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Old 04-04-04, 10:48 AM
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News clippy.

This is what cutting edge MRI technology looks like:

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Psychiatric News January 2, 2004
Volume 39 Number 1
© 2004 American Psychiatric Association
p. 26

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Clinical & Research News


Brain Scans Reveal Physiology of ADHD
Jim Rosack
High-resolution MRI pictures of the brains of children with ADHD are shedding light on the possible anatomical origins of this complex disorder.

New high-resolution, three-dimensional maps of the brains of children with attention-deficit/hyperactivity disorder (ADHD) indicate significant and specific anatomical differences within areas of the brain thought to control attentional and inhibitory control systems, compared with brain scans of children without ADHD.

The images are thought to be the most advanced to date to reveal the anatomical basis of the disorder. Elizabeth Sowell, M.D., an assistant professor of neurology at the David Geffen School of Medicine at the University of California at Los Angeles, and her colleagues used high-resolution magnetic resonance imaging (MRI) and sophisticated computer analysis to pinpoint more accurately the specific areas of the brain contributing to the symptoms of ADHD.

"Our morphometric procedures allow more precise localization of group differences than do the methods used in previous studies," Sowell said in a press release. "Our results therefore suggest that the disturbances in prefrontal cortices are localized to more inferior aspects of prefrontal regions than was previously appreciated. Our findings also indicate that prefrontal abnormalities are represented bilaterally, by contrast to the predominantly right-sided findings that were emphasized in other reports."

Sowell teamed with Bradley Peterson, M.D., the Suzanne Crosby Murphy Associate Professor of Psychiatry at Columbia University and the New York State Psychiatric Institute, to image 27 children (11 girls and 16 boys) with ADHD and compare them with 46 children without ADHD who were matched for age and sex. The results of the study, funded by several NIH grants as well as the Suzanne Crosby Murphy Endowment at Columbia, appear in the November 22, 2003, issue of Lancet.

Localizing Differences



A three-dimensional, high-resolution MRI image of the brain of a patient with ADHD shows reductions (in yellow and red) in the size of specific areas within the frontal and temporal lobes. (UCLA Laboratory of Neuro Imaging)


Sowell and Peterson observed significant differences in brain structure in the frontal cortices of both sides of the brains of the children with ADHD, with reduced regional brain size mainly confined to small areas of the dorsal prefrontal cortices (see images). Children with ADHD also were observed to have reduced brain size in anterior temporal areas, again on both sides of their brains.

In addition, substantial increases were noted in the volume of gray matter in large areas of the posterior temporal and inferior parietal cortices of children with ADHD, compared with children in the control group. These regions have previously been identified as areas of the brain controlling attention and impulse control.



A three-dimensional, high-resolution MRI image of the brain of a patient with ADHD shows regional increases in the density of gray matter. Areas in yellow and red average between 10 percent and 24 percent more gray matter than those of the average control subject. (UCLA Laboratory of Neuro Imaging)


"Disordered impulse control is often the most clinically debilitating symptom in children with ADHD," noted Peterson in the press release. "These findings may help us to understand the sites of action of the medications used to treat ADHD, particularly stimulant medications. In conjunction with other imaging techniques, these findings may also help us develop new therapeutic agents, given our knowledge of the cellular and neurochemical makeup of the brain regions where we detected the greatest abnormalities."

Building Complex Images

All of the children were imaged using the same MRI scanner at Yale University. The basic images were then processed at the UCLA Laboratory of Neuro Imaging using complex computer systems to build three-dimensional surface maps of each subject’s brain. The researchers then painstakingly identified on each brain image a series of 80 standardized anatomical landmarks, which were used to create a composite average for both the ADHD group and the control group. In this way, each child’s brain could be matched spatially, preserving differences in brain size and shape.

The resulting three-dimensional map of each child’s brain was indeed high resolution, representing more than 65,000 individual points on the surface of the cortex. The points on each subject’s brain were then compared with the average composite image created for both the ADHD group and the control group.

The researchers assessed differences in boys and girls, individually as well as combined, since recent studies have suggested that abnormalities in brain activity and structure may differ between boys and girls with ADHD. However, no significant differences were found. The researchers cautioned, however, that because their sample size was fairly small, differences may not have been appreciable.

The majority of the children with ADHD imaged in this study were taking stimulant medications at the time of imaging or had taken stimulant medications in the past. Sowell notes that it is not possible to determine with any significant certainty whether the anatomical differences they observed are due, in part or whole, to medication. However, other research has noted no anatomical changes associated with intermediate-term use of stimulant medications by children and adolescents with ADHD.

