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Emotional dysregulation - neurophysiological correlates


Emotional dysregulation - neurophysiological correlates

Emotional dysregulation in ADHD (and autism) was linked to specific dopaminergic gene variants in a study.1 Neurophysiological correlates have not yet been found.2

1. Neurophysiological elements of the regulation of emotion and mood

Emotion and mood are controlled by limbic-cortical-striatal-pallidal-thalamic circuits, consisting of connections between34

  • PFC
    • Orbitalmedial
      • Decision making
      • Emotional behavior
      • Reward-oriented behavior
      • Inhibition of impulsive behavior
        • Reduced dopaminergic excitation of the omPFC reduces its ability to inhibit impulsive behavior5
    • Orbital
      • Nutrition-related information
      • Expectation of rewards
      • Linking stimuli with a reward, in particular with the reward value of the stimulus
    • Medial
      • Decision-making, emotional and reward-oriented behavior
      • Projected onto control centers of the internal organs in the hypothalamus and periaqueductal gray
      • Modulation of the activity of the internal organs in response to affective stimuli
        • Breathing rate
        • Heart rate
        • Blood pressure
        • Digestion
      • Increased activity of the mPFC correlates with increased skin conductance, which in turn correlates with increased activity of the sympathetic nervous system, which is associated with increased emotional arousal
    • Dorsolateral
      • Selection of where attention should be focused
  • Striatum
    • Dorsal
      • Caudate nucleus
        • Its size correlates negatively with anhedonia
    • Ventromedial
      • Nucleus accumbens
      • Olfactory bulb
      • Globe Pallidum
        • Its size correlates negatively with anhedonia
      • Ventral pallidum
        • Its size correlates negatively with anhedonia
  • Hippocampus6
    • Ventral
      • Subiculum
    • Putting fear into context
    • Increase or decrease anxiety response based on past experiences and memories
    • A connection is assumed between stress-related impaired hippocampus and emotional dysregulation, especially anxiety6
  • Thalamus
    • Mediodorsal
    • Midline
  • Amygdala
    The amygdala - the stress conductor
    • Crucial for
      • Emotional learning
      • Fear conditioning
    • Conveys emotional reactions to stress

This network uses reciprocal connections with

  • Cortical regions that control higher cognitive functions
  • Regions that control autonomic functions, including
    • Periaqueductal gray
    • Hypothalamus

to balance higher cognitive functions with information from the body organs and external environmental conditions to influence mood and emotional states.7

Connections between oPFC / mPFC and the dlPFC mediate neurophysiological correlations in mood disorders between8910

  • Mood dysregulation
  • Working memory problems
  • Impairment of cognitive flexibility

Injuries to the right orbitofrontal PFC caused disinhibited emotional responses and inappropriate social behavior, including a blunted response to punishment, as well as (possibly only early in life) social and moral judgment problems.11

The impairment in the processing of negative emotional stimuli was associated with increased activity in the left anterior insula up to the inferior frontal gyrus.12

One study found evidence that emotional dysregulation is the symptom that links ADHD and gambling addiction.13

2. Emotional dysregulation in ADHD: sympathetic and parasympathetic nervous system

Several studies found deviations in the response of the sympathetic and parasympathetic nervous system in ADHD sufferers, which correlated with the emotional dysregulation of those affected.

According to this, healthy children show systematic variations in parasympathetic activity (RSA) depending on emotion valence (stronger activation for negative emotions, lower activation for positive emotions) and task demand (stronger activation for suppression than for induction). In contrast, children with ADHD showed a stable pattern of increased parasympathetic activity (RSA) under all task conditions compared to baseline.14

A more comprehensive replication study confirmed this and found that in ADHD, emotional negative and positive stimulation tasks correlated with significantly increased parasympathetic and sympathetic reactivity.15

Vagally mediated high-frequency heart rate variability in ADHD correlates with deficits in emotional self-regulation across the lifespan.16

3. Working memory and emotional dysregulation

Deficits in working memory can contribute to emotional dysregulation.17 Working memory is linked to emotion regulation.
A study of children with ADHD aged 6 to 16 years examined the interplay between identified working memory/emotion regulation patterns, demographic characteristics and the role of comorbid diagnoses. Two different, unchanging, non-restricted classes of working memory/emotion regulation were found:18

  • Class 1 (62 %):
    • Impaired working memory
      • significantly lower values in the digit span test
    • Emotion regulation consistently functional
  • Class 2 (emotionally dysregulated):
    • average working memory scores
    • increased emotion regulation problems.

