In this longitudinal neuroimaging study, we compared post-stroke changes in neuronal connectivity in patients with ischemic versus hemorrhagic stroke. Several cross-sectional and serial connectivity imaging studies have been reported in patients with ischemic stroke (12, 18, 19, 22, 27). However, to the best of our knowledge, this is the first longitudinal imaging study that evaluated DMN and SMN connectivity in both hemorrhagic and ischemic stroke patients. Our results showed that regardless of stroke type, every patient exhibited not only significant disruption in connectivity between the DMN and SMN, but also a global reduction among several brain networks. As compared to healthy controls, both ischemic and hemorrhagic stroke patients did not have expected negative correlations between the DMN and SMN at 1M. Furthermore, the decrease in connectivity in the positively correlated regions in the SMN and DMN were different between the two stroke types. For example, connectivity strength in the superior, left and right lateral SMN attenuated in the hemorrhagic patients, whereas it increased in ischemic stroke patients when compared to the healthy controls at 1M, as shown in Fig. 2. As compared to healthy controls, both IS and ICH patients exhibited a reduction in connectivity in most of the DMN regions at 1M. However, when comparing the two types of strokes, the ischemic patients had no connectivity between the medial prefrontal cortex and left lateral parietal regions of the DMN. The connectivity between the medial prefrontal cortex and posterior cingulate cortex was not affected in hemorrhage patients, but it decreased in ischemic patients. Connectivity between left and right parietal regions was unaffected in the ischemic stroke patients, but it decreased in hemorrhagic stroke. Our findings are in line with several post-stroke connectivity studies that reported acute decline or disruption in global connectivity regardless of ischemic or hemorrphagic stroke severity. However, Liu et al 2020 reported that this disruption in connectivity varies with ischemic lesion location. (22, 38–40)
The variance in interconnectivity change in individual participants substantiates the role of lesion size and location as shown in one of the IS patients (P06) with the biggest lesion volume who exhibited no improvement in interconnectivity over time. Another IS patient (P02) with the smallest pontine lesion showed a significant improvement in interconnectivity between 1M and 3M and then declined between 3M and 12M. Interestingly, one of the ICH patients (P2), who also developed an ischemic pontine lesion between 1M and 3M showed an opposite interconnectivity change as compared to the IS patient (P02). It is difficult to explain or speculate about the reasons for these changes due to pontine lesion. Temporally, both IS and ICH patients displayed an increase in negatively correlated connectivity between the DMN and SMN. However, this increase varied between the two types of stroke. The ischemic stroke patients displayed far more interconnectivity between the two networks as compare to hemorrhagic patients. The ischemic stroke patients exhibited strong connectivity between the left and right parietal region of the DMN to the left lateral sensory-motor, which was not observed in hemorrhagic stroke patients at 12 months. The hemorrhagic patents also lacked a connection between the right parietal and right sensory-motor cortex. Interestingly, as compared to IS patients, despite a significant reduction in hematoma volume, ICH patients exhibited a lesser magnitude of connectivity at 12M. However, our results are in contrast with a previous serial study that reported a significant increase in interhemispheric connectivity in hemorrhagic stroke as compared to ischemic stroke over 6 months (41). These differences could be due to lesion size, location, or different seed regions. This prior study investigated connectivity between the interior frontal cortex and motor-related regions whereas we investigated changes between the SMN and DMN. However, this variation in connectivity among studies could be due to several key factors such as age, gender, stroke severity, inclusion of both hemorrhagic and ischemic stroke, lesion size, and location, etc. Most of these studies including ours have small sample sizes.
In patients with ischemic stroke, our results are consistent with a previous longitudinal study that reported an increase in synchronization between the DMN and SMN after rehabilitation (21). Overall, the most consistent finding was the significant disruption in both local and global brain network connectivity in the acute phase, which strengthens during post-stroke recovery (19, 22, 23, 38); however, the role of interhemispheric connectivity remains controversial. Our data showed an increase in both inter and intrahemispheric connectivity whereas Park et al 2013 reported higher ipsilesional connectivity in the frontal and parietal cortices while Jungsoo Lee et al 2018 reported no change in intrahemispheric connectivity after stroke (33, 41, 42).
In conclusion, both IS and ICH stroke patients exhibited interconnectivity disruption between the DMN and SMN despite differences in pathology and location between the types of injuries. The restoration of the connectivity between these two networks was more prominent in ischemic stroke patients. Despite a significant decrease in hematoma volume as compared to the infarct lesion volume, ICH patients showed a weaker interaction between the DMN and SMN after one year. More detailed clinical assessments will be necessary in future studies to assess the clinical impact of disruption and restoration on interconnectivity between the DMN and SMN.