Abstracts

Rationale: Nonlesional mesial temporal lobe epilepsy is associated with cognitive deficits those underlying mechanisms presumably can be related to impaired hippocampal integration in the memory network. Hippocampal connectivity can be explored in living human brain by means of intracranial single pulse electrical stimulation (SPES), a method with high spatiotemporal resolution that provides information about cortico-cortical interactions including their directionality. Methods: We investigated directed functional (electrophysiological) connectivity among the structures of the human temporal network focusing on hippocampal interactions with temporal pole, amygdala and parahippocampal gyrus in 21 nonlesional epilepsy patients (10 male, mean age 35 years old), who underwent intracranial recording with multiple depth electrodes for clinical purpose. The patients were separated into two groups depending on the seizure onset zone (SOZ) precisely detected in SEEG: hippocampal SOZ (11 implanted hemispheres) and extrahippocampal SOZ (16 implanted hemispheres). In all patients, repeated bipolar single pulse electrical stimulation with biphasic square wave pulses of 2 ms duration between 2 and 4 mA was conducted via two adjoining contacts at the implanted contact pairs; the evoked responses were recorded from the other cortical contacts. Intratemporal cortical connectivity was measured as a function of the amplitude of cortico-cortical evoked potentials (CCEP). Results: We found reliable reproduction of CCEP with a threshold of 5 SD above pre-stimulus baseline of ongoing activity in all subjects. In the extrahippocampal SOZ group, the obtained evoked potentials displayed significant asymmetry in the strength of bidirectional information flow among the structures of hippocampal network. Reciprocal hippocampal connections were also observed in the hippocampal SOZ group; however, loss of asymmetrical amygdalar-hippocampal functional connectivity with significant decrease of the amygdalar input was detected. Hippocampal connections with temporal pole and parahippocampal gyrus remained asymmetrical and did not differ from the extrahippocampal SOZ group. Conclusions: In the extrahippocampal SOZ group, study of effective connectivity revealed strong asymmetry in reciprocal connections in the human hippocampal network, strongly in agreement with the data from anatomical tracing studies in non-human primates. Although hippocampal connections to temporal pole and parahippocampal gyrus did not alter in the hippocampal SOZ group, absent asymmetry of reciprocal connections between amygdala and hippocampus suggests weakened amygdalar input to the epileptogenic hippocampus. Funding: No funding