1. Jessica Hartstein Psyc 480 Oct. 29th, 2003
ADHD: Anatomic and neural differences in ADHD children vs. normal children
Jessica Hartstein
Psyc 480
Oct. 29th, 2003

2. Remember the people of ADHD
Considered the inability to block out (inhibit) unimportant information and to focus only on relevant input
Characterized by:
Inattentiveness
Hyperactivity
Impulsivity
Affects 3-5% of school-aged children

3. Current diagnosis and treatment
Investigating:
home/school life
Diet of children (are they just overly-caffeinated?)
Interviews with parents, teachers, and other close adults
Noting behavior in noisy and unstructured environments
Noting behavior with tasks requiring attention and analysis
Treatment (in US) is most often medication
Consider the implications of starting young children on permanent medication

4. Differential Patterns of Striatal Activation in Young Children with and without ADHD
Sarah Durston et al 2003

5. Question número 1
Using fMRI are there neuronal functional differences between subjects with and without ADHD?
Alt 1: No, children use the same parts of their brain for cognitive functioning regardless of whether they have ADHD or not.
In analysis could treat two groups as one
Alt 2: Yes, normal subjects would rely mostly on the caudate and globus pallidus, while ADHD subjects would have more activity in their cortex.
With question: And what are those differences?
Durston began with the 2nd alternative

6. Question número 2
Are there any behavioral differences between subjects with and without ADHD?
Alt 1: No, subjects with ADHD and subjects without ADHD perform the same on tests
Alt 2: Yes, normal subjects perform better and have less of an interference effect than do ADHD subjects
Expected the 2nd

7. Methods
14 right-handed subjects used in fMRI, 24 used in behavioral task
ADHD diagnosed in a structured interview
ADHD subjects withheld from taking their stimulant medication the day of the fMRI
Go/Nogo task, with Pokemon figures
1, 3, 5 intervening gos between nogos
500 ms stimulus duration and 3500 ms interstimulus interval
In scanner for about 1 hour for functional and anatomical imaging (also Pokemon figures)
2 and 4 intervening gos also done, but just so that the subjects wouldn’t figure out the paradigm, the data wasn’t actually analyzed

8. Behavioral results
ADHD subjects made significantly more errors on nogo trials than did normal subjects (79.1%accuracy vs. 90.4%accuracy)
Differences on accuracy and RT on go trials didn’t reach significance
Number of errors made on the nogo trials increased with number of preceding go trials in control children
ADHD performance with 1 intervening go is similar to that of control group with 3-5 intervening gos
Their conclusion doesn’t mention that ADHD did better at 5 than at 3 intervening. Potentially not significant….

9. Errors for the two groups on nogo task
Note that ADHD children are always comparatively worse
ADHD actually better at 5 intervening than 3, but choose to conclude:
ADHD at 1 intervening similar to normal at 3-5 intervening

10. Neural results Divided data into four groups for further analysis
Condition (go vs. nogo)
Group by condition (ADHD vs. control and go vs. nogo)
Condition for control children
Condition for ADHD children

11. Go Trials vs. Nogo Trials
MR signal increased for go trials (requiring motor task) compared to nogo trials in the left primary motor cortex
Inhibition of action activated the right inferior parietal lobe and bilateral posterior cingulate gyrus and posterior hippocampus

12. Effects of group by condition
Control group activated the left caudate nucleus (known for control)
Children with ADHD activated regions of the cortex: right superior frontal gyrus, right middle frontal gryrus, right inferior parietal lobe, bilateral posterior cingulate gyrus, bilateral precuneus, right superior temporal gyrus, and the bilateral occipital cortex

13. Effects of condition (lumped together)
In both the control subjects and the ADHD subjects the gos were treated distinctly from the nogos
In fact, for both ADHD and normal subjects, the gos were treated rather similarly (activating the left primary motor cortex)
Their behaviors diverge in the inhibition task
Using right hand to announce GO
Could specifically say what those differences are…but

14. Effect of preceding context
Remember that in control subjects, we saw performance decline as the number of intervening gos between nogos increased.
Scan analysis showed no such effect
This means that the changes in activation occurred regardless of number of intervening go trials

15. Picture the difference
Caudate
Globus pallidus
Increased activity for nogo to go trials
Different Z coordinates of brain
L (control): bottom—globus pallidus, above—caudate, part of the striatum
R: ADHD—increased activation of right inferior parietal lobe and posterior cingulate gyrus

16. Last week’s model
This model tried to explain four different disorders, while we are just dealing with one
Could be a decent explanation for the different structures activated in subjects with and without ADHD
Helps to explain potentially why so much of the cortex is activated in ADHD patients…the striatum doesn’t work quite right…when the striatum is less activated, it inhibits the GPi less, which activates the thalamus more which activates the frontal cortex more

17. Potential Errors
Effects of treating medicated/non medicated ADHD patients as 1 group
Sample size small
Group averages used
Select ages (development continues on past 10 years)
Different groups of ADHD subjects (combined and inattentive types)

18. Previous studies
Lou et al suggests that basal ganglia and prefrontal cortex may be hypoperfused in ADHD children (while others say they are different sizes)—not a credible study
Found atypical frontostriatal function in children with ADHD and no activation of the basal ganglia (where control subjects activated)

19. Inferences
ADHD subjects likely have a different trajectory in impulse control OR they exhibit less control earlier in development compared to normal subjects
Normal children activated the basal ganglia much more than ADHD children (caudate is the doorway to the basal ganglia)

20. Inferences continued
ADHD children rely on a more diffuse network of neural systems for cognitive control
Parts of brain used may implicate involvement of working memory and a need for or reliance on vigilance to sustain visual attention

21. Diagnosis of ADHD
What light does this study shed on our “how do you diagnose ADHD?” problem?
While Durston doesn’t outright say anything about diagnosis, she stands firm in her neural differences findings…might this be credibility for using fMRI as opposed to methods mentioned earlier for ADHD diagnosis?

