Source: Laboratories of Jonas T. Kaplan and Sarah I. Gimbel—University of Southern California
Our experience of memory is varied and complex. Sometimes we remember events in vivid detail, while other times we may only have a vague sense of familiarity. Memory researchers have made a distinction between memories that are recollected versus those that are familiar. A recollected item is one that is not only remembered, but carries with it details of the time at which it was learned or encoded. Like a recollected item, a familiar item is also remembered, but is void of any details about the circumstances surrounding its encoding. Many studies of recollection and familiarity have focused on the medial temporal lobe (MTL), specifically the hippocampus, since its involvement in memory encoding, consolidation, and retrieval is well-known and well-studied.1-3
This video shows how to administer the Remember-Know task4 to compare brain activation in these two types of memory retrieval. In this context, remember is another term for recollection, while know refers to memories that are familiar but not explicitly recollected. In this version of the Remember-Know task, participants are exposed to a series of color images, and asked to remember what they see. Inside an fMRI scanner, they will be exposed to both images that were studied and to novel images, and they will make a "remember," "know," or "new" judgment about each image, indicating what kind of memory they have for that item. Following the scan, whole brain and hippocampal activity will be examined to determine differential activity related to recollection and familiarity. This study is based on a study performed by Gimbel and Brewer.5
1. Participant recruitment
- Recruit 20 participants.
- Participants should be right-handed and have no history of neurological or psychological disorders.
- Participants should have normal or corrected-to-normal vision to ensure that they will be able to see the visual cues properly.
- Participants should not have metal in their body. This is an important safety requirement due to the high magnetic field involved in fMRI.
- Participants should not suffer from claustrophobia, since the fMRI requires lying in the small space of the scanner bore.
2. Pre-scan procedures
- Fill out pre-scan paperwork.
- When participants come in for their fMRI scan, instruct them to first fill out a metal screen form to make sure they have no counter-indications for MRI, an incidental-findings form giving consent for their scan to be looked at by a radiologist, and a consent form detailing the risks and benefits of the study.
- Have the participant sit in front of a laptop computer, and show them 256 color pictures of namable objects (e.g., fan, apple, baseball), each for 3 s.
- For each object, the participants press a button to indicate if it was a living or non-living object. This task ensures their attention to the stimuli.
- Prepare participants to go in the scanner by removing all metal from their body, including belts, wallets, phones, hair clips, coins, and all jewelry.
3. Provide instructions for the participant.
- In the scanner, show the participant all 256 pictures that were studied before the scan, and an additional 256 novel pictures.
- Participants judge each picture with "remember", "know", or "novel" responses via an MR-safe button-box.
- Instruct participants to respond "remember" if they saw the image during the study session and could recall specific details about its presentation.
- Instruct participants to respond "know" if the image was familiar but they did not recall specific details about seeing it before.
- Instruct participants to respond "new" if they had not seen the image before.
- Stress to the participant the importance of keeping their head still throughout the scan.
4. Put the participant in the scanner.
- Give the participant ear plugs to protect their ears from the noise of the scanner and ear phones to wear so they can hear the experimenter during the scan, and have them lie down on the bed with their head in the coil.
- Give the participant the emergency squeeze ball and instruct them to squeeze it in case of emergency during the scan.
- Use foam pads to secure the participants head in the coil to avoid excess movement during the scan, and remind the participant that it is very important to stay as still as possible during the scan, as even the smallest movements blur the images.
5. Data collection
- Collect high-resolution anatomical scan.
- Begin functional scanning.
- Synchronize the start of stimulus presentation with the start of the scanner.
- Present pictures via a laptop connected to a projector. The participant has a mirror above their eyes, reflecting a screen at the back of the scanner bore.
- Present each picture for 3 s.
- Picture presentation is interspersed with 1.5-4.5 s of a fixation cross baseline, as this is an event-related task. Differential overlap in the hemodynamic response to each trial makes the signals more separable.
6. Post-scan procedures
- Bring the participant out of the scanner.
- Debrief the participant.
7. Data analysis
- Preprocess the data.
- Perform motion correction to reduce motion artifacts.
- Perform temporal filtering to remove signal drifts.
- Smooth the data to increase signal-to-noise ratio.
- Model the data for each participant.
- Create a model of what the expected hemodynamic response should be for each task condition.
- Fit the data to this model, resulting in a statistical map, where the value at each voxel represents the extent to which that voxel was involved in the task condition.
- Register the participant's brain to a standard atlas in order to combine data across participants.
- Combine statistical maps across subjects for a group-level analysis of the data.
