Friday, October 16, 2009

Tests: Small Samples, Large Consequences

Dahlstrom, W. G. (1993). Tests: Small Samples, Large Consequences. American Psychologist, 4, 393-399.

Human decision making is a complex process, and one which often has large consequences, both positive and negative. However, this process is not uncommonly fraught with errors of judgment. Psychological tests can serve as a means to offset the impact of these distortions. The article gives several examples of proper and improper use of tests, such as the use of the Stanford-Binet to determine a defendant was not fit to stand trial as an adult, overturning recommendations formerly made by a psychiatrist employing informal ad hoc tests. They define a proper psychological test as meeting six key criteria: using standardized materials and procedures, ensuring optimal motivation in test-takers, recording data immediately, scoring objectively, and establishing test norms. The article is summarized nicely: "The samples of behavior that psychologists collect in the brief time that an hourglass takes to empty have been shown to reveal basic aspects of ability, personality, and temperament that are operative over long spans of an individual's life. Proper gathering of these data by means of well-executed administrations of standardized test instruments can provide gatekeepers with invaluable information to minimize risks of errors of judgment in decisions about their clients and increase the range of predictions that can have large consequences in the lives of those with whom they deal."

Sunday, September 27, 2009

Psychiatric Resident Conceptualizations of Mood and Affect within the Mental Status Examination

Serby, M. (2003). Psychiatric Resident Conceptualizations of Mood and Affect within the Mental Status Examination. American Journal of Psychiatry, 160, 1527-1529.

In the Mental Status Exam (MSE), affect is conceptualized as "external, objective, visible emotional tone. It is also the moment-to-moment measure, while may be labile or constricted, congruent or not with expressed ideas, and may be varied during any interview." Mood, on the other hand, is conceptualized as "an internal, subjective, and sustained emotional state and should be reported as such". However, this study revealed that psychiatric residents do not typically abide strictly to these definitions. They tend to understand that mood is subjective/internal and affect is objective/external, but appear to be less focused on the temporal distinction between the two.

Evidence-Based Assessment of Pediatric Bipolar Disorder

Youngstrom, E.A. & Duax, J. (2005). Evidence-Based Assessment of Pediatric Bipolar Disorder, Part I: Base Rate and Family History. Journal of American Academic Child and Adolescent Psychiatry, 44, 712-716.

Bipolar disorder is rare in children before puberty, there is controversy about how to diagnose it, and there are few published clinical trials to guide treatment. Additionally, there is evidence that use of stimulants or antidepressants might worsen the course of illness; the compounds most likely to be effective also have the potential for serious side effects and therefore should not be prescribed unless one is confident in the diagnosis and the potential for benefit. On the flip side, there are strong concerns that untreated bipolar disorder will follow a progressive and deteorating course. Therefore, diagnosis of pediatric bipolar disorder (PBD) is both controversial and high-stakes.

This article discusses how one might implement recommendations of Evidenced-Based Practice (EBP) to gather additional information and integrate it in order to obtain greater confidence regarding further testing or treatment. A recent meta-analysis indicates that children with a first-degree relative with bipolar have a 5-fold increase in risk, and children with a second-degree relative with bipolar have a 2.5-fold risk increase. Another recent meta-analysis reveals that no other risk factors besides family history have been sufficiently documented to justify integration into clinical decision-making. Therefore, combining the child's familial information with current diagnostic base rates (which can be obtained from publications reporting rates from similar demographies, clinical settings, and interviewing techniques), and using Bayesian methods can yield probabilities that the specific individual has the diagnosis (or alternately, the frequency with which people showing that test result at that particular clinic would have the condition). If the probability yielded is below the test/no-test threshold, then no further testing may be required. If the number is above the treatment threshold, then treatment may be warranted. (Note: Often the treatment threshold is determined by the clinician in consultation with the family, weighing information about the costs and benefits of treatment.) If the number falls in between these thresholds, then further assessment may be prudent.

