Neurobiological Models of ADHD

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DD214_DOC

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Does anyone have a link to something that does a good job of explaining the various neurobiologic models of ADHD? Particularly, the most recent neural circuits that are implicated in it? Ironically, my attention span isn't good enough to wade through the excessive drivel in research articles from pubmed to grasp it well.

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I was just about to say--the latest stuff I came across (although mind you, this was maybe 4 years ago while working on my dissertation) was heavily attempting to implicate the DMN in ADHD. In particular, if I'm remembering correctly, it involved maybe "incomplete" de-activation of the DMN, which resulted in regularly-recurrent, brief lapses of attention/poor cognitive activation and arrousal. I couldn't tell you off-hand which specific DMN structures were implicated, but I know folks have always suspected involvement of anterior cingulate and perhaps cerebellum. Both NE and DA have been implicated at various times, although when it comes to behavioral health conditions, when isn't that the case...

Castellanos (I think that was the name) did some interesting work looking at various CPT/reaction time performances in ADHD vs. control folks and using (again, I think) fourier transformations on the data for more in-depth analyses. Russell Barkley's obvoiusly also done a LOT of work in ADHD, both with adults and children; he doesn't typically focus as heavily on the neurobiology, but has developed some theoretical models implicating executive dysfunction as the primary underlying etiology.

Edit: I'll try to dig up some of my lit search material and get back with some citations if I have the chance.
 
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These 2 papers are most commonly cited as far as DMN, but there are certainly newer ones:

1) Castellanos FX, Margulies DS, Kelly C, Uddin LQ, Ghaffari M, Kirsch A, et al. Cingulate–precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder. Biol Psychiatry. 2008;63:332–337.

2)Uddin LQ, Kelly AM, Biswal BB, Margulies DS, Shehzad Z, Shaw D, et al. Network homogeneity reveals decreased integrity of default-mode network in ADHD. J Neurosci Methods. 2008;169:249–254.

Some of the most implicated neurobiologic models are attention networks, reward/feedback-based processing systems, and DMN.
 
I believe Pliszka's book hits on the topic in good depth.

Disclaimer: med student perspective
 
Thomas brown and Barkley both focus on executive dysfunction but neither clearly define what that is nor provide any meaningful neurobiology support imo
 
Even the dmn is intimately connected to other networks and I think it's impossible to separate anything out and daddy this is specifically what's wrong. It's such a complicated and interdependent system. It would be like trying to separate space and time and gravity. Sorta.
 
Dysfunctional modulation of default mode network activity in attention-deficit/hyperactivity disorder.
Metin, Baris; Krebs, Ruth M.; Wiersema, Jan R.; Verguts, Tom; Gasthuys, Roos; van der Meere, Jacob J.; Achten, Eric; Roeyers, Herbert; Sonuga-Barke, Edmund
Journal of Abnormal Psychology, Vol 124(1), Feb 2015, 208-214
The state regulation deficit model posits that individuals with attention-deficit/hyperactivity disorder (ADHD) have difficulty applying mental effort effectively under suboptimal conditions such as very fast and very slow event rates (ERs). ADHD is also associated with diminished suppression of default mode network (DMN) activity and related performance deficits on tasks requiring effortful engagement. The current study builds on these 2 literatures to test the hypothesis that failure to modulate DMN activity in ADHD might be especially pronounced at ER extremes. Nineteen adults with ADHD and 20 individuals without any neuropsychiatric condition successfully completed a simple target detection task under 3 ER conditions (2-, 4-, and 8-s interstimulus intervals) inside the scanner. Task-related DMN deactivations were compared between 2 groups. There was a differential effect of ER on DMN activity for individuals with ADHD compared to controls. Individuals with ADHD displayed excessive DMN activity at the fast and slow, but not at the moderate ER. The results indicate that DMN attenuation in ADHD is disrupted in suboptimal energetic states where additional effort is required to optimize task engagement. DMN dysregulation may be an important element of the neurobiological underpinnings of state regulation deficits in ADHD. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
 
