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Shuhan He MD Administrator
Shuhan He MD is an Emergency Medicine Physician at Harvard Emergency Medicine Department at the Massachusetts General Hospital. Dr. He is interested in making better tools to Conduct Science, especially regarding scientific outcomes. He is the founder of MazeEngineers.com, Conductscience.com, Sciencen.com and an array of tools to help scientists get the job done better and with more translation to the patient at the bedside.
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Shuhan He MD Administrator
Shuhan He MD is an Emergency Medicine Physician at Harvard Emergency Medicine Department at the Massachusetts General Hospital. Dr. He is interested in making better tools to Conduct Science, especially regarding scientific outcomes. He is the founder of MazeEngineers.com, Conductscience.com, Sciencen.com and an array of tools to help scientists get the job done better and with more translation to the patient at the bedside.
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Episodic Memory

Human long-term memory can be broadly classified into declarative memory and procedural (implicit) memory; The former category involves conscious and intentional recollection of factual information, previous experiences, and concepts. The declarative memory, or explicit memory, is further divided into episodic and semantic memory.

Endel Tulving first coined the term episodic memory in 1972, describing it as,

“Episodic memory receives and stores information about temporally dated episodes or events, and temporal-spatial relations among these events.” (Tulving, 1972)

He distinguishes episodic and semantic memory based on remembering versus knowing principle. While semantic memory is concerned with factual information (structured record of facts, concepts, and skills), episodic memory is concerned with remembering specific past events at a particular time and place. He further adds that episodic memory retrieval also feeds back as input to the system that results in changes in the episodic memory store (episodic learning). Episodic memory recollection, as defined by Tulving, is defined by three key properties: a subjective sense of time, connection to the self, and autonoetic consciousness.

Episodic memory in humans fully develops around the age of 4 years (Scarf, Gross, Colombo, & Hayne, 2011), and is retrieved differently among young and old humans (Maguire, 2003; Piolino et al., 2010). In animal models, episodic memory assessments are done using their episodic-like memory (Clayton, Salwiczek, & Dickinson, 2007), which meets Tulving’s definition. Apparatuses such as Fear Conditioning Chamber and Radial Arm Maze are often employed using protocols that require the rodent to recall an experience (For more behavioral research apparatus and equipment visit MazeEngineers). While animal models have extensively contributed to our understanding of learning and memory, the reliance on animal episodic-like memory has received some criticism. A popular criticism, based on the Bischof-Kohler hypothesis (Suddendorf, & Corballis, 1997), suggests that unlike humans, animals are incapable of mental time travel, a key feature of episodic memory recollection. This incapacity translates to experimentally observed behaviors in animals to be resultant of their immediate needs rather than anticipated future needs. Another argument suggests that animals could possibly be displaying Garcia-type learning rather than relying on episodic-like memory in tasks that make use of consumable rewards.

Virtual Reality and Human Memory Research

While animal models have their advantages, translation of results to human applications always needs to be done with certain considerations. On the other hand, real-world human experiments, however, can be affected by a variety of factors including cost and accessibility to participants. Further, self-scored questionnaires and ancillary tests that rely on the participant’s honesty and understanding (For digital health research tools visit Qolty) may not always provide a complete picture or sufficient information. In these scenarios, virtual reality (VR) offers an alternative, or addition to traditional approaches, that tends to be just as effective as real-world experiments. Further, the variety of virtual reality systems available and the flexibility they offer make them an excellent choice.

Pflueger, Stieglitz, Lemoine, and Leyhe (2018) found that their immersive VR based assessment of older adults provided a more accurate estimation of everyday memory demands. Pflueger et al.’s virtual environment (VE) involved a kitchen scene, an environment that is experienced in everyday life, with tasks that relied on common cognitive demands. As opposed to the California Verbal Learning Test, that uses learning of arbitrary word associations, the ecologically relevant VE provided an age-fair estimate of episodic memory in the healthy older adults. Despite both tests being structurally comparable, performance decrements were primarily observed in the California Verbal Learning Test.