Friday, May 1, 2009

The effect of exercise on depression, anxiety, and other mood states

Byrne, A. & Byrne, D.G. (1993). The effect of exercise on depression, anxiety, and other mood states. Journal of Psychosomatic Research, 37, 565-574.

This review supports the claim that exercise treatments are associated with positive psychological benefits for both clinical and non-clinical populations. Although most of the studies employed aerobic interventions, some studies even showed positive improvements associated with non-aerobic exercise (e.g. weight lifting). However, all of these results need to be interpreted with caution as the result of methodological limitations and indirect evidence. If future studies were to show unequivocally positive psychological gains are caused by exercise interventions, including exercise for people with affective disorders will undoubtedly have a number of advantages since it is time and cost effective by comparison to psychotherapy and pharmacotherapy, comes with few side effects if done correctly, and may even by used to prophylactically prevent the occurrence of future affective episodes.

Wednesday, April 29, 2009

Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex

Radley, J.J. et al. (2005). Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex. Cerebral Cortex, 16, 313-320.

The medial prefrontal cortex (mPFC) plays an important role in higher cognitive processes and in the regulation of stress-induced HPA axis activity. This study investigated the effect of stress on dendritic spine density in the mPFC. Rats were restrained for 6 hours daily for 21 days with wire mesh. Following the 21 days of stress, stressed rats weighed less than controls, had a 20% decrease in overall apical dendritic length, a 16% decrease in apical dendritic spine density, and hence an estimated 33% reduction in the total number of axospinous synapses on apical dendrites of pyramidal neurons in the mPFC. These morphological changes may have a significant impact on the functional properties of this region. Clinically, mPFC dysfunction is associated with PTSD and depression. One potential neuroanatomical substrate relevant to these disorders is the mPFC-amygdala circuit. Normally, the mPFC may inhibit amygdala output through its connections on the GABAergic intercalated cells at the border of the lateral and central nuclei of the amygdala. Experimental lesions of the mPFC support this, leading to an enhancement of amygdala-dependent behaviors such as emotionality and fear conditioning. Future studies are needed to investigate the extent to which these morphological changes from chronic stress are reversible.

Comparisons of Stimulus Learning and Response Learning in a Punishment Situation

Bolles, R.C., Holtz, R., Dunn, T., & Hill, W. (1980). Comparisons of Stimulus Learning and Response Learning in a Punishment Situation. Learning and Motivation, 11, 78-96.

Early on in the study of learning, learning was believed to consist of the attachment of a response to a stimuli (an S-R association). Later, in contrast with the long-held conventional view that all learning was of the S-R form, alternative forms were proposed by Pavlov and others. Examples include stimulus learning (S-S*) and response learning (R-S*). What type of learning underlied punishment, for example? This stimulated debate. In common punishment paradigms, it became obvious that is was unclear whether the animal was learning that shock is correlated there contextually with the bar (stimulus) or whether shock is correlated with its behavior of pressing the bar (response). The purpose of this paper was to attempt to disentangle these different forms of learning experimentally. Four novel experimental paradigms were explored.

Experiment 1 contained one single bar in the chamber which could either be pressed or pulled. Animals had to alternate their behavioral response (press to pull, and back again) in order to be rewarded. Punishment was delivered on every tenth press for half the animals or every tenth pull for the other half. Results showed a rapid initial suppression (fear to environmental stimuli), but later a return to baseline for the unpunishment response and continued suppression for the punished response. This seems to be evidence for both types of learning taking place within one paradigm. Experiment 2 simply adjusted the response contingencies (up and down) to see if results would be sensitive to this type of experimental manipulation. Instead of an FR-10 punishment schedule, rats were shocked on FR-4 or FR-25. FR-4 showed dramatic differences in responding from the outset. FR-25 differences only emerged in the second day of punishment.

