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Article 'Researchers Implant False Memories in Mice' on ABC Science Website:
http://www.abc.net.au/science/articles/2013/07/26/3811591.htm



1. Introduction

Memory – a fundamental process required for learning and a faculty that plays a pivotal role in human experience. Over the years, the idea of memory manipulation has become a rather popularised concept, being the subject of various box office hits, including Inception and Total Recall. However, as described in this article, current research is showing that this once fictional concept may well and truly become reality in the near future.

The article 'Researchers implant false memories in mice' relates to us, the progress of on ongoing study that seeks to understand the way in which memories are formed. By targeting particular cells in the hippocampus, scientists have been able to elicit a particular response from the mice, showing us the way in which memories can be modified. The experiment involved placing the mice in different environments and closely monitoring protein changes linked to memory formation and modification.

There are great implications of memory implantation and responses to these advances are quite varied. On the one hand, we are presented a possible solution for those suffering from memory-associated disorders such as phobias or Post Traumatic Stress Disorder. Memory insertion or deletions may serve as an alternative to current therapeutic measures or psychological strategies in the management of these disorders. Furthermore, the benefits of memory manipulation may further be extended to allow for memory reconstruction for those suffering from severe amnesia. Hence, the potential of becoming a promising procedure to improve the quality of life for such individuals.

On the other hand, however, these findings have potentially contentious implications, the greatest concern being the commercialised practice of memory manipulation. This is because it involves potential breaches of privacy and raises dispute over the right of ownership to personal memories. It is therefore imperative to have stringent regulations for the continuation of this study to ensure ethical standards are maintained and the rights of those involved are not impinged upon.

Studies looking into memory continues to be a growing area of research in neuroscience, as the more we begin to understand memory processes, the closer we may come to discover possible mechanisms that will enhance learning.




2. Neuroscientific Context


2.1 The Hippocampus


Situated in the medial temporal lobes, the hippocampus is one of the most extensively researched neuronal structures within the brain (Bird & Burgess, 2008). At its core, the hippocampus is comprised of the CA fields and the dentate gyrus; it can be further classified into the hippocampal formation to include the subiculum, and the hippocampal complex, which further encompasses the entorhinal cortex, perirhinal cortex and the parahippocampal gyrus (Nadel, Ryan, Hayes, Gilboa & Moscovitch, 2003). The hippocampus can be considered an extension of the neocortex, which it communicates with through the entorhinal cortex (Buszaki, 2011).

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Figure 1.1 Anatomy of the hippocampal formation (Hesselink, J.)
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Figure 1.2 The hippocampal complex (Baars, B.J. 2008)

















2.1.2 The Hippocampus and Episodic Memory


Although an understanding of its precise role remains incomplete, the consensus is that the hippocampal complex has a significant role in memory (Nadel, et al. 2003). This role lies in forming those memories that can be consciously declared, known as declarative or explicit memories (Buszaki, 2011). The cognitive map theory suggests that the hippocampus represents an animal’s environment, and the sections and contents within them, enabling spatial memory and flexible navigation (Burgess, Maguire & O'Keefe, 2002). The parrahippocampus is related to spatial processing, whilst the right hippocampus is important for remembering areas within an environment, and the left hippocampus is connected with context-dependent episodic memory (Burgess, et al. 2002).

Episodic memory involves the unique experiences of each individual, including data concerning the content of the event and the space and time in which it happened (Nadel, et al. 2003). Researchers have found that the hippocampus comprises considerably more episodic data than contiguous regions (Chadwick, Hassabis,Wieskopf & Maguire, 2010). Moreover, instead of being dispersed at random throughout the hippocampus, episodic memory is limited to particular areas, including the bilateral anterior and right posterior hippocampus (Chadwick, et al. 2010).

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Figure 1.3 The various memory systems. Researchers have separated long-term memory into numerous systems and processes. (Bird & Burgess, 2008)


The hippocampal complex is not responsible for permanently storing memory. Instead, it has a time-crucial, essential task in the transition from short-term into long-term memory. The time frame within which this transfer occurs is called the consolidation
period (Nadel, et al. 2003).
There are two theories on the mechanism of consolidation:
  1. ‘Memory’ is initially stored in the hippocampus and then ‘transmitted’ to the neocortex during consolidation.
  2. ‘Memory’ is always stored in the neocortex, but the hippocampus is required for connecting or coordinating the different components during consolidation. (Nadel, et al. 2003).