- Threshold the statistical maps, taking into account correction for multiple comparisons. Since statistical tests are performed at every voxel in the brain, we expect a considerable number of false-positive results with standard statistical thresholds. One way to deal with this is to only accept significant voxels if they also occur within a cluster of a given size.
Our experience of memory is varied and complex. Sometimes we can remember events in vivid detail, while other times we may only have a vague sense of familiarity.
The first type, a recollected memory, is one that is remembered with strong details about the time at which it was learned—such as a dining experience the previous evening, where not only was the lobster dinner recalled, but also were the paintings on the wall and the restaurant staff who served you.
On the other hand, a familiar memory is similar to a recollected one in that it is known, but differs in that it is recalled without any explicit details surrounding the event. That is, a familiar memory lacks specifics about the setting, like the waiter who served dinner or what the décor was.
This video demonstrates how to combine functional magnetic resonance imaging—fMRI—with a task called Remember-Know to investigate how the brain—especially the hippocampus—responds to judgments made towards repeated or novel images based on previous work performed by Gimbel and Brewer.
In this experiment, participants are asked to complete two phases: initial encoding and fMRI testing. In part one, encoding, they are exposed to colored pictures of nameable objects, such as an apple, which they must remember.
Following each item’s presentation, a question is asked, promoting participants’ attention during this process.
Afterwards, in the second phase—fMRI testing—participants are placed inside a scanner and, via a projection system, are shown images: those previously observed along with brand new ones.
A fixation cross precedes each picture to optimize the separation of the brain’s hemodynamic responses across the different presentations.
Upon seeing each image, participants are asked to respond in one of three ways: 'remember' if the item can be recalled along with specific details about its presentation; 'know', if it’s familiar but they cannot recall specific details about seeing it before; or 'new', if the object was not seen at all.
In this case, the dependent variable is the intensity of the hemodynamic signal measured after each response type. The extent of activation can then be visualized into clusters of voxels on an anatomical brain scan.
The hippocampus—a region in the medial temporal lobe notably studied in learning and memory studies—is expected to show greater activation during the 'remember' trials than during the 'know' and 'new' trials.
These findings would support a dual-process theory of memory recall, where the hippocampus supports recollection and a different neural region—one outside of the hippocampus—generates familiarity.
For experimental control and safety concerns, recruit participants who are right-handed, with normal or corrected-to-normal vision, no history of psychological disorders or suffering from claustrophobia, and without any metal in their body.
Have them fill out a magnetic resonance screening form, with additional questions related to their health and safety encompassing the scanning session.
Before sending the participant into the scanner, sit in front of a laptop and expose them to objects that they need to remember for the next session. Explain that they will now view 256 color images, each for 3 s. To ensure that they are paying attention, instruct them to press the 'F' key to indicate that an object is living or 'J' if the item is non-living.
After the participant views all of the images, further explain that those pictures, along with an additional 256 novel items, will be shown inside the scanner. Also introduce them to the MR-safe button-box that they will use to classify items—as 'remember', 'know', or 'novel'—when they appear onscreen.
In preparation to enter the scanning room, ask the participant to remove all metal objects from their body, including cell phones, watches or jewelry, wallets, keys, belts, and coins, due to the strong magnetic field. Use a metal detector to verify that no metal items remain.
Next, escort the participant near the scanner. Provide earplugs to protect their ears from loud noises and earphones so that they can hear you during the scan. Have them lie down on the bed with their head in the coil, and secure it with foam pads to avoid excessive movement and blurring during the scan.
Place a mirror above the participant’s eyes to reflect a screen at the back of the scanner bore. Make sure that they are equipped with a squeeze ball in case of an emergency during the scan and the button response box. Also, remind them that it’s very important to keep their head as still as possible throughout the experiment.
After raising the scanner bed, align the participant and send them into the bore. In the adjacent room, collect high-resolution anatomical images before starting the event-related, functional phase. Synchronize the start of the stimulus presentation with the start of the functional scan, and allow the participant to complete 512 trials.
To conclude the session, bring them out of the scanning room. Debrief them by providing an explanation of the study and compensation for their participation.
To begin the analysis, first pre-process the data by performing correction to reduce motion artifacts, temporal filtering to remove signal drifts, and spatial smoothing to increase the signal-to-noise ratio.
Then, create a model of the expected hemodynamic response for each task condition. Fit the data to this model, resulting in a statistical map for each subject, where the value at each voxel represents the extent to which that voxel was involved in the task condition.
Register the participant’s brain to a standard atlas to combine data across subjects. To perform a group-level analysis, threshold the statistical maps, taking into account correction for multiple comparisons. Only accept significant voxels if they also occur within a cluster of a given size to minimize false-positive results.