Working memory indicators and emotion regulation scores measured by parents (not teachers) correlated only slightly.
There was no correlation between class and comorbid diagnoses, age, gender or verbal IQ.

4. Correlation of emotional dysregulation with hyperactivity and inattention

One study found a link between hyperactivity/impulsivity and emotional dysregulation, but not between inattention and emotional dysregulation.17

In contrast, another study found that emotional dysregulation seems to correlate more with inattention than with hyperactivity/impulsivity.19 Higher inattention correlated here with

  • Reduced emotional clarity, which increased difficulties in interpersonal relationships
  • Less access to emotion regulation strategies, which increased the symptom burden
  • Impairments at school and at work.

5. Correlation of emotional dysregulation with fractional anisotropy of the white matter of the brain

The fractional anisotropy of 19 white matter lanes labeled with

  • Affective-processing
  • Sensory-processing
  • Integrating
  • Cognitive

Control circuits were positively correlated with the severity of emotional dysregulation in non-affected individuals, while they were negatively correlated with emotional dysregulation in ADHD sufferers.
The severity of ADHD symptoms and diagnosis correlated negatively with fractional anisotropy of these white matter tract bundles, whereas intelligence correlated positively.20

6. Empathy

Empathy is divided into emotional (affective) empathy and cognitive empathy. Emotional empathy develops earlier than cognitive empathy. Emotional empathy uses limbic and paralimbic regions of the brain. Cognitive empathy requires a finely tuned maturation of prefrontal and temporal networks. Injuries to the ofPFC, the vmPFC or right parietal brain regions impair both types of empathy.21
Emotional empathy is thought to be influenced by the oxytocinergic system, whereas22 cognitive empathy is thought to be influenced by the dopaminergic system.23
Although emotional and cognitive empathy work independently of each other, they appear to influence each other. Emotional empathy is seen as an automatic bottom-up process, while cognitive empathy is described as a top-down modulator.21

7. Emotional reactions as an early indicator of ADHD in infants

Specific emotional reactions occur in children of parents with ADHD as early as 6 months of age.24

Excursus: Treatment of emotional dysregulation

E. Excursus: Treatment of emotional dysregulation

E.1 Medication of emotional dysregulation

In our opinion, emotional dysregulation benefits somewhat less from drug treatment than other symptoms of ADHD. Particularly sensitive medication adjustment is required here.
In our experience, medications such as atomoxetine or guanfacine are particularly helpful for emotional dysregulation.

Experience has shown that stimulants (e.g. methylphenidate) not only improve attention and reduce hyperactivity and impulsivity, but also improve emotional self-regulation, which may be at least partly the result of reduced impulsivity.25
Barkley explained in a lecture,2627 , that stimulants can dampen emotions by inhibiting the limbic system, which is not affected in ADHD per se. The higher the dosage, the more the limbic system (including the amygdala) is inhibited. This naturally reduces affect. An individually excessive stimulant dosage can therefore lead to a restricted emotional experience, which occurs in around 20 % of patients treated with stimulants.
In this context, Barkley refers to the increasingly frequent use of combination medication (stimulants and atomoxetine or stimulants and guanfacine) in order to cumulate the positive effects and spread the side effects, which are usually located in different areas, and thus reduce them. In contrast to stimulants, atomoxetine does not affect the limbic system and therefore does not impair emotional perception. Atomoxetine activates the ACC and the frontal lobe and thus directly influences executive functions. Stimulants improve attention, cognition, executive functions and working memory. They are less suitable for improving emotion regulation.
In our opinion, a dampening effect of stimulants on the limbic system would be particularly helpful in the case of excessive impulsivity or anxiety, while patients who are more emotionally balanced should dose stimulants more carefully and reduce stimulants at the latest when their emotional perception is impaired and, if necessary, augment them with other substances or switch completely to other active substances.

A conspicuously high number of ADHD sufferers reported that their rejection sensitivity decreased significantly when taking stimulants. Individual sufferers (around 10%) reported that MPH increased RS, whereby even switching to a different MPH preparation showed differences.

