Tuesday, February 24, 2009

The brain is a very responsive organ that interacts with the body in an attempt to react with the environment and all the external experiences with grace (and hopefully survival). Traumatic events disrupt this 'grace' and it is up to the body to find a way to return- so survival can be a likely future event. This presentation explores what causes the body to return to homeostasis following a traumatic event and why exactly some individuals can’t.

It was first noted that an individual’s inability to recover from trauma might have some relation to the neural processing in the brain when it became viewed as a disorder. “For the Ancient Greeks, it was a ‘divine madness’ that infected the minds of soldiers. During the US Civil War, it became known as ‘soldier’s heart’. By the First World War it was called shell shock. Today the condition is known as Post-Traumatic Stress Disorder.” (New York times)

Posttraumatic stress disorder (PTSD) occurs when some individuals cannot seem to re
cover from the traumatic event and return to homeostasis. PTSD is not only dependent on the traumatic event, but also individual differences, such as preexisting traits or the specific composure of the neuroendocrine system of an individual, and the psychological, genetic, physical and social characteristics of that individual.

PTSD can be a permanent disorder because it changes the bodies response to stress. Specifically, it affects stress hormones and chemicals that carry information through neurotransmitters.

How does your body normally respond to trauma?

Normally, your body responds to stress in the following way: something traumatic happens- you get scared, hit by a car, kidnapped, you hear a loud noise, etc.- so your body responds accordingly. The Sympathetic Nervous System (SNS), which becomes more active during stress to comprise the fight-or-flight response, releases a catecholamine hormone (epinephr
ine, norephinephrine, dopamine, etc.) into the system by the adrenal glands in situations of stress. In response, cortisol is released from the adrenal cortex of the adrenal gland. Often called the “stress hormone,” cortisol responds to the increased catecholamine by increasing blood pressure and blood sugar and reducing immune responses. These occurrences help return the anxious body to homeostasis. In the words of LeDoux and Yehuda, “a critical feat
ure of the stress response is the autoregulation initiated by cortisol negative-feedback inhibition that restores stress-related reactions to baseline after the termination of the acute stressor.”(LeDoux) The stressful event then becomes a memory. Following any learn
ing event, the long-term memory is not instantaneously formed. Rather, information regarding the event is slowly assimilated into long-term storage. It is through the release of adrenaline that these stressful memories can begin to be consolidated. The amygdala, which is essential for decoding emotions and processing memory, sends impulses to the hypothalamus for important activation of the SNS. The amygdala’s activity is increased with more emotional activity. The central nuclei of the amygdala are involved in the genesis of many fear resp
onses including immobilization, rapid heart beat, increased respiration, and stress-hormone release. The amygdala is also involved in the modulation of memory consolidation. Therefore, since during the consolidation of a memory, it can be modulated, the emotional decoding of stressful situations can affect the way that the memory is stored. Emotional arousal following a stressful situation influences the strength of the memory. The greater the emotional arousal leads to an enhanced retention of that event- thus the more emotional the stimuli, the stronger
 the memory.

HPA Axis and overall functioning of feedback loop

What happens if the body cannot return to homeostasis?
Sometimes, differing circumstances inhibit the bodies ability return to homeostasis. Sometimes the stressful event is so strong, or certain neural s
tructures are not quite able to respond to an event with the appropriate SNS respons
e, the body cannot recover.

Figure 1  Figure 2


In the first diagram, a traumatic event can remove you from your safe zone and push y
ou into a war zone. It is the bodies job to try to return you to your safe place, but when you have PTSD, this process is more difficult. In the second diagram, you can see that everyone has a certain level of good stress- it is healthy. In the second cup, bad stress is introduced- paying bills, relationships, getting fired, etc. This all still leaves room for other things to occur. However, in the last cup, the stress is so consuming that there is no room for anything 
else. PTSD takes up a lot of space in our ability to handle actions. A person who suffers PTSD would be in a constant state of ‘war zone.’ This means that even the smallest arousals would prompt and immediate overreaction. Researchers have described war veterans as being in a sustained physiological state of hyperarousal.

The question that LeDoux and Yehuda pose is: why is it that the majority of trauma-exposed persons do not develop PTSD? They try to prove that PTSD cannot be understood independent of personal factors that can be extrapolated from a traumatic event alone. “Rather, PTSD represents a specific phenotype associated with a failure to recover from the normal affects of trauma.” (LeDoux) LeDoux and Yehuda therefore set out to find the individual, preexisting conditions that would explain the development of the disorder and the failure to return to homeostasis. 