Experiment 3 used two bars, each of which could be either pressed or pulled. Thus, four punishment conditions were possible, punishing a left-press, a left-lift, a right-press, or a right-lift. Results showed that when a rat was punished for a left-lift, for example, it quickly stopped lifting AND pressing the left bar. However, it continued to lift AND press the right bar. Thus, learning, in this case, seems to be mostly about stimuli. Experiment 4, like Experiment 2, changed the contingencies. Punishment was shifted from an FR-1 schedule to an FR-10 schedule. Punishment conditions were: press or lift left bar, press or lift right bar, lifting left or right, and pressing left or right. Across the conditions, the general trend that emerged was a rapid emergence of stimulus learning and then a slower but undeniable development of response learning.

Wednesday, April 1, 2009

Getting comfortable with conversations about race and ethnicity in psychotherapy

Cardemil, E. V., & Battle, C. L. (2003). Guess who’s coming to therapy? Getting comfortable with conversations about race and ethnicity in psychotherapy. Professional Psychology: Research and Practice, 34, 278-286.

This article urges therapists to engage in open conversations with their clients about race and ethnicity as it applies to the client, the therapist, and the therapeutic alliance. By taking a more active stance and initiating such discussions, especially early in treatment, the therapist may enjoy improved treatment retention, therapeutic alliance, and treatment outcome. After defining race and ethnicity as similar but distinct constructs, the article acknowledges that such conversations will vary in terms of frequency and intensity over different clients and times. It then goes on to provide six recommendations for becoming more comfortable and knowledgeable with having such discussions.

First, it is acknowledged that a client's racial/ethnic background may not be obvious and that it is best to suspend preconceptions about a client and their family members. It is recommended that clients be asked early on in therapy how they identify themselves. Second, it is acknowledged that wide variability exists within racial and ethnic groups and that a client's racial identity development and acculturation process may change over time, thus affecting therapy. Third, it is important to consider how the therapist's own racial/ethnic background may affect the therapeutic process in terms of differences in communication styles and conceptualization of mental health/illness, self, and family/community. Fourth, it is acknowledged that racism, power, and privilege can affect the therapeutic process and that failing to acknowledge such societal issues may invalidate a client's painful personal experiences. Fifth, it is recommended that a client expressing reticence and/or frustration with the topics of race and ethnicity be met with an open and non-defensive explanation that such topics are relevant to many clients, but needn't be pursued if they are found irrelevant or uncomfortable. Lastly, resources for further education/training in race and ethnicity are provided.

Wednesday, December 3, 2008

Symmetrical effects of amphetamine and alpha-flupenthixol on conditioned punishment and conditioned reinforcement: contrasts with midazolam

Killcross, A.S., Everitt, B.J., & Robbins, T.W. (1997). Symmetrical effects of amphetamine and alpha-flupenthixol on conditioned punishment and conditioned reinforcement: contrasts with midazolam. Psychopharmacology, 129, 141-152.

There is evidence to suggest that forebrain dopaminergic systems are likely to be involved in both appetitive and aversive motivation. These authors studied the effects of dopamine (DA) agents on conditioned punishment (aversive learning) and conditioned reinforcement (appetitive learning) paradigms using DA agonists and antagonists injected systemically. In conditioned punishment, a Pavlovian CS predicting punishment is added to an instrumental bar-pressing paradigm, but only on one of the bars. Normal animals will adjust their bar-pressing away from this lever. (Note: These authors, however, implemented a punishment procedure by presenting a CS and shock upon bar-press, rather than a conditioned punishment procedure which would only present the CS upon bar-press). In conditioned reinforcement, a CS predicting reward is added to the instrumental bar-pressing paradigm on one of the bars. Animals will naturally come to favor this bar paired with the appetitive CS.

DA agonists increased the effect of a punishing CS, causing the animals to further decrease their bar pressing. DA agonists also enhanced the effect of an appetitive CS, increasing bar pressing. DA antagonists, on the other hand, decreased the effect of a punishing CS. They also reduced the effect of an appetitive CS. Thus, it appears dopaminergic agents modulate the behavioral impact of both appetitively and aversively motivated conditioned stimuli on instrumental performance. Systemic benzodiazepene administration was also explored with results showing a selective impact on aversively-motivated stimuli (i.e. no effect on the appetitive CS).

