Objective:

To investigate the impact of subarachnoid hemorrhage (SAH) on neuronal and hemodynamic measures of resting state functional connectivity after SAH and assess its correlation with behavioral deficits. 

Background:

Survivors of SAH suffer from persistent neurocognitive deficits even in the absence of structural brain injury. There is evidence to suggest that long range functional neuronal networks may play a role in the mechanism of these deficits but testing this mechanism is difficult due to human study constraints. 

Design/Methods:

We used neuronal Thy1-GCaMP6f mice which express a calcium fluorophore in excitatory cortical neurons to simultaneously examine neuronal and hemodynamic connectivity under tribromoethanol anesthesia. We calculated several connectivity metrics including a bihemispheric connectivity index (BCI) to determine the overall connectivity between homotopic regions on each hemisphere. We assessed neurocognitive performance with the Barnes maze. 

Results:

Mice with SAH showed significant deficits in neuronal and hemodynamic resting state functional connectivity. The z-transformed correlation between GCaMP and oxy-hemoglobin fluctuations was 1.29 ± 0.17 before and 1.09 ± 0.23 after SAH (p=0.0096, n=16). The BCI using the neuronal signal was 1.01 ± 0.21 before and 0.81 ± 0.19 after SAH (p=0.01). The hemodynamic BCI was 1.10 ± 0.17 before and 0.85 ± 0.13 after SAH (p=0.003). Barnes maze testing in saline (n=7) vs. SAH (n=8) mice revealed differences in secondary escape times (44 vs. 165 sec, p=0.001) and errors (2.3 vs. 15.1, p=0.01). 

Conclusions:

SAH leads to deficits in neuronal and hemodynamic connectivity and associated behavioral deficits. These results provide insight into potential neuronal mechanisms underlying neurocognitive deficits in SAH patients.