22. Brain Imaging of Attention Deficit/Hyperactivity Disorder
Jay N. Giedd et al

23. Question hào má yī
Across anatomical and neurological studies, are there brain regions we can pinpoint as being responsible for normal and ADHD behavior?
Yes, across studies, the same regions continue to be found essential in the cognition (and inhibition during task) of children with ADHD and that other regions continue to be imperative for the cognition (and inhibition during task) of children without ADHD.
No, we find similar anatomical and neurological results in ADHD and normal subjects
No, we find differences in ADHD and normal subjects, but the findings cannot conclusively pinpoint any brain regions as being responsible for these differences

24. Functional Brain Imaging Studies Methylphenidate study
10 boys with ADHD and 6 controls, scanned with and without methylphenidate (even controls) while doing Go/Nogo tasks
Striking difference in caudate and putamen (more known for relationship to Tourette’s syndrome)
Both groups activated larger numbers of pixels in prefrontal cortex with drug than they did without drug
Hadn’t been medicated for 36 hours pre-scanning and potentially the controls were going through withdrawl
Caudate finding important because that was also found in the previous study

25. Stop Task 7 adolescent boys with ADHD and 9 controls
Scanned while performing the Stop Task and a delay task that required synchronization of a motor response to an intermittently appearing visual stimulus
Concluded that “the caudate…has been related to the response inhibition”
Again, caudate importance

26. Limitations of fMRI studies
While supportive of fMRI potential, Giedd highlights some limitations:
Extremely sensitive equipment
Bite-bar not ideal test-taking environment
Verbal responses sometimes withheld for fear of movement
Potential effects of medication—maybe none, but as of yet, we don’t know
Also mentions limitations of other studies, such as PET and recognizes ease of single-photon computer emission tomography

27. Inconclusive studies summary
Differences due to age and IQ
Small samples
ADHD associated with a subnormal activation of the prefrontal systems responsible for higher-order motor control

29. Anatomic studies Anatomic studies have been performed since the 70’s
Lots of technological advances have been made since then, basically rendering old studies insufficient/incorrect compared to current studies
Best studies will control statistically for differences among individuals in reference to brain sizes (because they vary), but most of studies to date have not done this

30. Fun with tables
Few anatomical studies as it is, and the ones he gives us he’s really critical about anyway…here we have horribly-matched control groups, a dependant group with more than just ADHD wrong with them
WHAT ARE THE IMPLICATIONS OF USING SIBLINGS?

31. Repeat offenders: Corpus callosum (fibers between R and L hemispheres) smaller in ADHD, caudate asymmetry reversal for ADHD, Globus Pallidus smaller in ADHD
Giedd is more supportive of these studies than others, but he’s still critical of them

32. Important brain structures
CORPUS CALLOSUM
Largest interhemispheric commissure in the brain
The myelinated fibers connecting the R and the L hemispheres
Some discrepancies, but overall, they’ve found this to be smaller in ADHD subjects
Even the rostrum, the most anterior portion of the corpus callosum, is smaller

33. Caudate Nucleus and Globus Pallidus
Caudate thought to play important role in ADHD
Abnormalities of caudate nucleus volume or asymmetry have been reported, although the studies differ as to what is abnormal asymmetry
Inconsistency may be due to methodology
Globus pallidus related to the basal ganglia and difficult to measure with fMRI
Found to be significantly reduced in size in ADHD subjects, although the studies have differed as to which sides have the larger difference in ADHD vs. normal subjects

34. Conclusions to the review
The studies suggest right frontal-striatal circuitry involvement in ADHD with a modulating influence from the cerebellum
Right frontal-striatal circuitry has been shown to be involved in hyperactivity of primates in that there is interference with orbital and other projections passing to the caudate
Other neuropyschological studies have found right-sided frontal striatal dysfunction in ADHD subjects
They mentioned that the cerebellum volume is about 5% smaller in ADHD than in normal subjects, but I didn’t really see studies where they talked about the cerebellum, unless it was via other brain structures

35. To make things better
Anatomic findings in ADHD are tentative, need replication of results and quantification of finer cerebral subdivisions
Higher statistical power of studies (brain variation large)
Investigate effects of medication on studies
Giedd hints that functional imaging provides more credible results

36. Can we use this information for diagnosis?
Giedd says:
NO!
Individual variation is too large, and studies are accurate with respect to large groups
Children with no symptoms and an ADHD-like brain shouldn’t be considered to have ADHD
Children with symptoms and no ADHD-like brain shouldn’t necessarily be considered to not have ADHD
But, Dunstun might say:
Yes! The neurological differences are so strong that ADHD can be defined by those differences
If you have A, B, C (neurological characteristics)…you have ADHD. If you have X, Y, Z you don’t.

37. Why study this, then?
We can hope to uncover the neuropathology of the disorder
We can educate families and the public that it is a biological entity
Some people think that it has to do with good parenting, TV watching, diet, etc.
Help us classify subtypes of ADHD
Can help guide treatment interventions