Saturday, November 29, 2008

The Value of Believing in Free Will

Vohs, K.D. & Schooler, J.W. (2008). The Value of Believing in Free Will. Psychological Science, 19, 1, 49-54.

This study found that weakening people's belief in free-will increased ignoble behaviors, specifically cheating. In the first experiment, a passive cheating paradigm was explored in which a computer "glitch" allowed the correct answer to a question to be flashed onto the screen unless the participant explicitly suppressed it. The experimental group was read a statement encouraging a belief in determinism, while the control condition was read an unrelated statement. Those in the experimental group showed weaker free will beliefs and more frequent cheating.

In the second experiment, an active cheating paradigm was explored. After reading either a pro-free-will statement or an anti-free-will statement, participants were left in the room on the "honor system" and told to reward themselves for their number of correct responses. In this experiment, as in the previous one, participants were under the impression that their anonymity was preserved. Results were similar with the determinism condition showing weaker free will beliefs and higher than average cheating. Thus, people's beliefs regarding their sense of control and self-agency may have social implications.

Saturday, November 22, 2008

Different lateral amygdala outputs mediate reactions and actions elicited by a fear-arousing stimulus

Amorapanth, P., LeDoux, J.E., & Nader, K. (2000). Different lateral amygdala outputs mediate reactions and actions elicited by a fear-arousing stimulus. Nature Neuroscience, 3, 1, 74-79.

One common reaction to threat is elicitation of unlearned species-typical defense reactions. Another is the ability to take novel actions in threatening situations, which may also prove advantageous. In escape-from-fear (EFF) tasks, animals come to learn that an arbitrary response (e.g. stepping into the adjoining chamber) terminates a CS which predicts shock. Authors placed lesions throughout the fear circuit to see try to elucidate function. Lateral amygdala (LA) is believed to be the sensory interface where CS information enters the amygdala; lesions here block acquisition of both conditioned freezing responses, as expected, but also block acquisition of the CS's reinforcement of a new response in the EFF task. Central nucleus (CE) lesions block expression of hard-wired motoric output (i.e. freezing itself), but not the EFF. Basal nucleus (B) lesions had no effect on conditioned freezing, but did block the EFF. By way of interactions between the B and striatal circuits, reinforcement in the amygdala may come to reinforce novel motor responses. Thus, it may be that activation of LA by a CS triggers a reactive response output system via the CE and an active output system via the B.

Thursday, October 23, 2008

Nonconscious mimicry as an automatic behavioral response to social exclusion

Lakin, J.L., Chartrand, T.L., & Arkin, R.M. (2008). I am too just like you: Nonconscious mimicry as an automatic behavioral response to social exclusion. Psychological Science, 19, 8, 816-822.

First, this study showed that following exclusion by a group, participants increased their nonconscious behavioral mimicry of a brand-new interaction partner, reinforcing the expectation that people should be motivated to engage in affiliative behaviors after exclusion. Second, the study attempted to see if this automatic behavior is carried out bluntly, or whether it is sensitive to other factors. Researchers found that individuals excluded by an in-group mimicked the behaviors of a subsequent interaction partner only if the partner was an in-group member (as opposed to an out-group member). Therefore, it appears that people are selective with their use of automatic mimicry, increasing employment of it with people who can potentially restore their status with the in-group. In this way, belongingness was seen as related to mimicry. (Other factors, such as mood, self-esteem, meaningful existence, and control did not appear to be as related.)

Thursday, October 9, 2008

Ethanol-conditioned flavor preferences compared with sugar- and fat-conditioned preferences in rats

Ackroff, K., Rozental, D., Scalfani, A. (2004). Ethanol-conditioned flavor preferences compared with sugar- and fat-conditioned preferences in rats. Physiology & Behavior, 81, 699-713.

