Basic Experimental Study of Hippocampal Memory Functions

Overview

This project tests the role of the human hippocampus in providing online representation of episodic content and providing the top-down signals to brain networks for visuospatial attention and visual processing needed to drive visual sampling for the formation of coherent episodic memories. This hypothesis will be tested in several experiments that measure and manipulate hippocampal activity within eye-tracking tasks designed to isolate the interplay between memory and visual sampling during memory formation. These experiments will be performed in individuals with epilepsy undergoing neurosurgical procedures as part of clinical care, as this provides invasive recordings of neural activity (intracranial electroencephalography, or "iEEG") from the hippocampus and other regions of interest with temporal resolution that matches the rapid pace of eye movements. The temporal resolution of iEEG is key to addressing the hypotheses concerning how the hippocampus drives visual sampling, in addition to responding to it. Direct electrical stimulation through the iEEG electrodes will also be used to test the necessary role of hippocampal processing in driving active visual sampling. By rigorously testing the role of hippocampus in interaction with large-scale networks during the process of memory formation that occurs via active sampling, this project aims to better understand mechanisms relevant to the disruptions of memory formation that occur in neurological and psychiatric disorders.

This is a basic experimental study performed with human subjects (BESH) that seeks to understand the mechanisms by which the human hippocampus supports visual sampling during episodic memory formation. Research subjects will be assigned to one of six study experiment conditions that each uses different experimental procedures to test a different portion of the mechanistic hypotheses that are the focus of the study. All of the study conditions involve memory experiments performed during eye-movement tracking, with different methods used to assess brain activity during standardized laboratory conditions in relation to the experimental task. Subjects will perform the experiments while their brain activity is recorded via intracranial EEG (iEEG), which is being performed for clinical purposes as part of epilepsy treatment unrelated to the experimental objectives. Study Experiment Condition 1: Subjects with iEEG electrodes implanted will perform an eye-tracking memory task in which they view pictures of naturalistic scenes and later undergo memory testing for these scene pictures. For the memory test, studied scenes will be repeated and presented along with novel (foil) scenes. Subjects will attempt to discriminate studied from novel scenes using button press responses. Eye movements will be remotely (noninvasively) tracked using a camera during both study and test. This memory task will take about 1.5 hours to complete. 20 subjects undergoing iEEG recordings as part of epilepsy treatment will be assigned to this study experiment condition. Study Experiment Condition 2: Subjects with iEEG electrodes implanted will perform an eye-tracking memory task in which they view arrays of everyday objects arranged as a grid and later undergo memory testing for these object image arrays. Half of the object-image arrays are studied actively (subjects view objects in any order they wish) and half are studied passively (viewing patterns are predetermined and subjects must follow along). For the memory test, subjects attempt to pick studied objects from among novel (foil) objects and replace them at studied locations using the computer mouse. Eye movements will be remotely (noninvasively) tracked using a camera during the study phases. This memory task will take about 1.5 hours to complete. 20 subjects undergoing iEEG recordings as part of epilepsy treatment will be assigned to this study experiment condition. Study Experiment Condition 3: The same 20 subjects with iEEG electrodes implanted who perform Study Experiment Condition 2 will perform the same eye-tracking memory task described for Study Experiment Condition 1. For these subjects, high-frequency electrical stimulation will be delivered through the iEEG electrodes on a subset of study trials, with half of stimulated trials receiving stimulation of the hippocampus and the other half receiving stimulation of the amygdala. This memory task will take about 1.5 hours to complete and will be performed on a different day of their inpatient visit than the procedures for Study Experiment Condition 2. Study Experiment Condition 4: The same 20 subjects with iEEG electrodes implanted who perform Study Experiment Condition 1 will perform the same eye-tracking memory task described for Study Experiment Condition 2. For these subjects, high-frequency electrical stimulation will be delivered through the iEEG electrodes on a subset of study trials, with half of stimulated trials receiving stimulation of the hippocampus and the other half receiving stimulation of the amygdala. This memory task will take about 1.5 hours to complete and will be performed on a different day of their inpatient visit than the procedures for Study Experiment Condition 1. Study Experiment Condition 5: Subjects with iEEG electrodes implanted will perform the same eye-tracking memory task as described for Study Experiment Condition 1. This is a different group of iEEG subjects selected based on having iEEG electrodes implanted in the hippocampus as well as in at least one location of the Dorsal Attention Network (DAN), which is a region of interest for the experiment condition. 20 subjects undergoing iEEG recordings as part of epilepsy treatment will be assigned to this study experiment condition. Study Experiment Condition 6: The same group of 20 iEEG subjects that are included in Study Experiment Condition 5 will perform the same eye-tracking memory task as described for Study Experiment Condition 2. This experiment condition will be performed on a different day of the inpatient visit than participation in Study Experiment Condition 5.