Even the dmn is intimately connected to other networks and I think it's impossible to separate anything out and daddy this is specifically what's wrong. It's such a complicated and interdependent system. It would be like trying to separate space and time and gravity. Sorta.
Yup. I have worked with quite a number of kids with disrupted early attachments who exhibit executive dysfunction and meet diagnostic criteria for ADHD. Obviously, this is a much different neurobiological mechanism than the DMN activity types and also different from other causes of executive dysfunction although as you mentioned they are all going to be interconnected and interrelated. Then there are trauma victims who can have very similar problems, as well. In my mind, attention and hyperactivity are merely symptoms and should never have become a disorder and we really need to separate out the various causes of these symptoms if we ever want to make sense of this.
 
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Yup. I have worked with quite a number of kids with disrupted early attachments who exhibit executive dysfunction and meet diagnostic criteria for ADHD. Obviously, this is a much different neurobiological mechanism than the DMN activity types and also different from other causes of executive dysfunction although as you mentioned they are all going to be interconnected and interrelated. Then there are trauma victims who can have very similar problems, as well. In my mind, attention and hyperactivity are merely symptoms and should never have become a disorder and we really need to separate out the various causes of these symptoms if we ever want to make sense of this.


"In my mind, attention and hyperactivity are merely symptoms and should never have become a disorder and we really need to separate out the various causes of these symptoms if we ever want to make sense of this."

I am confused. Are you saying that attentional problems alone are not severe enough or sufficiently disruptive in someone's life to merit medical intervention unless they are linked to a broader disorder?
 
"In my mind, attention and hyperactivity are merely symptoms and should never have become a disorder and we really need to separate out the various causes of these symptoms if we ever want to make sense of this."

I am confused. Are you saying that attentional problems alone are not severe enough or sufficiently disruptive in someone's life to merit medical intervention unless they are linked to a broader disorder?
Symptoms can always be severe enough to warrant treatment, I am just saying that with the current diagnostic system that classifies based on symptom clusters as opposed to etiology, we end up lumping discrete problems together inaccurately which leads to confusion. I was not using the word "merely" to diminish the fact that symptoms can be severe and impairing. What I meant was that a symptom should not be viewed at the same level as a disorder in a classification system.
 
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Symptoms can always be severe enough to warrant treatment, I am just saying that with the current diagnostic system that classifies based on symptom clusters as opposed to etiology, we end up lumping discrete problems together inaccurately which leads to confusion. I was not using the word "merely" to diminish the fact that symptoms can be severe and impairing. What I meant was that a symptom should not be viewed at the same level as a disorder in a classification system.

Thanks for your response. Unfortunately, I'm still confused. Depending on their severity, can "attentional deficits" be considered or defined as a disorder in a classification system and by excluding every other rationale for such a problem?
 
Thanks for your response. Unfortunately, I'm still confused. Depending on their severity, can "attentional deficits" be considered or defined as a disorder in a classification system and by excluding every other rationale for such a problem?
That is one of the ways that clinicians do view ADHD as a diagnosis of exclusion. I see why they do that and at this point in our science we are kind of stuck with that. In other words, kid has attention problems and we rule out as many possible causes as we can. Anxiety, emotional problems, specific learning disability, abuse, neglect, ODD, autism spectrum, executive function deficits (which could still be ADHD I guess). When we rule those out, then we say, "well it is ADHD" which really means attention problem of unknown etiology when used in that way. I am not saying that people can't have severe attention problems, what I am saying is that we don't have a real good grasp on what it is that we are calling ADHD. Barkley focuses on executive functioning deficits, others are beginning to look at DMN as being the issue. These could potentially be different variants and with either of those concepts we still aren't looking at etiology. I even question whether attention is really the right construct to be looking at. Constructs such as distractibility, novelty seeking, excitability are also related.

Notwithstanding all of that, some of my patients benefit tremendously from stimulant medications. We just don't know how to identify which will and we are not really sure why.
 
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