Past studies in rats have suggested that the postingestive effects of various nutrients can condition strong flavor preferences. Research has been conducted on ethanol using oral conditioning (where the ethanol is mixed in with the flavoring, thus adding its own flavor to the mixture) and intragastic conditioning (where the ethanol is injected into the rat’s stomach after it ingests the flavoring, thus eliminating the ethanol’s flavor as a conditioning factor). However, the findings of these studies have been somewhat contradictory. Mehiel and Bolles (1988) found that rats equally preferred a flavor paired with ethanol and a flavor paired with sucrose, while Sherman et al. (1983) found that rats preferred a flavor paired with glucose to a flavor paired with ethanol. These studies different in terms of design, route of administration, and sugar used, but it is unclear which of these factors are responsible for the confliction. The present study examined this question in a series of four related experiments.

In the first experiment, sucrose and ethanol were compared to each other as well as to a control of water. These nutrients were each paired with a different flavor and administered through intragastric infusion. Unlimited access to alternating flavor/nutrient combinations was provided during a training period and then the amount of each combination consumed was measuring during a test in which the rats could choose between different combinations. The results were that (1) the rats preferred both sucrose- and ethanol-paired flavors to the water-paired flavor, (2) the rats strongly preferred the sucrose-paired flavor to the ethanol-paired flavor, and (3) the rats ingested more sucrose mixture than ethanol mixture during the training period.

The second experiment attempts to control for finding (3) in experiment one by adding the additional constraint that sucrose mixture consumption was limited to the previous day’s ethanol mixture consumption. Findings (1) and (2) did not change as a result.

In the third experiment, the oral conditioning method was used in place of intragastric infusion for nutrient administration. Once again, the findings did not change.

Finally, in the fourth experiment, ethanol was compared to fructose and corn oil using the intragastic infusions. Similar to the sucrose findings, the rats preferred these new sugars to ethanol, while still preferring ethanol to water.

This study supports the findings of Sherman et al. (1983) and eliminates training intakes, route of administration, and specific sugar/fat as explanations of Mehiel and Bolles’ (1988) contradictory findings. Something other than energy concentration affects the efficacy of ethanol as a reinforcer, making it less powerful than other sugars/fats.

Monday, October 6, 2008

Evidence for episodic memory in a Pavlovian conditioning procedure in rats

O'Brien, Jamus; Sutherland, Robert J. Evidence for episodic memory in a Pavlovian conditioning procedure in rats. Hippocampus. Vol 17(12) 2007, 1149-1152.

Several requirements have been proposed for establishing episodic memory in nonlinguistic species. Clayton et al. (2003) suggest that episodic memory competence requires integrated representations of “what", "where", and "when” content that can be flexibly updated as more information is gathered. Tests of episodic memory should be novel and unexpected, exceed the capacity of short-term memory (Dere et al., 2006), be unsolvable by familiarity judgments (Gallistel, 1990), and involve memories formed in unique one-trial learning episodes (Morris, 2001). In this article, O’Brien and Sutherland design and run an experiment that attempts to meet these requirements while testing for the flexible and integrated representations required for episodic memory.

In this experiment, twenty-two male Long-Evans rats were run through three experimental phases. In Phase 1, rats were given time to explore two different “contexts” (boxes A and B). These boxes were Plexiglas modular test chambers with steel grid floors. Box A had black colored walls and was scented with Quatzyl-D-Plus, while box B was white and scented with Clinicide. Each rat visited Box A on three successive mornings and Box B on three successive evenings. In Phase 2, rats were exposed to a single immediate shock in a “chimerical” box that was half black, half white, and unscented. For half the rats, this occurred in the morning and for the other half, it occurred in the evening; this is the study’s independent variable. In Phase 3, during mid-day, rats were placed in one of the contexts from Phase 1 (either Box A or Box B). Fear responses (this study’s dependent variable) were then measured by timing conditioned “freezing” behavior.

