Nora Volkow: Stress, Mood, Drug Abuse, and the Brain

Yesterday featured a piece based on Nora Volkow's talk to the 9th International Conference on Bipolar Disorder several days ago. Dr Volkow is the head of the National Institute on Drug Abuse and manages to moonlight as one of the world's leading brain scientists. Yesterday, we had a look at her work on functional resting connectivity. Today features a selection of slides from part of a much larger presentation dealing with co-occurring mood and substance use disorders. The slides pretty much do all the talking, so I'll keep my commentary brief.

Basically, combine stress with genetic vulnerability and bad things happen. Drug abuse involves much the same process. And, of course, the two interrelate. Lifetime drug abuse amongst bipolars is in the 60 percent range.

An under-active prefrontal cortex combined with an over-active amygdala is a recipe for disaster. There is no end to variations on this theme. This one involves a certain genetic variation (allele). Another variation involves kids, whose brains have yet to mature. As opposed to the heart, Dr Volkow pointed out, the brain takes 20 years to develop. Plenty of time for risk-taking activities, such as drug use. Meanwhile, early childhood social neglect impairs brain development. Too much amygdala action, not enough from the PFC and other areas.

Significantly, a good many of the shared candidate genes for bipolar, schizophrenia, and substance abuse have to do with neuroplasticity. Neuroplasticity has a lot to do with how we react to our environment. If our neurons don't hold up well (such as to stress) and maintain cellular function, well, bad things only get worse. Neuroplasticity also plays a role in programmed brain development, all those gear changes that are supposed to represent smooth transitions into adulthood and beyond. Needless to say, for a good many of us, life is not a smooth transit.

Ah, dopamine.

This is your brain on drugs.

The brain may be highly differentiated, but with everything literally connected to everything in one way or another, mental illness tends to involve a system failure throughout the brain.

Nora Volkow and Brain Networks

At this year’s International Conference on Bipolar Disorder held in Pittsburgh, a whole session was given over to Nora Volkow (pictured here), head of the National Institute on Drug Abuse. As well as overseeing a high-profile agency with a $1 billion annual budget, Dr Volkow continues to crank out mind-boggling research. Her latest involves novel brain scan techniques that she pioneered to map out brain networks.

Resting state functional connectivity - savor the resonance. We know, for instance, the amygdala doesn’t operate in isolation, that it is networked to other areas of the brain. But in what ways? We are used to seeing what happens when the brain is activated, but figuring out the brain in its resting state may tell us more. 

The old way of mapping brains in their resting states was to zero in on a target area such as the amygdala and try to pick up what other signals from elsewhere may have been occurring at the same time. According to Dr Volkow (with Dardo Tomasi of the National Institute on Alcohol Abuse and Alcoholism), in an article in PNAS:

More recently researchers have started to use data-driven approaches that are based on graph theory to assess the functional connectivity of the human brain using datasets obtained with MRI.

I have no idea what this means, but the bottom line is the new way is 1000 times faster, which suddenly makes functional connectivity a doable exercise.

In her talk, Dr Volkow described scanning brains in a resting conscious state,  paying attention to oscillations - generally regarded as background noise - across different regions. Oscillations occurring at the same time could be assumed to be part of the same functioning network.  To test this, Volkow and Tomasi analyzed the brain scans of 979 subjects from 35 centers around the world. One of the things they were looking for was “local functional connectivity density.”

Brain hubs, to put it into layman’s terms. In the authors’ words:

Brain networks with energy-efficient hubs might support the high cognitive performance of humans and a better understanding of their organization is likely of relevance for studying not only brain development and plasticity but also neuropsychiatric disorders.

Volkow and Tomasi’s analysis located the mother of all hubs in the posterior cingulate, corresponding with Brodman Area 23. The cingulate snakes beneath the cortex and, among many things, plays a major role in mediating back and forth traffic between the limbic system and cortical regions of the brain. We have known for some time the cingulate acts as a major hub, but if I am interpreting the authors correctly, we are talking Grand Central Station dimensions.

In the image below, the red-orange indicates the highest signal strength, corresponding with the posterior cingulate/ventral precuneus.



The very strong implication is that things going smoothly in the cingulate bode well for things going smoothly in the brain. In her talk, Dr Volkow mentioned deep brain stimulation (DBS) for depression, focusing on Brodman Area 25, in the immediate hub neighborhood. DBS is also being applied to other brain regions that appear linked to BA 25. Food for thought.

From their hub findings, Volkow and Tomasi identified seven overlapping networks covering 80 percent of all the gray matter in the brain. These involved four major cortical networks (default mode, dorsal attention, visual, and somatosensory) linked to four hubs (ventral precuneus/posterior cingulate, inferior parietal cortex, cuneus, and postcentral gyrus), and three subcortical (tied to hubs involving the cerebellum, thalamus, and amygdala).

The authors note that to keep things simple, they kept the hub count low, based on signal strength and volume. I think this means that researchers will be kept busy for a long time mapping out minor hubs. But the low hub count confirms something that experts have known for a long time, namely that all manner of illnesses and conditions share many of the same pathways. Indeed, Dr Volker in her talk pointed out that both drug use and stress increase dopamine activity in the nucleus accumbens.

Below are renderings of the different networks. (Note, postcentral roughly corresponds to the posterior cingulate.)



This is what they look like together:



Here is a simple diagram illustrating the overlap:



Here is a more complex one:



In her talk, Dr Volkow indicated that the evidence points to the brain organized according to parallel architecture rather than central, sort of like this:



The field of resting state functional connectivity is so new that not even Wikipedia has an entry for it.  Don’t worry. It will.