R2.1 Understanding Extinction: Behavior and Neuroscience (PSYC2050)

• Extinction can serve as a leading theoretical framework
• Extinction can serve an the experimental model to describe how learned behaviors diminish
• Behaviors diminish through absence of anticipated reinforcement
• In the past decade, it moved beyond associative learning theory and behavioral experimentation in animals
• It has become a topic of interest in neuroscience of learning, memory, and emotion
• Pavlov termed it as the internal inhibition of conditioned reflexes in 1927
• Extinction is a learning process and a behavioral technique
• Traditional understandings warrant a re-examination.
• Neurobiology, cognitive factors, and major computational theories are important.
• Extinction results in new learning that interferes with expression of the original memory.
• Extinction limitations as a technique to prevent the relapse of maladaptive behavior is important to consider
• Contemporary theoretical advances augment traditional extinction methods target and potentially alter maladaptive memories.
• Understanding how computational learning theory and neuroscience of learning, memory, and emotion view extinction is key to understanding view extinction.
• The first section has a brief background on theoretical foundations.
• Details on the neurobiology of extinction are covered
• Psychological factors are investigated
• The article examines major associative learning models.
• Experimental extinction serves as the basis for exposure-based therapy
• Exposure-based therapy can be used for treatment for different psychiatric disorders like: anxiety disorders, addiction, stress and trauma related disorders.
• Experimental extinction is considered within the National Institute of Mental Health’s Research Domain Criteria
• Extinction provides objective neurobehavioral measures of mental illness in the domain of Negative Affect
• Experimental extinction rests on pavlovian conditioning, in which a conditional stimuli like tone or light is paired with a naturally salient unconditional stimulus

Current status of the Field

• Return of extinguished behavior is common following the time passage also known as spontaneous recovery
• The extinguished cues may be encountered outside the extinction context also known as contextual renewal
• There may be presentation of the unconditioned stimulus also known as reinstatement
• Contemporary computational models have been developed to reflect the understanding that extinction may be when a new state or association is created.
• Neurobiological models of extinction focus on interactions between processes within the medial prefrontal cortex, amygdala, and hippocampus
• The principles of extinction serve as the basis for clinical treatments such as exposure-based therapy for anxiety disorders and addiction

Future Directions

• In retrieval and updated fear memory as opposed to new extinction memory trace what are the determining factors?
• What is the neurobiological signature of updating of a persistent memory of an emotional response
• What conditions are necessary and sufficient to demonstrate that a memory has been persistently altered?
• What is the role of predisposing genetic and epigenetic variants associated with extinction learning?
• To what extent do individual differences such as early life stress, trait anxiety and intolerance of uncertainty moderate extinction and extinction retention in humans?
• Are extinction deficits a diagnostic biomarker of trauma, clinical anxiety disorders and stressor-related disorders?
• How can techniques used on animals translate to complex fear memories in humans.
• The canonical expression of experimental extinction rests on Pavlovian conditioning.
• Presentation of the CS initiates a conditioned response, e.g. increases in salivation
• Fear conditioning can take a form of emotional reactions like the increase in sweating, heart rate, freezing, and blood pressure
• Contemporary theoretical views of extinction are in many ways based directly on early formulations by Pavlov, who interpreted extinction as a form of internal inhibition.
• Spontaneous recovery is a measure of the depth of the extinction process itself and measured by time taken for spontaneous restoration
• Persistence for the original CS-US association includes contextual review, reinstatement, and rapid re-acquisition
• For Pavlov, the central mechanism involved inhibitory properties accruing to the CS over the course of extinction training, subserved by inhibitory cells in the cortex
• Erasure or modification of the original CS-US associative memory may occur.
• Razram proposed a two-stage process of extinction in which the early stage consists of partial erasure and the later stage consists of new learning that counteracts the residual excitatory CR.
• Spontaneous recovery is rarely complete suggesting some partial erasure of original learning
• Affirmative signatures of memory erasure or modification do not exist, weakened recovery might reflect strengthened inhibitory learning and not erasure.
• Effective extinction may only mimic erasure by eliminating a conditioned fear response, while leaving other elements of the CS-US association intact.
• Extinction may erase, inhibit, and have no effect on separate aspects of the same memory.
• The amygdala stores condtioned fear, the lateral nucleus is the site of synaptic plasticity that encodes the association between CS and US sensory imputs
• With the CS, the LA excites the central nucleus which mediates CR expression through projections to the brainstem and hypothalamus
• Pathways provide potential circuits for fating fear expression in extinction
• The amygdala, vmPFC and hippocampus support the acquisition, storage, retrieval, and contextual modulation of fear extinction
• Disruption of protein synthesis, MAPK blockade, and administration of an NMDA antagonist impairs retrieval of extinction
• Contextual information affects whether the original fear memory controls fear
• Hippocampal lesions show impaired contextural renewal, with functional neuroimaging, lesion and morphology indicating extinction learning depends on the amygdala, vmPFC, hippocampus
• Learned extinction is fragile, with acquired CR returning in situations that trigger memory of a conditioing experience
• Survival cost of disregarding is higher than the cost of responding when threat is not imminent
• Safety behaviors that interfere with success of exposure based therapy involve cognitive mechanism for inhibitory learning, what is referred as protection from extinction

