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Neurophysiological correlates of organizational and executive function problems in ADHD.

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Neurophysiological correlates of organizational and executive function problems in ADHD.

For a description of executive functions, see Organizational difficulties / executive problems In the article Overall list of ADHD symptoms by manifestations in the chapter Symptoms.

Executive functions are primarily controlled by working memory.

1. The working memory

Working memory consists of three memory units that are coordinated by a central entity:

  • Processing processor unit (“central executive”)
    • DlPFC
    • Processes information held in the two memory stores
  • Visuo-spatial memory
    • Right posterior parietal lobe
  • Acoustic-linguistic (“phonological”) memory
    • Lower left parietal lobe
  • Short-term memory
    • Episodic buffer for visuospatial and auditory-linguistic information for processing by the central executive. Storage capacity on average 7 (+/-2) units (Miller’s number)

Transferred to a PC, the central executive could be described as the main processor, the short-term memory as the random access memory (RAM), and the memory stores as different segments of the hard disk.

Working memory in the dlPFC is primarily controlled by dopaminergic and noradrenergic processes. Thereby, predominantly phasic and less tonic dopamine seems to control the processes of working memory.1
For example, DA neurons respond phasically to stimuli to be remembered and show no tonic activity during the retention interval, the time during which the information is kept active.2

ADHD is characterized by 3 pathways (according to Sonuga-Barke) that cause neurophysiological symptoms:

  • Dopamine deficiency (among others) in dlPFC (working memory)
    • Disorganized
    • Forgetfulness
  • Dopamine deficiency (among others) in the striatum (reinforcement center)
    • Motivation problems
    • Impulsivity
    • Hyperactivity
  • Changes in the cerebellum
    • Time perception problems

Whereas in ADHD norepinephrine, like dopamine, is decreased in the PFC, in PTSD norepinephrine is increased in the PFC, which (above a certain level) deactivates the PFC and activates the amygdala, which is why PTSD is typically treated with alpha-1 or beta adrenoreceptor antagonists, which counteract the shutdown of the PFC by too much norepinephrine.3

D1 agonists improve, D1 antagonists impair, working memory function.4 Excessive D1 stimulation, as in acute stress, leads to working memory deficits as does inadequate stimulation.5

D2 receptor agonists improve, D2 antagonists impair spatial (not nonspatial) working memory and thereby executive functions in healthy adults.6

CRH in general, as well as in PFC in particular, impairs visuospatial working memory in a dose-dependent manner, which is particularly impaired in ADHD.7 Nonspecific CRH receptor antagonists such as selective CRH-1 receptor antagonists remediated the impairment of working memory and were therefore considered by the authors as possible treatment targets in ADHD.

2. Working memory problems in ADHD

ADHD correlates with working memory problems.8 different from tic disorders.9

One study reported that the various components of working memory are impaired with varying frequency (and varying greatly among individuals) in AD()H)S. Around 70% of those affected showed impairment in one of the 3 areas:10

  • Reordering of the working memory (very often)
    • Retaining and rearranging information
  • Updating working memory (frequent)
    • Active monitoring of incoming information and replacing outdated information with relevant information
    • 8% of those affected showed particular strength in this area
  • Dual processing (rare)
    • Maintaining information during the execution of a secondary task
    • 20% of those affected showed particular strength in this area

In the dlPFC, sustained attention is mapped to problem solving. The ADHD symptoms caused by impaired sustained attention therefore correlate with a dysfunction of the dlPFC.11 Selective attention (distractibility), on the other hand, is located in the dorsal nucleus accumbens.

One long-term study found that working memory problems in ADHD do not diminish in adulthood. In some cases, a worsening of distractibility was noted.12

Another study surprisingly found that language acquisition and arithmetic-math skills, which require working memory, were not significantly worse in children with ADHD. However, performance plummeted significantly when those affected believed they were less gifted.13

In addition to executive problems, one study found problems with the Theory of Mind (ToM) in children with ADHD (in contrast to other studies). However, these did not correlate with the executive problems, so working memory involvement seemed unlikely.14 Another study found lowered Theory of Mind abilities in adults with ADHD that correlated with executive problems.15

One study found a correlation between working memory impairment and eye movement abnormalities in reading in children with ADHD. Visual scanning of words during reading was discontinuous, uncoordinated, and chaotic. ADHD groups showed higher entropy index among the four categories of saccades than non-affected.8

In ADHD, it takes 250 ms for an error in sentence structure to be detected. For non-affected persons, it takes only 100 ms.16

Organizational difficulties (disorganization) are further supposed to be frequently related to time perception problems.17 However, this is not consistent with the neurophysiological correlates of organization problems/executive problems described here (deficits in working memory located in the dlPFC), which differ from the neurophysiological correlates of time (perception) problems, which are primarily located in the cerebellum.