The reductions in size of prefrontal regions observed by Sowell and her colleagues are consistent with other reports of reduced frontal lobe volumes in children with ADHD. The more advanced imaging methods and analysis used in the current study, however, suggest that those reductions are localized to more inferior aspects of the prefrontal regions than was previously realized. Taken together, the evidence base continues to build, supporting smaller and hypo-functional lateral prefrontal cortices in children with ADHD.

Sowell and her coauthors also noted that "while we measured gray-matter density at the cortical surface, arguably a reduction of white matter in the same region could result in an apparent abundance of gray matter." The authors emphasized that, in fact, total white matter volume was reduced in the children with ADHD, but only at a level of significance suggesting a trend.

Lastly, the team attempted to correlate the severity of symptoms in the children with ADHD with the anatomical abnormalities they discovered. They found that children with lesser volumes of gray matter generally were more inattentive, whereas children with significantly larger frontal lobes had higher levels of hyperactivity.

"ADHD," Sowell and Peterson concluded in the study, "is almost certainly a disorder of heterogeneous etiologies that have correspondingly heterogeneous neuro-anatomical underpinnings."

They noted that their sample size was too small to permit a complete ADHD subgroup analysis; however, they called for further studies to confirm differing anatomical and functional disturbances in different areas of the brain’s action-attentional network.

An abstract of "Cortical Abnormalities in Children and Adolescents With Attention-Deficit Hyperactivity Disorder" is posted online at http://www.thelancet.com/journal/vol...earch.27787.1.




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Old 11-19-04, 02:06 AM
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a disorder of heterogeneous etiologies that have correspondingly heterogeneous neuro-anatomical underpinnings???????? WTF
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Old 11-19-04, 11:02 AM
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It means that there may be different causes of ADD. Or two (or more) different disorders being labelled together as ADD. Maybe inattentive type is caused by one difference in the brain, while ADD with hyperactivity is caused by another difference in the brain.
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Old 11-19-04, 12:43 PM
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Ah ha, thank you.
He lost me at, heterogeneous etiologies that have correspondingly heterogeneous neuro-anatomical underpinnings registered as Blah blah..blahblahblah blahblahblahblah blah blah
blahblahblahblahblah blahblahblahblahblahblah blahblahblahblah what am i suppose today?
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Old 12-06-04, 05:23 PM
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Hey, E-boy:

Thanks for posting this. We had a pretty strong reaction to it, and please don't take it as applying to you at all. We believe most imaging research of this sort is fundamentally flawed, and there is little excuse for the research community ignoring the flaws.

In other disciplines, there would have to be disclaimers up front about the unproven nature of the fundamental assumptions the conclusions rely on. For some reason surpassing understanding, AD/HD researchers seem to be exempt from that requirement.

While it's interesting imaging science, I'm afraid that it's lousy science in general. (I do have questions about the soundness of their data reduction techniques, having spent twenty years designing equipment that deals with exactly the same issues. But that's a different forum.)

There is absolutely no evidence for the conclusions drawn by the researchers, and BTW notice they don't offer any. (I know, it's just a news article.) We believe they're revealing their bias, a conviction that there must be some 'disordered operation' of the brains of ADDers.

They offer us no support for the assumption that a difference represents an aberration. Worse, the researchers clearly refer to higher-order functions (like "disordered impulse control") that they cannot even correlate with the differences their images reveal.

Note that I'm saying they don't even establish a correlation, let alone the association required to support statements like, "these findings may also help us develop new therapeutic agents, given our knowledge of the cellular and neurochemical makeup of the brain regions where we detected the greatest abnormalities."

We don't want to clog the thread up with verbiage, but the small picture of what upsets us about these studies isn't too hard to describe.

Consider that the images show neural function. What function is shown, and how do we know it? The truth is that there is a long and difficult chain of logic between understanding how individual neurons respond and the functional areas described in the article.

And with one or two exceptions, that chain has never been fully elucidated from end to end. In most cases, no commonly accepted hypotheses even exist.

Now consider what we can understand from first principles about higher functions of the brain. Without any supporting logic that connects neural function with the general evidence that -–loosely-- associates specific functionality with certain areas, we must necessarily limit the form of our conclusions.

So we're left with this: consider that we have two different brains, one AD/HD and one normal, showing a difference in neural activity in certain areas.

We know that these areas are associated with certain kinds of high level function in the individual through experiments that essentially look at what we lose or how we change when the area is changed or damaged, and by looking at differences in the images of individuals that exhibit anomalous forms of the high level function in question.

