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Neurophysiological correlates of emotional dysregulation.

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Neurophysiological correlates of emotional dysregulation.

1. Regulation of emotion and mood

Emotion and mood is controlled by limbic-cortical-striatal-pallidal-thalamic circuitry, consisting of connections between12

  • PFC
    • Orbitalmedial
      • Decision making
      • Emotional behavior
      • Reward-oriented behavior
      • Inhibition of impulsive behavior
        • Decreased dopaminergic excitation of the omPFC decreases its ability to inhibit impulsive behavior3
    • Orbital
      • Nutritional information
      • Expectation of rewards
      • Linking stimuli to a reward, especially to the reward value of the stimulus
    • Medial
      • Decision making, emotional and reward behavior
      • Projects to control centers of internal organs in 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 correlates with increased emotional arousal
    • Dorsolateral
      • Selection of where to focus attention
  • Striatum
    • Dorsal
      • Caudate nucleus
        • Whose size correlates negatively with anhedonia
    • Ventromedial
      • Nucleus accumbens
      • Olfactory bulb
      • Globus Pallidum
        • Whose size correlates negatively with anhedonia
      • Ventral pallidum
        • Whose size correlates negatively with anhedonia
  • Hippocampus4
    • Ventral
      • Subiculum
    • Put fear in context
    • Increase or decrease fear response based on past experiences and memories
    • A link is assumed between stress-related impaired hippocampus and emotional dysregulation, especially anxiety4
  • Thalamus
    Thalamus
    • Mediodorsal
    • Midline
  • Amygdala
    The amygdala - the stress conductor
    • Crucial for
      • Emotional learning
      • Fear conditioning
    • Mediates 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 match higher cognitive functions with information from the body organs and external environmental conditions to influence mood and emotional states.5

Connections between oPFC / mPFC and the dlPFC mediate neurophysiological correlations in mood disorders between678

  • 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 when occurring early in life) social and moral evaluation problems.9

Impairment in processing negative emotional stimuli was associated with increased activity in the left anterior insula to the inferior frontal gyrus.10

One study found evidence that emotional dysregulation was the symptom linking ADHD and gambling addiction.11

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

Several studies found abnormalities in ADHD sufferers in both sympathetic and parasympathetic nervous system responses that correlated with emotional dysregulation in sufferers.

According to these findings, healthy children showed 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) in all task conditions compared with baseline.12

A broader replication study confirmed this and found that in ADHD, emotionally negative and positive stimulation tasks correlated with significantly increased parasympathetic and sympathetic reactivity.13

Vagally mediated high-frequency heart rate variability correlates with deficits in emotional self-regulation across the lifespan in ADHD .14

3. Working memory and emotional dysregulation

Deficits in working memory can contribute to emotional dysregulation.15

4. Correlation of emotional dysregulation with hyperactivity and inattention

One study found a relationship between hyperactivity/impulsivity and emotional dysregulation, but not between inattention and emotional dysregulation.15

In contrast, another study found that emotional dysregulation seemed to correlate more with inattention than with hyperactivity/impulsivity.16 Higher inattention correlated here with

  • Decreased emotional clarity, which increased difficulties in interpersonal relationships
  • Lower access to emotion regulation strategies, which increased symptom burden
  • Impairments in school and work.

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

The fractional anisotropy of 19 lanes of white matter associated with

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

Control circuitry were positively correlated with emotional dysregulation severity in unaffected individuals, whereas they were negatively correlated with emotional dysregulation in ADHD sufferers.
ADHD symptom severity and diagnosis correlated negatively with fractional anisotropy of these white matter tract bundles, whereas intelligence correlated positively.17

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 brain regions. Cognitive empathy requires fine-tuned maturation of prefrontal and temporal networks. Injuries to the ofPFC, vmPFC, or right parietal brain regions impair both types of empathy.18
Emptional empathy is thought to be influenced by the oxytocinergic system, whereas19 cognitive empathy is thought to be influenced by the dopaminergic system.20
Emotional and cognitive empathy, while operating independently, appear to influence each other. Emotional empathy is considered an automatic bottom-up process, whereas cognitive empathy is described as a top-down modulator.18


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

  2. 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; http://dx.doi.org/10.1176/appi.ajp.2013.13070966

  3. 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.

  4. Grawe (2004): Neuropsychotherapie, Seite 354

  5. Drevets, Price, Furey (2008): Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Struct Funct. 2008 Sep;213(1-2):93-118. doi: 10.1007/s00429-008-0189-x.

  6. 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.

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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.