The persistence of memory

One of the many amazing things about the brain is its ability to form connections between associated events.

These links can have amazing staying power.  The smell of old books will forever remind me of my grandmother's attic, which was my bedroom for a year when I was about ten years old.  Dan Fogelberg's songs always bring back painful memories of my ex-wife (a shame to have that association, because I actually like Dan Fogelberg).  The pretty little flowers called "sweet williams" call to mind the small plot of garden I had in my parents' back yard -- they were the first flowers I had real success with, and I still remember the pure, unalloyed joy of watching them flower for the first time.

[Image licensed under the Creative Commons Jim Evans, Sweet William -- Dianthus barbatus, CC BY-SA 4.0]

That we form these kinds of associations is common knowledge; how we do it is another matter entirely.  But some new research at Columbia University's Zuckerman Mind-Brain Behavior Institute has shed some light on this innate and ubiquitous capacity of the human mind.

In "Hippocampal Network Reorganization Underlies the Formation of a Temporal Association Memory," by Mohsen S. Ahmed et al., which appeared a couple of weeks ago in the journal Neuron, we find out that memories are as persistent as they are not because of a change in the neural firing pattern -- but because they actually cause a reorganization of synaptic connections in the hippocampus, a part of the brain long known to be crucial in memory consolidation.

The researchers taught mice to associate a neutral sound with a short, startling puff of air.  They were quick to learn to link the two; which, after all, was no different than Pavlov's dog connecting a bell with being fed dinner.  Because the two events being linked in the brain occurred with a significant separation in time, the researchers didn't think it could be that the parts of the hippocampus responsible for storing the memory of each were engaging in some kind of continuing cross-talk.  "We expected to see repetitive, continuous neural activity that persisted during the fifteen-second gap, an indication of the hippocampus at work linking the auditory tone and the air puff," said Stefano Fusi, professor of neuroscience at Columbia's Vagelos College of Physicians and Surgeons and co-author of the study, in an interview with Science Daily.  "But when we began to analyze the data, we saw no such activity...  We were happy to see that the brain doesn't maintain ongoing activity over all these seconds because, metabolically, that's not the most efficient way to store information.  The brain seems to have a more efficient way to build this bridge, which we suspect may involve changing the strength of the synapses."

Understanding the way memories of different events become linked in the brain isn't just of academic interest, explaining the kinds of ordinary associations I described from my own life; it could be of real help in treating people with severe anxiety and/or post-traumatic stress syndrome, where traumatic events are linked to common stimuli (such as survivors of wartime who are triggered to panic by loud noises).  "While our study does not explicitly model the clinical syndromes of either of these disorders, it can be immensely informative," said study lead author Mohsin Ahmed.  "For example, it can help us to model some aspects of what may be happening in the brain when patients experience a fearful association between two events that would, to someone else, not elicit fright or panic."

The strength and persistence of memories can be a lifelong reminder of something joyful, or of something tragic, shocking, angering, or outright painful.  This experiment represents the first step on the road to understanding how our brain forms one memory and links it to another, and -- possibly -- gives us a direction to pursue in searching for how to disconnect that link, and allow people with severe anxiety and PTSD to live more normal lives.

And anything we can do to alleviate that suffering is a most laudable goal.

*************************************

This week's Skeptophilia book-of-the-week is one that should be a must-read for everyone -- not only for the New Yorkers suggested by the title.  Unusual, though, in that this one isn't our usual non-fiction selection.  New York 2140, by Kim Stanley Robinson, is novel that takes a chilling look at what New York City might look like 120 years from now if climate change is left unchecked.

Its predictions are not alarmism.  Robinson made them using the latest climate models, which (if anything) have proven to be conservative.  She then fits into that setting -- a city where the streets are Venice-like canals, where the subways are underground rivers, where low-lying areas have disappeared completely under the rising tides of the Atlantic Ocean -- a society that is trying its best to cope.

New York 2140 isn't just a gripping read, it's a frighteningly clear-eyed vision of where we're heading.  Read it, and find out why The Guardian called it "a towering novel about a genuinely grave threat to civilisation."

[Note: if you purchase this book using the image/link below, part of the proceeds goes to support Skeptophilia!]

Fear itself

Past experiences in my life have instilled into me a deep dislike of being the center of attention.  Talking about what you love, what you're interested in, is arrogance and conceit -- I learned that lesson early.  Also, protect what you care about, or it'll be ridiculed, demeaned, or taken away.  The result was that even in safe situations, I have always been afraid to open up, and even people I've known for years really hardly know me at all.

