EVERYTHING IS WRONG

...about protein synthesis and memory formation, apparently. In keeping with the general theme of propranolol as a "memory eraser," a brand new iconoclastic paper (Canal, Chang, & Gold, 2007) claims that massive fluctuations in neurotransmitter levels (including norepinephrine, whose receptors are the target of beta blockers like propranolol; also dopamine and serotonin) -- rather than inhibition of protein synthesis (e.g., Doyere et al., 2007) -- are responsible for the amnestic quality of drugs like anisomycin:

New protein synthesis not essential to memory formation

Neuroscientist Paul E. Gold and colleagues have demonstrated that new protein synthesis is not required for long-term memory formation, a discovery that challenges basic assumptions about the mechanisms of memory....

. . .

Brain researchers have long used drugs that enhance or hinder memory formation to gain insight into the mechanisms at play. Early experiments in rats found that protein synthesis inhibitors injected into brain regions involved in memory processing could disrupt long-term memory formation. This led some to hypothesize that new protein synthesis was essential to the creation of long-term memories.

A research team led by neuroscientist Paul E. Gold discovered an alternate explanation for this effect. The researchers observed that the protein synthesis inhibitor anisomycin, which is commonly used in memory studies, causes dramatic changes in brain chemistry – apart from protein synthesis inhibition – that interfere with memory formation. They found that exposing rat brains to anisomycin sets off wild fluctuations in neurotransmitter levels in the brain region targeted in the experiment – the amygdala, one of several brain structures involved in processing memories and emotions. Large fluctuations in neurotransmitter levels in the amygdala are known to interfere with memory formation.

If this paper is correct, the results invalidate the premise of much previous research in the field [at the very least, regarding the mechanism of action for anisomycin in memory studies]. More later, hopefully...

References

Canal CE, Chang Q, Gold PE. (2007). Amnesia produced by altered release of neurotransmitters after intraamygdala injections of a protein synthesis inhibitor. Proc Natl Acad Sci. 104:12500-5.

Amnesia produced by protein synthesis inhibitors such as anisomycin provides major support for the prevalent view that the formation of long-lasting memories requires de novo protein synthesis. However, inhibition of protein synthesis might disrupt other neural functions to interfere with memory formation. Intraamygdala injections of anisomycin before inhibitory avoidance training impaired memory in rats tested 48 h later. Release of norepinephrine (NE), dopamine (DA), and serotonin, measured at the site of anisomycin infusions, increased quickly by ~1,000–17,000%, far above the levels seen under normal conditions. NE and DA release later decreased far below baseline for several hours before recovering at 48 h. Intraamygdala injections of a beta-adrenergic receptor antagonist or agonist, each timed to blunt effects of increases and decreases in NE release after anisomycin, attenuated anisomycin-induced amnesia. In addition, similar to the effects on memory seen with anisomycin, intraamygdala injections of a high dose of NE before training impaired memory tested at 48 h after training. These findings suggest that altered release of neurotransmitters may mediate amnesia produced by anisomycin and, further, raise important questions about the empirical bases for many molecular theories of memory formation.

Doyere V, Debiec J, Monfils MH, Schafe GE, Ledoux JE. (2007). Synapse-specific reconsolidation of distinct fear memories in the lateral amygdala. Nat Neurosci. 10:414-6.

When reactivated, memories enter a labile, protein synthesis–dependent state, a process referred to as reconsolidation. Here, we show in rats that fear memory retrieval produces a synaptic potentiation in the lateral amygdala that is selective to the reactivated memory, and that disruption of reconsolidation is correlated with a reduction of synaptic potentiation in the lateral amygdala. Thus, both retrieval and reconsolidation alter memories via synaptic plasticity at selectively targeted synapses.

Talk to the Hand and Just Say No

A new fMRI paper (Grosbras et al., 2007) examined the hemodynamic response [an indirect reflection of neural activity] in 10 yr old children who were watching videos of angry faces and gestures (versus neutral faces and gestures and control stimuli, see Fig 1 below). The authors wanted to see whether there were differences in the way that kids who are susceptible to peer pressure respond to these stimuli, relative to those who are resistant to peer pressure. The kids who are better able to resist peer pressure [at least, as measured by self-report on Steinberg and Monahan's resistance to peer influence questionnaire] showed more "coordinated" neural activity across a network of brain regions related to decision making and the perception of action than did the more easily influenced kids.