A repeated measure ANOVA was conducted on the percent of time spent freezing during Phase 3, and it was predicted that rats placed in the context congruent to the time of day of their shock would exhibit more freezing than rats placed in the incongruent context. (For example, if a rat was in Box A in the morning and Box B in the evening during Phase 1 and received its shock in the morning during Phase 2, then the congruent context would be Box A and the incongruent context would be Box B.) The results were a significant relationship in the direction predicted (F(1,20) = 45.0, P < 0.001).

These findings support the idea that rats acquire memories laden with temporal context (or “when” content), such as the time of day, which is an important requirement of establishing episodic memory competence. Further studies could continue this line of research by establishing evidence for rats generating “what” and “where” content, and by exploring the nature of rats’ temporal cues – possibly endogenous circadian oscillators (Gallistel, 1990) or the age of granule cells in the dentate gyrus of the hippocampus (Aimone et al., 2006).

Friday, September 19, 2008

Modifying shyness-related behavior through symptom misattribution

Brodt, S.E. & Zimbardo, P.G. (1981). Modifying shyness-related behavior through symptom misattribution. Journal of Personality and Social Psychology, 41, 437-449.

In response to anxiety-evoking stimuli, people develop a complex constellation of reactions. Over time, a general categorical label may come to link these components together and serve as a central explanation. For some people, this label may undergo further transformation from its original situational attribution to a broader usage that includes the person's disposition (personal causality). For example, a person may immediately invoke the label "I am afraid of men" which in turn may kick off a response chain and impose constraints upon it, creating self-fulfilling prophecies. The authors of this study wanted to weaken the 3-part link between perceived symptoms of arousal, the corresponding dispositional label, and resultant behaviors by intervening with symptom misattribution.

In this experiment with 46 college women, the dispositional label studied was shyness -- an excessive self-focus in which potential rejection by other people and social anxiety are salient cognitions. Seeking to redirect the arousal from an anxiety-laden source (being alone with a member of the opposite sex) to a nonpsychological source, the researchers exposed all the groups to intense noise and led the "shy misattribution" group to believe that common side effects of noise bombardment was heart-pounding and increased pulse, symptoms normally associated with their social anxiety. Another group, the "shy comparison" group were led to believe the noise only caused dry mouth. Another "non-shy" group, unlike the other groups did not score high on shyness ratings, were given the same story as the "shy misattribution group". Results showed that shy women, when given an alternative explanation for their social anxiety, were able to overcome normal limitations of their shyness, talking significantly more, acting more assertive, and showing a stronger affiliative preference than the comparison group. Thus, misattribution demonstrates the power of social cognitions in controlling behavior.

Monday, September 15, 2008

Hippocampal involvement in contextual modulaton of fear extinction

Ji, J. & Maren, S. (2007). Hippocampal involvement in contextual modulaton of fear extinction. Hippocampus, 17, 749-758.

Responding to an extinguished CS is susceptible to many recovery effects. The first is renewal, in which changing the context favors recall of extinguished fear memory. Examination of its several forms (ABA, AAB, ABC) led researchers to postulate that following extinction the meaning of the CS becomes ambiguous and requires context to disambiguate; inhibitory association is "gated" so that its activation requires the simultaneous presence of the CS and the extinction context. The second is spontaneous recovery, or the return of conditional responding with the passage of time. Studies suggest that renewal and spontaneous recovery appear to result from a similar control mechanism, rather than simply erasure of the original fear memory. Therefore, some see SR as another renewal effect that occurs outside of the "temporal extinction context". Third is reinstatement, in which the extinguished response returns after extinction if the animal is merely exposed to the US alone in a distinct context. This, likewise, appears to be a context-dependent process.

These all suggest that extinction involves new learning, and that this learning is especially sensitive to context. The hippocampus, mPFC, and amygdala have been implicated in this learning. One model holds that when the animal is tested within the extinction context, hippocampus drives mPFC inhibition of LA. When animals are presented with an extinguished CS outside of the extinction context, the hippocampus may inhibit mPFC activation and thus promote excitation in the LA to renew extinguished fear under these conditions. Another model posits direct projection from hippocampus to LA subserving contextual modulation of extinction.

