Working memory network dysfunction in bipolar I vs. bipolar II disorder: a systematic review of task-fMRI evidence

Working memory impairment is one of the core cognitive phenotypes in bipolar disorder. However, whether the task-based functional magnetic resonance imaging mechanisms underlying working memory processing are consistent between bipolar disorder type I (BD-I) and type II (BD-II) remains unclear. This systematic review summarizes task-based fMRI evidence, with a focus on characterizing the neural correlates of working memory in BD-II and comparing them with BD-I.

Following the PRISMA 2020 guidelines, PubMed, Embase, and Web of Science were systematically searched for studies published between January 2011 and June 2025. Eligible studies included task-based fMRI investigations in adults using working memory paradigms that separately reported results for BD-I and BD-II. A total of 22 studies were included for qualitative synthesis.

Across 22 task-based fMRI studies, the qualitative evidence suggests potentially different patterns of working-memory network engagement in BD-I and BD-II; however, subtype-specific inference is constrained by the very limited BD-II literature, with only three studies including BD-II samples (one BD-II-only study and two direct BD-I vs BD-II comparisons). In BD-I, studies more often reported altered or less efficient recruitment of executive-control regions/networks and reduced task-related suppression of default-mode regions under higher cognitive load and/or emotional distraction. In BD-II (based on sparse evidence), euthymic samples were generally reported to show relatively preserved recruitment and performance, whereas depressive-state or higher-demand conditions were associated with attenuated load-related upregulation. In a single emotional-interference paradigm, BD-II showed stronger inverse DLPFC-amygdala coupling, which may reflect context-specific modulation of fronto-limbic interactions.

The current task-fMRI literature provides preliminary, hypothesis-generating indications that BD-I and BD-II may not be fully captured by a simple severity-continuum account, but firm subtype-specific conclusions are not yet warranted given the scarcity of BD-II studies and the limited number of direct BD-I/BD-II comparisons. Across studies, BD-I findings have more often been interpreted within neural inefficiency/limited-scalability accounts and reduced task-related DMN suppression, whereas BD-II findings-based on sparse evidence-have been reported as more state- and context-dependent. Larger, harmonized studies with direct BD-I/BD-II comparisons and mood-state stratification are needed to test these provisional patterns.