Fig 1 (Grosbras & Paus, 2006). Stimuli. Snapshots were taken at the beginning of representative clips of each condition. The video clips were displayed at 30 frames/s. Two consecutive images on the figure are separated by five frames.

Across all 35 participants [the data from 11 were thrown out due to excessive head motion],

the observation of hand movements engaged frontoparietal and middle temporal regions. Angry hand movements also recruited part of the parietal operculum/supramarginal gyrus, the medial prefrontal cortex, and the amygdala. The observation of angry or neutral faces engaged the premotor cortex, various parts of the inferior and medial frontal cortex, the fusiform cortex, the superior temporal sulcus, and the amygdala.

Next, an inverse correlation between RPI score and increased activity while watching angry hand or face movements (relative to neutral) was noted in the right dorsal premotor cortex and the left mid-dorsolateral prefrontal cortex. This means the less able to resist peer pressure, the greater the activity in those frontal areas. Hmm.

More sensitive children might engage more attentional resources when presented with salient stimuli such as angry hand movements.

OK, then. The children with high RPI scores (better able to resist peer pressure) showed greater functional connectivity (interregional correlations as determined by partial least-square analysis) between

both (1) regions involved in action observation, from the frontoparietal as well as from the temporo-occipital system..., and (2) regions in the prefrontal cortex.

What does this mean? Didn't we see greater frontal activity in the "just say yes" children?

It is important to note the difference between the findings obtained with univariate and multivariate analyses here. Univariate, voxel-by-voxel correlation between the fMRI signal and RPI scores showed a more robust response in low-resistance children independently in the premotor cortex and the prefrontal cortex. The multivariate analysis, in contrast, revealed stronger interregional correlations, or functional connectivity, between these and other regions in high-resistance children. We speculate that these two phenomena reflect, respectively, higher sensitivity of low-resistance children to socially relevant input and higher interregional integration of such inputs in high-resistance children. It is possible that the brains of the children with high RPI engage automatically executive processes when challenged with relatively complex and socially relevant stimuli. Interestingly, the children with higher RPI were also those who performed better in (explicit) executive tasks.

SO the kids who are better able to resist peer-pressure showed better executive control functions (no surprise there) and a higher correlation between prefrontal and posterior brain activity in response to those angry hands.

References

Grosbras M, Paus T. (2006) Brain networks involved in viewing angry hands or faces. Cereb Cortex 16:1087–1096.

Grosbras M-H, Jansen M, Leonard G, McIntosh A, Osswald K, Poulsen C, Steinberg L, Toro R, Paus T. (2007). Neural Mechanisms of Resistance to Peer Influence in Early Adolescence. J. Neurosci. 27:8040-8045.

During the shift from a parent-dependent child to a fully autonomous adult, peers take on a significant role in shaping the adolescent's behavior. Peer-derived influences are not always positive, however. Here, we explore neural correlates of interindividual differences in the probability of resisting peer influence in early adolescence. Using functional magnetic resonance imaging, we found striking differences between 10-year-old children with high and low resistance to peer influence in their brain activity during observation of angry hand movements and angry facial expressions: compared with subjects with low resistance to peer influence, individuals with high resistance showed a highly coordinated brain activity in neural systems underlying perception of action and decision making. These findings suggest that the probability of resisting peer influence depends on neural interactions during observation of emotion-laden actions.

Easy-Bake Finger

1M Easy-Bake Ovens recalled for burns, amputation dangers

Last Updated: Thursday, July 19, 2007 | 12:15 PM ET

Hasbro has issued a voluntary recall of about one million Easy-Bake Ovens because the toys pose an amputation and burn danger to children, the U.S. Consumer Product Safety Commission said Thursday.

. . .

Hasbro first announced a repair program in February, after learning of 29 incidents in which children's fingers or hands became trapped in the ovens. Five of those incidents included burns. The recall involved toys with the model number 65805.

