adhd: anatomic and neural differences in adhd children vs. normal children jessica hartstein psyc...
TRANSCRIPT
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