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Cognitive training may partially reverse cognitive deficits in people with HIV (PWH). Previous functional MRI (fMRI) studies demonstrate that working memory training (WMT) alters brain activity during working memory tasks, but its effects on resting brain network organization remain unknown.

To test whether WMT affects PWH brain functional connectivity in resting‐state fMRI (rsfMRI).

Prospective.

A total of 53 PWH (ages 50.7 ± 1.5 years, two women) and 53HIV‐seronegative controls (SN, ages 49.5 ± 1.6 years, six women).

Axial single‐shot gradient‐echo echo‐planar imaging at 3.0 T was performed at baseline (TL1), at 1‐month (TL2), and at 6‐months (TL3), after WMT.

All participants had rsfMRI and clinical assessments (including neuropsychological tests) at TL1 before randomization to Cogmed WMT (adaptive training,n = 58: 28 PWH, 30 SN; nonadaptive training,n = 48: 25 PWH, 23 SN), 25 sessions over 5–8 weeks. All assessments were repeated at TL2 and at TL3. The functional connectivity estimated by independent component analysis (ICA) or graph theory (GT) metrics (eigenvector centrality, etc.) for different link densities (LDs) were compared between PWH and SN groups at TL1 and TL2.

Two‐way analyses of variance (ANOVA) on GT metrics and two‐samplet‐tests on FC or GT metrics were performed. Cognitive (eg memory) measures were correlated with eigenvector centrality (eCent) using Pearson's correlations. The significance level was set atP < 0.05 after false discovery rate correction.

The ventral default mode network (vDMN) eCent differed between PWH and SN groups at TL1 but not at TL2 (P = 0.28). In PWH, vDMN eCent changes significantly correlated with changes in the memory ability in PWH (r = −0.62 at LD = 50%) and vDMN eCent before training significantly correlated with memory performance changes (r = 0.53 at LD = 50%).

ICA and GT analyses showed that adaptive WMT normalized graph properties of the vDMN in PWH.

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