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Attention problems in ADHD - neurophysiological correlates


Attention problems in ADHD - neurophysiological correlates

There are several types of attention. Focusing on individual, specific stimuli is a different form of attention than the wide-ranging perception of new stimuli. The former is associated with concentration, the latter with distractibility.

1. Automatic and controlled attention

The model of intrinsic and extrinsic motivation roughly correlates with the distinction between automatic (passive) attention and directed attention. Automatic attention is triggered in particular by novel stimuli (unfamiliar or unexpected in a particular environment) and signal stimuli (usually emotional: familiar and even expectable, but critical stimuli for the individual, such as food, mating partners or danger). The automatic attention mechanisms are unconscious and stimulus-driven (bottom-up)1 and appear to be located in the brain region of the ACC2
Directed attention is controlled top-down2 and is associated with concentration and effort in difficult or uninteresting tasks (e.g. tax return, cleaning the bathroom, boring homework). Directed attention is mediated by executive functions3, which are not automatically retrieved but cognitively coordinated. Executive functions are impaired in ADHD.

2. Attention problems in ADHD are located in the PFC

Inattention in ADHD is primarily caused by the dlPFC.4 In ADHD, functions in the PFC and in cortical and subcortical regions closely connected to it are weaker, particularly in the right hemisphere of the brain.5 The thinner the cortex, the greater the symptoms of inattention in ADHD.6

While the dlPFC harbors the working memory (sustained attention and executive problems = problem-solving behavior) (see Neurophysiological correlates of working memory problems in ADHD) Selective attention (above: “automatic” attention) is probably modulated by a cortico-striato-thalamo-cortical loop that originates in the dorsal anterior cingulate cortex (dACC) and projects to the striatum, then to the thalamus and back to the dACC. Inefficient activation of the dACC can lead to symptoms typical of ADHD,7 such as

  • Too little attention to detail
  • Negligence error
  • Do not listen
  • Losing things
  • Be distracted
  • Forgetting things

A significant increase in BOLD activation between the interference and non-interference conditions in the dorsal anterior cingulate cortex (dACC, Brodmann area 32) correlated with the scores of the inattention and hyperactivity subscales of the ADHD self-report scales in persons with ADHD as well as in non-affected persons.8

The Stroop test is said to be particularly good at examining selective attention.7
More about the Stroop test at Stroop Test In the subsection Attention and reaction tests in the section Tests in the article ADHD - diagnostic methods in the chapter Diagnostics.

The right hemisphere of the brain regulates the inhibition of inappropriate behavioral and emotional reactions. The (right) dlPFC regulates behavior in addition to sustained attention. Injuries in the right dlPFC cause attention problems (including attention direction and task switching problems), filtering problems and impulse control problems.591011

Emotion regulation, on the other hand, is carried out by the ventrolateral PFC.512

2.1. ACTH impairs concentration, increases distractibility

ACTH is a hormone secreted by the pituitary gland, the 2nd increment of the HPA axis, as part of its stress response. ACTH impairs selective and focused attention and causes an altered working mode in the PFC, in which the inhibition of the processing of “irrelevant” stimuli is reduced.
Find out more at ACTH. Irrelevant is placed in quotation marks because in the millions of years of hominid nomadism, a broadened attention (vulgo: distractibility) was probably conducive to survival in the case of acute stress, which serves to cope with survival-threatening dangers. We therefore regard the effects of ACTH not as harm, but as a benefit - even if this stress benefit is less useful since the enemies are no longer sabre-toothed tigers and hostile tribes, but deadline stress and overflowing email accounts.

Cortisol, on the other hand, influences memory more than attention.