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Figure 1.4 Cortical and subscortical connections of the hippocampus. Subcortical connections are depicted in red; cortical connections shown in black. The thickness of the lines indicates the strength of the connection. The majority of neocortical input to the hippocampus originates in the perirhinal and parahippocampal cortices through the entorhinal cortex. Most neocortical output is via the subiculum, also projecting back onto the entorhinal cortex (Bird & Burgess, 2008)


The Multiple Trace Theory proposes that:
  • The Hippocampal complex and neocortex are continuously interacting.
  • Data from divergent neocortical regions connects via the hippocampal complex, where an ‘ensemble trace’ is generated quickly via long-term potentiation.
  • This hippocampal trace (H trace), or ‘index’, links the incongruous neocortical traces (NS traces), which enables the different aspects of the memory to be reactivated together and perceived as an intact, complete memory.
  • The hippocampal complex and neocortex constantly work in conjunction with one another to store and retrieve episodic memory - the two structures form the ‘episodic memory system’, irrespective of how old the memory is.
  • The hippocampus does not simply serve as an index to memories in the neocortex, but itself stores circumstantial data concerning the episode (Nadel, et al. 2003).

2.1.3 Spatial Processing and Place Cells


Spatial processing is involved in navigation, assisting people in knowing where they are and remembering where to find certain items. Individuals with hippocampal damage will often have impaired spatial memory, and will get lost or forget where things are, for example, where they parked their vehicle (Bird & Burgess, 2008). Interest in spatial processing intensified with the discovery of 'place cells' in the hippocampi of rats, humans and monkeys. When a person is in a particular area of an environment (the 'place field'), these place cells fire and encode a 'sense of location' (Bird & Burgess, 2008). Place-cells are also motivated by 'self-motion signals', which identify the position of the animal based on its individual movements. Place fields from habitual environments maintain stability for several weeks, implying that place cells encode a long-term memory for that location. They generalise trivial adjustments to the environment, enabling animals to maintain orientation (Bird & Burgess, 2008). If an environment is altered drastically and becomes analogous to another familiarised environment, 're-mapping' occurs, in which the place cells indicate that the individual is in a different environment (Bird & Burgess, 2008).

2.1.4 Constructing Mental Images: The BBB Model


Byrne, Becker and Burgess developed a model of the neural process which underpin spatial memory and imagery, known as the BBB Model (Bird & Burgess, 2008). Reminiscing about experiences of the past often involve mentally visualising the event and focusing on some of the specifics. The BBB Model suggests the hippocampus plays a critical role in this capacity, with place cells reactivating illustrations of the spatial geometry and the positions of matter within it (Bird & Burgess, 2008). The BBB model predicts companionate conductivity between place cells and neocortical regions (parrahippocampal and perirhinal cortices), in which stimulating the place cells reactivates the complementary structures in the neocortex and enables events to be visualised rationally
(Bird & Burgess, 2008). Therefore, complete illustration of a place, including the position of the individual as well as the location itself and the appearance of its ambient features, can be recalled by simply seeing something that is a reminder of that event or environment (Bird & Burgess, 2008). Place cells restrict the recovery of information so that it complies with a specific environment and particular locations within that environment, which is crucial, when one considers the extensive amount of information that is available (Bird & Burgess, 2008).

2.2 Post-Traumatic Stress Disorder


2.2.1 What is Post Traumatic Stress Disorder?


More than 250,000 Australians experience Post Traumatic Stress Disorder in any one year, and approximately 5% of Australians have had PTSD at a period in their lives (Australian Centre for Posttraumatic Mental Health, 2013). PTSD is a system of reactions which may develop in individuals who have endured or observed an event which endangered their life or safety, or of those around them, and developed into feelings of extreme fear, vulnerability or panic (ACPMH, 2013).

