Friday, March 6, 2009

Do ADHD Kids Use Their Brain Regions Diffferently?

There is a fair amount of debate as to whether ADHD is a developmental delay type of disorder. We are seeing a growing body of research which supports this assertion. One of these supporting pieces of evidence is a recent study done by McAlonan and coworkers on the topic of how relative volumes of specific brain regions correlates to ADHD behaviors such as inhibiting certain responses (a deficiency marked by impulsivity, a key attribute of ADHD), as well as the ability to shift attention to another area and refocus (a deficiency which is especially pronounced in ADHD individuals who exhibit symptoms or diagnoses of comorbid Obsessive Compulsive Disorders or OCD). Additionally, a relatively mild (but still notable) association was seen between age and improvement in reaction times for inhibiting responses and shifting focus, which suggests that the increasing of brain volumes (for specific brain regions) during the childhood developmental process can result in subsequent improvements with regards to efficiency in the impulsive behavior inhibition process as well as in attentional shifting capabilities.

Overview of the methods used in the study:

These next few paragraphs outline the method used in the McAlonan study to measure the two key reaction times which would later correspond to certain brain volume differences. Although a bit lengthy, I felt it necessary to include the details for the sake of understanding what these reaction times and their values are actually measuring.

The McAlonan study involved a computer-simulated measure in which the children watched a computer screen for an airplane to appear on either the left or right hand side. Once one appeared, they were to press a button corresponding to the correct side of the screen in which the airplane appeared. However, in one fourth of the cases, an auditory "stop" signal was presented and the children were instructed to push a third button instead as soon as possible. The timing of these responses were recorded throughout the test. There were actually two measurable components to this exercise, the stop signal reaction time portion of the response (the amount of advanced warning time the auditory "stop" signal needed to appear before the airplane for the child to avoid pressing one of the two airplane direction buttons), and the "change signal reaction time" portion of the response (the amount of time it took for the child to push the third button during the quarter of the trials involving stop behaviors).

To clarify, let's assume that it takes a particular child 0.500 seconds to press the correct button once an airplane flashes on the screen. This is the child's typical response time. If the auditory stop signal is given 0.499 seconds after the airplane appears, it is doubtful that the child could stop from pressing one of the "airplane buttons", since they only had 0.001 seconds to respond to the auditory warning. However, if the auditory signal is given at 0.200 seconds after the airplane appears, the child would have 0.300 seconds to stop from pressing the airplane button. The "stop" reaction time is essentially the amount of time needed for the auditory stop cue to precede the normal reaction time (which, in this child's case, is 0.500 seconds) for the child to successfully avoid pressing one of the airplane buttons.

The change response reaction time is measured by the amount additional time it takes for the child to press the correct third button beyond the stop time. In other words, it addresses how long it takes the child to re-engage in the behavior of choosing the correct button once he or she has successfully stopped the "wrong" behavior.

I realize that the test description above might not make intrinsic sense, but the two main things we should take home from these measurements from the article:
  1. Stop signal reaction time (SSRT): The time it takes for a child to inhibit a particular behavior (i.e. the amount of warning time a child needs to avoid pressing an airplane button after receiving a stop signal in the process described above). For a frame of reference, the average stop signal reaction time was around 0.45 seconds for the ADHD children and 0.36 seconds for the non-ADHD children. Interestingly, in addition to their slower stop signal reaction times, there was a much higher degree of variability within the ADHD group. We have seen this trend of higher variability with response times in ADHD individuals before, in an earlier post on nicotine withdrawal effects in ADHD smokers. Additionally, there was a much greater improvement in stop signal reaction times with the ADHD group compared to the non-ADHD group, and that, around the age of 12, the ADHD kids often "caught up" to their peers with regards to reaction times. This may support the idea that ADHD children may suffer from functional delays in development early on, but can catch up over time.

  2. Change response reaction time (CRRT): This is the amount of time it takes to shift gears and execute an appropriate response (pushing the correct third button in the airplane task described above). The average change response reaction times were around 0.188 seconds for the non-ADHD kids and 0.263 seconds for the ADHD kids. Once again, there was a much greater variability in reaction times for this category for the ADHD children than the non-ADHD children, and the differences between the ADHD and non-ADHD groups diminished with age.
As a quick aside, errors (i.e. pushing the wrong button after an auditory stop signal was presented) were, not surprisingly, significantly higher in the ADHD group than the non-ADHD group.

Relevance and applications of the study:
For comparison purposes, the association between volumes of specific brain regions and reaction times for inhibition and attention shifting tasks was carried out in both ADHD and non-ADHD children. Interestingly, there was a fair amount of difference between the specific brain regions involved for the ADHD children vs. the specific brain regions involved in the non-ADHD children for inhibition of response and attention-shifting behaviors. This may at least suggest that ADHD children may be using different parts of their brains to elicit certain responses than their non-ADHD counterparts.

Given the fact that specific brain regions develop at different rates (some are mostly developed by early childhood, while others continue on into late adolescence and even into one's 20's), it is entirely possible that ADHD individuals may use slower-developing brain regions for certain tasks than their non-ADHD counterparts to control certain behaviors. This combined with the fact that an overall delay in brain maturation is often evident in ADHD individuals, may provide clues as to why ADHD children (and even adults) are less likely to elicit age-appropriate control of certain behaviors.

Reaction Timing vs. Brain Region Volumes:
To elucidate this possible connection, I have constructed a chart which highlights the brain regions whose volumes were connected to faster response times for inhibiting for inhibiting responses and shifting attention in both ADHD and non-ADHD children according to the McAlonan study. These assertions were based on the premise that larger volumes in the following specific brain regions are connected to improvements in stop signal reaction times (related to impulsivity, a key factor in ADHD) and change response reaction times (related in the ability to shift topics, which is often a difficulty in obsessive compulsive disorders, which can also co-occur alongside ADHD) described above.

