Cognitive Neuroscience: How the Brain Generates Cognitive Function

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Cognitive Neuroscience: How the Brain Generates Cognitive Function




Guest:  Dr. Gary Aston-Jones – Neurosciences/Neuroscience Research

Host:  Dr. Linda Austin – Psychiatry


Dr. Linda Austin:  I’m Dr. Linda Austin.  I’m talking, today, with Dr. Gary Aston-Jones, who is Professor of Neurosciences and holds the Murray Chair of Excellence in Neuroscience at the Medical University of South Carolina.  Dr. Aston-Jones, tell us about, first of all, the Centers of Excellence and the Center for Neuroscience, in particular.


Dr. Gary Aston-Jones:  Okay.  The Centers of Excellence is a program that is funded partly by the state and partly by matched funding from private donors.  The idea behind it is to attract senior investigators to universities in South Carolina, including MUSC, that would then establish a nexus for attracting other investigators in a particular area, the overall idea, then, being to attract more economic activity to the state by attracting high-tech, biotech, pharmaceutical jobs and opportunities, and investments.


Dr. Linda Austin:  Tell us, now, about the center of which you are director.


Dr. Gary Aston-Jones:  The center that I’m directing, the main focus is cognitive neuroscience.  We’re just starting this.  We are in the midst of recruiting a couple of new faculty members, junior faculty members, to join us.  The idea is to understand how the brain generates cognitive functions, such as learning, memory, and attention, the kinds of functions that are important for everyday life, but that go awry, very badly, in disorders like Alzheimer’s disease, Parkinson’s disease, Attention Deficit Hyperactivity Disorder, and a whole host of other disorders.


Dr. Linda Austin:  So, as you look into the future and envision the Center of Cognitive Neuroscience explorers, do you see that involving animal models, human models?  What do you envision?


Dr. Gary Aston-Jones:  Both.  My vision is to have animal researchers and human researchers working side-by-side.  We have a new animal and a new human imaging system, here at MUSC, that could work in conjunction with people doing animal experiments that are more invasive.  We’re obtaining electrophysiology and other types of signals in animals.  I’ve found, in my experience, that the combination of people working at a very basic level in animals, combined with people working at a more psychological level in humans, yields more applicable results and better translational activity from basic neuroscience that then can be applicable to clinical issues.


Dr. Linda Austin:  Okay.  So, for those us who do not have PhDs in cognitive neuroscience, break that down, give an example of how you might develop an animal model, how the imaging technology, that you just referred to, might work, and how that scientist might work, cheek by jowl, with someone who studies human psychology to understand a particular disorder better. 


Dr. Gary Aston-Jones:  Okay.  Well, one example would be Attention Deficit Hyperactivity Disorder.  Human researchers have studied that over the last several years with increasingly sophisticated psychological tests and found that it involves deficits in what’s called response inhibition, the inability to inhibit a response once it’s been generated.  They’ve been able to develop very sophisticated behavioral tests to tap into the ability to inhibit responding.  Then, they’ve been able to image humans, including those with ADHD, Attention Deficit Hyperactivity Disorder, while they’re performing that test, and they’ve found altered activity in brain areas of ADHD, compared to normal, people while performing these response inhibition tests.


That, then, can lead animal researchers to go in, in more invasive studies, and do more detailed recordings of neurons in those areas, and in areas connected to those areas, and look at how the different neurotransmitter systems are interacting in those areas of the brain.  That, then, can lead to insights as to what kinds of new drugs might be used to treat disorders such as ADHD.


Dr. Linda Austin:  So, currently, now, what is the thrust of your research?  What disorders are you particularly interested in?


Dr. Gary Aston-Jones:  The thrust of my research is attentional disorders like that and, also, addiction disorders.  The attentional disorders, it’s a very broad subject, include not only attentional function, but also, really, what’s called executive control, or behavioral control, and response inhibition.  We’re studying areas in the brain that we think are really important for determining what you decide to do at any moment, day-to-day, and year-to-year. 


Dr. Linda Austin:  Which areas of the brain in particular?


Dr. Gary Aston-Jones:  There’s an area of the brain called the locus caeruleus, which means blue spot, because it’s blue, in your brain, right now, even thought it’s not stained.  Most of the brain is just sort of this milky white color, but there are a few areas that have some pigment, and this is one of them.  The locus caeruleus has two different modes, or patterns, of activity.  One pattern of activity encourages focused attention, which is, of course, important and adaptive.  But, another pattern of activity encourages what we call exploration, and that’s also important. 


You can imagine that if the locus caeruleus is in an overly exploratory mode, that’s a little bit like ADHD, because it would prevent focusing properly.  And if the locus caeruleus was too much in the focus mode, that’s a little bit like autism, because, then, the subject wouldn’t be able to disengage when the context changed, and it was adaptive to change what the focus was.  So, we think this area, and its connected regions in the brain, are important for adaptively transitioning from focused attention, when that’s adaptive, to disengaging from what you were focused on and finding the next thing to focus when it’s adaptive to make that change and explore for other sources of reward or other things that need your attention at any particular moment.


Dr. Linda Austin:  So, I would imagine, then, that, as you examine the locus caeruleus, there might be some folks who are in the exploratory phase too much of the time; there might be some folks who are in the focused phase too much of the time, but I would think there might be other people who have trouble shifting back and forth as optimally as they might.  Is that true?


Dr. Gary Aston-Jones:  We study this in animals, and we do see that kind of thing in animals.  I’m sure it would also happen in humans.  But, in our animal models, there’s a lot of variability even among animals.  People don’t fully appreciate that sometimes.  But, not all rats are the same.  I’ve done a lot of studies in primates also and, certainly, not all monkeys are the same.  Some animals have a very exploratory type of behavior.  Basically, they’re highly distractible, and it can be difficult to engage them in a task that requires focused attention.  Other animals are so overly focused that it’s difficult to get them to attend to other stimuli while there in the task context.


Dr. Linda Austin:  When you say other animals, do you mean other species?


Dr. Gary Aston-Jones:  I mean other individuals within a species.


Dr. Linda Austin:  Within a species, you see a lot of variability?


Dr. Gary Aston-Jones:  There is a lot of individual variability, just like in humans.  And the effectiveness of drugs in improving performance varies a lot with the animal’s baseline activity on the task, and the baseline activity of the locus caeruleus.  So, for example, in highly distractible animals, if we give a drug called Clonidine, which is used in treating ADHD, that improves performance.  But, if an animal is already performing well and we give Clonidine, that worsens performance.  So, the individual variability corresponds with individual responsiveness to the drugs, and it underlines the need to understand, in each individual, how these systems are functioning to really tailor the best pharmacological treatment for disorders that they might have along these lines. 
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Dr. Linda Austin:  Dr. Aston-Jones, it’s fascinating work that you’re doing.


Dr. Gary Aston-Jones:  Thanks.


Dr. Linda Austin:  We’re lucky to have you.  Good luck with your center.


Dr. Gary Aston-Jones:  Thank you very much.

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