Working memory (WM) deficits are frequently observed in patients with insomnia disorder (ID), but their neural basis is unclear. Glymphatic dysfunction and disrupted structural-functional coupling have been implicated, yet they have rarely been examined together, particularly in clinical populations.

We conducted a multimodal MRI study in 391 ID patients. Glymphatic function was estimated using the diffusion tensor image analysis along the perivascular space (DTI-ALPS). The SFC was derived by correlating structural connectivity and functional connectivity. WM was measured by the longest span on the digit span backward task. Partial correlations and mediation analyses were performed to examine associations among sleep quality (Pittsburgh Sleep Quality Index, PSQI), DTI-ALPS, SFC, and WM performance.

DTI-ALPS was negatively correlated with PSQI (r = −0.17, p = 0.006), indicating reduced glymphatic clearance with poorer sleep quality. Global SFC was positively associated with DTI-ALPS (r = 0.32, pFDR < 0.001), but not with WM (r = 0.01, p = 0.84). At the network level, SFC within the subcortical network (Sub-SFC) correlated with both DTI-ALPS (r = 0.29, pFDR < 0.001) and WM performance (r = 0.28, pFDR < 0.001). Mediation analysis revealed that DTI-ALPS and Sub-SFC jointly mediated the association between PSQI and WM performance, with a significant indirect effect (indirect effect = −0.074).

This study provides novel evidence that impaired glymphatic clearance and reduced Sub-SFC form key neural pathways linking poor sleep quality to working-memory deficits in ID, and that DTI-ALPS and Sub-SFC may serve as useful biomarkers of cognitive vulnerability.

Working memory deficits are common in mood disorders and severely affect everyday functioning. Serotonin (5-HT) signalling has been implicated in depression and is also involved in cognitive functioning. However, its relevance for working memory remains largely unexplored.

Using positron emission tomography (PET) brain imaging, we investigated the link between working memory and multiple 5-HT brain features in both healthy individuals and patients with mood disorders in a cross-sectional analysis of pooled data-sets.

We used multiple linear regression to test the associations between working memory performance and 5-HT 1B receptor (5-HT1BR) (healthy controls: 28), 5-HT 2A receptor (5-HT2AR) (healthy controls: 116), 5-HT 4 receptor (5-HT4R) (healthy controls: 97, patients: 98) and 5-HT transporter (5-HTT) (healthy controls: 137, patients: 12) PET binding in the frontal cortex. The frontal cortex was chosen as region of interest as it is critical for working memory functions.

There was no association between working memory and 5-HT1BR (p = 0.14), 5-HT2AR (p = 0.99) or 5-HTT (p = 0.80) frontal cortex binding in healthy controls. For the 5-HT4R, we observed a significant interaction effect of group status (p = 0.01), with patients showing a positive association (β = 6.51, p = 0.02) and healthy individuals showing no significant association (p = 0.16).

We found no evidence that key 5-HT receptor systems are associated with working memory performance in healthy individuals, but did observe a positive association for 5-HT4R in patients with mood disorder. We speculate that although 5-HT neurotransmission markers may map onto working memory performance in the healthy state, pathologically altered 5-HT signalling may contribute to working memory deficits in mood disorders, possibly through downstream signalling and/or interactions with other neurotransmitter systems.

Working memory (WM) impairment is a core cognitive deficit in schizophrenia, associated with dysfunction of large-scale brain networks, particularly the triple-network system comprising the default mode, frontoparietal, and salience networks. Given the role of environmental risks like childhood trauma (CT) in cognitive deficits, we investigated whether trauma relates to altered triple-network flexibility and WM in schizophrenia.

We enrolled 190 patients with schizophrenia (SZ) and 117 healthy controls (HCs). Among them, 162 SZ and 99 HCs underwent n-back task-based functional magnetic resonance imaging. We computed temporal variability (TV) in the triple-network connectivity, defining ΔTV as the change between 0-back and 2-back conditions. Subgroup comparisons of ΔTV were conducted within each group based on trauma status. Associations of ΔTV with WM performance and clinical symptoms were examined in SZ, followed by mediation analyses testing whether ΔTV mediates the relationship between trauma and WM.