3. D4 receptor abnormalities correlate with inattention

In humans, the DRD4 receptor is found exclusively in the PFC, but not in the striatum.1314

In ADHD, polymorphisms of the DRD4 gene therefore have more effects on the (cognitive) symptoms mediated by the PFC, such as inattention or working memory problems, and less on the symptoms mediated by the striatum (such as hyperactivity or impulsivity):

  • DRD4 7-repeat allele1516
  • Single nucleotide polymorphisms (SNP) in the promoter region of DRD417

Consequently, DRD4-7R does not correlate with hyperactivity or impulsivity.181920

4. D2/D3 receptor deficiency in the striatum and inattention

The reinforcement center (the term reward center is inappropriate because it not only rewards pleasant experiences but also influences every form of action) of the brain is located in the nucleus accumbens, a part of the striatum, which in turn is part of the basal ganglia. A reduced number of dopamine D2 and D3 receptors in the striatum leads to less dopamine being absorbed from the synaptic cleft in people with ADHD, which is why fewer things are found (rewarding) or sufficiently exciting than in people without ADHD. The degree of motivational problems as well as the degree of inattention in ADHD correlate with the reduced number of D2 and D3 dopamine receptors in the reinforcement center of the brain. In contrast, other altered personality parameters in ADHD did not correlate with the number of D2 and D3 receptors.2122
This view initially leads to the conclusion that attention problems are not exclusively mediated by the PFC, but also by the striatum.
According to another account, the blockade of dopamine D1, D2 and D4 receptors by corresponding antagonists does not improve attention or response inhibition.23

Agonists and antagonists of the D3 receptor improve deceleration after errors and compulsive nose-poke behavior, but impair performance in other tasks.23

5. Thinking blocks / inability to make decisions due to PFC deactivation

While slightly elevated levels of dopamine and noradrenaline, which occur during mild and manageable stress, increase the performance of the PFC, the further increase in noradrenaline and dopamine levels at even higher stress levels (especially during unmanageable, threatening stress) leads to a shutdown of the PFC and a shift in behavior control to other brain regions.
In the case of noradrenaline, this occurs via the noradrenergic α-1 receptors, which have a lower noradrenaline affinity than α-1 and β receptors and are therefore only activated by very high noradrenaline levels. α1-receptor agonists such as phenylephrine or (in high concentrations) SKF81297 can mimic these effects of high NA or DA levels.24 Agonists stimulate the receptors.
α1 receptor agonists reduce the PFC in this way.2425

Cortisol also addresses the noradrenergic α-1 receptors and thus enhances the PFC-deactivating effect of high noradrenaline levels.

A similar model is found with cortisol, which controls the “normal” mode at high-affinity mineralocorticoid receptors and only switches off the HPA axis at high levels at the low-affinity glucocorticoid receptors.

6. Distractibility from PFC, inattention from boredom from striatum?

This may be due to the different nature of attention problems in the various subtypes. While inattention in hyperactivity is primarily provoked by a high level of distractibility, people with ADHD-I (without hyperactivity) tend to get bored quickly and therefore quickly turn their attention to new stimuli. This pattern can certainly be understood as a motivational problem that is located in the striatum.

We therefore form the following working hypothesis:

  1. Attention problems in ADHD-HI and ADHD-C (with hyperactivity) result from the ADHD-HI-typical overactivation of the PFC and are therefore more likely to be characterized by distractibility
  2. Attention problems in ADHD-I (without or little hyperactivity) result from the ADHD-I-typical underactivation of the PFC, are therefore characterized more by motivation, boredom and are neurophysiologically more strongly located in the striatum.

We hypothesize that ADHD-HI and ADHD-C are characterized by sustained mild (in the sense of: below levels that would cause PFC shutdown) stimulation of the PFC by dopamine and noradrenaline, whereas ADHD-I and SCT are characterized by very strong stimulation by noradrenaline and dopamine during stress, which causes frequent PFC shutdown via the alpha-1 adrenoceptors.
⇒ Section Neurophysiological and endocrine differences between ADHD-HI/ADHD-C and ADHD-I in the article The subtypes of ADHD: ADHD-HI, ADHD-I, SCT and others
Neurophysiological correlates of mental blocks and decision-making problems

Volkow’s discussion can be easily reconciled with this.26

There are differences in regions of the dopaminergic reinforcement system on the left side of the brain, all of which correlate with attention problems (r = 0.3 to 0.35).27

6.1. Overexpression of the THRSP gene and inattention

According to a study, overexpression of the thyroid hormone-responsive gene (THRSP) in the striatum leads to the development of a purely inattentive phenotype in mice.28 THRSP overexpression correlated with overexpression of dopaminergic genes (DAT, tyrosine hydroxylase, dopamine D1 and D2 receptors) in the striatum. Methylphenidate improved attention and normalized the expression levels of dopaminergic genes in the THRSP OE mice.

