Memory: Consolidation, Extinction, Reconsolidation
August 8, 2013
Background
Classical conditioning is a form of memory. The “classic” example of classical conditioning derives from the experimental studies of Ivan Pavlov with dogs. The sound of a bell, announcing the impending arrival of meat for dinner, caused the dogs to salivate in anticipation. After a short time they learned to salivate whenever the bell sounded, even if meat did not arrive soon afterwards. We now refer to the bell as a “conditioned” stimulus and the meat as an “unconditioned” stimulus for salivation.
Fear can also be conditioned, for example, when the sound of a bell predicts an unpleasant feeling (a pinch or a mild shock) on the skin. In this example, the bell is the conditioned stimulus and the pinch or mild shock is the unconditioned stimulus for pain. Fear arises in anticipation of the painful sensation predicted by the sound of the bell.
The bell remains a conditioned stimulus as long as it predicts the arrival of the unconditioned stimulus. If the bell ceases to predict the arrival of meat or a skin shock, it gradually loses its efficacy as a conditioned stimulus. This process of weakening of a conditioned stimulus with time is known as extinction.
Another important concept in the domain of memory is consolidation. Learned associations (bell-food; bell-pain) are relayed to particular brain locations to be stored in memory. The consolidation of memory, the conversion of short-term to long-term memory, takes place shortly after learning. Most memory consolidation takes place during sleep. Different kinds of memory are consolidated in different phases of sleep (rapid eye movement or REM sleep, and non-REM sleep). Procedural memories (e.g., riding a bicycle) and emotional memories (e.g., a car accident) are thought to be consolidated in REM sleep; episodic memories (e.g., memories of specific episodes and settings in one’s life) in non-REM sleep.
The gradual extinction of conditioned responses over time is a normal process. As mentioned at the outset, conditioned responses are memories, and memories generally fade with time, unless periodically renewed. The renewal of an old memory is known as reconsolidation. For a conditioned stimulus like a bell to regain its former strength, the meat (or skin pinch) needs to reappear after the sound of the bell, not necessarily every time, but often enough to maintain the anticipation.
Implications for Treatment
The process of fear extinction seems to fail in anxiety disorders such as simple phobias, social phobia, obsessive compulsive disorder (OCD), panic disorder, and posttraumatic stress disorder (PTSD). The extinction of conditioned fear is thought to take place in the amygdala of the brain, and to be mediated by the neuronal transmitter glutamate, and in particular, the N-methyl-D-aspartate (NMDA) receptors for glutamate in the amygdala. A drug known as d-cycloserine (DCS), initially marketed to treat tuberculosis, has been known for some time to activate NMDA receptors in the brain, and has been shown in recent studies, in both animals and humans, to facilitate fear extinction. The most widely used type of therapy for anxiety disorders, cognitive behavioral therapy (CBT), utilizes exposure and response prevention (ERP) to increase the rate of fear extinction. DCS thus acts as a booster for CBT in the treatment of anxiety disorders.
To be effective as a booster for CBT, DCS must be given during an exposure therapy session that succeeds in reducing anxiety, i.e., ideally, just after a successful session. Giving DCS during or after an unsuccessful session may cause an increase in fear (i.e., a reversal of fear extinction), so it is important to reinforce only successful sessions.
Just as the failure of fear extinction offers the possibility of CBT psychotherapy to enhance extinction by exposure to the feared stimulus, memory reconsolidation offers the possibility of dream revision psychotherapy to modify the original memory. Memory reconsolidation is of particular interest in the treatment of PTSD, since it allows for change in memories that may have become toxic over days, months, or years.
PTSD is maintained in strength and toxicity by flashbacks and nightmares, which effectively repeat the original trauma. Each PTSD trigger (i.e., each sensory stimulus that recalls the trauma) serves as a conditioned stimulus for the entire toxic trauma experience. Each nightmare serves to reconsolidate the original trauma memory.
Dream revision therapy, as described in earlier blogs in this series provides a means of altering the reconsolidated trauma memory by changing the nightmare. The nightmare then becomes an ordinary dream, and the trauma memory becomes less toxic and less disturbing.
CBT depends upon exposure, which can be difficult for PTSD sufferers to experience. In addition, CBT seems to act on extinction of memory, a largely passive process, which makes recovery slower. Dream revision therapy, on the other hand, does not require as much exposure as CBT, and may block memory more actively by interfering with the consolidation process. In this sense, dream revision acts more rapidly, sometimes in a single therapy session, as Michele Rosenthal and I have recently demonstrated on her radio call-in show, “Changing Direction.”
