Understanding ADHD: Current Research and Practice | Week 3 | Step 3.

7 |
The brain and ADHD

ADHD and the brain: Part 1 Please note that this is

a transcript of an online
Dr Mark Kennedy | Senior Research Fellow and Researcher lecture or interview, and
Professor Katya Rubia | Professor of Cognitive Neuroscience is not an academic paper.

Dr Mark Kennedy: So, back in Week 1, we very briefly discussed that it's
possible to see differences in the brains of those with ADHD. Can you tell
us a bit more about the structural differences?

Professor Rubia: ADHD patients have multi-system deficits in several

networks, in several regions, not just one area of the brain. They've shown
to have a delay of normal brain development and are particularly impaired
in brain regions that develop late in the child's development and that
mediate higher-level cognitive functions or emotion control.
As I mentioned in Week 1, ADHD children have a delay in the maturation of
the structure and the function of the brain, in particular, in frontal,
temporal and parietal areas, as well as the basal ganglia and the
interconnections between these regions. Another area that develops very
late in the child's development is the cerebellum. And this region is also
smaller in ADHD patients. And this area is very important for timing as well
as learning, attention and several other higher cognitive functions, as well
as motor functions.

So, ADHD children are basically limping behind normative development.

And there's evidence that adults with ADHD, who still have the disorder,
also have similar structural and functional brain abnormalities as children
with ADHD; although this has been controversial, as the latest meta- and
mega-analysis, collected across 2,000 patients, across 36 centres in the
world, including King's College, in this large meta-analysis and mega-
analysis, we did not find that adults were impaired in the brain structure,
but only children were impaired. However, these large meta-analyses are
underestimating the true effect, as they are conducted on very
heterogeneous patient groups.

So, this latest mega-analysis, which I just mentioned, of over 2,000 ADHD
patients, which is called the ENIGMA ADHD study and where, as I said,
King's College is also one of the centres, we found that ADHD children
have smaller structure in several prefrontal regions and several temporal
and parietal regions, as well as smaller volumes in subcortical areas of the
brain, like the basal ganglia and the limbic system, in particular, the
amygdala and the hippocampus.
Several of the structure abnormalities, in particular, frontal and anterior
cingulate areas, have been related to poor self-control, impulsiveness and
poor inhibitory control, while, in particular, frontal-parietal areas and
connections have been associated to inattention symptoms.

Arnsten AF, Rubia K. (2012) ‘Neurobiological circuits regulating attention, cognitive

control, motivation, and emotion: disruptions in neurodevelopmental psychiatric
disorders’. J Am Acad Child Adolesc Psychiatry. 51(4): 356-67. doi:
10.1016/j.jaac.2012.01.008.

Overall, the structural brain differences between ADHD patients and

controls are relatively small, with very, very small effect sizes in the order
of 0.1 and 0.2. This is interesting in view that ADHD was historically called
'minimal brain dysfunction' before it was renamed to ADHD. So, the frontal
lobes, together with the basal ganglia, form what we call frontal-striatal
networks. And the frontal lobes, together with the cerebellum, they form
frontal-cerebellar networks. Both the cerebellum and the basal ganglia are
important for fine modulating the output of the frontal lobes. And together,
these frontal-striatal and frontal-cerebellar networks are crucial for top-
down control and for the fine modulation of behaviour.

There are many frontal-striatal networks, hundreds of frontal-striatal

networks, which connect different parts of the frontal lobe with different
parts of the basal ganglia or different parts of the cerebellum. And they
regulate different, mature adult behaviours, like, for example the control
of attention, being able to sustain attention, being able to inhibit
distractions, inhibitory self-control, timing functions like forward thinking,
time estimation, control of movement, control of motivation or emotional
self-control.

The frontal lobes also connect to other cortical areas, like the parietal and
temporal lobes, which are crucial for attention, for switching, for working
memory and other higher-level cognitive functions. The frontal lobe is the
superlative region of the brain. We can call it the CO of the brain. And it
exerts top-down control over other regions. And together, with its
connections to these other parts of the brain, it controls a wide range of
behaviours.

So, these frontal-striatal, frontal-cerebellar and frontal-parietal networks,

these networks are abnormal in ADHD, both in their structure and in their
function. Which means these regions are smaller in volume, they have less
cortical thickness and they're less recruited when ADHD children perform
cognitive tasks. And they're also less well-connected, both in their
structural and functional connections. So, we know that in normal child
development, these regions mature in their structure and function and
then mature in the structural and functional connections with increasing
age, which means they become more and more interconnected, they
become more and more recruited and they become more and more
refined and specialised in their functions with age.

And, through this development of these networks, the child becomes more
and more efficient in the top-down control of his emotions, of his cognition,
of his motivation, etc. So, this process of increasing maturity and the
development of these frontal-striatal and frontal-cerebellar connections
with age, this process seems to be delayed in ADHD patients. And this has
been related to their problems with behaviour and inattention and with
their impulsiveness, as well as with their cognitive and motivation
problems.