7. Attention and brain networks

7.1. Connectivity of the cerebellum with the noradrenergic attention center and the default mode network

Functional connectivity of the cerebellum to the anterior and posterior DAN (dorsal noradrenergic attention center) and DMN (default mode network) correlates with attention. Reduced connectivity decreases attention.29

The noradrenergic attention center controls selective attention.
The dopaminergic and the noradrenergic attention center

More on the deviant function of the DMN in ADHD and its normalization by stimulants, including further references at DMN (Default Mode Network) In the article Neurophysiological correlates of hyperactivity.

Another study reports on a network consisting of a default mode network (DMN) and task positive network (TPN), which shows significant deviations during inattention. During inattention, a negative correlation was found between delta in the anterior cingulate and precuneus and delta and theta in the mPFC as well as alpha and gamma in medial frontal regions.30

One study found reduced hierarchical functional integration of the DMN and increased segregation (= separation, splitting) of the DMN in ADHD. The abnormalities in the DMN in ADHD are thought to be caused by changes in functional segregation and integration in its higher-level subnetworks. The adaptive reorganization capacity of brain network states was reduced in people with ADHD, and therefore reduced adaptive regulation between the DMN subnetworks in ADHD was hypothesized to support corresponding normal cognitive functions.31

7.2. Reduced connectivity in the dorsal frontoparietal executive network

One study reports reduced connectivity in the dorsal frontoparietal executive network, consisting of

  • Right dlPFC
  • Posterior parietal cortex

which correlated with the severity of attention problems in ADHD. This correlation was independent of age or gender.
Increased connectivity was also associated with increased attention and better accuracy in NoGo tasks.32

In addition, there were deviations in the connectivity of the Salience network, consisting of

  • Right anterior insula
  • Right dorsal anterior cingulate cortex (rdACC)
  • Right ventrolateral PFC (rvlPFC)

7.3. Low fractional anisotropy

A reduction in fractional anisotropy was associated with reduced attention in a study on the white matter of the brain.33

Another study found that in children with and without ADHD, the mean fractional anisotropy of inattention correlated with significantly increased lateralization of the external capsule.34

8. EEG and attention

8.1. Alpha modulation in response to human eye gaze correlates with severity of inattention

In children with ADHD, the level of inverse alpha activity in the left parieto-occipital region of the brain compared to unaffected children is thought to predict the severity of inattention.35

8.2. Reduced 12-HZ spindles in sleep phase 2 in the frontal EEG

12-HZ spindles in stable non-REM sleep relative to 14-HZ spindles in frontal EEG correlated negatively with inattention and positively with reaction time variability.36

8.3. Current density of delta, theta and alpha in the parietal lobe

One study reports significant differences in the current density of the delta, theta and alpha frequency bands in the parietal lobe between children with ADHD and those not affected. This correlates with problems in shifting attention.37

8.4. Smaller amplitudes and longer P-300 latency for event-related potentials

Attention disorders are said to be associated with smaller amplitudes and P300 waves with longer latency in event-related potentials.38

9. Proactive - not reactive - cognitive control impaired

One study found evidence of problems with proactive cognitive control in ADHD, but less so with reactive cognitive control.39 Proactive control is understood as a form of active, goal-relevant information activation and maintenance in preparation for cognitively challenging events. Reactive control, on the other hand, involves the reactivation of temporary goal-relevant information after Disorders have been recognized and resolved.

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