Thomas Ågren

Disruption of Reconsolidation Erases a Fear Memory Trace in the Human Amygdala

Removing Fear Memories Disruption of reconsolidation of an activated fear memory prevents subsequent fear expression. After a memory reminder, extinction training can disrupt fear memory. In rodents, this process is dependent on a brain area called the amygdala. Agren et al. (p. 1550) used functional magnetic resonance imaging and a fear conditioning paradigm to show in humans that, after an associative fear memory was formed, reactivation and reconsolidation left a signature in the basolateral amygdala. This memory trace predicted later fear expression, which was linked to activity in areas forming the fear circuit of the brain. Extinction alone did not change this signal. However, extinction in the reconsolidation window blocked fear expression by erasing the fear memory trace in the amygdala and weakened the connection in the wider fear circuit of the brain. Interfering with memory formation at the right moment removes the signature of fear memories in human brain imaging studies. Memories become labile when recalled. In humans and rodents alike, reactivated fear memories can be attenuated by disrupting reconsolidation with extinction training. Using functional brain imaging, we found that, after a conditioned fear memory was formed, reactivation and reconsolidation left a memory trace in the basolateral amygdala that predicted subsequent fear expression and was tightly coupled to activity in the fear circuit of the brain. In contrast, reactivation followed by disrupted reconsolidation suppressed fear, abolished the memory trace, and attenuated fear-circuit connectivity. Thus, as previously demonstrated in rodents, fear memory suppression resulting from behavioral disruption of reconsolidation is amygdala-dependent also in humans, which supports an evolutionarily conserved memory-update mechanism.

Human fear reconsolidation and allelic differences in serotonergic and dopaminergic genes

Fear memory persistence, central for the development and maintenance of anxiety disorders, is partially genetically controlled. Recently, consolidation and reconsolidation processes have been reported to affect fear memory stability and integrity. This study explored the impact of reconsolidation processes and genetic make-up on fear reacquisition by manipulating reconsolidation, using extinction performed outside or inside a reconsolidation interval. Reacquisition measured by skin conductance responses was stronger in individuals that extinguished outside (6 h) than inside (10 min) the reconsolidation interval. However, the effect was predominantly present in val/val homozygotes of the functional val158met polymorphism of the catechol O-methyltransferase (COMT) enzyme and in short-allele carriers of the serotonin-transporter length 5-HTTLPR polymorphism. These results demonstrate that reconsolidation of human fear memory is influenced by dopamine and serotonin-related genes.

Disruption of Memory Reconsolidation Erases a Fear Memory Trace in the Human Amygdala: An 18-Month Follow-Up.

Fear memories can be attenuated by reactivation followed by disrupted reconsolidation. Using functional magnetic resonance imaging we recently showed that reactivation and reconsolidation of a conditioned fear memory trace in the basolateral amygdala predicts subsequent fear expression over two days, while reactivation followed by disrupted reconsolidation abolishes the memory trace and suppresses fear. In this follow-up study we demonstrate that the behavioral effect persists over 18 months reflected in superior reacquisition after undisrupted, as compared to disrupted reconsolidation, and that neural activity in the basolateral amygdala representing the initial fear memory predicts return of fear. We conclude that disrupting reconsolidation have long lasting behavioral effects and may permanently erase the fear component of an amygdala-dependent memory.

Enlargement of visual processing regions in social anxiety disorder is related to symptom severity

Social anxiety disorder (SAD) is associated with altered brain function and structure, but most structural studies include small samples and findings are mixed. This study compared regional gray matter volume between 48 SAD patients and 29 healthy controls (HC) as well as the relationship between volume and symptom severity. Structural magnetic resonance images from SAD patients and HC were evaluated using standard voxel-based morphometry (VBM) processing in the SPM8 software package. Social anxiety symptom severity was rated in SAD patients by a clinician using the Liebowitz Social Anxiety Scale (LSAS). SAD patients had greater regional gray matter volume in the lingual gyrus and lateral occipital cortex than the controls, and within the SAD group a positive correlation was found between symptom severity and regional gray matter volume in the lingual gyrus and the retrosplenial cortex. These findings replicate and extend earlier reports of enlarged visual processing areas in SAD. Increased gray matter volume in regions involved in visual processing and self-consciousness could underlie, or be the result of, abnormal emotional information processing and self-focused attention previously demonstrated in patients with SAD.

