Introduction: Accurate localization of depth electrodes within the CA3 and CA1 subfields of the hippocampus is critical for the detailed analysis of the neuronal circuitry and potential future applications in memory restoration. Prior human clinical studies of depth electrode localization were based solely on imaging, a method limited by the imaging resolution. Preclinical studies revealed that hippocampal CA3 and CA1 principal cells exhibit firing rate peaks during the sample phase of the delayed-match-to-sample (DMS) task in rodents and nonhuman primates. Interneurons and dentate granule cells do not respond to task events in this manner. We hypothesize that precise localization of electrode placement within the CA3 and CA1 subfields of the hippocampus can be verified by combining post-operative high-resolution MRI imaging with task related analysis of neuronal firing patterns.
Methods: Eleven adult patients with medically-refractory epilepsy underwent stereotactic electrode placement for seizure localization. Each had at least one electrode placed within the head of the hippocampus and agreed to participate in this study. Electrode placement was first confirmed using post-operative, high-resolution 3T MRI. Neuro-cognitive tasks were then performed in 8 patients, consisting of image sample presentation with DMS response. Accurate placement within the CA3 and CA1 subfields was assessed through single unit neuronal firing patterns and CA3 to CA1 pairwise correlograms in response to sample image and match presentation.
Results: Pairwise correlations were used to confirm simultaneous or feedforward activation of proposed CA3 and CA1 neurons. In two patients, one electrode was determined to have missed the CA3 and CA1 layers.
Conclusions: Electrode locations putatively identified as CA3 vs. CA1 (on the basis of probe morphology and post-operative MRI) were confirmed to exhibit feedforward correlation consistent with CA3-to-CA1 projections between neurons recorded from those locations. Precise localization of electrode placement within the specified hippocampal subfields was, therefore, verified.
Patient Care: Precise localization of depth electrodes within the CA3 and CA1 subfields of the hippocampus is critical to the study of neuronal circuitry within the hippocampus and for potential development of prosthetics for memory restoration. Current methods of electrode localization based on imaging alone do not adequately verify electrode placement within the specified cell layers. Localization of electrode placement within the CA3 and CA1 subfields of the hippocampus may be verified by combining post-operative high-resolution MRI imaging with task related analysis of neuronal firing patterns.
Learning Objectives: By the conclusion of this session, participants should:
1) Describe the challenges of identifying of depth electrode localization within specified cell layers.
2) Be able to discuss the feedforward correlation of CA3 to CA1 subfields within the hippocampus and how to utilize this pattern to verify electrode placement within these subfields.
3) Understand the importance of precise electrode localization in regards to developing potential prosthetics for memory restoration.