Comorbid anxiety disorders, depression and aggression can be exacerbated by stimulants, as anxiety and moods are regulated by the dopaminergic activity of the ventromedial prefrontal cortex in conjunction with the limbic system. In these cases, noradrenaline reuptake inhibitors or α2A adrenergic agonists are recommended instead.28
One (quite small) study found no short-term change in state anxiety with a single dose of MPH, but did find evidence of a possible long-term worsening.29
Experience has shown that amphetamine medications have better effects on mood in ADHD.

According to a (very small, n = 26) study, memantine (given in addition to stimulants) is said to further improve emotional executive functions and self-regulatory functions.30

E.2 Psychotherapeutic treatment of emotional dysregulation

Mindfulness training is able to improve the balance between thinking and feeling, which is shifted towards thinking in ADHD-typical alexithymia (lack of emotion).

Exercises such as those done with trauma patients, who also often suffer from a lack of emotion, can improve the perception of emotion.

The 5-4-3-2-1 exercise31

  1. Sit quietly and breathe consciously.
  2. Look around you and name 5 things you see.
  3. Now name 5 things that you hear. If there are fewer, name them several times.
  4. Now close your eyes. Name 5 things that you feel.
  5. Repeat the exercise with 4 things instead of 5, then with 3, then with 2 and again with 1 thing.

Further sources:

Smart but Stuck: Emotions in Teens and Adults with ADHD; Thomas E. Brown (Jossey-Bass/Wiley, 2014).## 10.12. Treatment of Emotional Dysregulation

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  2. Hirsch, Chavanon, Christiansen (2019): Emotional dysregulation subgroups in patients with adult Attention-Deficit/Hyperactivity Disorder (ADHD): a cluster analytic approach; Sci Rep. 2019; 9: 5639. doi: 10.1038/s41598-019-42018-y; PMCID: PMC6449354; PMID: 30948735

  3. Ongür, Ferry, Price (2003): Architectonic subdivision of the human orbital and medial prefrontal cortex. J Comp Neurol. 2003 Jun 2;460(3):425-49.

  4. Shaw, Stringaris, Nigg, Leibenluft (2014): Emotion Dysregulation in Attention Deficit Hyperactivity Disorder; The American Journal of Psychiatry, Volume 171, Issue 3, March 2014, pp. 276-293;

  5. 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.

  6. Grawe (2004): Neuropsychotherapie, Seite 354

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  8. Grimm, Beck, Schuepbach, Hell, Boesiger, Bermpohl, Niehaus, Boeker, Northoff (2008): Imbalance between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional judgment: an fMRI study in severe major depressive disorder. Biol Psychiatry. 2008 Feb 15;63(4):369-76.

  9. Tekin, Cummings (2002): Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. J Psychosom Res. 2002 Aug;53(2):647-54.

  10. Koenigs, Grafman (2009): The functional neuroanatomy of depression: distinct roles for ventromedial and dorsolateral prefrontal cortex.Behav Brain Res. 2009 Aug 12;201(2):239-43. doi: 10.1016/j.bbr.2009.03.004.

  11. Anderson, Bechara, Damasio, Tranel, Damasio (1999): Impairment of social and moral behavior related to early damage in human prefrontal cortex. Nat Neurosci. 1999 Nov;2(11):1032-7.

  12. Vetter, Buse, Backhausen, Rubia, Smolka, Roessner (2018): Anterior insula hyperactivation in ADHD when faced with distracting negative stimuli. Hum Brain Mapp. 2018 Mar 23. doi: 10.1002/hbm.24053.

  13. Mestre-Bach, Steward, Potenza, Granero, Fernández-Aranda, Mena-Moreno, Magaña, Vintró-Alcaraz, Del Pino-Gutiérrez, Menchón, Jiménez-Murcia (2019): The Role of ADHD Symptomatology and Emotion Dysregulation in Gambling Disorder. J Atten Disord. 2019 Dec 30:1087054719894378. doi: 10.1177/1087054719894378.

  14. Musser, Backs, Schmitt, Ablow, Measelle, Nigg (2011): Emotion regulation via the autonomic nervous system in children with attention-deficit/hyperactivity disorder (ADHD). J Abnorm Child Psychol. 2011 Aug;39(6):841-52. doi: 10.1007/s10802-011-9499-1. n = 66

  15. Morris, Musser, Tenenbaum, Ward, Martinez, Raiker, Coles, Riopelle (2019): Emotion Regulation via the Autonomic Nervous System in Children with Attention-Deficit/Hyperactivity Disorder (ADHD): Replication and Extension. J Abnorm Child Psychol. 2019 Dec 5. doi: 10.1007/s10802-019-00593-8. n = 259

  16. Christiansen, Hirsch, Albrecht, Chavanon (2019): Attention-Deficit/Hyperactivity Disorder (ADHD) and Emotion Regulation Over the Life Span. Curr Psychiatry Rep. 2019 Mar 2;21(3):17. doi: 10.1007/s11920-019-1003-6. PMID: 30826879.