3. Measurement of working memory problems

The problem-solving skills and sustained attention items associated with working memory can be measured with tests.

3.1. Measuring working memory problems with the N-back test

Working memory and sustained attention can be tested with the N-back test.18

For more on this topic, see N-back test In the subsection Attention and reaction tests in the section Tests in the section ADHD - Diagnostic methods in the section Diagnostics.

4. Other executive functions

Inhibition (control of reaction inhibition)19

  • PFC right inferior20
  • Basal Ganglia
    • Nucleus subthalamicus21

Fault detection

  • PFC medial20
  • ACC rostral and the temporoparietal junction22

Control of interference (a component of response inhibition)

  • ACC23
  • PFC lateral23
  • Cortex parietal19

Planning and solving problems19

  • DlPFC22
  • ACC22
  • OFC22
  • Motor/premotor areas22

correct execution of working memory tasks19

  • DlPFC
  • VlPFC
  • Rostral PFC
  • Parietal cortex (bilateral and medial-posterior)

Word fluency:19

  • Phonemic word fluency
    Number of words with a given initial letter that a proband can form

    • Frontal regions24
      • Left motor/premotor regions
      • Left or bilateral opercular regions
      • Left lateral orbitofrontal regions
      • Right dorsolateral regions
  • Semantic / categorical word fluency
    Number of words a respondent can form from a given semantic category (e.g., animals), regardless of the initial letter

    • Temporal regions24

cognitive flexibility19

  • Cortex inferior parietal
  • Superior colliculus
  • Thalamus posterior lateral
  • Medial frontal regions
  • Pre-supplementary motor area(28)

  1. Cohen, Braver, Brown (2002): Computational perspectives on dopamine function in prefrontal cortex. Curr Opin Neurobiol. 2002 Apr;12(2):223-9.

  2. Hollerman, Tremblay, Schultz (1998): Influence of Reward Expectation on Behavior-Related Neuronal Activity in Primate Striatum. Journal of Neurophysiology 1998 80:2, 947-963

  3. Levy (2009): Dopamine vs noradrenaline: inverted-U effects and ADHD theories. Aust N Z J Psychiatry. 2009 Feb;43(2):101-8. doi: 10.1080/00048670802607238.

  4. Arnsten (1997): Catecholamine regulation of the prefrontal cortex. J Psychopharmacol. 1997;11(2):151-62.

  5. Arnsten (2001): Dopaminergic and noradrenergic influences on cognitive functions mediated by prefrontal cortex. In Solanto, Arnsten, Castellanos (Herausgeber): Stimulant drugs and ADHD: Basic and clinical neuroscience (p. 185–208). Oxford University Press. Zitiert nach Solanto (2002): Dopamine dysfunction in AD/HD: integrating clinical and basic neuroscience research. Behav Brain Res. 2002 Mar 10;130(1-2):65-71.

  6. Mehta, Sahakian, Robbins (2001): Comparative psychopharmacology of methylphenidate and related drugs in human volunteers, patients with ADHD, and experimental animals. In Solanto, Arnsten, Castellanos (Herausgeber): Stimulant drugs and ADHD: Basic and clinical neuroscience (p. 303–331). Oxford University Press. Zitiert nach Solanto (2002): Dopamine dysfunction in AD/HD: integrating clinical and basic neuroscience research. Behav Brain Res. 2002 Mar 10;130(1-2):65-71.

  7. Hupalo, Berridge (2016): Working Memory Impairing Actions of Corticotropin-Releasing Factor (CRF) Neurotransmission in the Prefrontal Cortex. Neuropsychopharmacology. 2016 Oct;41(11):2733-40. doi: 10.1038/npp.2016.85. PMID: 27272767; PMCID: PMC5026742.

  8. Mohammadhasani, Caprì, Nucita, Iannizzotto, Fabio (2019): Atypical Visual Scan Path Affects Remembering in ADHD. J Int Neuropsychol Soc. 2019 Dec 12:1-10. doi: 10.1017/S135561771900136X.

