Dear readers of ADxS.org, please forgive the disruption.

ADxS.org needs about $19740 in 2023. In 2022 we received donations from third parties of about $ 13870. Unfortunately, 99.8% of our readers do not donate. If everyone who reads this request makes a small contribution, our fundraising campaign for 2023 would be over after a few days. This donation request is displayed 12,000 times a week, but only 140 people donate. If you find ADxS.org useful, please take a minute and support ADxS.org with your donation. Thank you!

Since 01.06.2021 ADxS.org is supported by the non-profit ADxS e.V..

$0 of $19740 - as of 2023-01-03
0%
Header Image
Neurophysiological correlates of inhibition problems and impulsivity in ADHD.

Sitemap

Neurophysiological correlates of inhibition problems and impulsivity in ADHD.

1. Impulsivity

Impulsivity is something other than an affect breakthrough.
Affect breakthroughs are (brief) emotional outbursts, i.e., intense uncontrolled reactions, e.g., brief outbursts of anger.

Symptoms of impulsivity in ADHD are1

  • Excessive talking
  • Blurting out
  • Not being able to wait your turn
  • Interrupt.

1.1. Inhibition problems

Impulsivity is, among other things, the result of a problem with self-regulation and thus inhibition.23
Inhibition is the ability to suppress an impulse.
Inhibition problems are primarily attributed to ADHD-HI and ADHD-C.4
Inhibition problems often manifest themselves, but not only through impulsivity problems.

The dopamine receptors D1 and D5 (D1 group) have activating function, the receptors D2 to D4 (D2 group) inhibitory function. If dopamine binds to receptors D1 or D5, the subsequent synapse is activated = depolarized (excitatory postsynaptic potential); if, on the other hand, dopamine binds to D2 to D4 (“D2 group”), the subsequent synapse is deactivated = hyperpolarized (inhibitory postsynaptic potential).5
In ADHD, the function of the (inhibitory) receptors D2, D3 and D4 is impaired.6

As is known from decision research, the signal to perform an action can be measured up to 10 seconds earlier than the person is aware that he or she has made a decision.7 Even 200 milliseconds before execution, the person can abort the decision that has already been made.8
The long duration between the start of the signal and the actual execution of the decision ultimately serves to ensure that the “made” decision can still be stopped for a relatively long time. Many instances are actively involved in the process of inhibition, that of stopping a decision option.
Figuratively speaking, one brain area puts decisions “up for discussion” and gives other brain regions the opportunity to assess them and then allow or disallow them.

This testing and aborting mechanism is controlled quite significantly by dopamine. If the dopamine control circuit is disturbed, the mechanism that serves to abort decisions is impaired. A disturbance of inhibition is conceivable, for example, in that the dopamine levels are too low or too high, so that the signal transmission is too weak or noisy, so that the weakening (inhibitory) impulse does not arrive.
The known dysfunction of the dopamine system explains the impulse control problems in ADHD.

1.2. Preference for immediate reward (Delay Aversion, Reward Discounting)

One element of impulsivity problems is likely to be a devaluation of more distant rewards (whereas immediate rewards have an unchanged effect).9103111213

In ADHD, more temporally distant rewards are less motivating (reward discounting). A COMT inhibitor increased (in healthy individuals) the choice of more distant rewards. Since COMT degrades dopamine in the PFC, this suggests decreased dopamine levels in the PFC.13 This leads to impairments in the striatum.

Impulsivity appears to result from avoidance of negative affective states associated with delay. ADHD sufferers perceive a delay before (personally desired) outcomes or events as particularly aversive, which reinforces the motive to avoid this delay. Fittingly, in ADHD, the amygdala is hypersensitized to cues of delay (of personally desired events).14

1.3. Higher affinity for risky behavior

Impulsivity is further associated with a tendency to engage in risky behavior.11

1.4. Time estimation problems

Impulsivity and delay aversion seem to correlate with timing skills.12

2. Impulsivity correlates with externalizing symptoms

Impulsivity correlates with

  • Externalizing rather than internalizing mental problems9
  • Less sleep on weekends15
  • A lower affinity for food according to the Mediterranean diet15
  • Use of technical equipment for more than 3 hours/day15
  • Birth via cesarean section15
  • Birth weight of more than 2.5 kg15
  • Not breastfed15
  • Sports more than 3 days / week (low correlation)15

Except for birth circumstances and breastfeeding, we believe the correlates are likely to be consequences rather than causes of impulsivity.