Another study performed by Howett et al. (2019) showcased the promising potential of VR assessments in early detection of Alzheimer’s disease. The study involved patients with mild cognitive impairment with and without cerebrospinal fluid biomarkers (MCI+ and MCI-, respectively). Participants, which also included healthy controls, were evaluated in an immersive virtual reality path integration task using an open, grassy field VE. Compared to healthy controls, MCI patients displayed significantly larger absolute distance errors with the parameter value being significantly larger in MCI+ patients than MCI- patients. The VR task that was based on the central role of the entorhinal cortex in navigation exhibited higher diagnostic sensitivity and specificity for differentiating biomarker than the traditionally used pen-and-paper cognitive tests.

As seen with Pflueger et al. and Howett et al.’s study, conventional neuropsychological tools though useful, tend to offer a partial measure of the episodic memory. This limitation can be attributed to their decontextualized and simplified design that does not fully exploit the complex system’s capacity. In neurodegenerative diseases such as Alzheimer’s disease, episodic memory is the first to be affected. Thus, given the important role that episodic memory plays in everyday life and the fragility of this memory, it is essential that investigation of it is done in spatially and temporally rich naturalistic contexts which virtual reality offers.

Given episodic memory’s subject-specific nature, that makes verification of recollected information difficult; investigations often rely on spatial navigation tasks that are quite similar to the protocols used in rodent based apparatuses such as the Morris Water Maze and the Radial Arm Maze. Of all navigation strategies, sequential egocentric strategies, similar to allocentric spatial learning, require memorization of body turns and sequential ordering of events within a maze which share functional similarity to episodic memory (Arleo, & Rondi-reig, 2007; Iglói, Zaoui, Berthoz, & Rondi-Reig, 2009). Igloi, Doeller, Berthoz, Rondi-Reig, and Burgess (2010) investigation highlighted the contribution of the lateralized hippocampal activity in a spatial navigation task to different aspects of episodic memory. Participants were tasked with navigating a Virtual Star-Maze (see also Virtual Radial Arm Maze), an analog of the rodent Star Maze, using distant environmental cues for orientation. The virtual environment used was an open landscape with the maze consisting of 5 central alleyways that formed a pentagon with an additional 5 alleyways radiating out from the angles of the pentagon. Supported by fMRI scans, distinct roles of left and right hippocampus could be seen as the participants searched for the fixed goal that did not have any visible identifiers. While the left hippocampus involved in the sequential organization of successive choices, the right hippocampus activated during spatial navigation. The lateralized activation of the left hippocampus also lends to its involvement in the mediation of spatiotemporal associations of events, which is a characteristic of episodic memory.

As opposed to traditional real-world experiments, where maintenance of experimental parameters such as consistency of the test environment tends to be difficult, virtual reality allows easy manipulation and control of the test environment. Further, an environment transition, for example, from a closed room to a bustling city, is quite easily done in virtual reality than real-world. This flexibility, in addition to the overall control of the environment, can be of great help when it comes to assessments of episodic memory in neuropsychiatric diseases and disorders.

Variety of studies have suggested that individuals with anxiety and anxiety-related disorders display an enhanced implicit/explicit memory bias (Baños, Medina, & Pascual, 2001; Friedman, Thayer, & Borkovec, 2000; Itoh et al., 2018). Dysfunctional retrieval of experiences from the autobiographical and the episodic memory in response to a phobic stimulus can be attributed to the preservation of maladaptive emotional responses, negative beliefs, and avoidance behaviors (Zlomuzica et al., 2014). In their study, Zlomuzica, Preusser, Totzeck, Dere, and Margraf (2016), showed that emotional states modulate episodic memory alterations. Healthy participants performed a virtual task based on the what-where-when paradigm to assess quantitative and qualitative aspects of episodic memory following induction of different emotional states. Participants were shown a short video clip that elicited either anxious, happy, or neutral state of emotion before being asked to explore all four rooms of a virtual apartment. The process was repeated twice, with variations in the event and person encountered with respect to the room they were located in and their content. After a 20-minute delay following the third walkthrough, participants were subjected to an unexpected memory test. Zlomuzica et al. observed that participants that were exposed to anxiety-inducing clip had lower scenario-related memory scores, in particular, they showed difficulty in the recollection of the location of events, than the happy and neutral group. On the other hand, the happy group displayed a better memory of spatial context.

