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

ADxS.org needs about $53200 in 2024. In 2023 we received donations from third parties of about $ 32200. Unfortunately, 99.8% of our readers do not donate. If everyone who reads this request makes a small contribution, our fundraising campaign for 2024 would be over after a few days. This donation request is displayed 19,000 times a week, but only 40 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..

$3391 of $53200 - as of 2024-02-01
6%
Header Image
Impulsivity in ADHD - Neurophysiological correlates

Sitemap

Impulsivity in ADHD - Neurophysiological correlates

1. What impulsivity correlates with

Impulsivity correlates with:

  • Externalizing rather than internalizing mental problems1
  • Less sleep on weekends2
  • A lower affinity for food according to the Mediterranean diet2
  • Use of technical equipment for more than 3 hours/day2
  • Birth via cesarean section2
  • Birth weight of more than 2.5 kg2
  • Not breastfed2
  • Sports more than 3 days / week (low correlation)2
  • Tendency to engage in risky behavior3
  • Impulsivity and delay aversion seem to correlate with timing skills.4

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

2. Neurophysiological correlates of impulsivity

Impulsivity is associated with activity in a network of orbitofrontal cortex (OFC) → striatum → thalamus.5

2.1. Neurophysiological correlates

2.1.1. Neurophysiological correlates of action impulsivity

Neurophysiologically, inhibition problems is modulated by a circuit consisting of:6

  • pre-supplementary motor area (preSMA)
  • right inferior frontal gyrus (rIFG)
  • Striatum
  • subthalamic nucleus (STN) comprises.

Action impulsivity and choice impulsivity are moderated by the genes for:6

  • D4R
  • DAT
  • COMT
  • α2AR

2.1.2. Neurophysiological correlates of elective impulsivity

Choice impulsivity (CI) is modulated by brain circuitry consisting of6

  • ventromedial prefrontal cortex (vmPFC)
    • glutamatergic neurons
  • posterior cingulate cortex (pCC)
    • glutamatergic neurons
  • Nucleus accumbens (NAc)

Action impulsivity and choice impulsivity are moderated by the genes for:6

  • D4R
  • DAT
  • COMT
    • A COMT inhibitor increased (in healthy subjects) the choice of more distant rewards. This leads to impairments of the striatum. Since COMT degrades dopamine in the PFC, this suggests a correlation of decreased dopamine levels in the PFC and devaluation of distant rewards 7
  • α2AR

In SHR, in vivo electrophysiological recordings found neural encoding of discounting behavior in prefrontal and orbitofrontal cortex in the presence of rewards:8

  • OFC neurons
    • were activated regardless of the value of the reward
    • exhibited significantly higher neuronal discharge rates
    • the reward-predicting OFC neurons
      • coded the value of rewards in control animals
      • were strongly activated at SHR after receiving a small immediate amplifier
  • mPFC neurons
    • for large rewards: similarly active as for controls
    • for smaller rewards: higher discharge rates than controls
    • no reaction to the value of the rewards

2.1.3. Neurophysiological correlates of impulsivity

Impulsivity correlates with higher activity in the following brain regions:

  • Ventral amygdala (bilateral)910
  • Parahippocampal gyrus9
  • Left dorsal anterior cingulate (Brodmann area 32)9
  • Caudate nucleus (bilateral)9

Impulsivity correlates with lower activity in the following brain regions:

  • Dorsal amygdala9
  • Ventral PFC (Brodmann area 47)9
  • Anterior cingulum1112 and posterior cingulum12
  • Right medial frontal gyrus11
  • Right precentral gyrus11

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

  • Right (anterior lateral) obitofrontal cortex (OFC)1310 or dorsolateral PFC.14
  • Orbitomedial PFC
    Decreased dopaminergic excitation of the omPFC decreases the ability to inhibit impulsivity.7

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.15

2.2. Overexpression of the ATXN7 gene

Hyperactivity and impulsivity is also caused by overexpression of the Atxn7 gene in the PFC and striatum.16 Atomoxetine was able to resolve the hyperactivity and impulsivity in this case.

2.3. 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.12

Delay aversion (impatience) correlates with a reduced amygdala.17

2.4. 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.18
This follows empirical experience that ADHD sufferers, especially children, can sometimes appear apathetic under MPH. In our opinion, this indicates an overdose following this study.

2.5. 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.19

2.6. 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 conspicuous at the same time. Knockdown of IMPase1 in the infralimbic PFC increased impulsivity.20
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.21

2.7. 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.22

2.8. Nucleus accumbens

In rodents, lesions of the nucleus accumbens or basolateral amygdala lead to impulsive decision-making, 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 the magnitude of rewards 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.23

2.9. 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.24

3. Impulsivity and neurotransmitters / hormones

3.1. Dopamine

Impulsivity (like distractibility and depression) is characterized by:1

  • 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.25 Therefore, the former is more amenable to dopaminergic treatment. Emotion regulation and affect control, on the other hand, are better treated noradrenergically.

3.2. Serotonin

Other sources describe that impulsivity is induced by a deficiency of serotonin.2627 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. 28

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

High serotonin levels in the PFC reduce aggression and impulsivity.2930313233
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.34 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.35

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.

3.3. 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.36
In contrast, a cannabinoid antagonist reduced impulsivity and increased preference for later, but larger, rewards.36

3.4. Corticoids

Response inhibition (inhibition) enhanced by mild stress in healthy subjects in a stop-signal task is worsened by a mineralocorticoid antagonist.37
This suggests involvement of mineralocorticoid receptors or the balance between mineralocorticoid receptors and glucocorticoid receptors upon inhibition.

4. Sleep deprivation impairs inhibition

ADHD correlates with sleep deprivation. Increasing sleep duration significantly improved inhibition in children with ADHD.38


  1. 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

  2. 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.

  3. 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

  4. 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

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

  6. Ferré S, Belcher AM, Bonaventura J, Quiroz C, Sánchez-Soto M, Casadó-Anguera V, Cai NS, Moreno E, Boateng CA, Keck TM, Florán B, Earley CJ, Ciruela F, Casadó V, Rubinstein M, Volkow ND (2022): Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variants. Front Endocrinol (Lausanne). 2022 Sep 30;13:1014678. doi: 10.3389/fendo.2022.1014678. PMID: 36267569; PMCID: PMC9578002. REVIEW

  7. 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.

  8. Cao A, Hong D, Che C, Yu X, Cai Z, Yang X, Zhang D, Yu P (2023):The distinct role of orbitofrontal and medial prefrontal cortex in encoding impulsive choices in an animal model of attention deficit hyperactivity disorder. Front Behav Neurosci. 2023 Jan 6;16:1039288. doi: 10.3389/fnbeh.2022.1039288. PMID: 36688128; PMCID: PMC9859629.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

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

  22. 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

  23. 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

  24. 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.

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

  26. 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.

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

  28. 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.

  29. 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

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

  31. 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.

  32. 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.

  33. 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.

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

  35. 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

  36. 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.

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

  38. 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 20.05.2023 zuletzt aktualisiert.