What exactly is PTSD?  What are the side effects?

PTSD exhibits three distinct symptoms. 

Reexperiencing symptoms- spontaneous, insuppressible recollections of the event.
Avoidance symptoms- restricting oneself from the event; withdrawal emotionally and socially.
Hyperarousal symptoms- physiologically manifested: insomnia, irritability, impaired concetration.

6.8% of people in the U.S. develop PTSD at some point in their life, yet more than 75% of people are exposed to at least one traumatic event that could lead to PTSD.

What do neuroscientists believe happens to cause this?

LeDoux and Yehuda believe that several factors cause PTSD to occur in particular individuals, and they believe this has to do with preexisting conditions. Some of these factors include lower levels of cortisol, higher levels of catecholamines, a smaller hippocampus (which some would say is the result of PTSD) etc.

Researchers believe that acute exposure to a traumatic event includes “increases in
 sympathetic, and decreases in parasympathetic, tone and the release of adrenocorticotropic hormone (ACTH), cortisol, and catecholamines from the pituitary, adrenal cortex, and adrenal medulla.” This occurs out of the bodies attempt to accommodate immediate demands on the body. PTSD, therefore, comes out of a person’s inability to respond to the immediate demand in a stressful situation.

PTSD is associated with low levels of cortisol and high levels of catecholamenes. There was notably a low secretion of cortisol and a high secretion of catecholamines with a norepinephrine to cortisol ratio higher than non-diagnosed individuals. This was exhibited in war veterans, abused children, and other people suffering from PTSD. But, what could cause this reaction? Could the initial stressor be so intense that levels of adrenaline quickly consolidated the memory before cortisol came in for the uptake? Could the amygdala further strengthen this memory bond? LeDoux and Yehuda beg to differ.

They assert: “because the release of adrenaline facilitates consolidation of the threat memory, failure to contain the SNS response might lead to more strongly encoded, hence more 
subjectively distressing memories of the event. If low cortisol levels represent a preexistin
g characteristic, reinforced by “overconsolidation” at the time of trauma, then failing to properly contain the SNS response to traumatic reminders could perpetuate the intrusive and hyperarousal symptoms of PTSD, leading to the elaboration of avoidance symptoms that commonly occurs in the disorder.” Compounded with low cortisole levels- or a low level of hormones that respond to adrenaline and help return the body to homeostasis- the body cannot return to homeostasis in a normal way.

Further, high levels of cortisol released during stress- in response to a high release of catecholamenes- were associated with damage to neurons in the CA3 region of the
 hippocampus and a loss of neurons and dendritic branching in this area. This is because glucocorticoids such as coritisol disrupt cellular metabolism, or the cells burning of energy, and increases the vulnerability of hippocampal neurons to excitatory amino acids like glutamate. The hippocampus is very sensitive to stressful situations and this is correlated to memory loss and damage. Exposure to abuse in early childhood is often correlated with reduced volume of the hippocampus and thus a hindered ability to learn and remember things. These children typically have delayed recall of the abusive memories.

LeDoux and Yehuda studied the hippocampus further to question whether a smaller hippocampus was a predisposition or a result of PTSD. They assert that it is difficult to say that, due to cortisol toxicity the hippocampus is reduced in volume. LeDoux and Yehuda suggest that a smaller hippocampus is a preexisting condition because due to a lack of initial memory, recalling the events may make it difficult for persons to “contextualize and reinterpret the experience of trauma in a way that can facilitate recovery.” (LeDoux)  

In regards to the amygdala, a hypothesis of fear conditioning could explain why, following the traumatic
 event, there was still persistence biological and psychological fear. Fear conditioning occurs through the convergence of information from the initial traumatic event to trauma-related cues in the lateral nucleus of the amygdala “where synaptic plasticity occurs.” This is in turn connected to the hypothalamus. The ability to properly process a threat is key to the release of the hormones previously discussed such as catecholamines, ACTH, and cortisol. It is believed that chronic exposure or reliving of stress can lead to hyperactivity in the amygdala. As seen in the diagram of HPA axis, the balanced flow is crucial, and in PTSD, the hypersensitivity of the amygdala throws this process off. The hypersensitivity of the amygdala in assessing threat is then connected to the hypothalmus and brainstem areas that in turn control behavior and central arousal responses that help the organism cope with threat. This can happen at a totally unconscious level in an individual. It is not, however, known whether a hyperactive amygdala is a response to PTSD or a preexisting condition.

