Fear extinction
Fear Extinction
Extinction is learning that a cue no longer predicts danger — the mechanism exposure therapy uses. It is nmda-dependent learning, so blocking that receptor impairs it while a glycine-site partial agonist enhances it. BDNF is the currency: when BDNF availability falls after trauma, the fear response is locked in place. Sleep consolidates it, arousal blocks it, and endogenous estrogen supports it.
In depth
The capacity to update a threat prediction when the threat stops arriving — what exposure therapy trains.
What drives it
Supports BDNF signaling increases it.
BDNF gene expression and activation of its TrkB receptor are necessary in the amygdala, hippocampus and prefrontal cortex for the formation of emotional memories; BDNF appears to enhance extinction of fear. doi 10.1111/j.1601-183X.2012.00801.x · PMC2787650
Endocannabinoid tone increases it.
Activation of CB1 receptors within the vmPFC during fear extinction induces neuronal plasticity and increases inhibition of brain areas involved in the expression of conditioned fear; intra-basolateral-amygdala CB1 agonists enhance recall of extinction learning. doi 10.1111/j.1601-183X.2012.00801.x · PMC2787650
Quiets overexcitation increases it.
While NMDA receptor antagonists impair extinction, the receptor partial agonist D-cycloserine facilitates it, acting at the glycine modulatory site on the NR1 subunit to increase calcium influx. doi 10.1111/j.1601-183X.2012.00801.x · PMC2787650
Sleep increases it.
Named in the extinction-circuit reviews as a modulator of fear-extinction learning and its consolidation. doi 10.1111/j.1601-183X.2012.00801.x · PMC8598288
Lowers cortisol reduces it.
The hypothalamic-pituitary-adrenal axis is named alongside the endocannabinoid system as a system that alters fear extinction through BDNF modulation; stress-induced extinction impairments contribute to relapse of fear in patients undergoing exposure therapy. doi 10.1111/j.1601-183X.2012.00801.x · PMC2787650
Stress & cortisol reduces it.
Extinction tends to be less effective when performed soon after an emotionally arousing event — the immediate extinction deficit — which is associated with reduced neuronal activity and reduced spontaneous spike firing in the vmPFC. doi 10.1111/j.1601-183X.2012.00801.x · PMC2787650
Alertness chemical reduces it.
A locus coeruleus to amygdala circuit disrupts prefrontal control to impair fear extinction. doi 10.1111/j.1601-183X.2012.00801.x · PMC2787650
Brain inflammation reduces it.
Named in the extinction-circuit reviews as a modulator of fear-extinction learning and its consolidation. doi 10.1111/j.1601-183X.2012.00801.x · PMC8598288
Mood (serotonin) increases it.
MDMA's combined effects of increasing serotonergic activity, and the release of oxytocin and BDNF, are proposed as the mechanism of memory reconsolidation and fear extinction in MDMA-assisted therapy. doi 10.1176/appi.focus.20220088 · PMC9567733
Social bonding hormone increases it.
Oxytocin modulates the amygdala and PFC substrates implicated in fear extinction; reduction in amygdala and insula activation with increased amygdala-hippocampus connectivity creates a tolerance window of neuroplasticity for reprocessing traumatic memories. doi 10.1176/appi.focus.20220088 · PMC9567733
Growth restraint increases it.
Extinction consolidation is protein-synthesis dependent; mTOR-dependent translation is required for the durability of extinction memory. doi 10.1111/j.1601-183X.2012.00801.x · PMC2787650
Motivation increases it.
Dopaminergic prediction-error signaling drives the update that the conditioned cue no longer predicts the aversive outcome. doi 10.1111/j.1601-183X.2012.00801.x · PMC2787650
Calm increases it.
Inhibitory gating within the amygdala by infralimbic input is the circuit substrate of extinction expression. doi 10.1111/j.1601-183X.2012.00801.x · PMC2787650
Estrogen balance increases it.
Women with high estradiol levels (mid-cycle) and men exhibit better extinction retention compared to women with low estradiol levels (early follicular phase or using oral contraceptives). doi 10.1111/ejn.14602 · PMID 39116520 · PMC4652367
What it drives
It reduces Trauma symptoms.
PTSD is characterized by an inability to extinguish fear memories. A clinical characteristic of PTSD is persistently elevated fear responses to stimuli associated with the traumatic event. doi 10.1111/j.1601-183X.2012.00801.x · PMC2787650
It reduces Calm under stress.
Extinction of conditioned fear is the laboratory model of exposure therapy; failure of extinction recall underlies the persistence of pathological fear. doi 10.1111/j.1601-183X.2012.00801.x · PMC2787650
It increases Mood.
Successful extinction reduces the persistently elevated fear responses that drive avoidance and negative affect. doi 10.1111/j.1601-183X.2012.00801.x · PMC2787650
It increases Stress resilience.
Extinction learning is the capacity to update a threat prediction when the threat no longer materialises — the operational definition of recovering from an aversive event. doi 10.1111/j.1601-183X.2012.00801.x · PMC2787650
It increases Sleep.
Sleep-dependent consolidation of extinction memory is bidirectional — sleep supports extinction and successful extinction reduces the arousal that fragments sleep. doi 10.1111/j.1601-183X.2012.00801.x · PMC2787650
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.