When we think back on our lives, we generally try to dwell on good times and come to terms with bad. But for those who suffer from anxiety disorders, including post-traumatic stress disorder and phobias, just one intractable and unwelcome memory can influence a lifetime of perceptions, emotions and behavior, despite therapists' best efforts.
But thanks to better imaging technology, neuroscientists and psychologists are able to explore the neural mechanisms by which memories are made and stored. And their research has uncovered several physiological interventions — including electrical currents and well-timed pharmacology — that appear to help destabilize fearful memories, a finding that could lead to more effective, targeted psychotherapy in the future.
While practitioners today rely solely on patient reports, "in years to come, neuroscience will inform clinical practice," says Stefan Hofmann, PhD, who directs the Psychotherapy and Emotion Research Laboratory at Boston University. "We will use both biological and neurological measures to give us clues as to treatment."
How fearful memories are made
Though just beginning to plumb the brain's depths, scientists have formulated some theories on how our brains process fearful memories. First, as we witness a scary event, the thalamus relays sensory information to the amygdala, which stamps the memory as emotionally significant and stores it for future use, to help us avoid related threats. Neural networks in the hippocampus busily begin building a map of the memory's context in the first few hours after an event, and related synaptic connections grow stronger in a process called long-term potentiation, consolidating the memory. It is, however, not set in stone.
"Whenever you're learning something, multiple corners of the brain are talking to each other to represent the sights and sounds and smells that you're learning," says Steve Ramirez, PhD, a neuroscientist at the Massachusetts Institute of Technology (MIT). "Yet the process of actually recalling a memory renders it susceptible to modification. [These memories] feel like a bona fide representation of the past, but memories are constantly modified with new information."
Extinguishing the traumatic aspect of a memory involves creating new, safer mental associations to the same sensory cues. Even long-term memories, when recalled, have plasticity and the potential to be updated, an ability psychologists co-opt during exposure therapy, in which a patient faces his or her fears in a non-threatening environment in the hope of gaining control of them. This requires neural communication among a number of areas in the brain: The hippocampus cues the ventromedial prefrontal cortex of changed conditions, which inhibits neuron activity — and the conditioned fear response — in the amygdala (Annual Review of Psychology, 2012).
In some people, though, the process goes awry, and they're unable to escape intrusive thoughts.
"We really don't know why people respond so differently to traumatic experiences," says Gregory J. Quirk, PhD, who investigates the neuroscience of fear at University of Puerto Rico School of Medicine. "It may be that the prefrontal cortex is less connected to the amygdala, so it can't say, ‘No, you're not in danger right now.'"
Malleable memories
Some scientists are trying to manipulate the reconsolidation process. Ramirez co-authored a 2014 study in which he and a team from RIKEN-MIT Center for Neural Circuit Genetics were able to change bad memories to good in male mice. Using a technique called optogenetics, in which genetically encoded, light-responsive proteins are inserted into cells, the scientists were able to pinpoint where a mouse's negative memory of a shock to the foot was formed, in the neural circuitry that connects the dentate gyrus in the hippocampus to the amygdala. The researchers then manipulated those neurons with lasers. Each time the mice ventured to a certain part of their enclosure, the negative memory was reactivated, and they quickly learned to fear the area.
The male mice were then allowed to frolic with female mice, while the same neurons were tapped, helping to switch their messages from one of pain to one of pleasure. The next time the male mice ventured into the chamber, their fear reactions had vanished (Nature, 2014).