This tells us exactly nothing about the observed differences. We only allow for the sake of argument that an association actually exists; in some cases, especially when talking about extremely abstract functions like Barkley's "executive", we dispute the assumption that an association in fact has been established. (Barkley offers no support for his claim that we have been able to find.)

But given an association of some sort, what do we know about the differences in higher level functioning of the individuals? Simply what we can observe about AD/HD, another potential hotbed of disputed methods and poor assumptions about experimental results.

But we'll pass that for the moment, too, even though it's horrible science to do so. Let's assume we have a known difference in two individuals, and an associated difference in the images of their neural activity. What do we know?

Again, it's very difficult to say we really know anything. The only way to assume we've made a significant connection is if we limit our imagination to one preconceived class of possible conclusions.

We can say that the brain of the ADDer is functioning differently that the normal brain. We can see that in the image, but note that it's as likely to represent a compensating mechanism as a deficiency.

No research has established (for example) that some particular activity in a particular area is associated with the function being demonstrated, rather than the expression of that function. (See? Two different classes of activity.)

What that means is that we don't know if the neural activity in the image is due to the brain function that gives rise to the difference in higher level function in the AD/HD individual, or if it's associated with the activity that allows that functional difference to be observed.

Either one will be different, by definition, in the same way that a distorted image on a movie screen may be due to either a poor image on the film or poor optics in the projector. And if the film image is distorted, note these two interesting facts: (1) it reflects poor optics that are not even present to be examined, and (2) the projector is functioning correctly, despite the distorted image it projects.

The analog in MRI imaging terms is that we don't know if the 'aberrant' brain activity in the ADDer was evident at the time that the scans were made. It's entirely possible that the difference in the ADDer's brain was normal activity showing evidence of the result of a different process that operated over many years, leaving subtly different structures before fading into the background.

If so, that's the 'aberrant' process that the researchers are looking for, and there's no way to tell that from the information they've gathered. It's just bad science to assume the 'aberrant' process they're seeking must be present at the time they peek into the subjects brains, or that the difference is directly due to the operation of that process.

Notice how this line of reasoning calls into question any possible conclusions about how drugs are actually affecting the function of the brain, as seen in images like Amen's PET scans.

Until someone sets out the rigorous reasoning they used to establish the connection between what their scans show and the high level behavioral differences they supposedly are studying, there is no excuse for representing these findings as anything but interesting pictures of unknown significance.

We were both steeped in the scientific tradition as we were growing up, and trained in college to be both rigorous and honest to a fault. We can guarantee you that the majority of the scientific establishment is on board with our analysis; these kinds of poorly supported claims would be soundly rejected in many mainstream disciplines.

Science doesn't come in different flavors. You either do it correctly, or it's not really scientific. The idea that there are 'pure' sciences (like physics or chemistry) and ?impure? sciences (like perhaps the behavioral sciences) is pure bunk.

The science is supposed to be as rigorous either way; the only difference is in how difficult it is to be scientific. Some fields of study are so broad or so new that it may be inherently difficult to be rigorous about certain questions. There may be years of work necessary before the questions can even be properly formulated. This study falls right in the "very difficult indeed" bin.

When we set out to understand a particular problem with human communications, we found it relatively easy to map out the path we would need to take. But the path itself was a bear. The fact that it took over twenty years to formulate a set of working hypotheses didn't surprise us; it was obvious from the start that the problem was huge.

Nothing has changed in that time with regard to the rigor necessary to make the claims in the article, except perhaps an acceptance in certain disciplines of the idea that problems that are too big can be ignored.

Attitudes don't make logic, however, and the same requirements are still there, if anyone cares to point them out.

We do, and we usually take every chance we get to do it. This is one of them; the research in this article is flawed, in basic ways, and no valid scientific conclusions about AD/HD can be drawn from the reported results.

As far as we're concerned this kind of speculative pseudoscientific mumbo-jumbo comes perilously close to promoting an agenda of bigotry against people having/being AD/HD. This isn't science, and these people should be ashamed of themselves.

We don't care what institution they're associated with or how big their reputations. They don't have a license to define what's logically correct. Anybody that can see logical errors has the right to step up and point them out. They have the right to defend their conclusions, or be embarrassed.

We welcome any dialog about our criticisms with any interested party. We’ve occasionally sent a critique directly to one or another research team, and we've never had a reply. Amen, Barkley, various main stream University sponsored research efforts like the one in the article, and so on. Even Hartmann, who doesn't really fall into the same class. Ignorance is bliss, I guess.