How did they prove this?

As in the newspaper article, the research team led by UC Irvine neuroscientists tested this idea with rats. When rats entered in to a particular room, they received a foot shock. When this shock was activated by a stimulation to the amygdala, the rats tended to know what rooms not to go in. When the shock was compounded with a deactivating agent, they tended to easily forget the foot shock. This highlights the interconnected importance of the emotional processing of an event in the amygdala and how that transfers in to long-term memory.

On top of this, damage to the medial prefrontal cortex (mPFC) inhibits fear extinction.  Specifically, the way the mPFC interacts with the amygdala causes lasting traumatic memories and responses.  The mPFC helps regulate fears that have been acquired, a
nd mediate conditioned fear responses- as described above.  Those with PTSD showed to have a "failure of activation in metabolism in parts of the mPFC." (Bremner)

While this is all incredibly important in understanding how people deal with trauma and why recovery is difficult, and sometimes impossible for some, it is also very illuminating in understanding the way short-term and long-term memory work in general. This helps understand exactly why things that are emotionally arousing stand out in our memory and why things that are kind of dull do not. It also gives us insight into the importance of traumat
ized people giving verbal testimonies to their experiences. How facing your traumatic memory can allow you to understand it better; how you can unlearn the initial fear of the event through therapy; how fear conditioning in the amygdala can be counter acted with consistent conscious recollection of the traumatic event until it doesn’t release such dramatic internal neural responses; and how some cortisol drugs just might do the trick.

Yehuda and LeDoux, Response Variation following Trauma: A Translational Neuroscience Approach to Understanding PTSD http://www.cell.com/neuron/abstract/S0896-6273(07)00704-0
Bremner. "The Lasting Effects of Psychological Trauma on Memory and the Hippocampus." www.lawandpsychiatry.com

Hypnosis Presentation

Origins of Hypnosis

Hypnosis s famous for its roots in pseudoscience and metaphysical innuendo. Dr. Franz Mesmer in the 18th centuryclaimed he could influence his patients minds by manipulating their "magnetic fluids." At first he used actual magnets, before later favoring careful hand movements from a distance to his subjects.

Franz Mesmer

It would be Dr. James Braid, a scottish philosipher who would hone Mesmer's in a rational matter, devoid of any supernatural claims. He would latter coin the term 'Hypnotism'.

"It may here be requisite for me to explain, that by the term Hypnotism, or Nervous Sleep, which frequently occurs in the following pages, I mean a peculiar condition of the nervous system, into which it may be thrown by artificial contrivance, and which differs, in several respects, from common sleep or the waking condition. I do not allege that this condition is induced through the transmission of a magnetic or occult influence from my body into that of my patients; nor do I profess, by my processes, to produce the higher [i.e., supernatural] phenomena of the Mesmerists. My pretensions are of a much more humble character, and are all consistent with generally admitted principles in physiological and psychological science. Hypnotism might therefore not inaptly be designated, Rational Mesmerism, in contra-distinction to the Transcendental Mesmerism of the Mesmerists." -Observations on Trance or Human Hybernation, 1850, 'Preface.'

Braid found that he induced trances with intense, unwavering stares.

James Braid

Raz's Study

Hypnosis has since undergone many connotations and applications. Recently, scientists like Amir Raz, a former professional magician and current assistant professor at Columbia University, have been attempting to bring hypnotism back into the realm of neurological study.

Raz conducted a study with groups of adults who were highly susceptible to hypnotic influence to see if they could perform a "stroop test" with greater aptitude after hypnotic induction

A stroop test is an experiment in which subjects are asked to identify colors as quickly as possible. The colors however are presented in the context of colored letters spelling the names of different colors, for instance the word "Blue" with yellow lettering. This briefly confuses the subjects, as their literate associative minds are forced to reconcile with sensory input before generating a response.

Raz found that through hypnotic induction, he could override the literate functions in his subjects. After suggesting to his subjects through hypnosis that the words would appear as gibberish.

As the study progressed, Raz found that subjects highly susceptible to hypnosis did not show brain activity in the areas used for visual language recognition, and thus recognized the colors instantly.

This data indicates that the powers of hypnotic suggestion are powerful enough to temporarily suspend ones recognition of language. By suggestion, Raz was able to manipulate the higher brain functions of his subjects so as to manipulate or at least "deafen" lower function sensory input.