The fact that I no longer have to spend my life in a protective crouch has not eradicated that fear.  It's a significant part of why I'm as shy and socially awkward as I am, and why I'm the guy at parties (if I get invited in the first place) who's standing there with a glass of scotch, looking around frantically for a dog to socialize with.  I've tried for years to be okay with graciously accepting compliments when they come, and to open up to others about my interests, but to say it doesn't come naturally to me is a wild understatement.

This all comes up because of some research released last month from scientists at the RIKEN Center for Brain Science in Saitama, Japan.  A team consisting of Ray Luo, Akira Uematsu, Adam Weitemier, Luca Aquili, Jenny Koivumaa, Thomas J.McHugh, and Joshua P. Johansen published a paper in Nature: Communications called "A Dopaminergic Switch for Fear to Safety Transitions," wherein we find out that a single neurotransmitter (dopamine) acting in a single part of the brain (the ventral tegmental area) is apparently responsible for unlearning fear responses.

The authors write:

Exposure therapy, a form of extinction learning, is an important psychological treatment for anxiety disorders such as post-traumatic stress disorder (PTSD).  Extinction of classically conditioned fear responses is a model of exposure therapy.  In the laboratory, animals learn that a sensory stimulus predicts the occurrence of an aversive outcome through fear conditioning.  During extinction, the omission of an expected aversive event signals a transition from fear responding to safety.  To switch from fear responding to extinction learning, a brain system that recognizes when an expected aversive event does not occur is required.  While molecular changes occurring in the ventromedial prefrontal cortex (vmPFC) and amygdala are known to be important for storing and consolidating extinction memories, the brain mechanisms for detecting when an expected aversive event did not occur and fear responses are no longer appropriate are less well understood... 

[Our] findings show that activation of VTA-dopamine neurons during the expected shock omission time period is necessary for normal extinction learning and the upregulation of extinction-related plasticity markers in the vmPFC and amygdala.  Notably, inhibition of VTA-dopamine neurons during the shock period of fear conditioning facilitates learning, suggesting that activity in VTA-dopamine neurons is not simply important for learning in response to any salient event.  These results also reveal that distinct populations of VTA-dopamine neurons... are important for the formation of stable, long-term extinction memories.

Team leader Joshua Johansen was unequivocal about the potential for this research in treating long-term anxiety and PTSD.  "Pharmacologically targeting the dopamine system will likely be an effective therapy for psychiatric conditions such as anxiety disorders when combined with clinically proven behavioral treatments such as exposure therapy," he said in a press release from RIKEN.  "In order to provide effective, mechanism-based treatments for these conditions, future pre-clinical work will need to use molecular strategies that can separately target these distinct dopamine cell populations."

Illustration from Charles Darwin's Expression of the Emotions in Man and Animals (1872), captioned, "Terror, from a photograph by Dr. Duchenne."  [Image is in the Public Domain]

I have suffered from serious anxiety most of my life, and I have a dear friend who has PTSD, and believe me -- this is welcome news.  My one attempt to use an anxiolytic medication was a failure (it killed my appetite, which someone with as fast a metabolism as I have definitely doesn't need), and "exposure therapy" has, all in all, been a failure.  The idea that there could be a way to approach these debilitating conditions by targeting a specific molecule in a specific part of the brain is pretty earthshattering.

I know it's a long way between identifying the brain pathway involved in a disorder and finding a way to alter what it's doing, but this is a significant first step.  The idea that I might one day be able to go to social gatherings without feeling a sense of dread, and to talk to people rather than just dogs, is kind of amazing.  Until that happens, I'm probably still going to have to deal with my anxiety, but it's nice to know someone is working on the problem.

************************************

This week's book recommendation is especially for people who are fond of historical whodunnits; The Ghost Map by Steven Johnson.  It chronicles the attempts by Dr. John Snow to find the cause of, and stop, the horrifying cholera epidemic in London in 1854.

London of the mid-nineteenth century was an awful place.  It was filled with crashing poverty, and the lack of any kind of sanitation made it reeking, filthy, and disease-ridden.  Then, in the summer of 1854, people in the Broad Street area started coming down with the horrible intestinal disease cholera (if you don't know what cholera does to you, think of a bout of stomach flu bad enough to dehydrate you to death in 24 hours).  And one man thought he knew what was causing it -- and how to put an end to it.

How he did this is nothing short of fascinating, and the way he worked through to a solution a triumph of logic and rationality.  It's a brilliant read for anyone interested in history, medicine, or epidemiology -- or who just want to learn a little bit more about how people lived back in the day.

[If you purchase the book from Amazon using the image/link below, part of the proceeds goes to supporting Skeptophilia!]