Another study by Zlomuzica et al. (2018) revealed that mnestic impairments in individuals with post-traumatic stress disorder (PTSD) result in incompetent utilization of episodic memory. PTSD is associated with flash-backs triggered by trauma-related stimuli or spontaneous flash-backs due to retrieval-cue generalization, which reflects the role of the episodic memory system in PTSD. Assessment of episodic memory capacities in the PTSD participants was compared with healthy controls on a VR Episodic Memory Test and Mental Time Travel test. The virtual assessments were also further supported by ancillary assessments; the D2 test of attention and Rivermead Behavioural Memory Test. The PTSD participants’ lower standardized concentration performance score (D2 test) highlighted the diminished concentration, which possibly contributed to the performance differences in the VR tasks. The virtual tasks revealed PTSD participants’ impairments in remembering the item and temporal information. The poor VR task performances of the PTSD participants, as opposed to the healthy controls, suggests their incapacity to utilize the episodic memory store in problem-solving, both in present and future.

Fear expression resulting from phobias and other conditioned-fear reflects the modulation of the episodic memory as a consequence of the acquisition of traumatic memory. Fredrikson, Annas, and Hettema (2015), in their twin pair study, observed the distinct genetically influenced process in fear-learning and episodic memory. The study involved fear conditioning using pictures and mild shocks. Taking the same idea of mild-shocks, Huff et al. (2011) investigated the context-specificity of cued fear conditioning. Fear-Conditioning Chambers are often used in animal models to assess associative learning and fear extinction. Huff et al.’s set-up used a similar approach using a fully immersive 3D virtual reality that used dynamic snakes and spiders as the condition stimuli.  As for the unconditioned stimuli, mild electric shocks were given to the participants when they encountered the snake in the environment during the acquisition phase. Performance observations suggested that context fear is rapidly consolidated in the short-term memory, while differential fear is learned at a slower rate. However, the retention test (performed 24 hours after acquisition in the same or different context) showed that cued fear learning is strongly retained in a context-specific manner in the long-term memory. Studies such as that of Huff et al., offer new insights into the translation of rodent paradigms and reliable application of human Pavlovian fear conditioning to understand fear expression in different neuropsychiatric and psychiatric disorders.

Summary

Virtual reality is seeing growing acceptability in human behavioral research and as a training tool in healthcare. An advantage of VR as opposed to traditional approaches to assessing episodic memory is the opportunity to introduce multisensory stimuli without any additional requirements. Experiments that assess extinction of fear can safely use virtual stimuli, for example, a dynamic spider. The use of virtual stimuli that is accompanied by other sensory stimuli, such as auditory and haptic, not only permits observation of natural responses but also quick removal in case of an overwhelmed participant. This flexibility of controlling and manipulating the environment is also beneficial when adapting traditional animal mazes into VE for human experiments. Considerations while designing the VE should also include the level of immersion they allow. While researching episodic memory, Bréchet et al. (2019) observed that first-person view of the participant’s body during the task enhanced consolidation of episodic memory, though not when encoding was immediately followed by retrieval. This simple inclusion incorporates characteristic of normal everyday perception, which enhances the experimental value. Different view-points in a VR experiment of a rich VE can permit exploration of episodic memory in more ways than one.

Though the variety of available VR systems permit experiments at different budget levels as well as immersive levels, they can hinder standardization of experiments across studies. Further, experiments conducted using keypads and joysticks can potentially result in participants overestimating the amplitude of the movements in the virtual environment while underestimating the distances (Burgess, Maguire, & O’Keefe, 2002). On the other hand, mixed-reality set-ups are limited by the area that the participants can traverse in the real world. Another aspect to be considered while employing VR tests is the participant’s familiarity with the system. Virtual reality experiences can be accompanied by virtual reality sickness similar to that of motion sickness. However, despite these minor concerns, VR can be used with the same effectiveness as real-world experiments of episodic memory; especially when real-world landmarks and objects are used, and the immersion level is adequately managed.

References

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