2.2.2 Signs and Symptoms of PTSD


An individual with PTSD experiences three main types of afflictions:
  • Re-living the traumatic event - through unpleasant and persistent memories and intense nightmares. When recalling the event, acute behavioural or physical reactions may occur, including sweating, heart palpitations or panic.
  • Being hyper-alert or anxious - difficulty sleeping, irascibility, lack of attention, becoming easily alarmed, and constant vigilance for any signs of danger.
  • Evading triggers for the event and feeling emotionally aloof - deliberately avoiding activities, locations, people, thoughts or emotions affiliated with the event. People may become disinterested in everyday activities and feel isolated from friends and family, or feel lifeless and apathetic (ACPMH, 2013).

2.2.3 Biological Aspects of PTSD


Knowledge of the biological changes associated with PTSD has helped clarify why some individuals recover from traumatic events and others develop PTSD. Patients with long-term PTSD have elevated levels of norepinephrine and hyperactivity of α2-adrenergic receptors. These changes, along with the discovery that thyroid hormone levels are elevated in people with PTSD, may assist in explaining some of the symptoms of the disorder (Yehuda, 2002).

Recent neuroanatomical research in people with PTSD has detected changes in two major brain structures - the amygdala and the hippocampus. Positron-emission tomography (PET) and functional magnetic resonance imaging (fMRI) have demonstrated that the sensitivity of the amygdala and anterior paralimbic region to trauma-related stimuli is elevated, whilst the reactivity of the anterior cingulate and orbitofrontal areas is lowered. These are the regions of the brain which are active in the fear response. Alterations in hippocampal function and in memory processes have also been identified, proposing a neuroanatomical basis for the obtrusive memories and other cognitive issues that typify PTSD (Yehuda, 2002).

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Figure 2.1 fMRI in PTSD patient showing hyperactivity of amygdala (right) with weaker connectivity with frontal cortex (left) (Yan, 2012)


A new study on PTSD, using fMRI (as shown in Figure 2.1), found that the amygdala was overactive even in resting state, i.e. with no extrinsic stimuli, as well as having a deficiency in connectivity with the middle frontal cortex, proposing that the amygdala can be perpetually active in the absence of any stimuli, along with decreased inhibition from the frontal cortex (Yan, 2012).

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Figure 2.2 Showing activation of limbic regions in patients with PTSD compared with normal controls, and veterans without PTSD (combat controls) (Liberzon, et al. 1999)



In PTSD, the reactivity of the negative-feedback loop of the hypothalamic-pituitary-adrenal axis is elevated, reflected in the increased inhibition of cortisol in response to the administration of dexamethasone and the heightened sensitivity of lymphocyte glucocorticoid receptors (Yehuda, 2002).

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Figure 2.3 Stress response in a normal subject (A), a patient with major depression (B) & a patient with PTSD (C). The thickness of the arrows indicates the strength of the biologic response. (Yehuda, 2002)


As shown in Figure 2.1, in normal subjects and those with major depression, fleeting or prolonged periods of stress are paired with elevated levels of cortisol and corticotropin-releasing factor. Corticotropin-releasing factor stimulates the release of corticotropin, which subsequently stimulates the release of cortisol. Cortisol suppresses the release of corticotropin and corticotropin-releasing factor. Patients with PTSD have low levels of cortisol and high levels of corticotropin-releasing factor. Additionally, the reactivity of the negative-feedback system of the hypothalamic-pituitary-adrenal axis is heightened in patients with PTSD instead of decreased (Yehuda, 2002).

Reduced levels of cortisol during a traumatic event may extend the availability of norepinephrine to synapses in the peripheral and central nervous system, which subsequently may affect the consolidation of the memory of the event. When cortisol levels are low, the activation of adrenergic receptors promotes learning in animals. When this occurs in traumatised individuals, the memory is not only strongly encoded, but also correlates with intense, subjective feelings of anxiety (Yehuda, 2002).

2.2.4 Potential Treatments for PTSD


The article describes a study in which mice underwent context-dependent classical conditioning with both a neutral and a conditioning environment with the aim of associating an aversive outcome, experienced in the conditioning environment, with the neutral context thus, supporting the hypothesised creation of a false memory in which the mice experienced adversity in the neutral environment. In order to achieve such, the target hippocampal place cell associated with the neutral environment was stimulated during fear conditioning in the conditioning environment.