The CPSC said in its release Thursday the company has since received 249 reports of children's hands or fingers catching in the oven...

And don't forget the recent recalls of Playskool Sippy Cups and Payless Clog Shoes, both of which pose a choking hazard to young children. The perils of preschool...

no, no, no, no drama

Like many female celebrities, Canadian singer Alanis Morissette has struggled with an eating disorder (particularly as a teenager). She's been open about it in her song lyrics and during interviews.

However, she isn't all about misery and serious issues. She certainly does have a sense of humor...

My Humps, Black Eyed Peas

If you touch it I'ma start some drama,
You don't want no drama,
No, no drama, no, no, no, no drama

"I'm Not As Slim As That Girl"

Fig. 1 (Friederich et al., 2007). Subjective anxiety ratings in response to images of interior design and body shape images (n = 16 healthy women). 0 = not anxious at all, 10 = very anxious. [NOTE: different results may be obtained in avid fans of Martha Stewart Living or HGTV or Queer Eye for the Straight Guy.]

The incidence of body dissatisfaction is notoriously high among women in western industrial society, and the constant stream of skinny skinny celebrities appearing in the media influences self-esteem. A meta-analysis of 25 published studies (Groesz et al, 2002) revealed that

Body image was significantly more negative after viewing thin media images than after viewing images of either average size models, plus size models, or inanimate objects. ... Results support the sociocultural perspective that mass media promulgate a slender ideal that elicits body dissatisfaction. Implications for prevention and research on social comparison processes are considered.

A recent neuroimaging study (Friederich et al., 2007) evaluated the brain activity of non-eating disordered¹ women as they viewed photographs of slim models and stylish interior designs. The stimuli were

Images of slim female bodies and interior design were provided by a women’s magazine. The images were selected from a larger database in a pilot study, if they were rated by 38 healthy female volunteers as (1) easy to recognize, (2) interesting and (3) provoking anxiety in self-comparison. ... The body shape images of fashion models depicted either the whole or part of the body (head excluded) of slim women dressed in clothes that revealed their shape (e.g., bikinis or body fitting sports clothing). The comparison (control) images were of interior designs (inanimate objects only, e.g., rooms containing designer cupboards, drawers, curtains, lights).

One weakness in the experimental design is that images of "average-sized" female bodies (or plus size models) were not included. This would seem to be an obvious comparison, as it would control for the appearance of bodies yet provoke lower anxiety ratings (in fact, one could run a pilot study to match the interior designs and everyday bodies on anxiety ratings).

A procedural aspect that was well-controlled was the task for each condition: compare one's own body/house to the ones in the pictures. Seems that comparing one's tiny apartment to Architectural Digest displays might induce greater anxiety in some individuals not included in the current study (the "Martha Stewart effect").

Nonetheless, results indicated that

Anxiety ratings in response to body models were positively correlated with activation in the left amygdala, bilateral basal ganglia (left putamen, left caudate body, right globus pallidus, right claustrum), bilateral dorsal anterior cingulate (maximum response in BA 32), left ventrolateral PFC (maximum response in BA 47), left apical PFC (maximum response in BA 10), right dorsolateral PFC (maximum response in BA 8), right precentral cortex (maximum response in BA 6) and left lingual gyrus (maximum response in BA 19).

Some of these brain regions are associated with responses to fear and anxiety (e.g., amygdala, portions of the basal ganglia). In addition, scores on the Eating Disorder Examination Questionnaire (global score, shape concern, and weight concern measures) correlated with anxiety ratings. The authors noted that dissatisfaction with one's body is not limited to eating disordered (ED) populations, and suggested that ED prevention programs could incorporate training in the top-down control of emotional responses [perhaps indexed by PFC and ACC activity here] when comparing one's self to an overly thin model.


Footnote

¹ For inclusion in the study, the participants had to have a body mass index between 17.5 and 25.0 kg/m². The former value is right at the cutoff for anorexia. However, the mean BMI was a healthy 21.9, and the 16 participants had never received diagnoses of an eating disorder or other psychiatric illnesses.


