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. 2025 May 2:55:e130.
doi: 10.1017/S0033291725001060.

Cognitive and neural abnormalities: working memory deficits in bipolar disorder offspring

Ye Xie  1   2   3 , Wenjin Zou  4 , Yuanqi Shang  3 , Weicong Lu  4 , Xiaoyue Li  4 , Qi Chen  1 , Robin Shao  5 , Yixuan Ku  3   6 , Kangguang Lin  4   7   8
Affiliations

Cognitive and neural abnormalities: working memory deficits in bipolar disorder offspring

Ye Xie et al. Psychol Med. .

Abstract

Background: Offspring of parents with bipolar disorder (BD offspring) face elevated risks for emotional dysregulation and cognitive deficits, particularly in working memory. This study investigates working memory deficits and their neural correlates in BD offspring.

Methods: We assessed 41 BD offspring and 25 age-matched healthy controls (HCs) using a spatial N-back task and task-related functional magnetic resonance imaging (fMRI).

Results: Compared to HCs, BD offspring exhibit reduced accuracy and lower signal-detection sensitivity (d') on the 1-back task. fMRI reveals hyperactivation in the right intracalcarine cortex/lingual gyrus (ICC/LG) in BD offspring, particularly during the 1-back condition. Psychophysiological interaction (PPI) analyses show reduced connectivity between the right ICC/LG and the left postcentral gyrus in BD offspring as task load increases from 0-back to 1-back. This connectivity positively correlates with 1-back task performance in HCs but not in BD offspring. Additionally, using bilateral dorsolateral prefrontal cortex (DLPFC) as regions of interest, PPI analyses show diminished condition-dependent connectivity between the left DLPFC and the left superior frontal gyrus/paracingulate cortex, and between the right DLPFC and the left postcentral gyrus/precentral gyrus in BD offspring as the task load increases.

Conclusions: These findings suggest that BD offspring exhibit working memory deficits and impaired neural connectivity involving both sensory processing and higher-order cognitive systems. Such deficits may emerge at a genetically predisposed stage of bipolar disorder, underscoring the significance of early identification and intervention strategies.

Keywords: BD offspring; bipolar disorder; functional magnetic resonance imaging; prefrontal cortex; working memory.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1.
Figure 1.
Task design of the spatial N-back working memory paradigm. Illustration of the N-back task structure, highlighting the sequence and timing of stimulus presentation and response requirements for 1-back and 2-back conditions. The inter-stimulus interval (ISI) is indicated.
Figure 2.
Figure 2.
Behavioral performance in the N-back task. (a) Accuracy (ACC) across 0-back and 1-back conditions, demonstrating a significant interaction between task load and group. (b) Reaction time (RT) for the same conditions, with no significant group differences. (c) The d′ measure for 1-back task performance, showing significant between-group differences. *Indicates p < 0.05, Holm’s Bonferroni corrected for multiple comparisons, with age as a covariate.
Figure 3.
Figure 3.
Group differences in brain activation during working memory task. (a) Activation in the right intracalcarine cortex/lingual gyrus (ICC/LG), showing a significant main effect of group. (b) and (c) Enhanced activation in the right ICC/LG during 0-back and 1-back tasks in BD offspring compared to HCs. Abbreviations: ICC, intracalcarine cortex; LG, lingual gyrus; R, right. *, **, *** indicate p < 0.05, p < 0.01, p < 0.001, respectively, Holm’s Bonferroni corrected for multiple comparisons in post-hoc analyses, with age as a covariate.
Figure 4.
Figure 4.
Psychophysiological Interaction (PPI) analysis revealing connectivity differences. (a) and (b) PPI analysis demonstrating significantly higher condition-dependent connectivity between the right ICC/LG and the left postcentral gyrus/precentral gyrus/supramarginal gyrus (postCG/preCG/SMG) in the BD offspring group compared to the HC group during the transition from 0-back to 1-back tasks. Abbreviations: ICC, intracalcarine cortex; LG, lingual gyrus; postCG, postcentral gyrus; preCG, precentral gyrus; SMG, supramarginal gyrus; L, left; R, right.
Figure 5.
Figure 5.
PPI analyses of DLPFC connectivity during task load transition. (a) Targeted area of the left dorsolateral prefrontal cortex (DLPFC). (b) Significant difference in condition-dependent connectivity between the left DLPFC and the left superior frontal gyrus/paracingulate cortex (SFG/paraCC) in BD offspring compared to HCs. (c) Targeted area of the right DLPFC. (d) Significant difference in condition-dependent connectivity between the right DLPFC and the left postcentral gyrus/precentral gyrus (postCG/preCG) in BD offspring compared to HCs. (e) Overlapping central areas (green) between the regions targeted by the right ICC/LG (blue) and the right DLPFC (red). Abbreviations: DLPFC, dorsolateral prefrontal cortex; paraCC, paracingulate cortex; SFG, superior frontal gyrus.
Figure 6.
Figure 6.
Correlation between brain connectivity and behavioral performance. Condition-dependent connectivity between the right ICC/LG and left postCG/preCG/SMG was positively correlated with (a) accuracy and (b) d′ of the 1-back task in HCs but not in BD offspring. Age was used as a covariate. Abbreviations: ACC, accuracy; ICC, intracalcarine cortex; LG, lingual gyrus; postCG, postcentral; preCG, precentral gyrus; SMG, supramarginal gyrus.
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