The possibility to create false memories proposes an avenue to potentially reduce symptoms of PTSD by adapting the animal model. Patients would undergo a form of cognitive behavioural therapy in which propitious emotions are aroused during the stimulated recollection of the traumatic memory. Consistent with the Pavlovian Model of fear extinction, creating an association between the PTSD source memory and a less adverse outcome will negate the extreme anxiety initially attributed to the memory. Assumedly, this psychotherapeutic treatment would normalise the negative-feedback of the hypothalamic pituitary adrenal axis to increase levels of cortisol to that of someone void of deficits in fear regulation.


3. Critical Analysis


The article ‘Researchers Implant False Memories in Mice’ summarises a study in which neuroscientists successfully stimulate mice to recall experiences that haven’t occurred. It was published on ABC Science which comprises of the latest science news with little to no advertisements.

The team of researchers led by MIT neuroscientist and Nobel Laureate Susumu Tonegawa manipulated neural connections involved in true memory and created the first artificially implanted memories into minds of mice via a technique called 'optogenetics'. They have previously pinpointed the location and assemblage of brain cells that hold memory and have now successfully transformed original memory. This advancement will contribute greatly to the current understanding of memory formation and modulation. The experiment could further be recreated on human subjects and its success has implications for therapy and legal settings.

The article is directed at a wide audience including young people interested in popular culture where movies like Inception are gradually resembling reality. Surely patients suffering from amnesia (e.g. anterograde, post-traumatic, dissociative) have high interest in memory implantation advancements if it is suggested that lost or distorted memories can be regained in therapy. It would most likely attract an age demographic of 15 to 30 who are attentive to neuroscientific based articles or related media such as ABC catalyst – a program that views science as a ‘dynamic force changing the world’.

The article is presented in an informal manner primarily consisting of layman’s terms and an absence of references. Its purpose is to stimulate the interest of the audience on the topic of false memory implantation and is recommended not to be used as a definitive source of information. It does not delve into the complex findings of the research and excludes a vast amount of scientific terminology. The audience can simply search for the referred journal article if they require further information. Hence, the language is effectively tailored to the target audience.

Overall, the article has an objective view point of the content and conclusions of the research. However, the journalist only mentions the positive outcomes of producing false memories such as treatments of phobias and PTSD in humans but dismisses questionable intentions and unknown adverse effects in the future.

After cross referencing the media item and the context of the research, consistency of the information held. Inevitably, intricate detail is lost but this produces a harmless effect on the accuracy of the research, for example, the sentence ‘injected an adreno-associated virus (AAV) encoding TRE-ChR2-mCherry into the DG or CA1 of c-fos-tTa animals’ is simplified to ‘injected the gene-toting virus into a part of the mouse’s brain called the hippocampus’ in the media item. The journalist, Jesse Empsak, presented his article on the same day the study published its findings in the latest issue of Science. Science is an academic journal of the American Association for the Advancement of Science (AAAS) and is considered one of the world’s top scientific journals. This further establishes the accuracy and reliability of the research.


4. Appendix


4.1 Topic Choice

A collective interest in this article was initially generated upon reading the phrase ‘false memories’ in the title, and upon completion, the article proved to be rather intriguing and thought provoking. It left us to acknowledge the fallibility of memory, but also raised questions about a more confronting issue: mind control.

It was made sure that the choice for this article was unanimously agreed upon.

4.2 Search Strategy

Neuroscientific context:

Research began from reading the ABC article and obtaining the original research article published in Science via a provided link. The ABC article mentioned previous research from the same group of scientists, so using the original paper, the researchers listed were 'clicked' on to find additional papers written by them. This was how another paper concerning the hippocampus and episodic memory was found. From reading the two papers as well as the ABC article, 'key' words or themes were identified such as the hippocampus and its role in memory, particularly episodic memory. These keywords were then entered into Google under the 'scholar' section, in order to find peer-reviewed articles. Since these articles were in significant detail, very specific, with scientific jargon, a general search of the hippocampus was needed, to gather information on structure and function. Performing a simple Google search led to websites with good, general information and useful pictures which demonstrated hippocampal anatomy. All other pictures are from the articles and papers already mentioned.