3. Neurophysiological correlates of impulsivity

Impulsivity is associated with activity in a network of orbitofrontal cortex (OFC) → striatum → thalamus.1

3.1. Activity patterns in brain regions

Impulsivity correlates with higher activity in the following brain regions:

  • Ventral amygdala (bilateral)1617
  • Parahippocampal gyrus16
  • Left dorsal anterior cingulate (Brodmann area 32)16
  • Caudate nucleus (bilateral)16

Impulsivity correlates with lower activity in the following brain regions:

  • Dorsal amygdala16
  • Ventral PFC (Brodmann area 47)16
  • Anterior cingulum1819 and posterior cingulum19
  • Right medial frontal gyrus18
  • Right precentral gyrus18

Impulse inhibition (inhibition) correlates neurologically with increased activity in the

  • Right (anterior lateral) obitofrontal cortex (OFC)2017 or dorsolateral PFC.21
  • Orbitomedial PFC
    Decreased dopaminergic excitation of the omPFC decreases the ability to inhibit impulsivity.13

One study found no evidence of abnormalities in neurocognitive processes as represented by the diffusion decision model (DDM) or in go/no-go performance in ADHD. However, responses to failed inhibition in brain regions associated with error monitoring correlated closely with more efficient task performance, externalizing behavior, and ADHD symptoms. This study thus sows doubt as to whether go/no-go task activation truly reflects the neural basis of inhibition and found evidence that error-related contrasts provide better information.22

3.2. Overexpression of the ATXN7 gene

Hyperactivity and impulsivity is also caused by overexpression of the Atxn7 gene in the PFC and striatum.23 Atomoxetine was able to resolve the hyperactivity and impulsivity in this case.

3.3. Amygdala

Connectivity of brain networks is increased locally around the amygdala and decreased to the anterior cingulate and posterior cingulate in the cortex. The preponderance of connections around the amygdala relative to cortical connections results in an increased impulsive response to stimuli with decreased cortical inhibition.19

Delay aversion (impatience) correlates with a reduced amygdala.24

3.4. Ventral striatum

A study in monkeys concluded that low doses of MPH reduce impulsivity, whereas higher doses have a sedative effect. The impulsivity-inhibiting effect occurred particularly in the ventral striatum.25
This follows the empirical experience that ADHD sufferers, especially children, can sometimes appear apathetic under MPH. In our opinion, this indicates an overdose following this study.

3.5. Increased connectivity between ventral tegmentum and middle cingulum

One study found a correlation between subjectively perceived impulsivity and significantly increased functional connectivity between ventral tegmentum and middle cingulate with L-dopa administration.26

3.6. Decreased myo-inositol levels in the vlPFC but not in the striatum

In rats with high impulsivity, significant reductions in myo-inositol levels were reported in the infralimbic PFC, but not in the striatum, compared with rats with low impulsivity. In the infralimbic PFC, significant reductions in transcript levels of key proteins involved in the synthesis and recycling of inositol (IMPase1) were striking at the same time. Knockdown of IMPase1 in the infralimbic PFC increased impulsivity.27
Myo-inositol (cyclohexane-cis-1,2,3,5-trans-4,6-hexol) is the most common isomer of inositol (inositol = cyclohexane hexol, a hexahydric cyclic alcohol). It is an intracellular “second messenger.” Oral administration improves insulin resistance and fat and glucose metabolism and lowers androgen levels.28

3.7. Increased lateralization of the “posterior thalamic radiation”

A significantly higher lateralization of posterior thalamic radiation (PTR) was found in children with ADHD. PTR lateralization correlated with inhibition in healthy controls but not in children with ADHD.29