Among HCs, individuals with childhood trauma showed reduced ΔTV across triple-network connections, whereas no such differences appeared in SZ. In SZ, greater ΔTV within the frontoparietal network (FPN) was correlated with lower positive symptom severity (r = −0.211, p-fdr = 0.046) and better n-back target accuracy (r = 0.303, p-fdr = 0.002). Furthermore, ΔTV within the FPN partially mediated the association between trauma and n-back accuracy.

Our findings highlight the central role of FPN flexibility in mediating childhood trauma’s effect on working memory in schizophrenia. This outlines a key pathway through which an early environmental risk (trauma) translates into cognitive and clinical manifestations in schizophrenia.

Although there are several evidence-based treatments for post-traumatic stress disorder (PTSD), up to half of patients do not experience significant symptom relief. Executive functioning (EF) impairment is believed to impede PTSD recovery and diminish treatment response, but is not directly targeted by traditional treatments. Cognitive training for EF has emerged as a promising treatment alternative for PTSD, but may only benefit certain patients. The present study aimed to identify, validate, and characterize the subgroup of patients with PTSD who respond to an EF training program.

Veterans with PTSD (N = 79) completed neuropsychological tests and a working memory task during functional magnetic resonance imaging scanning, followed by 16 sessions of an EF training program (working memory training [WMT]). Growth mixture modeling identified subgroups based on session-by-session working memory changes. Mixed-effects models then evaluated differences in spatial working memory and PTSD symptom improvement among these subgroups. Finally, the subgroups were compared on baseline neuropsychological performance and neural activity.

Three subgroups were extracted, with one subgroup (labeled low-WM/steep improvement subgroup) exhibiting steeper working memory improvement across training and greater spatial working memory and PTSD symptom improvement following training. The low-WM/steep improvement subgroup was uniquely characterized by a combination of lower EF task performance and lower working memory-related neural activity at baseline.

WMT may be a promising alternative PTSD treatment for Veterans with EF impairments. Patients likely to benefit from WMT could be identified using a combination of neuropsychological and neuroimaging assessments, but further research is needed to confirm these indicators.

Functional magnetic resonance imaging (fMRI) has revealed inconsistent neural activity patterns in major depressive disorder (MDD) across cognitive and affective domains, and this study used an activation likelihood estimation (ALE) meta-analysis to examine brain function abnormalities in working memory, reward processing, and emotion processing.

A systematic search was conducted in PubMed, Embase, Web of Science, ScienceDirect, and CNKI for fMRI studies comparing MDD patients with healthy controls (HCs), including data up to 3 December 2024. ALE meta-analysis was performed to examine activation patterns. Jackknife sensitivity analysis, risk of bias, and Newcastle–Ottawa scale were used to assess robustness and publication bias. Meta-regression analyses were conducted to explore the impact of covariates on the results.

Sixty-nine studies (2,073 MDD individuals and 2,009 HCs) were included. MDD individuals showed hyperactivation in the bilateral parahippocampal gyrus, subcallosal gyrus, lentiform nucleus, left claustrum, insula, and anterior cingulate cortex, alongside hypoactivation in the right lentiform nucleus, parahippocampal gyrus, fusiform gyrus, and other regions. Domain-specific analyses revealed working memory-related hyperactivation in the right middle and superior frontal gyrus, reward-related hyperactivation in the bilateral lentiform nucleus, right claustrum, and left caudate, and emotion-related hyperactivation in the bilateral parahippocampal gyrus, bilateral lentiform nucleus, right subcallosal gyrus, right anterior cingulate cortex, and left claustrum. Jackknife sensitivity analysis confirmed robustness, with no significant publication bias or covariate impact.

Aberrant activation in the lentiform and caudate nuclei across reward and emotion tasks suggests striatal dysfunction plays a key role in emotion-motivation interplay, highlighting the striatum as a potential target for future therapies.