Brain Network Dysfunction in Poststroke Delirium and Spatial Neglect: An fMRI Study

Abstract

Background and purpose: Delirium, an acute reduction in cognitive functioning, hinders stroke recovery and contributes to cognitive decline. Right-hemisphere stroke is linked with higher delirium incidence, likely, due to the prevalence of spatial neglect (SN), a right-brain disorder of spatial processing. This study tested if symptoms of delirium and SN after right-hemisphere stroke are associated with abnormal function of the right-dominant neural networks specialized for maintaining attention, orientation, and arousal.

Methods: Twenty-nine participants with right-hemisphere ischemic stroke undergoing acute rehabilitation completed delirium and SN assessments and functional neuroimaging scans. Whole-brain functional connectivity of 4 right-hemisphere seed regions in the cortical-subcortical arousal and attention networks was assessed for its relationship to validated SN and delirium severity measures.

Results: Of 29 patients, 6 (21%) met the diagnostic criteria for delirium and 16 (55%) for SN. Decreased connectivity of the right basal forebrain to brain stem and basal ganglia predicted more severe SN. Increased connectivity of the arousal and attention network regions with the parietal, frontal, and temporal structures in the unaffected hemisphere was also found in more severe delirium and SN.

Conclusions: Delirium and SN are associated with decreased arousal network activity and an imbalance of cortico-subcortical hemispheric connectivity. Better understanding of neural correlates of poststroke delirium and SN will lead to improved neuroscience-based treatment development for these disorders. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03349411.

Keywords: MRI, functional; attention; basal ganglia; delirium; incidence; ischemic stroke; prevalence.

Figures

Figure 1.

Study timeline. Patients with first-ever ischemic stroke were enrolled 24.6 days post-stroke. Functional disabilities due to spatial neglect were assessed using KF-NAP within 5 business days of hospital admission. Delirium and spatial neglect assessments were conducted within 1 week and MRI within 10.4 days of study enrollment.

Figure 2.

Results overview. A. Stroke lesion overlay. Areas of greater lesion overlap appear in green-red. B. Group rsFC associated with delirium and SN severity. C. Sample correlation plots of significant rsFC-syndrome severity associations. Plots constructed using peak voxel beta-weights from participant-level analysis and BIT-c and CAM-S z-scores, shaded areas represent 95% confidence intervals. Significance was established using group-level general linear model with non-parametric cluster-level correction (p