ADHD: Anatomic and neural differences in ADHD

children vs. normal children

Jessica Hartstein

Psyc 480

Oct. 29th, 2003

Remember the people of ADHD

Considered the inability to block out (inhibit) unimportant information and to focus only on relevant input Characterized by:

InattentivenessHyperactivityImpulsivity

Affects 3-5% of school-aged children

Current diagnosis and treatment

Investigating: home/school lifeDiet of children (are they just overly-caffeinated?) Interviews with parents, teachers, and other close

adultsNoting behavior in noisy and unstructured

environmentsNoting behavior with tasks requiring attention and

analysisTreatment (in US) is most often medication

Consider the implications of starting young children on permanent medication

Differential Patterns of Striatal Activation in Young Children with

and without ADHD

Sarah Durston et al 2003

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.

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 testsAlt 2: Yes, normal subjects perform better and

have less of an interference effect than do ADHD subjects

Methods

14 right-handed subjects used in fMRI, 24 used in behavioral task

ADHD diagnosed in a structured interviewADHD subjects withheld from taking their

stimulant medication the day of the fMRIGo/Nogo task, with Pokemon figures

1, 3, 5 intervening gos between nogos 500 ms stimulus duration and 3500 ms

interstimulus intervalIn scanner for about 1 hour for functional and

anatomical imaging (also Pokemon figures)

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

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

Neural results

Divided data into four groups for further analysisCondition (go vs. nogo)Group by condition (ADHD vs. control and go

vs. nogo)Condition for control childrenCondition for ADHD children

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

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

Effects of condition (lumped together)

In both the control subjects and the ADHD subjects the gos were treated distinctly from the nogosIn 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

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 effectThis means that the changes in activation

occurred regardless of number of intervening go trials

Picture the difference

Globus pallidus

Caudate

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

Potential Errors

Effects of treating medicated/non medicated ADHD patients as 1 group

Sample size smallGroup averages used

Select ages (development continues on past 10 years)

Different groups of ADHD subjects (combined and inattentive types)

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)

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)

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

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?

Brain Imaging of Attention Deficit/Hyperactivity Disorder

Jay N. Giedd et al

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

Functional Brain Imaging StudiesMethylphenidate 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

Stop Task

7 adolescent boys with ADHD and 9 controlsScanned 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”

Limitations of fMRI studies

While supportive of fMRI potential, Giedd highlights some limitations:Extremely sensitive equipment

Bite-bar not ideal test-taking environmentVerbal responses sometimes withheld for fear of

movementPotential effects of medication—maybe none, but

as of yet, we don’t knowAlso mentions limitations of other studies, such

as PET and recognizes ease of single-photon computer emission tomography

Inconclusive studies summary

Anatomic studies

Anatomic studies have been performed since the 70’sLots 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

Fun with tables

Important brain structures

CORPUS CALLOSUMLargest interhemispheric commissure in the

brainThe myelinated fibers connecting the R and the L

hemispheres

Some discrepancies, but overall, they’ve found this to be smaller in ADHD subjectsEven the rostrum, the most anterior portion of the

corpus callosum, is smaller

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 asymmetryInconsistency may be due to methodology

Globus pallidus related to the basal ganglia and difficult to measure with fMRIFound 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

Conclusions to the review

The studies suggest right frontal-striatal circuitry involvement in ADHD with a modulating influence from the cerebellumRight 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

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

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 differencesIf you have A, B, C (neurological characteristics)…you

have ADHD. If you have X, Y, Z you don’t.

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 entitySome people think that it has to do with good

parenting, TV watching, diet, etc.

Help us classify subtypes of ADHDCan help guide treatment interventions