The central autonomic nervous system. Physiology and pathophysiology.

The central autonomic nervous system. Physiology and pathophysiology.

The brain controls the autonomic nervous system. Important areas are: the insula, the anterior cingulate cortex, medial prefrontal cortex, amygdala, and hypothalamus. This presentation will summarize:
1. The anatomy and physiology of the ANS
2. Central control of the ANS
3. Clinical relevance of autonomic dysregulation
4. Modulation of ANS activity


Peter Sörös

August 12, 2018


  1. The central autonomic nervous system. Physiology and pathophysiology. Dr. Peter

    Soros Department of Neurology University of Oldenburg Germany
  2. Outline • The anatomy and physiology of the ANS •

    Central control of the ANS • Clinical relevance of autonomic dysregulation • Modulation of ANS activity
  3. Anatomy of the ANS Sympathetic vs. parasympathetic branch

  4. How can we measure sympathetic and parasympathetic activity?

  5. Heart rate variability Kubios User Guide Software: Kubios HRV Standard

    Tarvainen et al. Computer Methods and Programs in Biomedicine 2014
  6. Heart rate variability Heart rate Heart rate variability Sympathetic NS

    Increase Decrease Parasympathetic NS Decrease Increase
  7. Time domain parameters Standard deviation of normal R-R- intervals Software:

    Kubios HRV Standard
  8. Frequency of heart rate variability • Low frequency: 0.04 –

    0.15 Hz • mediated by sympathetic and parasympathetic branch (mostly sympathetic) • High frequency: 0.15 – 0.40 Hz • mediated by parasympathetic branch
  9. Frequency domain parameters Software: Kubios HRV Standard

  10. Which areas of the brain control the ANS?

  11. Uncovering brain–heart information through advanced signal and image processing Theme

    issue compiled and edited by Gaetano Valenza, Nicola Toschi and Riccardo Barbieri ISSN 1364-503X | Volume 374 | Issue 2067 | 13 May 2016 Phil. Trans. R. Soc. A | Volume 374 | Issue 2067 | 13 May 2016 Uncovering brain–heart information through advanced signal and image processing 17/03/16 1:25 pm 17/03/16 1:25 pm
  12. Western University, London, Ontario, Canada Prof. David Cechetto Prof. Kevin

    Shoemaker Prof. Vladimir Hachinski
  13. Central autonomic nervous system Insula Cingulate gyrus Hypothalamus Amygdala Modified

    from: Sörös and Hachinski. Lancet Neurology 2012 Medial prefrontal cortex
  14. P~im 2h 3 4h '" "f? 6h 8h A 1

    Prestim 8h30 5h30 8h35 3 7h 8h45 7h10 8h55 ,, ,,,-------- 7h15 8h55 11 *t' r 7 h 30 B Fig. 1. A: serial EC(;s obtained during stimulation of the sensorimotor cortex in a control animal. This shows the absence of chan characteristics over an 8 h period, typical of control animals. The stimulus artifact present in all but the prestimulation trace (labelle is identified by the 3 arrows in tracing A5. B: serial ECGs obtained during insular stimulation in an experimental animal. The stimu was at the border of the granular insular and somatosensory cortices. These traces illustrate the characteristic pattern of ECG change in all but one of the experimental animals in both the ventilated and unventilated groups. The stimulus artifact is identifiable in prestimulation trace. Electric stimulation of the insula • Electric stimulation of the posterior insula in rats • stimulation 100 ms prior to the T wave • widening of the QRS complex • bradycardia • asystolic arrest Oppenheimer … Cechetto. Brain Research 1991
  15. Handgrip: Regulation of blood pressure D.F. Cechetto, J.K. Shoemaker /

    NeuroImage 47 (2009) 795–803 Cechetto and Shoemaker. Neuroimage 2009;47:795-803
  16. Serial subtraction: Regulation of heart rate Block design: 20 s

    blocks Statistical model functional MRI Sina Briese: Master’s Thesis (unpublished results)
  17. Serial subtraction: Regulation of heart rate functional MRI Sina Briese:

    Master’s Thesis (unpublished results) right insula R R R medial prefrontal cortex anterior cingulate cortex
  18. Viewing a movie: Regulation of heart rate • Viewing a

    movie in the MR scanner • Pulse recording • Correlating heart rate and heart rate variability with functional MRI of the brain • Hypothesis: modulation of the central autonomic nervous system Theresa Thäßler: Master’s Thesis (unpublished results)
  19. None
  20. Meta-analysis of functional MRI studies Vargas et al. Annals of

    Neurology 2016
  21. What are the clinical consequences of ANS dysregulation?