3.8. Nucleus accumbens

In rodents, lesions of the nucleus accumbens or basolateral amygdala lead to impulsive decisions, but lesions of the ACC or mPFC do not. Lesions of the OFC reduce impulsivity. Impulsive decisions could thus represent the result of abnormal processing of reward magnitude or a reduced effect of delayed reinforcement.
Rodents with a lesion of the nucleus accumbens perceive reward magnitude normally but show a selective deficit in learning instrumental responses with delayed reinforcement. This may suggest that the nucleus accumbens is a reinforcement learning system that mediates the effects of delayed rewards.30

3.9. No evidence of parietal involvement

One study found no evidence of expected parietal modulation in the presence of increased inhibition. However, this lack of modulation was mediated by individual ADHD symptom severity. A correlation between intraparietal sulcus (IPS) activity and events to be inhibited was evident in less severe ADHD symptoms. However, this correlation disappeared in more severe ADHD symptoms. Similarly, functional connectivity between the IPS and the right inferior frontal gyrus correlated with conditions of high inhibitory demand, whereas this correlation decreased with increasing symptom severity.31

4. Impulsivity and neurotransmitters / hormones

4.1. Dopamine

Impulsivity (like distractibility and depression) is characterized by:9

  • A reduced tonic (long-lasting) dopamine level
    and
  • A reduced phasic (short-term) dopamine response to stimuli in the mesolimbic system.

The ADHD symptom of lack of inhibition of executive functions is caused dopaminergically by the basal ganglia (striatum, putamen), whereas the lack of inhibition of emotion regulation is caused noradenergically by the hippocampus.32 Therefore, the former is more amenable to dopaminergic treatment. Emotion regulation and affect control, on the other hand, are better treated noradrenergically.

4.2. Serotonin

Other sources describe that impulsivity is induced by a deficiency of serotonin.3334 Low affinity of the serotonin transporter in platelets correlated with high impulsivity, whereas increased SERT affinity correlated moderately with increased aggressiveness and externalizing behavior. SERT expression had no effect. Serotonin availability in the synaptic cleft seems to depend more on affinity than on the number of SERTs 35

Serotonin inhibits aggression, so a deficiency of serotonin (combined with high testosterone and low cortisol) promotes aggression. More ⇒ Aggression as a result of high testosterone with concomitant attenuated cortisol response.

High serotonin levels in the PFC reduce aggression and impulsivity.3637383940
Zuckermann’s theory that impulsivity is accompanied by increased dopamine levels does not seem to be confirmed. Rather, Cloninger’s theory seems to be confirmed, according to which impulsivity is promoted by low serotonin and low dopamine levels.41 Against the background of the inversed-U theory, according to which too low as well as too high neurotransmitter levels in one brain area cause almost identical problems, these two possibilities would not have to exclude each other,

One study found identical serotonin concentrations in platelets in ADHD-affected and non-affected children, and no relation to attention problems or hyperactivity, but a positive correlation to impulsive behavior.42

We have observed that in ADHD-HI, low doses (2 to 5 mg/day) of SSRIs (e.g., escitalopram) produce very rapid improvement in impulsivity. There seems to be an immediate effect of serotonin in this case, as the effect does not occur after several weeks, as it does as a result of downregulation of the 5-HT receptors with higher-dose SSRI administration as an antidepressant (escitalopram: 10 to 20 mg / day). Downregulation of the receptors should be avoided as far as possible in this case, which is why the lowest dosage that is still helpful should be used.

4.3. Adenosine, cannabinoids

SHR rats, representing a model of ADHD-HI, responded to a cannabinoid CB1 receptor agonist with increased impulsivity (enhanced preference for short-term reward). This response was prevented by a single administration of caffeine (a nonspecific adenosine receptor antagonist) but was enhanced by chronic caffeine administration.43
In contrast, a cannabinoid antagonist reduced impulsivity and increased preference for later, but larger, rewards.43

4.4. Corticoids

Response inhibition (inhibition) enhanced by mild stress in healthy subjects in a stop-signal task is worsened by a mineralocorticoid antagonist.44
This suggests involvement of mineralocorticoid receptors or the balance between mineralocorticoid receptors and glucocorticoid receptors upon inhibition.