The implications of this and similar studies are manifold. Hypnosis while often dramatized and embellished, is a very real phenomenon. Hypnosis does indeed have many current clinical uses for treating depression, performance anxiety, addiction and other things. It can however also be used in studies similar to Raz's in order to more specifically identify brain structure and cognition. Hypothetically, if one were to devise a test similar to the stroop test, with more layers of sensory input (smell, touch sound etc.) one could use hypnotic suggestion to more firmly postulate the "pecking order" of each of these sensory inputs in the gestalt of experience.

Dr. Amir Raz Stroop test Case Study

Additional Material

Images from:

False memory presentation

Here is my hopefully successful attempt at creating a presentation exploring Yoko Okado and Craig Stark's findings regarding the encoding of false memories.

What is false memory?

False memory refers to altered or distorted memories which are experienced by the subject as accurate. Okado and Stark describe a number of forms false memories take: "changes in the context of a memory," for example (in which the source of a memory is inaccurately attributed, so that a subject may report that he or she personally experienced an event rather than having seen it on television, heard about it from a friend, or dreamed it), or "changes in the content of a memory," in which details in the memory (such as the season or year in which an event took place, what someone was wearing, et cetera) are confused.

How were false memories created in this study?

Okado and Stark describe an experiment in which subjects were twice shown eight vignettes: first in an Original Event phase, and secondly in a Misinformation phase. In the Misinformation phase, the vignettes contained changes made to 12 "critical items." In order to further clarify subjects' experiences of memory, a "source memory test" was administered which asked the subjects to attribute their memory to a specific source.

What did the fMRIs show?

I quote from Okado & Stark to ensure that I don't misrepresent their findings:

"During encoding of the Original Event, there was significantly more activity when participants subsequently remembered the item shown in this phase (a true memory), compared with when participants subsequently did not remember the item. That is, there was more encoding activity when an item was later remembered compared with when it was forgotten (or another item was remembered instead). During the Misinformation phase, this same Dm effect was observed. There was more activity for subsequent false memories than for subsequent true memories. This difference in activity was significant in the left hippocampus tail, but not in the left perirhinal cortex. Again, there was more encoding activity for items subsequently remembered (Misinformation items) compared with items subsequently not remembered (Original Event items).

"In the left hippocampus tail, activity for subsequently true memories was greater during the Original Event phase than during the Misinformation phase, and activity for subsequently false memories was significantly greater during the Misinformation phase than during the Original Event phase. In the left perirhinal cortex, the same pattern of results was observed. Thus, the relative activity during the two encoding phases was predictive of which version of the item would later be remembered. " (italics mine)

"The traditional Dm effect (greater activity for subsequently remembered items than for forgotten items) was observed in the left hippocampus tail and left perirhinal cortex. When encoding activity was greater during the Original Event phase, the Original Event items (true memories) were subsequently recollected. When encoding activity was greater during the Misinformation phase, the Misinformation items (false memories) were subsequently recollected. Thus, in these two regions, activity was correlated with successful encoding of an item later remembered, whether it was from the Original Event phase or from the Misinformation phase."

What is the significance of these results?

What is significant about this study is that it allows us to look at the formation of false memories, and shows that activity in specific regions of the brain can be correlated to memory formation regardless of whether the memory is "true" or "false."

It can be misleading to talk about "true" or "false" memories in this context, as what is really being addressed in this study is misattribution and confusion (in the literal sense of two experiences being mixed together and thus remembered as one). The "false" memories (as I understand it) were memories which either attributed the Misinformation phase changes in vignettes to the original vignette or registered the Misinformation phase changes in the vignettes as the only version seen. In this sense these are not "false" memories; the subject did, in fact, see these versions of the vignettes-- but the activity levels shown in the fMRIs suggest that they encoded the Original Event vignettes weakly, and the Misinformation vignettes strongly, leading to the errors in memory described.

This suggests that memories are in some sense "rewritable." A weakly encoded memory, when confronted by a more strongly encoded memory with an overlapping context, can be altered to reflect the more strongly encoded memory-- without the subject becoming aware of the alteration. It is truly a sub-conscious change.

My remaining questions include: what prompts this "rewriting"? How weak or strong must an encoded memory be for it to be susceptible or resistant to this? Is there any distinction between the process of "original" memory formation and memory alteration, or are all our memories essentially shifting, constantly edited narratives?

Okado and Stark's paper, "Neural activity during encoding predicts false memories created by misinformation," can be found here.

Saturday, February 21, 2009

Tuesday, February 10, 2009