References

Friederich HC, Uher R, Brooks S, Giampietro V, Brammer M, Williams SC, Herzog W, Treasure J, Campbell IC. (2007). I'm not as slim as that girl: Neural bases of body shape self-comparison to media images. Neuroimage Jun 2; [Epub ahead of print].

The aim of the present study was to assess the impact of images of slim female fashion models on healthy young women. Brain responses to images of slim-idealized bodies (active condition) and interior designs (control condition) were measured using functional neuroimaging in 18 healthy young women. Instructions encouraged the participants to compare their own body shape/own home with the one in the images. Participants rated the level of anxiety that they experienced while exposed to the images. In the active relative to the control condition, participants activated body shape processing networks, including the lateral fusiform gyrus on both sides, the right inferior parietal lobule, the right lateral prefrontal cortex and the left anterior cingulate. The level of reported anxiety during the exposure to slim bodies correlated with established measures of shape and weight concern and with brain activations in bilateral basal ganglia, left amygdala, bilateral dorsal anterior cingulate, and left inferior lateral prefrontal cortex. Brain networks associated with anxiety induced by self-comparison to slim images may be involved in the genesis of body dissatisfaction and hence with vulnerability to eating disorders.

Groesz LM, Levine MP, Murnen SK (2002). The effect of experimental presentation of thin media images on body satisfaction: a meta-analytic review. Int J Eat Disord 31:1–16.

I Forgot...

Fig. 1. (A) Experimental procedure [adapted from Depue et al., 2007]. Individuals were first trained to associate 40 cue faces with 40 nasty target pictures. During the fMRI phase, individuals viewed only faces. On some trials they were instructed to think of the previously learned picture; on other trials they were instructed not to let the previously associated picture enter consciousness [no-think]. The presentation of only the cue (i.e., the face) ensures that individuals manipulate the memory of the target picture. Additional faces not shown during this phase acted as a behavioral baseline. During the test phase, participants were shown the 40 faces and asked to describe the previously associated picture.

Can you selectively and willfully forget (or at least, suppress) the past, particularly the most negative events? Not with a drug or ECT, but by using your brain's intrinsic "executive control"¹ abilities? As mentioned the other day in I Forget, the promise of propranolol has been overhyped. But can PTSD patients (and others with traumatic memories) be trained to forget their waking nightmares? Can one harness the intrinsic plasticity of the brain to "unlearn" (rather than learn)? As Dr. Michael Merzenich wrote recently:

BRAIN PLASTICITY IS A TWO-WAY STREET. It is “negative” plasticity that generates the changes in the brain that underly the impaired operational state of the depressed or stressed or anxious or obsessed or traumatized individual. PTSD, for example, is a PRODUCT of brain plasticity. Just as I can plausibly create a positive brain plasticity-based approach to re-normalize the brain of the PTSD patient, so, too, can I create the malady itself, at will, by training the brain in ways that drive specific “negative” changes within it.

These questions were not answered by a brand new fMRI paper in Science (Depue et al., 2007), but a more modest goal was to determine whether the neural activity (or rather, the hemodynamic response) in certain brain regions dipped below baseline levels when participants were actively trying to suppress thinking about unpleasant pictures (see above) that were paired with neutral faces. The study adapted the "think/no-think" paradigm of Dr. Michael C. Anderson (et al., 2001, 2004), who heads the Memory Control Lab at the University of Oregon.

Further details on the procedure were contained in the Supporting Online Material:

Similar to Anderson and Green, in the Think condition, participants were told "Think of the picture previously associated with the face", whereas in the No-Think condition they were told "Do not to let the previously associated picture come into consciousness." Within each condition (Think/No-Think), participants viewed the faces 12 times. The 8 faces not shown in the experimental phase served as a zero-repetition behavioral baseline.

The behavioral manipulation was effective in suppressing memory: mean recall rates were 71.1% in the think condition, compared to 53.3% in the no-think condition. Baseline recall was 62.5% (when subjects viewed the face-picture pair only in the training phase, but did not get 12 presentations of the face only in the experimental phase).

What were the brain imaging results? First, let's look at the data from the 2004 experiment of Anderson et al., which used word pairs as stimuli (e.g., roach-ordeal, steam-train, jaw-gum) instead of face-picture pairs.