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Old 12-06-04, 07:00 PM
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No offense taken Stabile. Taken in context, my post was meant to point up the fact that I found Amen's claims ludicrous in the face of his peers inability to duplicate his results, and this article on "Cutting Edge" brain imagery was just the trick to help explain why. Because his peers, even using particularly good and high resolution equipment cannot make anything even approaching what he claims to do with his SPECT machines. I don't endorse the article as anything remotely promising in the diagnostic or behavioral study fields.

I think I've made no secret of my feelings regarding ADHD not being a "pathological" disorder. We differ in what being ADHD means, but we are in agreement that it is NOT pathology or an inherently wrong way to be wired.
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Old 12-06-04, 07:25 PM
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Quote:
Originally Posted by E-boy
I think I've made no secret of my feelings regarding ADHD not being a "pathological" disorder. We differ in what being ADHD means, but we are in agreement that it is NOT pathology or an inherently wrong way to be wired.
*queue dark and forboding music* I on the other hand do not agree with that assessment. More on that in a minute!

First, heterogeneous etiologies with correspondingly heterogeneous anatomical differences means in normal English "different causes caused by different differences in anatomy." That is, there are different things that can be different, and they all result in somewhat similar things.

However, I would argue that this demonstrates that ADHD typifications can be determined by anatomical structural malformations. The particular type of difference should be indicative of the type of ADHD.

As far as Amen's typifications work, I've made it no secret in my time that I dislike Amen's work and theories and find it mostly to be bunk. His 6 types are somewhat absurd, and, in fact, they step outside the normal range of ADHD diagnostic criteria. "Ring of Fire" ADHD is closer to anger-control type personality disorders than it is to ADHD.

As far as the pathology thing, I think I will write a paper on that later, and we'll keep this on topic.
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Old 12-06-04, 10:34 PM
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Good comments. I don't think it's a secret that we're all pretty much in the same church, if perhaps not in exactly the same pew. Keith's views on whether AD/HD should be considered due to some pathology, which we’ve talked about before, aren't even in the same zip code with what these guys are trying to show.

Of course Kay is particularly rabid about not considering AD/HD as arising from pathology because of her strong focus on finding the benevolent view, both within yourself and in others. But she thinks that Keith's ideas of what exactly is bent in a pathological sense will turn out to be the same stuff we’re talking about when corrected for where the model actually sits in the structure of our experiential reality.

We appreciate seeing news items like this, because it seems like human nature to fall prey of the idea that simple pictures will reveal underlying function in any significant way.

I've put a post-it up to check out the UCLA image analysis stuff; I've been around techniques like these forever, and this one gives me a little bit of that slippery, there-ain't-no-such-thing-as-a-free-lunch feeling. I'm particularly interested in how they justified morphing the maps of individual structures.

This is an idea that pops up periodically everywhere number crunching like this is done, and usually the advantages are chimerical. One of the problems with imaging things like the brain is that the noise and moment-to-moment variability between (and within) individuals makes it difficult to see any structure at all.

Only by using lots of statistical tricks can you get a view of structure, and I recall in the early days there was a general lament over the fact that, once they could see structure, no two scans looked alike. To me, that sounds like data, but someone looking for something hard enough can always find a way to justify throwing it away to get a more uniform data set.

I know they said they're preserving the differences in brain size and structure, while still allowing direct comparisons, but what the morphing gets them is not one but two averaged master images: data bye-bye, IMHO.

I hope our basic objection is starting to sink in – that the 'functions' assumed to be associated with certain areas of the brain haven't (in many cases) been correctly linked to those areas by any existing data. Power dissipation is not logic, regardless of how closely related to the operation of the mechanism expressing the logic.

That's not to say that we aren't correct in assuming that a certain part of the brain has the observed effect on (for example) some aspect of speech when it's damaged by disease or accident. We've got to make the assumption of a physical reality at some point, and here's as good a place as any. (We can sort out the details later.) (grin…)

What we have been trying to point out is that the observed evidence of the changed behavior is very likely supported by logical structures expressed in neurons, rather than being expressed directly in the physical neural structures.

Thus, our example of the movie projector; you really don’t know what the active brain tissue is doing, processing and projecting an image that arises in a different context, or participating directly in the construction of the image being projected.

If you think in terms of how most brain probing techniques actually infer neural activity and imagine using the basic method to study the operation of the motherboard of your PC, what we mean should be obvious. Much of the logical structure and operation of a typical program is defined in a logical image of those structures in memory.

When the underlying manipulations of the significant parts of those structures occurs, there isn't any way to differentiate that activity from any other manipulations on memory resident data structures.

Even if you could infer the logic of the actual operations performed to manipulate the data in memory (which is light years away in terms of brain scans), you still wouldn't have a picture of the logic inherent in the manipulation itself.

