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

8 |
The brain and ADHD

ADHD and the brain: Part 2 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: OK, so, what about the functional differences?

Professor Rubia: So, as I mentioned earlier, at the functional level, several

frontal-striatal networks are less well recruited in ADHD patients when
they perform cognitive tasks, and which explains why they have deficits in
these tasks.

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.

So, for example, the dorsal and the ventral prefrontal regions, together
with the basal ganglia and parietal areas, form the dorsal and ventral
attention networks that are crucial for attention control, for example,
concentration, inhibition of distraction, working memory, etc.
Hart H, Radua J, Mataix D, Rubia K (2013) ‘Meta-analysis of fMRI studies of
inhibition and attention in ADHD: exploring task-specific, stimulant medication and
age effects’. JAMA Psychiatry. 70(2): 185-98.

The structural and the functional abnormalities in these networks have,

therefore, in fact, been associated with inattention at the behavioural level
and with poor performance in attention tasks.

Hart H, Radua J, Mataix D, Rubia K (2013) ‘Meta-analysis of fMRI studies of

inhibition and attention in ADHD: exploring task-specific, stimulant medication and
age effects’. JAMA Psychiatry. 70(2): 185-98.
So, another functional deficit has been observed in the connection
between the inferior frontal cortex, together with the basal ganglia and the
thalamus. So, these regions and networks are crucial for inhibitory self-
control and their under activation, as well as the smaller volume and
cortical thickness in these regions, have been associated in ADHD with
impulsiveness and with poor performance in cognitive tasks, where
inhibition is required.

Hart et al., (2012) ‘Meta-analysis of fMRI studies of timing in attention-deficit

hyperactivity disorder (ADHD)’. Neuroscience Biobehavioural Review. 36(10):
2248-2256.

The inferior frontal cortex, together with the basal ganglia and the
cerebellum, is also crucial for timing functions, which are impaired in
ADHD, and which are closely related to impulsiveness. So, for example,
ADHD patients overestimate time intervals. And this has been associated
with poor waiting behaviour because time seems subjectively elongated
and hence is probably more insufferable. They have, therefore, what we
call delay aversion, which means they do not like waiting.
Shaw P. and Szekeley E. (2018) ‘Insights from neuroanatomical imaging into ADHD
throughout the lifespan’, in Oxford Handbook of ADHD, Banaschewski T et al. (ed),
Oxford: Oxford University Press.

ADHD patients also typically have less consideration of the consequences

of their acts, which reflects poor temporal foresight, poor forward
planning, poor future planning, which is mediated by the inferior prefrontal
cortex. This poor temporal foresight has also been related to impulsive
choice behaviour. For example, in tasks where children have to choose
between a small, immediate reward or a larger, delayed reward, ADHD
children are more likely to choose the small, immediate reward. And this
has been related to poor functioning of the inferior frontal cortex, which is
important for looking into the future and actually understanding the value
of the larger, future reward.

Related to poor choice behaviour are functional abnormalities in regions

of the reward processing network, which consists of the ventromedial
prefrontal cortex, the orbitofrontal cortex, and the ventral basal ganglia.
These regions are important for reward evaluation and for reward-based
decision making. So, as I mentioned before, ADHD patients make more
impulsive decisions and they're more likely to choose, for example, a small
reward now than a large reward later. And this is not only because of the
under recruitment of frontal regions, which look into the future and
understand the value of the larger, delayed reward, but also because the
frontal lobe has less top-down control over limbic areas, which are
activated and which respond to the immediate reward, the reward here
and now.

So, with increasing age, the frontal lobe develops progressively more
inhibitory control over these underlying limbic areas, which process the
thrill of the moment. And with this progressive control of the frontal lobe
over the limbic regions, the child learns to inhibit the thrill of the moment
and to actually make more reflective decisions, which are more future
oriented. So, because this control of the frontal lobe over the limbic
system is immature in ADHD patients, they have less control over their
emotions and their motivation, and they make more impulsive and
immature choices. So, at the brain level, this is shown as less activation of
the ventromedial prefrontal cortex and less top-down control of the
ventromedial prefrontal cortex over those limbic areas, which then results
in more impulsive and less reflective choices.

So, these problems with motivation and impulsiveness, characterised by

poor choice behaviour, where the consequences among acts are less
considered due to immature frontal lobe recruitment, has been
associated in ADHD with increased criminal behaviour and increased
substance abuse. These behaviours are typical for ADHD. And both of
these behaviours have been related to a lack of consideration of the
future consequences of behaviour due to an immature control of the
frontal lobe over the limbic system.

There's also evidence that ADHD patients have abnormal activation in

limbic regions during emotion processing, such as the mediofrontal
cortex, the orbitofrontal cortex, and amygdala. However, the field of
emotion processing is far less researched in ADHD than the cognitive
domain, despite the fact that it is now recognised that emotional
dysregulation is a key feature of ADHD.

Another typical feature of ADHD patients is that they have more intrusive
mind wandering, both at rest and when they perform cognitive tasks.
Subjectively, they report that they have more mind wandering and more
intrusive thoughts than other people.
In imaging studies, this is reflected by an increased activation of the
network that is associated with mind wandering, which is called the default
mode network. This default mode network consists of medial frontal
cortex, praecuneus, and posterior cingulate and is related to task-
irrelevant thoughts or mind wandering. Or, we can also call it mental
clutter.

So, normally, when we do challenging tasks, like a concentration or an

attention task, we have to switch off our mind wandering. In fMRI, this is
reflected in progressively more enhanced deactivation of this default
mode network.

Christakou, A., Murphy, C., Chantiluke, C., Cubillo, A., Smith, A., Giampietro, V., . .
. Rubia, K. (2013) ‘Disorder-specific functional abnormalities during sustained
attention in youth with Attention Deficit Hyperactivity Disorder (ADHD) and with
Autism’. Molecular Psychiatry, 18(2), 236-244.

And others have found that ADHD children do not switch off their default
mode network to the same extent as healthy children do. And this is
associated with poor performance in cognitive or attention tasks.

Now, this poor ability to switch off the default mode network has been
related to a maturation delay, because with increasing age, the default
mode network is progressively more switched off doing cognitive tasks.
And it is progressively more anticorrelated with task-important networks,
like the attention network.
Rubia, K. (2018) ‘Cognitive Neuroscience of Attention Deficit Hyperactivity
Disorder (ADHD) and Its Clinical Translation’. Frontiers in Human Neuroscience, 12,
1-23. doi: https://doi.org/10.3389/fnhum.2018.00100

So, this development has been associated with less attention lapses in
ADHD children. In large ADHD data sets of functional networks, an inverse
relationship was found between ADHD and age in these networks, which
means the older the child and the less ADHD, the better the
anticorrelation between attention networks and the default mode network,
which means the better their ability to switch off their mind wandering
during attention performance.

In conclusion, less recruitment of task-relevant brain regions during

cognitive and motivation tasks and reduced ability to switch off their mind
wandering, both of these have been associated with poor task
performance. And both of these features reflect a more immature brain
functional organisation.