Using these extracted clusters, overlay them on an average anatomical brain. Note that the activation measured during the 'know' trials was subtracted from that in the 'remember' trials. The hippocampus, outlined here in yellow, showed significantly more activation for 'remember' trials compared to 'know' trials.
To examine hippocampal activation in more detail, plot the percentage of signal change across time after the onset of the stimulus.
Inspection of this time-course of activity revealed that the hippocampus responded positively when participants explicitly reported remembering the stimuli and when identifying new stimuli—noted here with a positive deflection.
In contrast, it responded negatively or very little when participants reported feelings of familiarity or did not remember images at all.
These results support a dual process theory of memory recall, where the hippocampus is involved with memory recollection but not familiarity.
Now that you are familiar with designing an fMRI experiment to understand brain activation during judgments of recollection and familiarity in typical adults, let’s look at additional studies that apply the Remember-Know paradigm.
If the hippocampus plays a central role in recollection, its absence might reveal dissociations in memory retrieval. This scenario can be addressed by comparing patients with bilateral hippocampal damage versus controls—individuals without any such damage.
Interestingly, patients with damage showed impaired memory recollection compared to controls, whereas both groups performed equally well during familiarity trials. Taken together, these results support a specific role of the hippocampus in recollection processes.
On the contrary, if individuals showed increased hippocampal volumes, we’d predict that they’d also display enhanced recollection.
One such example exists and involves London taxicab drivers, who were shown to augment their hippocampal gray matter after years of memorizing extensive and complex routes around the city. With their larger hippocampi and superb memory, they transport passengers to their correct destination in a timely manner.
Researchers are also interested in gaining further insight into the mechanisms responsible for memory retrieval in order to enhance it in other ways. Take for instance, a college psychology lecture, where large amounts of information are presented. Knowing that material is familiar is not helpful for an exam.
Instead, a student needs something else—beyond having that cup of coffee—to aid in remembering. Perhaps, taking a memory-enhancing compound would allow improved recall of the entire discussion to ace that important test.
You’ve just watched JoVE’s introduction to Remember-Know task. Now you should have a good understanding of how to design and conduct the memory recall experiment in conjunction with functional neuroimaging, how to analyze and interpret differential brain activation results, and finally how to apply the paradigm to real-life scenarios.
Thanks for watching!
Regions more active for remember responses than for know responses are shown in Figure 1. Notably, the hippocampus, a structure located in the MTL and known to be involved in many stages of memory formation and retrieval, showed greater activity for remember compared with know trials.
Figure 1: Cluster maps of Remember minus Know. Hippocampus is outlined in yellow. Clusters are overlaid on an average anatomical brain of the study participants (p < 0.01, corrected for multiple comparisons). Please click here to view a larger version of this figure.
Inspection of the time-course of activity in the hippocampus (Figure 2) shows that this structure is selectively responding when participants report explicitly remembering the stimuli, and is not responding when they only have feelings of familiarity, or when they do not remember the stimuli at all.
Figure 2. Hippocampal activity over time. Each line shows activity in the hippocampus over the course of trials of each type. "Remember" and "Know" are trials in which participants correctly reported remembering the stimuli. "Miss" trials refer to stimuli that were presented before but not correctly remembered by the participant. "Correct Rejections" are new stimuli that participants correctly identified as new. Y-axis is percent signal change from baseline; X-axis is time (s) after the onset of the stimulus.
These results suggest that the hippocampus is involved in the process of memory retrieval, but that it does not contribute to feelings of familiarity, supporting a dual-process theory. According to this view, a second cognitive process, one that does not depend on the hippocampus, generates familiarity. However, in the Remember-Know task, memory strength may be confounded with memory type. In other words, it is possible that hippocampal activity is greater for remember trials because those memories are stronger, and not because they are qualitatively different from know trials. To distinguish between these explanations, memory strength would have to be equated across trial types.
Applications and Summary
This experiment demonstrates how cognitive neuroscientists attempt to tease apart the specific contributions of a brain region to a cognitive task. Isolating subtle variations within a cognitive domain, in this case the different subjective experiences associated with memory retrieval, can reveal dissociations in the neural systems that support those functions. Understanding how the brain functions during different types of memory retrieval is important for understanding memory impairments such as those that result from traumatic brain injury or from degenerative diseases. Furthermore, an understanding of the cognitive neuroscience of memory retrieval may also inform strategies for improving memory.
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- Scoville, W.B. & Milner, B. Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry 20, 11-21 (1957).
- Yonelinas, A.P. Components of episodic memory: the contribution of recollection and familiarity. Philos Trans R Soc Lond B Biol Sci 356, 1363-1374 (2001).
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