Interhemispheric Functional Hypoconnectivity Is an Early Marker of Cortical Epileptogenesis

Area of Science:

• Neuroscience
• Systems Neuroscience
• Epilepsy Research

Background:

• Epilepsy is recognized as a network disorder, prompting increased interest in network-based diagnostic and therapeutic strategies.
• Identifying prognostic markers for epileptogenesis and long-term epilepsy risk post-brain injury remains a critical challenge.

Purpose of the Study:

• To investigate whether intracortical connectivity patterns can indicate early epileptogenic changes in the cortex.
• To explore the role of hemispheric decoupling and reduced synchronization in the initial stages of epileptogenesis.

Main Methods:

• Utilized the audiogenic kindling model in rats, where cortical epileptogenesis is induced by repeated subcortically-driven seizures.
• Applied mutual information and mean phase coherence to electrocorticographic recordings from parietal cortex during interictal and postictal periods.
• Assessed interhemispheric connectivity and synchrony in non-kindled and partially kindled rats, using cortical spreading depolarization (SD) as a marker for early kindling.

Main Results:

• Kindled animals exhibited significantly lower baseline hemispheric connectivity and gamma band synchrony compared to seizure-naive rats.
• Early in the kindling process, seizures induced widespread postictal depression and a marked decrease in hemispheric connectivity.
• Subcortical seizures prior to kindling caused mild postictal depression of gamma oscillations without altering interhemispheric connectivity.

Conclusions:

• Epileptogenesis involves primary network alterations, including sustained and transient hemispheric decoupling and reduced synchronization.
• The breakdown of long-range intracortical communication might represent homeostatic plasticity aimed at limiting epileptogenic network reorganization.
• Resting-state hemispheric hypocoupling is proposed as a potential early marker for epileptogenesis, with seizure-induced SD contributing to postictal events.