Wednesday, February 18, 2009

I Need a Pill to Erase Stupid People


In this month's issue of Nature Neuroscience (1), there is an article titled "Beyond extinction: erasing human fear responses and preventing the return of fear." Anyone who has taken a general psych course knows that the term "extinction" refers to the process of unpairing a conditioned response from a conditioned stimulus. It's a component of classical conditioning.

"I'm bored." Wait, it gets better...

It works like this: You have an - unconditioned response-UR (e.g., hardened nipples), which is evoked reflexibly by the unconditioned stimulus-US (ice cubes). When you pair the US with a neutral stimulus that does not cause hardened nipples (e.g., Jonas Brothers), this is called the conditioned stimulus-CS. After the US, which leads to the UR, has been paired repeatedly with the CS, then the CS alone will elicit the same response, this is called the conditioned response-CR. Finally, when the CS is presented in the absence of the US repeatedly, the CR frequency is reduced, thus rendering the Jonas Brother incapable of hardening nipples; this is referred to as extinction.

This study (1) used a paradigm known as fear conditioning. It's identical to the process-above, except the CS is usually a noxious stimulus (e.g., Fall Out Boys). This form of memory is a type of implicit (i.e., unconscious) memory and primarily involves a subcortical structure called the amygdala. Take note of the word unconscious, because it will reveal how big an idiot you are, if you work for a print media outlet.

The study found "that oral administration of the beta-adrenergic receptor antagonist propranolol before memory reactivation in humans erased the behavioral expression of the fear memory 24h later and prevented the return of fear. Disrupting reconsolidation of fear memory opens up new avenues for providing a long-term cure for patients with emotional disorders." (1).

In response to these findings, which are not new (2), the following headlines were generated: "Beta-Blocker Erases Bad Memories" (3), "Pill Could Erase Bad Memories" (4), and my favorite, "Pill to erase bad memories: Ethical furore over drugs 'that threaten human identity'"(5). In that last article, an expert in "biological" ethics (the ethics caused by a chemical imbalance) opines, "It is obviously up to the individual whether or not she wishes to risk the possible effects, including psychological discontinuity, of erasing unpleasant memories. An interesting complexity is the possibility that victims, say of violence, might wish to erase the painful memory and with it their ability to give evidence against assailants. Similarly criminals and witnesses to crime may, under the guise of erasing a painful memory, render themselves unable to give evidence." Wow, he's a special kind of stupid.

The type of memory this cognitively retarded individual is discussing is called declarative memory, the knowledge to which we have conscious access (e.g., events and facts). Implicit memory, in contrast, is the knowledge to which we typically have no conscious access (e.g., motor skills, fear responses). Typically, I'd go easy on someone who lacks neuroscience training; however, if you read the damn article, it says, in black-and-white print, that propranolol (which suppresses the activity of the sympathetic nervous system) reduced the conditioned fear response, while leaving the "declarative memory for the acquired contingency between the conditioned and unconditioned stimulus intact" (1).

First, the authors should not have used the word "erased." Media types jump all over stuff that evokes images (a conditioned response) of 1930's science-fiction movies. Secondly, blink-rate was the behavior measured. No other behavioral measure of fear was studied. Thus, it is inconclusive that the fear response was completely erased. Moreover, in the body of the article, the authors state, "...that the fear memory may either be erased (storage theory) or may be unavailable as a result of retrieval failure (retrieval theory). Note that no behavioral procedure is currently available that differentiates between these two views of amnesia." They don't even know which process it is, or if it's either process. Personally, I throw my support behind a connectionist model of memory.

"What's that?"

Look! Midgets! (6).

Just like all other researchers who lack clinical experience and want to make their results seem more important than they are, they threw in this whopper, "disrupting the reconsolidation of fear memory opens up new avenues for providing a long-term cure for patients with emotional disorders." The disorder they specifically mention is post-traumatic stress disorder (PTSD).

The specific memory process they are trying to disrupt is called "reconsolidation," the process by which a memory (either declarative or implicit), after encoding and consolidation, is strengthened when recalled. This is actually a more efficient way of learning than through repetition alone (that's why flashcards are better than reading notes, 7). Their hypothesis is that the administration of a drug that partially suppresses the sympathetic nervous system (SNS) when a conditioned fear response is cued (i.e., recalled) supposedly disrupts reconsolidation, and the fear response is dampened (i.e., not strengthened).

The reason why this won't be a "long-term cure" for emotional disorders, especially PTSD, is due to the fact that "bad" memories are both declarative (i.e., hippocampus-dependent) and implicit (i.e., amygdala-dependent). The two memory systems are separate (known as double dissociation) and can function independently. This is the reason why the fear response was suppressed, but the memory for the conditioning events were intact. At the same time, this does not mean that one system cannot influence the other.

For example, amygdala activity (e.g., fear) has been shown to strengthen the consolidation (as opposed to reconsolidation) of memories. This happens through enhancement of hippocampal functioning (8). Moreover, amygdala activity can interact directly with the hippocampus during the initial encoding phase of an experience, which also positively affects long-term consolidation.
In other words, amydala activity can modulate declarative memory at multiple stages (encoding, consolidation, and reconsolidation) leading to a net effect of enhanced retention. IMPORTANT POINT: the more intense the stimulus (e.g., severe trauma), the better consolidated the memories will be (both declarative and implicit).

People (such as soldiers) who experience severe trauma, have very vivid declarative memories and intense emotional memories of their trauma. Both unconscious and conscious stimuli can provoke intense emotional and cognitive reactions (e.g., autonomic arousal, flashbacks). A soldier, who was a patient where I work, reported that s/he witnessed 19 of his/her fellow soldiers being killed (2 by suicide). That's a little more intense than a gentle electric shock or pictures of spiders. Do you think propranolol (half life of 3.4-6 hrs) will "erase" his/her fear response? I don't.

Cognitive-behavioral therapists will tell you that in addition to emotions leading to certain thoughts, thoughts can lead to experiencing emotions. Since the emotional memory process (amygdala-dependent) can enhance declarative memories during encoding, consolidation, and reconsolidation; administration of a beta-blocker before the reconsolidation phase (which was done in this study) could be too late. To truly help these people, you would have to prevent initial consolidation. This means people would have to be treated prophylatically (i.e., give people the drug before the trauma). The problem for a soldier is that propranolol reduces reaction times, something that could mean life or death for a soldier (plus there is no evidence that it prevents fear conditioning).

As it relates to memory reconsolidation, propranolol produces results similar to sedatives (i.e., benzodiazepines, 9, 10), which are commonly prescribed to people with PTSD and only manage anxiety (i.e., not a cure). I'm failing to see the scientific breakthrough here. If you really want to help our veterans, be sure to blow smoke in faces of the children they hardly ever see (11).

Merel Kindt, Marieke Soeter, Bram Vervliet (2009). Beyond extinction: erasing human fear responses and preventing the return of fear Nature Neuroscience DOI: 10.1038/nn.2271

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The Nerd said...

I'm almost grasping the implications of this, but I'm wondering about a different application of fear management beyond PTSD. What would be the best way of removing the fear response to viewing microbiological images? I have mild panic attacks whenever I see (for example) an electron-microscope photograph of a neuron, but I will have to take a college course in Microbiology within the next year and a half. I will fail that class if I don't prepare myself somehow. Any ideas?

Doug Bremner said...

Ha ha, very funny post. When this came out I called my post about it "More bullshit research about a pill to erase bad memories." Felt good getting that one off of my chest