5. Sleep deprivation impairs inhibition

ADHD correlates with sleep deprivation. Increasing sleep duration significantly improved inhibition in children with ADHD.45


  1. Stahl (2013): Stahl’s Essential Psychopharmacology, 4. Auflage, Chapter 12: Attention deficit hyperactivity disorder and its treatment, Seite 474

  2. Gawrilow, Schmitt, Rauch (2011): Kognitive Kontrolle und Selbstregulation bei Kindern mit ADHS; Kindheit und Entwicklung 20 (2011), 1, S. 41-48; ISSN 0942-5403

  3. Perry, Carroll (2008): The role of impulsive behavior in drug abuse. Psychopharmacology (Berl). 2008 Sep;200(1):1-26. doi: 10.1007/s00213-008-1173-0.

  4. Diamond: Attention-deficit disorder (attention-deficit/hyperactivity disorder without hyperactivity): A neurobiologically and behaviorally distinct disorder from attention-deficit (with hyperactivity), Development and Psychopathology 17 (2005), 807–825, S. 819, Seite 810

  5. https://de.wikipedia.org/wiki/Dopamin

  6. Diamond: Attention-deficit disorder (attention-deficit/hyperactivity disorder without hyperactivity): A neurobiologically and behaviorally distinct disorder from attention-deficit (with hyperactivity), Development and Psychopathology 17 (2005), 807–825,, Seite 809

  7. Soon, Brass, Heinze, Haynes (2008): Unconscious determinants of free decisions in the human brain; Nature Neuroscience 11, 543–545 (2008); doi:10.1038/nn.2112

  8. Interview mit John-Dylan Haynes in Technologie Report Heft 04 2016, Seite 46

  9. Zisner, Beauchaine (2016): Neural substrates of trait impulsivity, anhedonia, and irritability: Mechanisms of heterotypic comorbidity between externalizing disorders and unipolar depression; Dev Psychopathol. 2016 Nov;28(4pt1):1177-1208

  10. Reynolds, Ortengren, Richards, de Wit (2006): Dimensions of impulsive behavior: Personality and behavioral measures, Personality and Individual Differences, Volume 40, Issue 2, 2006, Pages 305-315, ISSN 0191-8869, https://doi.org/10.1016/j.paid.2005.03.024.

  11. Ashare, Hawk (2012): Effects of smoking abstinence on impulsive behavior among smokers high and low in ADHD-like symptoms; Psychopharmacology (Berl). 2012 Jan; 219(2): 537–547. doi: 10.1007/s00213-011-2324-2, PMCID: PMC3184469, NIHMSID: NIHMS300102, PMID: 21559802, n = 56

  12. Blume, Kuehnhausen, Reinelt, Wirth, Rauch, Schwenck, Gawrilow (2019): The interplay of delay aversion, timing skills, and impulsivity in children experiencing attention-deficit/hyperactivity disorder (ADHD) symptoms. Atten Defic Hyperact Disord. 2019 Mar 29. doi: 10.1007/s12402-019-00298-4. n = 88

  13. Kayser, Allen, Navarro-Cebrian, Mitchell, Fields (2012): Dopamine, corticostriatal connectivity, and intertemporal choice. J Neurosci. 2012 Jul 4;32(27):9402-9. doi: 10.1523/JNEUROSCI.1180-12.2012.

  14. Chronaki , Benikos, Soltesz, Sonuga-Barke (2019): The reinforcing value of delay escape in attention deficit/hyperactivity disorder: An electrophysiological study. Neuroimage Clin. 2019;23:101917. doi: 10.1016/j.nicl.2019.101917.

  15. San Mauro Martin, Sanz Rojo, Garicano Vilar, González Cosano, Conty de la Campa, Blumenfeld Olivares (2019): Lifestyle factors, diet and attention-deficit/hyperactivity disorder in Spanish children – an observational study. Nutr Neurosci. 2019 Sep 3:1-10. doi: 10.1080/1028415X.2019.1660486.

  16. Brown, Manuck, Flory, Hariri (2006): Neural Bases of individual differences in impulsivity: contributions of corticolimbic circuits for behavioral arousal and control. Emotion. 2006 May;6(2):239-45.