A logical OR in one context sets your user privileges, and in another context modifies the state of a logical engine that determines the next operation or series of operations of that engine.

The same holds true for the brain. For many reasons, we believe the operation of neurons in the brain supports logical function in an analogous way. There is evidence to suggest that some neural modeling is intended to emulate neural function itself, which then in turn expresses a logical engine in the logical neurons.

So it's distinctly possible that there are several levels of different logical engines involved in expressing a particular higher-level function like "the brain's action-attentional network". (This term is pure bull, by the way. There ain't no such animal; the evidence typically used to connect anything on the logical level of 'attention' of any kind with a network in the brain of any kind is imaginary. It's like looking at the lights of passing cars and imagining where the driver's are going. It tells you more about yourself than anything else.)

There isn't any reason to particularly pick out those supporting physical neural structures (which are the only part of the logical operation that the scans can image) as implicated directly in AD/HD. They could just as well represent an adaptation of brain function to some unseen radically different logical structures actually responsible for the difference in behavior observed.

They may be functioning in a perfectly normal way, operating differently in the same way a projector with adaptive optics might when projecting a distorted image. The difference is related to the distortion, but it's not the anomaly. The distortion is.

This is where Kay thinks our view of brain function starts to generate what we think Keith means when he's talking about something being out of whack. There's a perfectly valid view that the distorted image is out of whack indeed, but there could be a reasonable utility for it in a different context.

If the distortion is spherical, it would need a lot of correction to be shown on a flat screen. But if we project it backwards on a hemispherical screen and view it from behind, we get a 180 degree undistorted view that is much closer to what we see under ordinary circumstances than a traditional rectangular presentation.

We argue that there must be an element of AD/HD analogous to this, in which we process information in different ways that offer certain advantages, and adapt our method of presentation to distort the view we present to others into a more conventional form.

If turns out to be the case, everything that researchers think they know about what brain scans represent is going to have to be tossed out, and the whole field of study reset back to square one.

I'm not holding my breath, though…
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Old 01-03-05, 11:57 AM
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K,

It would be nice if it did indicate one could "type" or "Diagnose" ADHD reliably in this manner, but even the authors of the article only "Suggest" this is possible and that is based on the assumption that consistent physiological differences exist in the different types of ADD, something that at present they only theorize because they don't have the resolution in this equipment, or the sample sizes to test. My statement was simply that, AT PRESENT, it is not a reliable diagnostic. This is why the DSM IV criteria and a good screening is the only accurate diagnostic to date.
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Old 01-03-05, 12:01 PM
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Besides, ADD being a "syndrome" or collections of different, but overlapping symptomologies rather than a single hard and fast "malfunction" (I being a non-believer in pathology here use the terms loosely), it would be difficult to have an imaging technology cover the whole continuum. There may well be an entire suite of differences, in more than one nueral pathway that results in ADD symptomology of various stripes. At least one or two of these has been identified as being connected to a specific variation in a gene coding for dopamine uptake sites. The change wrought by that gene occurs on a molecular level and it isn't known whether that can, does, or would create recognizable changes in brain morphology or if, in fact, it is some other presently unrecognized change doing this. In short, we still have more questions than answers in this department, but the research is always more exciting in this type of environment. :-)
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Old 01-25-10, 12:58 PM
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Re: Brain Scans Reveal Physiology of ADHD

I just found this forum today. Any and all info about damage... tumors/lesions or location of them via MRI is important to me. I have 12 of em. I was diagnosed Adult ADD along the way, in my journey starting Aug.06 @ the age of 46. Long story...biopsy,atypical M.S....too long here anyway @ this time. Anyway, I am thankful for any info. about the subject. I wonder Brain Damage/Adult A.D.D./or Both?

Thank you for being here!!.....Scott Hutson.
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Old 01-19-11, 12:28 PM
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Re: Brain Scans Reveal Physiology of ADHD

is there no sumarised versions of this???
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Old 01-19-11, 12:36 PM
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Re: Brain Scans Reveal Physiology of ADHD

i gotta be honest , i have no idea how someone can read page long posts

let alone write them
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Old 01-19-11, 01:39 PM
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Re: Brain Scans Reveal Physiology of ADHD

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Originally Posted by daveddd View Post
i gotta be honest , i have no idea how someone can read page long posts

let alone write them
No need. This thread is almost six years old.
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Old 01-19-11, 01:41 PM
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Re: Brain Scans Reveal Physiology of ADHD

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Originally Posted by nova2012 View Post
No need. This thread is almost six years old.
oops, i just use the new post button
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