Tuesday, September 9, 2008

Switching on and off fear by distinct neuronal circuits

Herry, C. et al. (2008). Switching on and off fear by distinct neuronal circuits. Nature, 454, 600-605.

Whereas firing of amygdala neurons is necessary for retrieval of conditioned fear memories, extinction of these fear memories is thought to be controlled by constraining this neural activity by local inhibitory circuitry (under the influence of mPFC). However, fear extinction is known to be a fragile behavioral state, readily influenced by context, i.e. changing context can result in spontaneous recovery. This raises the question of whether there are specialized circuits driving behavioral transitions in opposite directions, namely fear-on and fear-off. This paper showed that neurons in the BA could be divided into distinct functional classes: those exhibiting selective increases in CS+ evoked spike firing during and after fear conditioning (fear neurons) and those exhibiting selective increases in CS+ evoked spike firing during extinction (extinction neurons). Further, close analysis revealed that these two groups were not only functionally different but also differentially connected, with (1) fear neurons selectively receiving input from the hippocampus, and (2) extinction neurons being reciprocally connected to the mPFC while fear neurons only projected unidirectionally to the mPFC. This would indicate that co-localized within the same nucleus, two discrete neuronal circuits exist, intermingled in a salt-and-pepper-like manner. Their close anatomical proximity may serve to facilitate local interactions, although these mechanisms remain unexplored. Taken together with evidence showing emotional perseveration (persistent lack of state change) concomitant with inactivation of the BA, results suggest that the BA is unlikely to be associated with the storage, retrieval, or expression of conditioned fear and extinction memories, but is more likely to mediate context-dependent behavioral transitions between low and high fear states.

Monday, September 8, 2008

mPFC neurons signal memory for fear extinction

Milad, M.R. & Quirk, G.J. (7 November 2002). Neurons in the medial prefrontal cortex signal memory for fear extinction. Nature, 420, 70-74.

Extinction is a process thought to form a new memory that inhibits the once-learned conditioned response. This paper suggests that consolidation of extinction learning potentiates activity in the infralimbic cortex (IL) of the mPFC which inhibits fear during subsequent encounters with fear stimuli. Electrophysiological recording showed that IL activity remained unresponsive during the conditioning phase and also during extinction training on Day 1. However, by Day 2, activity in the IL in response to tone was present from the start of the extinction phase. Further, stimulation of the IL paired with tone presentation resulted in less freezing behavior and also accelerated extinction learning. Therefore, enhanced extinction learning could be mediated directly by the stimulation or indirectly by the behavioral feedback of decrease freezing. Since the BLA sends excitatory projections to IL, it is possible that these inputs serve to potentiate IL neurons during the consolidation of extinction. The IL is then likely to inhibit expression of fear behavior via its projections to intercalated (ITC) cells in the CE, dampening the output of the amygdala. Pairing reminder stimuli with activation of the ventral mPFC through transcranial magnetic stimulation (TMS) might help strengthen extinction of fear in clinical settings.

Neural mechanisms of extinction

Quirk, G.J. & Mueller, D. (2007). Neural mechanisms of extinction learning and retrieval. Neuropsychopharmacology Reviews, 1-17.