  22. Sudden cardiac death after earthquake All tests were by the

    De- during the hrough 16, ke ( January ds in 1991, of the estigated by January 10 iods. There ths, from a days before aths on the on the day ious years, 0). ned by the e. Fifty per- e related to isease. Not quent cause lar Disease otic cardio- earthquake and 109 during the week of the earthquake. However, analysis of the number of deaths each day that were de- termined to be related to atherosclerotic cardiovascular disease (Fig. 2) revealed a sharp increase, from an av- erage of 15.6Ϯ3.9 deaths per day during the seven days before the earthquake to 51 on the day of the earth- quake (relative risk as compared with the same period in previous years, 2.6; 95 percent confidence interval, Figure 3. Daily Numbers of Sudden Deaths Related to Athero- 0 30 20 10 23 20 17 14 11 January 1994 No. of Deaths sclerotic Cardiovascular Disease from January 10 through 23, 1994. On January 17, the day of the earthquake, there were 24 cases of sudden death related to atherosclerotic cardiovascular dis- ease (zϭ4.41, PϽ0.001). There was a decline in number of sud- den deaths on each of the six days after the earthquake (zϭ1.73, Pϭ0.084). The New England Journal of Medicine ESTERN ONTARIO on January 12, 2012. For personal use only. No other uses without permission. © 1996 Massachusetts Medical Society. All rights reserved. Southern California Earthquake Center 4.6 ± 2.1 (mean ± SD) per day in the preceding week 24 on the day of the earthquake (z = 4.41, P < 0.001). 2.7 ± 1.2 per day in the following week Leor et al. New England Journal of Medicine 1996
  23. Sudden cardiac death • Natural, sudden, unexpected death • Potential

    causes: • emotional stress • stroke • sudden unexpected death in epilepsy (SUDEP)
  24. Heart failure 1. Beginning of heart failure 2. Increase of

    sympathetic activity, decrease of parasympathetic activity 3. Adverse effects on the heart. E.g., toxic effects of catecholamines on cardiac myocytes 4. Increase of heart failure
  25. Pain • Complex interaction between the nociceptive system and the

    ANS on all levels (periphery, spinal cord, brain) • Pain causes modulation of the ANS • Does a dysregulation of the ANS contribute to the chronification of pain?
  26. How can we modulate the ANS?

  27. Pharmacological treatment • Sympathetic branch: adrenergic • Parasympathetic branch: cholinergic

    • peripheral vs. central action (blood brain barrier)
  28. Acupuncture

  29. Invasive vagus nerve stimulation George and Aston-Jones. Neuropsychopharmacology Reviews 2010

    Ben-Menachem et al. European Journal of Neurology 2015,
  30. Non-invasive vagus nerve stimulation • Epilepsy • Pain • Depression

    NEMOS. Cerbomed, Erlangen, Germany
  31. Summary • The ANS is controlled by cortical areas, including

    insula, anterior cingulate and medial prefrontal cortex • Dysregulation of the ANS is involved in the pathogenesis of severe heart disease including sudden death, chronic pain and many other disorders • Modulation of the ANS may be achieved by pharmacotherapy, acupuncture, meditation and vagus nerve stimulation.
  32. Acknowledgements • Prof. Vladimir Hachinski, London, ON, Canada • Prof.

    Kevin Shoemaker, London, ON, Canada • Dr. Carsten Bantel, Oldenburg, Germany • Sina Briese, M. Sc., Oldenburg, Germany • Leona Buschmann, Oldenburg, Germany • Theresa Thäßler, Oldenburg, Germany
  33. Oldenburg, Germany Oldenburg

  34. Oldenburg, Germany

  35. Oldenburg, Germany

  36. Oldenburg, Germany

  37. Thank you for your attention!