Associative Learning Theories of Extinction

• As previously seen, theoretical views of extinction fall within two general classes which are; Associative Loss Or Unlearning and New Inhibitory Learning or Interfence
• Learning of acquired information relies on statistical relationships of sound statistical evidence known as Rescorla-Wagner
• Second key account of conditioning is by Pearce and Hall, in this case extinction involves new inhibitory learning
• The Pearch Hall model is considered by some that expression of CR diminishes due to an inhibitory relationship between the CS-US association and the CS-no US association.

Extinction As A Form of Memory Interference

• Bouton suggest after extinction you view it as a context dependent form of new inhibitory learning then memory retrieval can interfere with expression of excitory memory
• Then context plays a key role resolving ambiguous meaning that come after extinction, otherwise, it can simply refer to to favor CS-US memories due prominent learning from the past

Altering Latent Causes

• One can infer that conditioning occurs as statistical interference to create cause-effect relations by creating observable stimulated such as CSs and USs
• This is in exception to Kalman filter, instead event is known to be casualy linked to the US, this assumption allows third non observe causes
• That class of models use statistical inference to determine if underlying parts structures of latent causes created experience patterns of observable stimuli such as CSs and USs, this includes other context.
• Over time CR can determined in terms of this structure to predict which cause is likely to be active at current time including if one can expect US.
• Overall process of inferring latent cause for a trial is much like clustering in which trials are clustered into categories based on patterns of CSs and USs, which association occurs after via single latent cause that creates the stimuli
• Later afterword one can deduce from renewal and sensitivity that the context will depend of organism estimating latent cause.
• Latent causes formualse Bouton's idea of what a contex is, meaning model fully encapsulates much sensitivity of extinction learning

Augmenting Extinction

• Since defensive behaviors are recovered over time, it leads to the goal to reduce unwanted behavior for good if the goal of extinction is a way to diminish bad behavior.

What's Wrong with Current Extinction Methods

• These methods have limitation, one being they operate at the basic level, therefore clinical treatments based on extinction principles face an uphill battle due to the brain's mechanism to forget safety and remember threat
• Traditional CS procedures also have challenge, as it relies on negative feedback, thus if the US predicted is violated.
• Furthermore is that memory is poorly correlated with memory strength.

Targeting The Fear Memory Consolidation

• To abolish permanent conditional stimulus is to block the process entirely with synthesis inhibitors. With time time expression long term decreases but short term increases
• Feasable alternative uses pharmacological agents due noradregeneric system to impede on emotional memory
• For patients with PTSD, early intervention reduce the likely hood
• There are potential limitations here, if patients start treatment long after memories.

Reconsolidation

• As with any consolidation, using protiens is not realistic unless by administering drugs after reactivation the memory trace and before it is recosolidated,

Targeting the fear memory has key practical limitations

• However, what does is the the the ability to update fear memories on is desired level, as that for many elements that link PTSD etc There are things what one use with US, the fact is no eliminate the memory in most anxiety treatment one want instead want negative. One method is called Emotional Processing Theory Is the effect targeting the CS-US in association are due to memory or inhibition learning

Strengthening Extinction

• Deepened Extinction can involve the prescence of other the feared stimous- Two or more CSs, the key principle
• Then what is left would only reduce stimis like with compound
• The is the thought the the summation idea, like what happens if two css are pre-sented at one the joint of the prediction goes US in the is a hieghtning when the US goes it is a way.

Exposure to Novelty

• Learning is most related by surprise and newer events this promotes learning so there is a way.
• The a number of system with attention and more respond novelty and a memory like one system, may also favor a consolidation- of information of the
• Furthermore, the is that these system use by having an effect to the extent in which it can change during the