Hippocampal-Neocortical Networks underlying Episodic Memory and their Clinical Relevance in Medial Temporal Lobe Epilepsy

The hippocampus is strongly structurally and functionally connected to one of the core resting state networks of the human brain, the Default Mode Network (DMN). In addition, regions of the DMN are often co-activated with the hippocampus during episodic autobiographical memory (AM) retrieval tasks. Patients with unilateral medial temporal lobe epilepsy (mTLE) are characterized by a reasonably focal damage to the hippocampus and a specific episodic memory deficit, therefore offering the opportunity to examine the impact of hippocampal damage on DMN connectivity and how these disruptions map onto the specific deficit in episodic memory capacity. Together, these findings led to the main focus of the current thesis; that is to examine how hippocampal-neocortical networks underlying episodic memory are affected by mTLE. The first two studies of this thesis focused on resting state DMN connectivity in patients with mTLE, and revealed that functional connectivity between both hippocampi and the posterior part of the DMN, including the posterior cingulate cortex (PCC) was indicative of episodic memory capacity in this patient population. The last two studies of this thesis focused on how the hippocampus is at the center of transient episodic AM networks. In healthy controls, we were able to show that the left hippocampus was connected to different sets of brain regions during different stages of AM retrieval, construction and elaboration. Lastly, this flexible hippocampal-neocortical interplay was hindered in patients with mTLE. Together, we conclude that DMN connectivity reflects episodic memory capacity in patients with mTLE and might be of potential use in the clinical management in this patient population. Additionally, our data provide evidence that episodic memory is supported by an extensive repertoire of flexible, transient hippocampal-neocortical networks and that these dynamic networks extend beyond the regions of the DMN centering on the hippocampus as a major episodic memory hub of the brain.Ph.D