The top half of the chart entitled "Stop and Inhibitory Behaviors" refers to the brain regions whose relative volumes corresponds to stop signal reaction times (for both ADHD and non-ADHD children) and the bottom half, entitled "Response Changing Behaviors" deals with the brain regions whose relative volumes correspond to change response reaction times.

I have attached a handful of diagrams showing the approximate locations of several of the key brain regions listed above in the chart. These three diagrams (with brief descriptions) are shown below:
Above: The reddish region in the center part of the brain in the image above (the individual is facing to the left, and we're looking at a side view) is the basal ganglia (for original image source, click here). It is comprised of several parts, which are labeled above (don't worry about these sub-components for this article, it is possible we may explore them in further detail in later postings). Actually, a sub-region of the basal ganglia which has been cited by the McAlonan as the major player in response timing for ADHD individuals is called the lentiform nucleus. It is comprised of the Putamen region and globus pallidus, both of which are shown above. Again, don't worry about the exact locations or functions of these subregions, just realize that they show a connection to reaction response timing in ADHD individuals, in addition to their many other functions.

Above: The Cerebellum, Temporal Lobe and Frontal Lobe (which includes the Prefrontal Cortex, which is listed in the chart above in its outer layer) are all shown above (for orignal image source, please click here). We should note that individuals with ADHD generally exhibit lower activity in the prefrontal cortex (in most cases) and the temporal lobe (in several cases).
Above: The Anterior Cingulate region of the brain is approximated by the numbers "24" , "32" and "33" in the brain region chart listed above (for original file source, click here). Note that we are looking from the side at a brain diagram of a person facing to the left. The cingulate acts as a "gear shifter" in the brain. Obsessive behaviors and constant worrying are indicative of an overactive cingulate (think of a car whose gear shift gets "stuck" in a particular gear), while an underactive cingulate region often results in a constant shifting of thoughts and behaviors. Not surprisingly, individuals with ADHD show underactivity in the cingulate (note the similarities between over and underactivity of the cingulate and basal ganglia in OCD and ADHD individuals, respectively).

From the brain region chart listed above, we should note a few of the overall trends:
  1. In general (as mentioned earlier in this post), the correlation between age and volume of specific brain regions was more pronounced in the ADHD children than the non-ADHD children. This refers to the "Age dependent" column in the chart listed above, and may suggest that these brain regions mentioned above may experienced delayed growth patterns in ADHD children but are more likely to be "full-grown" in non-ADHD children. This would explain the age-related effects of brain volume, and possibly (again, assuming that volume of these specific brain regions is connected to faster response times) the resulting differences in response times between ADHD and non-ADHD children.

  2. * The stop response reaction time and change response reaction time utilized different brain regions, with the exception of the right basal ganglia (which was present in both reaction times, but only in the cases of ADHD children). It is interesting to note that the basal ganglia region of the brain essentially governs how fast "idle" is for a specific individual. Individuals with ADHD typically have underactive basal ganglia, while individuals with Obsessive Compulsive Tendencies and workaholics typically have overactive basal ganglia. In addition, symptoms such as poor concentration, poor handwriting and poor fine motor skills, all of which commonly exist in ADHD individuals, are often indicative of underactive basal ganglia.

  3. **There was a tremendous amount of difference with regards to the brain regions associated with reaction times between the ADHD and non-ADHD groups. Of all the brain regions listed above, only the left cerebellum had a correlation between its relative volume and improved reaction time (change response reaction time to be more specific) for both ADHD and non-ADHD cases.

**There are a number of direct implications here. For those of us who parent or work with ADHD children, we often find ourselves directing the child to stop a certain negative behavior and restart an appropriate one such as: "Billy, stop spinning in circles and pick up your truck!". We may often find ourselves frustrated by the length of time it takes for the child to follow both portions of the directions, but we should keep in mind that at least part Billy's slow response may be due to innate delays in stop and change reaction times highlighted in the McAlonan article. Thus, there may be practical implications to the findings of this study beyond the general overview of brain regions at work here.

One last thing to note (which was not brought up by the study):
In the computerized airplane task mentioned above to test for "stop" and "change" signal reaction times, the authors used an audible stop signal to get the child to stop. However, we have recently investigated the co-occurrence of ADHD and auditory processing disorders. Given the relatively high prevalence of this association, it is entirely possible that part of the delay in reaction times for the ADHD group may, in fact be attributed to an underlying comorbid auditory processing disorder (which often goes undetected as a side disorder in a number of cases involving ADHD children).

In fact, the temporal lobes of the brain (see diagrams above) play a critical role in auditory processing. From the chart of brain regions listed above, we see that both the left temporal lobe (whose volume is associated with stop signal reaction times in ADHD children) and the right temporal lobe (whose volume correlates to change response reaction times in non-ADHD children) are both key components with regards to reaction timing, at least based on the McAlonan paper. It would be interesting to see if there was much of a difference in reaction times had the "stop" signal been a visual instead of auditory cue instead, and whether the correlation between temporal lobe size and reaction times would still exist in either the ADHD or non-ADHD cases.

To summarize, we have seen that multiple brain regions have been implicated in both the reaction times related to impulse control/stop behaviors as well as change response time/shifting behaviors. We should also note that the two processes often utilize completely different brain regions, whose rates of development can differ significantly. Furthermore, the correlation of specific brain region volumes to these two types of reaction times was significantly different in ADHD vs. non-ADHD children. This may indicate either a developmental delay in some of these brain regions for ADHD children, or an entirely different set of functioning of specific brain regions in ADHD vs. non-ADHD children.

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