  17. Groves, Kofler, Wells, Day, Chan (2020): An Examination of Relations Among Working Memory, ADHD Symptoms, and Emotion Regulation. J Abnorm Child Psychol. 2020 Jan 3. doi: 10.1007/s10802-019-00612-8.

  18. Leib, Miller, Chin E (2022): Latent structure of working memory and emotion regulation in pediatric ADHD. Child Neuropsychol. 2022 Aug 16:1-22. doi: 10.1080/09297049.2022.2107626. PMID: 35975287.

  19. O’Neill, Rudenstine (2019): Inattention, emotion dysregulation and impairment among urban, diverse adults seeking psychological treatment. Psychiatry Res. 2019 Oct 24:112631. doi: 10.1016/j.psychres.2019.112631.

  20. Tsai, Lin, Tseng, Gau (2021): White matter microstructural integrity correlates of emotion dysregulation in children with ADHD: A diffusion imaging tractography study. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Apr 12:110325. doi: 10.1016/j.pnpbp.2021.110325. PMID: 33857524.

  21. Fantozzi, Sesso, Muratori, Milone, Masi (2021): Biological Bases of Empathy and Social Cognition in Patients with Attention-Deficit/Hyperactivity Disorder: A Focus on Treatment with Psychostimulants. Brain Sci. 2021 Oct 24;11(11):1399. doi: 10.3390/brainsci11111399. PMID: 34827398; PMCID: PMC8615705. REVIEW

  22. Hurlemann, Patin, Onur, Cohen, Baumgartner, Metzler, Dziobek, Gallinat, Wagner, Maier, Kendrick (2010): Oxytocin enhances amygdala-dependent, socially reinforced learning and emotional empathy in humans. J Neurosci. 2010 Apr 7;30(14):4999-5007. doi: 10.1523/JNEUROSCI.5538-09.2010. PMID: 20371820; PMCID: PMC6632777.

  23. Lackner, Bowman, Sabbagh (2010): Dopaminergic functioning and preschoolers’ theory of mind. Neuropsychologia. 2010 May;48(6):1767-74. doi: 10.1016/j.neuropsychologia.2010.02.027. PMID: 20206642.

  24. Sullivan, Holton, Nousen, Barling, Sullivan, Propper, Nigg (2015): Early identification of ADHD risk via infant temperament and emotion regulation: a pilot studyJ Child Psychol Psychiatry. 2015 Sep;56(9):949-57. doi: 10.1111/jcpp.12426.

  25. Gamli, Tahiroglu (2018): Six months methylphenidate treatment improves emotion dysregulation in adolescents with attention deficit/hyperactivity disorder: a prospective study. Neuropsychiatr Dis Treat. 2018 May 22;14:1329-1337. doi: 10.2147/NDT.S164807. eCollection 2018.

  26. Barkley (2014): Dr Russell Barkley on ADHD Meds and how they all work differently from each other; Youtube – Ausschnitt

  27. Barkley (2014): Dr Russell Barkley on ADHD Meds and how they all work differently from each other; Youtube – Langfassung

  28. Stahl (2013): Stahl’s Essential Psychopharmacology, 4. Auflage, Chapter 12: Attention deficit hyperactivity disorder and its treatment, Seite 490

  29. Kritchman, Koubi, Bloch, Bloch (2019): Effect of Methylphenidate on State Anxiety in Children With ADHD-A Single Dose, Placebo Controlled, Crossover Study. Front Behav Neurosci. 2019 May 15;13:106. doi: 10.3389/fnbeh.2019.00106. eCollection 2019.

  30. Biederman, Fried, Tarko, Surman, Spencer, Pope, Grossman, McDermott, Woodworth, Faraone (2017): Memantine in the Treatment of Executive Function Deficits in Adults With ADHD. J Atten Disord. 2017 Feb;21(4):343-352. doi: 10.1177/1087054714538656. n = 26

  31. Bambach (2003): Die 5-4-3-2-1-Übung, nach Dolan (1991): Resolving Sexual Abuse