  17. New, Hazlett, Buchsbaum, Goodman, Mitelman, Newmark, Trisdorfer, Haznedar, Koenigsberg, Flory, Siever (2007): Amygdala-prefrontal disconnection in borderline personality disorder. Neuropsychopharmacology. 2007 Jul;32(7):1629-40.

  18. Wingenfeld, Rullkoetter, Mensebach, Beblo, Mertens, Kreisel, Toepper, Driessen, Woermann (2009): Neural correlates of the individual emotional Stroop in borderline personality disorder. Psychoneuroendocrinology. 2009 May;34(4):571-86. doi: 10.1016/j.psyneuen.2008.10.024.

  19. Vogt (2019): Cingulate impairments in ADHD: Comorbidities, connections, and treatment. Handb Clin Neurol. 2019;166:297-314. doi: 10.1016/B978-0-444-64196-0.00016-9.

  20. Horn, Dolan, Elliott, Deakin, Woodruff (2003): Response inhibition and impulsivity: an fMRI study. Neuropsychologia. 2003;41(14):1959-66., n = 19

  21. Fernandez-Ruiz, Hakvoort Schwerdtfeger, Alahyane, Brien, Coe, Munoz (2019): Dorsolateral prefrontal cortex hyperactivity during inhibitory control in children with ADHD in the antisaccade task. Brain Imaging Behav. 2019 Sep 6. doi: 10.1007/s11682-019-00196-3.

  22. Weigard, Soules, Ferris, Zucker, Sripada, Heitzeg (2019): Cognitive Modeling Informs Interpretation of Go/No-Go Task-Related Neural Activations and Their Links to Externalizing Psychopathology. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Dec 10:S2451-9022(19)30310-6. doi: 10.1016/j.bpsc.2019.11.013. PMID: 32007431.

  23. Dela Peña, Botanas, de la Peña, Custodio, Dela Peña, Ryoo, Kim, Ryu, Kim, Cheong (2018): The Atxn7-overexpressing mice showed hyperactivity and impulsivity which were ameliorated by atomoxetine treatment: A possible animal model of the hyperactive-impulsive phenotype of ADHD. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Aug 17;88:311-319. doi: 10.1016/j.pnpbp.2018.08.012.

  24. Van Dessel, Sonuga-Barke, Moerkerke, Van der Oord, Lemiere, Morsink, Danckaerts (2019): The amygdala in adolescents with attention-deficit/hyperactivity disorder: Structural and functional correlates of delay aversion. World J Biol Psychiatry. 2019 Apr 4:1-12. doi: 10.1080/15622975.2019.1585946.

  25. Martinez, Pasquereau, Drui, Saga, Météreau, Tremblay (2020): Ventral striatum supports Methylphenidate therapeutic effects on impulsive choices expressed in temporal discounting task. Sci Rep. 2020 Jan 20;10(1):716. doi: 10.1038/s41598-020-57595-6. PMID: 31959838.

  26. Grimm, Kopfer, Küpper-Tetzel, Deppert, Kuhn, de Greck, Reif (2019): Amisulpride and l-DOPA modulate subcortical brain nuclei connectivity in resting-state pharmacologic magnetic resonance imaging. Hum Brain Mapp. 2019 Dec 27. doi: 10.1002/hbm.24913.

  27. Jupp, Sawiak, van der Veen, Lemstra, Toschi, Barlow, Pekcec, Bretschneider, Nicholson, Robbins, Dalley (2020): Diminished Myoinositol in Ventromedial Prefrontal Cortex Modulates the Endophenotype of Impulsivity. Cereb Cortex. 2020 Jan 2. pii: bhz317. doi: 10.1093/cercor/bhz317.