Fig. 2 (Anderson et al., 2004). Activation for Suppression trials compared with Respond trials during the think/no-think phase. Areas in yellow were more active during Suppression trials than during Respond trials, whereas areas in blue were less active during Suppression (P less than 0.001, uncorrected). White arrows highlight hippocampal deactivation in the Suppression condition.

A network of brain regions was more active during suppression than during retrieval, including bilateral dorsolateral and ventrolateral prefrontal cortex (DLPFC and VLPFC, respectively; Brodmann's area (BA) 45/46, stronger on left); anterior cingulate cortex (ACC; BA 32); the contiguous pre-supplementary motor area (preSMA; BA 6), a lateral premotor area in the rostral portion of the dorsal premotor cortex (PMDr; BA 6/9); and the intraparietal sulcus (IPS; BA 7) (also in bilateral BA 47/BA 13, and right putamen).

Furthermore, the degree of activity in bilateral DLPFC and left VLPFC [and a few other places] was related to an individual's ability to suppress remembering in the no-think condition (Anderson et al., 2004). So were the results similar in the current study, or did they differ due to the use of yucky pictures (from the IAPS) as the suppressed stimuli?

Prefrontal regions, right-sided and spanning BA 8, 9/46, 47, and BA 10, exhibited NT > T contrast. A conjunction analysis indicated that these differences resulted from an increase in activity for NT trials rather than a decrease in activation for T trials relative to baseline (Fig. 2A), which suggests that these regions are specifically involved in controlling the suppression of emotional memories.

Fig. 2 (Depue et al., 2007). Functional activation of brain areas involved in (A) cognitive control, (B) sensory representations of memory, and (C) memory processes and emotional components of memory. ... Red indicates greater activity for NT trials than for T trials; blue indicates the reverse. Conjunction analyses revealed that areas seen in blue are the culmination of increased activity for T trials above baseline as well as decreased activity of NT trials below baseline.

Brain areas underlying the sensory representation of memory that showed such an effect [NT greater than T, NT negative relative to baseline, and T positive relative to baseline] were the visual cortex, including bilateral BA17, BA18, and BA37 [fusiform gyrus (FG)], and the pulvinar nucleus of the thalamus (Pul; Fig. 2B). Suppression of emotional memories thus involved decreased activity in sensory cortices that are normally active when memories are being retrieved, as well as in regions (i.e., Pul) that play a role in gating and modulating attention toward or away from visual stimuli.

And the hippocampus and amygdala showed no-think reductions in activity (Fig 2C), as would be expected for structures involved in memory and emotion, respectively.

Finally, the authors divided the data up into quartiles based on the order of experiment trials -- i.e., Q1 was comprised of trials 1-3, Q2 was 4-6, etc. to reveal the two phases of memory suppression:

Two patterns of temporal change in activation were observed, each associated with different groupings of prefrontal and posterior brain areas. The two groupings were composed of (i) right inferior frontal gyrus (rIFG), Pul, and FG, and (ii) right middle frontal gyrus (rMFG), Hip, and Amy [Hip and Amy! love the abbreviations!] ... rIFG showed early activation in the time course of suppression, which lasted through the second quartile of repetitions... Greater activity in rIFG in the second quartile was significantly associated with decreased activity in Pul and FG during the second quartile...

In contrast to rIFG, rMFG activation increased later and remained active. Activity in Hip and Amy appeared to follow that of rMFG in reverse... Increased activity in rMFG did not predict activity in Hip and Amy in the first or second quartiles, but did so significantly in the third and fourth quartiles.

But who's controlling these controllers? Why, Brodmann area 10 (frontopolar cortex) is the orchestra's conductor! And that's not all! It seems to me that the hippocampus showed a wacky pattern of activity.







Fig S3 (Depue et al., 2007). Percent signal change analysis in the hippocampus over all quartiles for NT trials that were forgotten (NTf, red solid line), NT trials that were remembered (NTr, red dashed line), T trials that were forgotten (Tf, green dashed line), and T trials that were remembered (Tr, green solid line).

