and fronto-parietal connectivity in healthy control subjects, by bottom-up striatal-frontal connectivity in MDD, and by sparse connectivity lacking fronto-striatal connections in BDD. Win anticipation was characterized by dense connectivity of medial frontal with striatal and lateral frontal cortical regions in BDD, by sparser bottom-up striatum-medial frontal cortex connectivity in MDD, and by sparse connectivity in healthy control subjects. In summary, this is the first study to demonstrate that BDD and MDD with comparable levels of current depression differed from each other and healthy control subjects in density of connections, connectivity path length, and connectivity direction as a function of win or loss anticipation. These findings suggest that different neurobiological mechanisms may underlie aberrant anticipation processes in BDD and MDD, and that distinct therapeutic strategies may be required for these individuals to improve coping strategies during expectation of positive and negative outcomes.

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Prefrontal cortical activation during working memory task anticipation contributes to discrimination between bipolar and unipolar depression.

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