Altered functional connectivity after pilocarpine-induced seizures revealed by intrinsic optical signals imaging in awake mice

Abstract

SIGNIFICANCE: Comorbidities such as mood and cognitive disorders are often found in individuals with epilepsy after seizures. Cortex processes sensory, motor, and cognitive information. Brain circuit changes can be studied by observing functional network changes in epileptic mice's cortex. AIM: The cortex is easily accessible for non-invasive brain imaging and electroencephalogram recording (EEG). However, the impact of seizures on cortical activity and functional connectivity has been rarely studied in vivo. APPROACH: Intrinsic optical signal and EEG were used to monitor cortical activity in awake mice within 4 h after pilocarpine induction. It was divided into three periods according to the behavior and EEG of the mice: baseline, onset of seizures (onset, including seizures and resting in between seizure events), and after seizures (post, without seizures). Changes in cortical activity were compared between the baseline and after seizures. RESULTS: Hemoglobin levels increased significantly, particularly in the parietal association cortex (PT), retrosplenial cortex (RS), primary visual cortex (V1), and secondary visual cortex (V2). The network-wide functional connectivity changed post seizures, e.g., hypoconnectivity between PT and visual-associated cortex (e.g., V1 and V2). In contrast, connectivity between the motor-associated cortex and most other regions increased. In addition, the default mode network (DMN) also changed after seizures, with decreased connectivity between primary somatosensory region (SSp) and visual region (VIS), but increased connectivity involving anterior cingulate cortex (AC) and RS. CONCLUSIONS: Our results provide references for understanding the mechanisms behind changes in brain circuits, which may explain the profound effects of seizures on comorbid health conditions.