4.3 Reviewer's Comments

In response to the comments received from the peer review, the following items were addressed:
  • The hyperlink to our chosen media item was initially linked at the bottom of the page. However comments suggested that the link should be included at the top of the page for ease of access. Accordingly, such was obliged.
  • The comments noted that there was an inconsistency in the format of our in-text citations. After referring to the UNSW refworks program the referencing system was rectified to mimic the (Surname et al., date) format.
  • It was noted in the reviews that the article placed particular emphasis upon the relevance of the findings to potentiate new treatments for PTSD symptoms. Our first draft did not include a section on PTSD in the Neuroscientific Context. We consequently added an additional section on the mechanics of PTSD and the potential for memory implantation to cultivate alternative treatment options.
  • The peer reviews suggested that we include a summary of the study outlined in our chosen media item and the implications of such link the Neuroscientific Context to the media item. This was rectified in the addition of the Potential Treatments for PTSD section which contextualised the preceding information in the neuroscientific context.
  • A few word choices were altered in the Critical Analysis as suggested.
  • The introduction was edited according to the suggestions made which included: a short overview of the main points as discussed in the article; interest of this to the wider in neuroscience; removing the paragraph stating how the group became interested in the article was moved from the introduction to the appendix.




References


Australian Centre for Posttraumatic Mental Health. (2013). Posttraumatic stress disorder (PTSD). Retrieved 17/09, 2013, from http://www.acpmh.unimelb.edu.au/trauma/ptsd.html

Baars, B. J. (2008). Hippocampal system. Retrieved 06/09, 2013, from http://bernardbaars.pbworks.com/f/entorhin+=+paraHippocampal+system+-+good.jpg

Bird, C., & Burgess, N. (2008). The hippocampus and memory: Insights from spatial processing. Nature Reviews, 9, 182.

Burgess, N., Maguire, E., & O'Keefe, J. (2002). The human hippocampus and spatial and episodic memory. Neuron, 35, 625.

Buzsaki, G. (2011). Hippocampus. Retrieved 28/08, 2013, from http://www.scholarpedia.org/article/Hippocampus

Chadwick, M., Hassabis, D., Weiskopf, N., & Maguire, E. (2010). Decoding individual episodic memory traces in the human hippocampus. Current Biology, 20, 544.

Hesselink, J. The temporal lobe & limbic system. Retrieved 06/09, 2013, from http://spinwarp.ucsd.edu/neuroweb/Text/br-800epi.htm


Liberzon, I., Taylor, S. F., Amdur, R., Jung, T. D., Chamberlain, K. R., Minoshima, S., Keoppe, R. A., & Fig, L. M. (1999). Brain activation in PTSD in response to trauma-related stimuli. Biological Psychiatry,45(7), 817-826.

Nadel, L., Ryan, L., Hayes, S. M., Gilboa, A., & Moscovitch, M. (2003). The role of the hippocampal complex in long-term episodic memory. International Congress Series, 1250, 215.

Yan, X. (2012). Amygdala, childhood adversity and psychiatric disorders. In B. Ferry (Ed.), The amygdala- A discrete multitasking manager. Available from: http://www.intechopen.com/books/the-amygdala-a-discrete-multitasking-manager/amygdala-childhood-adversity-and-psychiatric-disorders

Yehuda, R. (2002). Post-traumatic stress disorder. The New England Journal of Medicine, 346(2), 108.








Topic: Implanting False Memories

Annie Le: z3422360
Christel Macdonald: z3464773
Sadia Rahman: z3416904
Stephanie Terreiro: z3417999



Nice topic - relates well to what you are covering in stress, but with a novel slant.
You should post a photo of one of your meetings to verify that everyone is 'in'.

Approved.



Jobs:

Sadia: Forming & storing memories/ future prospects of research/Introduction
Annie: Analysis
Christel: Channelrhodopsin-2 Protein/Hippocampus & episodic memories (Neuro-scientific Context)
Steph: Context & Editing/ compiling appendix

Deadlines for rough DRAFTS of:
Neuro-scientific context: Monday 26th of August
Intro & Analysis: Wednesday 28nd of August
Appendix: Friday 30th of August



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Sadia, Annie, Steff & Christel at our first group meeting