  28. Egarter (2019): Myo-Inositol. Gynäkologische Endokrinologie, February 2019, Volume 17, Issue 1, pp 11–15

  29. Wu, Wang, Yang, Liu, Sun, An, Cao, Chan, Yang, Wang (2020): Altered brain white matter microstructural asymmetry in children with ADHD. Psychiatry Res. 2020 Jan 28;285:112817. doi: 10.1016/j.psychres.2020.112817. PMID: 32035376. n = 205

  30. Cardinal, Winstanley, Robbins, Everitt (2004): Limbic corticostriatal systems and delayed reinforcement. Ann N Y Acad Sci. 2004 Jun;1021:33-50. doi: 10.1196/annals.1308.004. PMID: 15251872. REVIEW

  31. Kolodny, Mevorach, Stern, Biderman, Ankaoua, Tsafrir, Shalev (2019): Fronto-parietal engagement in response inhibition is inversely scaled with attention-deficit/hyperactivity disorder symptom severity. Neuroimage Clin. 2019 Dec 9;25:102119. doi: 10.1016/j.nicl.2019.102119.

  32. Müller, Candrian, Kropotov (2011): ADHS – Neurodiagnostik in der Praxis, Springer, Seite 85

  33. Montoya, Terburg, Bos, van Honk (2012): Testosterone, cortisol, and serotonin as key regulators of social aggression: a reviewand theoretical perspective.Motiv Emot 2012;36(1):65–73.

  34. Brandau (2004): Das ADHS-Puzzle; Systemisch-evolutionäre Aspekte, Unfallrisiko und klinische Perspektiven. Seite 35

  35. Oades, Slusarek, Velling, Bondy (2002): Serotonin platelet-transporter measures in childhood attention-deficit/hyperactivity disorder (ADHD): clinical versus experimental measures of impulsivity. World J Biol Psychiatry. 2002 Apr;3(2):96-100.

  36. Nelson, Trainor (2007): Neural mechanisms of aggression. In: Nature Reviews Neuroscience. Band 8, Nr. 7, Juli 2007, S. 536–546, doi:10.1038/nrn2174, PMID 17585306

  37. Stadler, Zepf, Demisch, Schmitt, Landgraf, Poustka (2007): Influence of rapid tryptophan depletion on laboratoryprovoked aggression in children with ADHD. Neuropsychobiology 56:104–110

  38. Carrillo, Ricci, Coppersmith, Melloni (2009): The effect of increased serotonergic neurotransmission on aggression: a critical meta-analytical review of preclinical studies. Psychopharmacology (Berl). 2009 Aug;205(3):349-68. doi: 10.1007/s00213-009-1543-2.

  39. Ferrari, Palanza, Parmigiani, de Almeida, Miczek (2005): Serotonin and aggressive behavior in rodents and nonhuman primates: predispositions and plasticity. Eur J Pharmacol. 2005 Dec 5;526(1-3):259-73.

  40. Huber, Smith, Delago, Isaksson, Kravitz (1997): Serotonin and aggressive motivation in crustaceans: altering the decision to retreat. Proc Natl Acad Sci U S A. 1997 May 27;94(11):5939-42.

  41. Wanke (2003): Impulsivität und dopaminerge resp. serotonerge Reagibilität. Ein Vergleich der Impulsivitätskonzepte von Cloninger und Zuckerman; Dissertation

  42. Hercigonja Novkovic, Rudan, Pivac, Nedic, Muck-Seler (2009): Platelet Serotonin Concentration in Children with Attention-Deficit/Hyperactivity Disorder); Neuropsychobiology 2009;59:17–22; DOI:10.1159/000202825; n = 114

  43. Leffa, Ferreira, Machado, Souza, da Rosa, de Carvalho, Kincheski, Takahashi, Porciúncula, Souza, Cunha, Pandolfo (2019): Caffeine and cannabinoid receptors modulate impulsive behavior in an animal model of Attentional Deficit and Hyperactivity Disorder. Eur J Neurosci. 2019 Jan 22. doi: 10.1111/ejn.14348.

  44. Schwabe, Höffken, Tegenthoff, Wolf (2013):Stress-induced enhancement of response inhibition depends on mineralocorticoid receptor activation; Psychoneuroendocrinology (2013) 38, 2319—2326

  45. Cremone-Caira, Root, Harvey, McDermott, Spencer (2019): Effects of Sleep Extension on Inhibitory Control in Children With ADHD: A Pilot Study. J Atten Disord. 2019 May 29:1087054719851575. doi: 10.1177/1087054719851575.

Diese Seite wurde am 09.08.2022 zuletzt aktualisiert.