Investigating Disruptions in Information Flow due to Sickle Cell Disease Using Granger Causality

Area of Science:

• Neuroscience
• Neuroimaging
• Systems Neuroscience

Background:

• Sickle cell disease (SCD) is an inherited blood disorder causing chronic complications, including cognitive decline, particularly affecting executive functions.
• Neuroimaging reveals structural and functional brain abnormalities in SCD, but the directionality of information flow and its link to cognitive deficits are poorly understood.

Purpose of the Study:

• To investigate effective connectivity and information flow directionality between brain regions and resting-state networks in adult patients with SCD using Granger causality (GC) analysis.
• To explore how disruptions in brain network interactions contribute to cognitive deficits in SCD.

Main Methods:

• Employed ultra-high-field 7T MRI in 51 adult SCD patients and 44 matched controls.
• Utilized Granger causality (GC) analysis for whole-brain network and specific network (DMN, ECN, DAN, VAN) analyses, assessing both magnitude and directionality of information flow.
• Conducted subtype analysis for mild vs. severe SCD and multiple regression to correlate network measures with cognitive performance.

Main Results:

• SCD patients showed a higher magnitude of information flow at the brain region level compared to controls.
• Significantly greater afferent flow from the dorsal attention network (DAN) and ventral attention network (VAN) to the executive control network (ECN) was observed in SCD patients.
• Severe SCD patients exhibited higher information flow magnitude and distinct afferent flow patterns to ECN compared to mild SCD patients and controls, with controls showing higher R² values in regression analyses, indicating reduced network efficiency in SCD.

Conclusions:

• This study is the first to apply GC-based effective connectivity analysis in SCD, revealing unique information exchange pathways.
• Altered network dynamics, particularly increased afferent flow to the ECN, may represent compensatory mechanisms for SCD-related brain disruptions.
• Findings highlight the importance of investigating network-level dynamics to understand SCD's impact on brain organization and cognitive function.