So do these findings have any relevance for suppressing traumatic memories in PTSD? Opinions are mixed:

Rather not remember? You can fuggedaboudit
by Kavita Mishra

. . .

New research suggests that people can push out memories, even highly emotional ones, simply by deciding to do so.

The researchers believe the new findings will help scientists understand disorders like post-traumatic stress disorder and obsessive-compulsive disorder, in which the brain's mechanism of suppressing unwanted memories may be dysfunctional, said lead author Brendan Depue, a graduate student in neuroscience and clinical psychology at the University of Colorado at Boulder.

But many experts are wary of linking the findings -- published today in the online journal Science -- to debilitating disorders like PTSD. They believe the mind developed to actively forget some memories to keep from cluttering the brain with unpleasant memories and irrelevant information, like unnecessary phone numbers. But highly emotional memories may never be forgotten.

"We have these mechanisms to try to stamp out and suppress these things when we want to try to avoid uncomfortable thoughts. On the other hand, we do know that very serious emotional memories are, in general, very remembered," UC Berkeley psychologist Art Shimamura said.

. . .

Dr. Thomas Neylan, a PTSD expert at the San Francisco Veterans Affairs Medical Center, said training in memory suppression is not the goal of treatment in many disorders. "Effective treatment (in PTSD) is to promote a new form of learning," he said. "When a person retrieves the memory of the trauma, they no longer associate it with all the same feelings of fear and arousal. With repetition, they are no longer as aroused, upset or angry. That process involves a new form of learning, not memory suppression."

Footnote

¹ Or as it is more fashionably called these days, "cognitive control."

References

Anderson MC, Green C. (2001). Suppressing unwanted memories by executive control. Nature 410:131-134.

Anderson, M.C., Ochsner, K.N., Kuhl, B., Cooper, J., Robertson, E., Gabrieli, S.W., Glover, G.H., Gabrieli, J.D.E. (2004). Neural systems underlying the suppression of unwanted memories. Science 303:232-235.

Depue BE, Curran T, Banich MT. (2007). Prefrontal Regions Orchestrate Suppression of Emotional Memories via a Two-Phase Process. Science 317:215-219.

I Forget...

Forgotten, by Linkin Park

From the top to the bottom
Bottom to top I stop
At the core I’ve forgotten
In the middle of my thoughts
Taken far from my safety
The picture is there
The memory won't escape me
But why should I care

Chester Bennington of Linkin Park

Forgetting the most traumatic parts of one's past would seem to be of benefit to the lead singer of Linkin Park (as it would be to many of us). And now you can!! [according to recent reports in the press.] The first irresponsible story is old hat at this point (i.e, more than a week old), but since news cycles last for, oh, about 24 seconds these days [before collective amnesia supposedly sets in], let's review some of the most egregious headlines:

New Drug Deletes Bad Memories
By Bill Christensen
posted: 02 July 2007

Do you have a really bad memory, or past heartache, that you would prefer to forget?

Researchers at Harvard and McGill University (in Montreal) are working on an amnesia drug that blocks or deletes bad memories. The technique seems to allow psychiatrists to disrupt the biochemical pathways that allow a memory to be recalled.

In a new study, published in the Journal of Psychiatric Research, the drug propranolol is used along with therapy to "dampen" [not delete, after all?] memories of trauma victims....

AND

Scientists find drug to banish bad memories
By Richard Gray, Science Correspondent
Last Updated: 12:01am BST 01 July 2007

It failed to bring Jim Carrey happiness in the award-winning film Eternal Sunshine of the Spotless Mind, but scientists have now developed a way to block and even delete unwanted memories from people's brains.

Researchers have found they can use drugs to wipe away single, specific memories while leaving other memories intact. By injecting an amnesia drug at the right time, when a subject was recalling a particular thought, neuro-scientists discovered they could disrupt the way the memory is stored and even make it disappear.

But really, propranolol does no such thing! [as discussed recently in Psych Central and Mind Hacks.] Back in March, The Neurocritic reviewed the literature on post-traumatic stress disorder and norepinephrine:

So what about propranolol for PTSD? According to Strawn & Geracioti (2007),

The utility of these anti-adrenergics in the clinical treatment of PTSD remains to be determined, though it is possible that they may prove to have primary roles in a disorder that is only modestly responsive to antidepressant treatment.

