Examining the Characteristics of Episodic Memory using Event-related Potentials in Patients with Alzheimer's Disease

The overall goal of the following experiment is to understand differences in brain physiology associated with recognition of pictures versus words in patients with amnestic mild cognitive impairment and Alzheimer's disease. This is achieved by using EEG to measure scalp electrical activity. While patients with Alzheimer's disease are making recognition memory decisions for pictures and words.

To accomplish this, the subject should be prepared for electrode placement and DEG setup and scalps. Spatial localization data should be acquired using a special 3D digitizer. Next, the behavioral memory tasks should be run while raw EEG data are recorded.

Then in order to examine event related potentials related to memory for pictures and words, the raw EEG data must be post-process and averaged into ERP wave forms For each condition, these averaged ERPs can then be statistically compared across conditions. The results obtained in this study show that memorial familiarity or conceptual processing of pictures, but not words, appears to remain intact for patients with Alzheimer's disease compared to healthy, older adults. This is accomplished by examining the early frontal ERP old new effect, which occurs from approximately 300 to 500 milliseconds post stimulus onset.

Hi, I am Brandon Ally, an assistant professor in the Department of Neurology and Director of the Memory Disorders Research Lab at Vanderbilt University. Hi, I'm Aaron Hussey and I'm the lab manager for the Memory Disorders Research Lab. Today we're gonna be showing you some experimental methodology to understand brain physiology in patients with Alzheimer's disease.

This method can help us answer key questions such as what aspects of memory remain intact in these patients, and Aaron will be showing us the methodology today To begin this protocol. First, the EEG equipment that will be used during the experiment must be properly set up here. A 128 channel bios semi active two acquisition system with active electrodes will be used in conjunction with the active two electrode cap to obtain ERP data, assure that the battery is fully charged and attached to the amplifier.

Now, gather all materials necessary for participant setup, including a syringe gel, a tape measure, various sized EEG caps, alcohol swabs, facial electrode stickers, and Velcro straps to secure the electrode cables. Place the stickers on five facial electrodes to ready them for the experiment. Next, turn on both the stimulus presentation computer and the data acquisition computer and set up the software.

In this protocol, ePrime software will be used to present stimuli and acquire the behavioral data bios. Semi-active view will be used to acquire the raw EEG data check to make sure that the amplifier is sending the appropriate trigger codes to the data acquisition computer. To do this first turn on the amplifier in the participant chamber without any electrodes or cables plugged in.

Then open the software on the data acquisition computer and start data acquisition, but do not save. Next, go to the stimulus presentation computer. Open the experiment file, and run the paradigm.

The trigger codes programmed into the experiment file should now appear in the data acquisition software program. When the participant arrives first, explain all study procedures and address any safety concerns, then obtain written consent to assure that the subject fully understands the protocol. Have them report back the protocol in his or her own words.

Have the participant sit comfortably in a medium height, hard backed wooden chair in the experiment room. Then measure to ensure that his or her line of vision to the stimulus display is the standard distance for the experiment. Here, the distance used is 48 inches.

Next, measure the circumference of the participant's head in order to determine which EEG cap should be used. Then ask the participant to remove any jewelry or hair accessories to ensure proper fit of the EEG cap and accurate recording. Also, if the participant wears glasses, it is best to remove them at this point.

Using an alcohol swab, cleanse the participant's skin in the areas where the facial electrodes will be placed. One will be placed on each mastoid, one on each temple, and one directly below the left eye. Next place a small amount of conducting gel onto each facial electrode.

Then remove the backing from the sticker and place them on the participant. Apply a small amount of pressure to ensure that the electrode will stay in place. Now the participant may put his or her glasses back on if needed.

Then place the EEG cap onto the participant's head and fasten the strap under the chin. Next, measure from the nasion to the inion in centimeters. Multiply this measurement by 0.5 to find the midpoint and place electrode, A one here from front to back.

Next measure from the preauricular point on one ear to the other. The midpoint of this measurement is where electrode A one should be placed from side to side. Next, we will acquire a three dimensional representation of electrode positions on the participant's head to control for variability in skull shape between subjects and coregister with MRI data if possible in the future.

Here, the palus Patriot Digitizer locator is first place the localization transmitter under the cap behind the subject's left ear with the excess cord tucked under the chin strap to keep it in place. Then attach the receiver to a wooden chair in a position below the participant's head approximately six inches from the transmitter. Now open the digitizing software and take measurements of electrode locations with the stylus as prompted by the software.

A 3D head model of electrode positions can now be generated using the MR Locator software. Next, except for localization of the raw EEG data. Once the 3D head model for the participant has been verified on the computer display, fill the electrode wells on the cap with the conducting gel.

Then place the electrodes at each predefined location on the active two cap. At this point, it is best to offer older participants a break. This is especially true for patients with Alzheimer's disease who may require frequent breaks to maintain focus and sustained attention to the experimental task.

After the break, plug the cables and facial electrodes into the amplifier. Next offset levels of the electrodes should be checked on the data acquisition. Computer assured that the offset levels are within 25 microvolts.

Once all resistance levels are acceptable and all electrodes are free of artifact, the experiment is ready to be run. In this experiment, bios semi-active use software is used to acquire and view the raw EEG data. To begin load the behavioral data presentation file and enter the participant number.

The experimental software saves the participant's responses and automatically generates a data file. Once the experiment finishes running, check to ensure the participant is seated 48 inches from the center of the display monitor. Once the experiment is loaded, read and verify the behavioral instructions with the participant.

Now begin saving raw EEG data on the acquisition computer. Then start the stimulus delivery. On the stimulus presentation computer.

Have a researcher ready to work with older adults or patients with cognitive impairment to input responses via the button box here. This experiment begins with the study phase in which the participant will be presented with either a series of pictures or words, monitor the participant during the behavioral task and assess the need for breaks. Once all behavioral stimuli have been presented, be sure to save the raw EEG data file.

Next, the previous steps will be repeated for the test phase in which the participant will again be presented with either a series of pictures or words During the test phase, half of the items presented will be from the previous study phase, and half of the items will be novel. Participants will identify if the items are old or new by reporting their answer aloud to the researcher. The researcher will then input the participant's response via the button box to begin data post processing.

The raw data must first be prepared and digitally filtered to remove noise and artifact from the signal before analysis can be completed here. EMSE Suite 5.3 software is used first. Temporal filters such as infinite impulse response and band pass filters must be applied.

Next, the data must be referenced to some point on the head here, the common average reference is selected. Next, the data must be filtered spatially and any bad channels should be interrelated. Perform visual inspection of the data and use appropriate filters.

Finally, ocular artifact correction methods must be utilized to correct the signal for eye blink and eye movement artifacts. Here we see frontal ERP activity associated with the successful retrieval of words and pictures For patients with very mild Alzheimer's disease and healthy older controls. These images were taken during the 300 to 500 millisecond time interval, typically associated with conceptual processing or memorial familiarity.

Notice the similar frontal old new effect for pictures, but diminished effect for words between groups. So after you've finished analyzing the brain responses for old and new responses, then you can subsequently easily do statistics to compare groups of patients with Alzheimer's disease to healthy older adults. It's important to remember when doing this technique that patients tend to move around and talk a lot, creating unwanted artifact in the signal.

So it's important to remember to include enough trials so that if you have to throw out any trials for that unwanted artifact, that you have enough to do reliable statistics. Thanks for watching.