The simplest form of emotional regulation is extinction, is which conditioned responding to a stimulus decreases when the reinforcer is omitted. Exinction, like any learning process, occurs in 3 phases: acquisition, consolidation, and retrieval. Cannabinoid and opioid receptors appear to be implicated in the acquisition of extinction since anandamide and opioid antagonists impair within-session extinction of fear. Consolidation appears to depend on protein synthesis within the BLA, frequency bursting of the infralimbic region (IL) of the vmPFC shortly after extinction, and general involvement of the hippocampus, especially in tasks such as inhibitory avoidance and contextual fear. Retrieval of extinction memories involves the expression of inhibitory circuitry and is highly context-specific. Inhibition circuitry within the amygdala includes local inhibitory neurons within the BLA and CE, as well as islands of GABAergic neurons between these two sites known as the intercalated (ITC) cells. ITC cells could serve as a site of extinction memory since they inhibit CE output neurons and BLA neurons, acting as an off-switch for the amygdala. ITC cells receive strong projection from the IL mPFC, and IL activity is correlated with the extent of extinction retrieval. In fact, electrical stimulation of IL reduces conditioned fear and strengthens extinction memory. The prelimbic (PL) mPFC, on the other hand, excites fear expression and can augment fear expression via projections to the basal nucleus of the amygdala. Thus, the PFC can fully control overall fear expression. Individuals with PTSD show reduced vmPFC and hippocampal volume and activity, as well as increased amygdala activity. Stress may also impair extinction, since chronic stress is shown to decrease dendritic branching and spine count in hippocampus and mPFC, but increase it in BLA, which could be expected to increase conditioning and impair extinction. Pharmacological adjuncts to current extinction-based exposure therapies may accelerate and strengthen extinction. Among them D-cycloserine, yohimbine, sulpiride, and methylene blue show promise. Administration of glucocorticoids such as cortisol before exposure therapy may also help.

Sunday, September 7, 2008

Dopamine gates LTP in lateral amygdala

Bissiere, S., Humeau, Y., & Luthi, A. (June 2003). Dopamine gates LTP induction in lateral amygdala by suppressing feedforward inhibition. Nature Neuroscience, 6, 6, 587-591.

It has been known that both long-term potentiation (LTP) and concomitant activation of dopaminergic nerves to the amygdala underlie the acquisition of fear conditioning. In fact, dopamine is known to be released in the amygdala during stress and intra-amygdala injection of dopamine receptor antagonists prevents fear conditioning. This study investigated the mechanisms supporting this and showed how dopamine could modulate fear conditioning by modulating inhibitory synaptic transmission within the amygdala. Specifically, D2 dopamine receptors could enable the induction of LTP by suppressing feedforward inhibition from local inhibitory interneurons.

Friday, September 5, 2008

Neuronal Signalling of Fear Memory

Maren, S. & Quirk, G.J. (November 2004). Neuronal Signalling of Fear Memory. Nature Reviews Neuroscience, 5, 844-850.

Plasticity within the CNS is necessary for the representation of new information, and can range from synthesis and insertion of synaptic proteins to whole-brain synchronization of neuronal activity. Pavlovian fear conditioning is an especially interesting phenomenon since such fear memories are acquired rapidly and are long-lasting. Research first noticed conditioning-induced changes in the midbrain, thalamus, and cortex; however, it was unclear whether or not these were primary sites of plasticity or were simply downstream from other plastic sites. Eventually the lateral nucleus of the amygdala (LA), receiving direct projections from the auditory thalamus, was posited to be vital for auditory fear conditioning. The dorsal subdivision of the nucleus (LAd) seems to be the first site in the auditory pathway to show associative plasticity that is not fed forward passively from upstream sites, is not dependent on downstream sites, and is crucial for conditioned behavior. And LA neurons appear to drive plasticity at both thalamic and cortical levels.

Fear memories are useful to anticipate and respond to dangers within the environment. However, when signals for aversive events no longer predict those events, fear to those signals subsides. This is an inhibitory learning process known as extinction. It appears that although fear subsides after extinction, the fear memory is not erased. Extinction seems to be highly context dependent and sometimes short-lived. Fear responses can be spontaneously recovered over time. It seems biology has deemed it better to fear than not to fear. It is more likely that additional memories which interfere with pre-existing excitatory responses are learned in the extinction process. Again the amygdala seems to be essentially involved here. Further, the mPFC, which has an inhibitory influence on both the LA and the CE (the main output regions of the amygdala) through a rich network of inhibitory interneurons embedded in the amygdala, appears to be a major participant, and is perhaps modulated by context via hippocampus.