In vivo human hippocampal cingulate connectivity: a corticocortical evoked potentials (CCEPs) study

Objective: To investigate the human limbic system using cortico-cortical evoked potential (CCEP), which reveals the brain networks.

Methods: Five patients with nonlesional medically intractable focal epilepsy with ictal onset outside the limbic system were enrolled. All patients underwent stereoelectroencephalogram electrode implantation in order to delineate the epileptogenic zone. Alternating 1Hz electrical stimuli were delivered to the hippocampus and posterior cingulate gyrus. A total of sixty stimuli were averaged in each trial to obtain CCEP responses.

Results: Hippocampal stimulation elicited prominent CCEP responses in the posterior cingulate gyrus. The latencies of early (N1) and late (N2) negative peak ranged 20-60 ms and 102-175 ms respectively. In addition, CCEP responses were observed in the posterior parahippocampal gyrus, medial superior frontal gyrus (SFG) and orbitofrontal cortex. Stimulation of posterior cingulate contacts induced CCEPs in the hippocampus with N1 and N2 latencies of 25-43 ms and 90-234 ms respectively in all five patients.

Conclusion: This finding supports the assertion that the hippocampus is connected with the posterior cingulate gyrus, posterior parahippocampal gyrus, medial SFG and orbitofrontal cortex. The hippocampus and posterior cingulate gyrus have a bidirectional network through the cingulum.

Significance: The present study provides new insight into the human limbic network.