So you might imagine that the discerning and jaded eye would be skeptical if confronted with the latest headline:

You can forget the unhappy past: study
By Ishani Ganguli

WASHINGTON (Reuters) - Researchers have confirmed what common wisdom has long held -- that people can suppress emotionally troubling memories -- and said on Thursday they have sketched out how the brain accomplishes this.

They said their findings might lead to a way to help patients with post-traumatic stress disorder or anxiety to gain control of debilitating memories.

"You're shutting down parts of the brain that are responsible for supporting memories," said Brendan Depue, a neuroscience doctoral student at the University of Colorado who worked on the study. He said his team discovered the brain's emotional center is also shut down.

Dude, do you really shut off the visual cortex and thalamus and hippocampus and amygdala entirely? Stay tuned...

Depue BE, Curran T, Banich MT. (2007). Prefrontal Regions Orchestrate Suppression of Emotional Memories via a Two-Phase Process. Science 317:215-219.

Whether memories can be suppressed has been a controversial issue in psychology and cognitive neuroscience for decades. We found evidence that emotional memories are suppressed via two time-differentiated neural mechanisms: (i) an initial suppression by the right inferior frontal gyrus over regions supporting sensory components of the memory representation (visual cortex, thalamus), followed by (ii) right medial frontal gyrus control over regions supporting multimodal and emotional components of the memory representation (hippocampus, amygdala), both of which are influenced by fronto-polar regions. These results indicate that memory suppression does occur and, at least in nonpsychiatric populations, is under the control of prefrontal regions.

So let mercy come
And wash away
What I've done

I'll face myself
To cross out what I've become
Erase myself
And let go of what I've done

-- Linkin Park, What I've Done

References

Brunet A, Orr SP, Tremblay J, Robertson K, Nader K, Pitman RK. (2007). Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder. J Psychiatr Res. Jun 21; [Epub ahead of print]

The β-adrenergic blocker propranolol given within hours of a psychologically traumatic event reduces physiologic responses during subsequent mental imagery of the event. Here we tested the effect of propranolol given after the retrieval of memories of past traumatic events. Subjects with chronic post-traumatic stress disorder described their traumatic event during a script preparation session and then received a one-day dose of propranolol (n = 9) or placebo (n = 10), randomized and double-blind. A week later, they engaged in script-driven mental imagery of their traumatic event while heart rate, skin conductance, and left corrugator electromyogram were measured. Physiologic responses were significantly smaller in the subjects who had received post-reactivation propranolol a week earlier. Propranolol given after reactivation of the memory of a past traumatic event reduces physiologic responding during subsequent mental imagery of the event in a similar manner to propranolol given shortly after the occurrence of a traumatic event.

Strawn JR, Geracioti TD Jr. (2007). Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder. Depress Anxiety Mar 12; [Epub ahead of print].

The catecholamine norepinephrine is a critical effector of the mammalian stress response and has been implicated in the pathophysiology of posttraumatic stress disorder (PTSD) -- a syndrome intrinsically related to the experience of extraordinary stress. Symptom-linked hypernoradrenergic derangements have been observed in PTSD and several studies have examined the potential therapeutic effects of agents that dampen the centrally hyperactive noradrenergic state. These agents include compounds that decrease norepinephrine release (e.g. centrally acting alpha(2) agonists such as clonidine) and those which block post-synaptic norepinephrine receptors (e.g. centrally acting alpha(1) or beta receptor antagonists such as prazosin or propranolol). In this article, we review studies of central noreadrenergic hyperactivity under both basal and challenge conditions and explore the evidence for these derangements as potential psychopharmacologic targets in patients with PTSD. Given the significant involvement of CNS norepinephrine hyperactivity in PTSD, and its link to intrusive and hyperarousal symptoms, it is not surprising that interventions directed at this system have therapeutic potential in PTSD. The utility of these anti-adrenergics in the clinical treatment of PTSD remains to be determined, though it is possible that they may prove to have primary roles in a disorder that is only modestly responsive to antidepressant treatment.