  9. Openneer, Forde, Akkermans, Naaijen, Buitelaar, Hoekstra, Dietrich (2019): Executive function in children with Tourette syndrome and attention-deficit/hyperactivity disorder: Cross-disorder or unique impairments? Cortex. 2019 Dec 3;124:176-187. doi: 10.1016/j.cortex.2019.11.007.

  10. Fosco, Kofler, Groves, Chan, Raiker (2020): Which ‘Working’ Components of Working Memory aren’t Working in Youth with ADHD? J Abnorm Child Psychol. 2020 Jan 27;10.1007/s10802-020-00621-y. doi: 10.1007/s10802-020-00621-y. PMID: 31989344. n = 86

  11. Stahl (2013): Stahl’s Essential Psychopharmacology, 4. Auflage, Chapter 12: Attention deficit hyperactivity disorder and its treatment, Seite 472

  12. Torgalsbøen, Zeiner, Øie (2019): Pre-attention and Working Memory in ADHD: A 25-Year Follow-Up Study. J Atten Disord. 2019 Oct 18:1087054719879491. doi: 10.1177/1087054719879491.

  13. Turker, Seither-Preisler, Reiterer, Schneider (2019): Cognitive and Behavioural Weaknesses in Children with Reading Disorder and AD(H)D. Sci Rep. 2019 Oct 23;9(1):15185. doi: 10.1038/s41598-019-51372-w.

  14. Mohammadzadeh, Khorrami Banaraki, Tehrani Doost, Castelli (2019): A new semi-nonverbal task glance, moderate role of cognitive flexibility in ADHD children’s theory of mind. Cogn Neuropsychiatry. 2019 Oct 29:1-17. doi: 10.1080/13546805.2019.1681951.

  15. Tatar, Cansız (2020): Executive function deficits contribute to poor theory of mind abilities in adults with ADHD. Appl Neuropsychol Adult. 2020 Mar 18:1-8. doi: 10.1080/23279095.2020.1736074. PMID: 32186409. n = 80

  16. Gonzalez-Perez, Hernandez-Exposito, Perez, Ramirez, Dominguez (2018): Electrophysiological correlates of reading in children with attention deficit hyperactivity disorder. Rev Neurol. 2018 Mar 16;66(6):175-181. n = 79

  17. Krause, Krause (2014): ADHS im Erwachsenenalter, S. 62

  18. Stahl (2013): Stahl’s Essential Psychopharmacology, 4. Auflage, Chapter 12: Attention deficit hyperactivity disorder and its treatment, Seite 473

  19. Pitzianti, Spiridigliozzi, Bartolucci, Esposito, Pasini (2020): New Insights on the Effects of Methylphenidate in Attention Deficit Hyperactivity Disorder. Front Psychiatry. 2020 Sep 30;11:531092. doi: 10.3389/fpsyt.2020.531092. PMID: 33132928; PMCID: PMC7561436.

  20. Rubia, Smith, Brammer, Taylor (2003): Right inferior prefrontal cortex mediates response inhibition while mesial prefrontal cortex is responsible for error detection. Neuroimage. 2003 Sep;20(1):351-8. doi: 10.1016/s1053-8119(03)00275-1. PMID: 14527595.

  21. Aron, Poldrack (2006): Cortical and subcortical contributions to Stop signal response inhibition: role of the subthalamic nucleus. J Neurosci. 2006 Mar 1;26(9):2424-33. doi: 10.1523/JNEUROSCI.4682-05.2006. PMID: 16510720; PMCID: PMC6793670.

  22. Lie, Specht, Marshall, Fink (2006): Using fMRI to decompose the neural processes underlying the Wisconsin Card Sorting Test. Neuroimage. 2006 Apr 15;30(3):1038-49. doi: 10.1016/j.neuroimage.2005.10.031. PMID: 16414280.

  23. Peterson, Skudlarski, Gatenby, Zhang, Anderson, Gore (1999): An fMRI study of Stroop word-color interference: evidence for cingulate subregions subserving multiple distributed attentional systems. Biol Psychiatry. 1999 May 15;45(10):1237-58. doi: 10.1016/s0006-3223(99)00056-6. PMID: 10349031.

  24. Baldo, Schwartz, Wilkins, Dronkers (2006): Role of frontal versus temporal cortex in verbal fluency as revealed by voxel-based lesion symptom mapping. J Int Neuropsychol Soc. 2006 Nov;12(6):896-900. doi: 10.1017/S1355617706061078. PMID: 17064451.