Think twice, it’s all right: Long lasting effects of disrupted reconsolidation on brain and behavior in human long-term fear

HighlightsExposure to feared cues after memory actvation attenuates phobic fear expression.Effect of reconsolidation disruption on long term fears are long lasting.Disrupting reconsolidation attentuates amygdala activity over 6 months.Disrupting reconsolidation facilitates approach behavior over 6 months. Abstract Memories can be modified when recalled. Experimental fear conditioning studies support that amygdala‐localized fear memories are attenuated when reconsolidation is disrupted through extinction training immediately following memory activation. Recently, using functional brain imaging in individuals with lifelong spider fears, we demonstrated that fear memory activation followed by repeated exposure to feared cues after 10 min, thereby disrupting reconsolidation, attenuated activity in the amygdala during later re‐exposure, and also facilitated approach behavior to feared cues. In contrast, repeated exposure 6 h after fear memory activation, allowing for reconsolidation, did not attenuate amygdala activity and resulted in less approach behavior as compared to the group that received disrupted reconsolidation. We here evaluated if these effects are stable after 6 months and found that amygdala activity was further reduced in both groups, with a tendency towards greater reductions in the 10 min than the 6 h group. Hence, disrupted reconsolidation results in long lasting attenuation of amygdala activity. The behavioral effect, with more approach towards previously feared cues, in the 10 min than the 6 h group also persisted. Thus, the brain effect of disrupted reconsolidation is stable over 6 months and the behavioral effect also remained. We therefore conclude that disrupted reconsolidation result in a long‐lasting diminished fear memory representation in the amygdala which may have clinical importance.

Disruption of human fear reconsolidation using imaginal and in vivo extinction

&NA; Memories are not set forever, but can be altered following reactivation, which renders memories malleable, before they are again stabilized through reconsolidation. Fear memories can be attenuated by using extinction during the malleable period. The present study adopts a novel form of extinction, using verbal instructions, in order to examine whether fear memory reconsolidation can be affected by an imaginal exposure. The extinction using verbal instructions, called imaginal extinction, consists of a recorded voice encouraging participants to imagine the scene in which fear was acquired, and to envision the stimuli before their inner eye. The voice signals stimuli appearance, and identical to standard (in vivo) extinction, participants discover that the conditioned stimulus no longer is followed by unconditioned stimulus (UCS). In this way, imaginal extinction translates clinically used imaginal exposure into the standard experimental fear conditioning paradigm. Fear was acquired by pairing pictorial stimuli with an electric shock UCS. Then, both standard and imaginal extinction were given following fear memory reactivation, either after 10 min, within the reconsolidation interval, or after 6 h, outside of the reconsolidation interval. In vivo and imaginal extinction produced comparable reductions in conditioned responses during extinction and importantly, both disrupted reconsolidation of conditioned fear and abolished stimulus discrimination between reinforced and non‐reinforced cues. Thus, disrupted reconsolidation of fear conditioning can be achieved without in vivo stimulus presentation, through purely cognitive means, suggesting possible therapeutic applications. HIGHLIGHTSImaginary extinction, a novel form of fear extinction using verbal instructions, is introduced.In vivo and imaginary extinction produce comparable reductions in fear responses.Both in vivo and imaginary extinction affect the reconsolidation of fear memories.

Biological preparedness and resistance to extinction of skin conductance responses conditioned to fear relevant animal pictures: A systematic review

&NA; Preparedness theory is one of the most influential ideas in explaining the origin of specific phobias. The theory proposes that fear conditioning is selective to animals that have posed a threat to survival throughout human evolution, and that acquired fear memories to such threats are resistant to extinction. We reviewed fear conditioning studies testing whether autonomic responses conditioned to pictures of snakes and spiders show greater resistance to extinction than neutral cues. We identified 32 fear conditioning experiments published in 23 studies including 1887 participants. Increased resistance to extinction of conditioned responses to snake and spider pictures was found in 10 (31%) of the experiments, whereas 22 (69%) experiments did not support the hypothesis. Thus, the body of evidence suggests that preparedness theory does not explain the origin of specific phobias.

Disentangling the effects of serotonin on risk perception: S-carriers of 5-HTTLPR are primarily concerned with the magnitude of the outcomes, not the uncertainty.

Serotonin signaling is vital for reward processing, and hence, also for decision-making. The serotonin transporter gene linked polymorphic region (5-HTTLPR) has been connected to decision making, suggesting that short-allele carriers (s) are more risk averse than long-allele homozygotes (ll). However, previous research has not identified if this occurs because s-carriers (i) are more sensitive to the uncertainty of the outcomes or (ii) are more sensitive to the magnitude of the outcomes. This issue was disentangled using a willingness-to-pay task, where the participants evaluated prospects involving certain gains, uncertain gains, and ambiguous gains. The results clearly favored the hypothesis that s-carriers react more to the magnitude of the outcomes. Self-reported measures of everyday risk-taking behavior also favored this hypothesis. We discuss how these results are in line with recent research on the serotonergic impact on reward processing.