Peripheral, autonomic regulation of locus coeruleus noradrenergic neurons in brain: putative implications for psychiatry and psychopharmacology

the new data seem to allow a better understanding of how autonomic vulnerability or visceral dysfunction may precipitate or aggravate mental symptoms and disorder.

T. H. Svensson¹

(1)	Department of Pharmacology, Karolinska Institute, Box 60 400, S-104 01 Stockholm, Sweden

Received: 20 June 1986 Revised: 25 November 1986
Psychopharmacology

"Locus coeruleus (LC) is located in the ventrallateral side of the fourth ventricle in the pontine, most of which are noradrenergic neurons projecting to the cortex, cingulate cortex, amygdala nucleus, thalamus, hypothalamus, olfactory tubercles, hippocampus, cerebellum, and spinal cord (Swanson and Hartman, 1975). Norepinephrine (NE) released from the nerve terminal of LC neurons contributes to about 70% of the total extracellular NE in primates brain (Svensson, 1987). It plays important roles not only in arousal, attention, emotion control, and stress (reviewed in Aston-Jones and Cohen, 2005; Berridge and Waterhouse, 2003; Bouret and Sara, 2005; Nieuwenhuis et al., 2005; Sara and Devauges, 1989; Valentino and Van Bockstaele, 2008), but also in sensory information processing (Svensson, 1987). LC directly modulates the somatosensory information from the peripheral system. Under the stress condition, LC could completely inhibit the input from painful stimuli through the descending projection to the spinal cord (Stahl and Briley, 2004). Dys-regulations of LC neurotransmission have been suggested to be involved in physical painful symptoms, attention deficit hyperactivity disorder (ADHD), sleep/arousal disorder, post-traumatic stress disorder, depression, schizophrenia, and Parkinson's disease (reviewed in Berridge and Waterhouse, 2003; Grimbergen et al., 2009; Mehler and Purpura, 2009)."
http://journal.frontiersin.org/Journal/10.3389/fnmol.2012.00029/full

Patients complain of emotional blunting following endoscopic thoracic sympathectomy for hyperhidrosis and blushing

Hohmann, G.W. : The effect of dysfunction of the autonomic nervous system on experienced feelings and emotions

Paper read at Conference on Emotions and Feelings at New School for Social Research, New York, Oct 1962.

Sherrington, C.S.: Experiments on the value of vascular and visceral factors for the genesis of emotion 

Proc. Roy.Soc., 1900, 66, 390-403

Wenger, M.A.: Emotion as visceral action: an extension of Lange's theory. In Reymert, M.L., Feelings and emotions: the Moosehart ymposium, New York: McGraw-Hill, 1950. Pp.3-10.

Wynne, L.C., and Solomon, R.L.: Traumatic avoidance learning: acquisition and extinction in dogs deprived of normal peripheral autonomic function. 

Genet. psychol. Monogr., 1955, 52, 241-84

Landis, C., and Hunt, W. A. Adrenalin and emotion. 

Psychol. Rev., 1932, 39, 467-85.

Schachter, S., and Wheeler, L.: Epinephrine, chlorpromazine, and amusement. 

J. of abnorm. soc. Psychol., 1962, 65, 121-28.

Limbic-cortical dysregulation: a proposed model of depression

cognition and reward processing

Recent functional magnetic resonance imaging (fMRI) investigations of the interaction between cognition and reward processing have found that the lateral prefrontal cortex (PFC) areas are preferentially activated to both increasing cognitive demand and reward level. Conversely, ventromedial PFC (VMPFC) areas show decreased activation to the same conditions, indicating a possible reciprocal relationship between cognitive and emotional processing regions. We report an fMRI study of a rewarded working memory task, in which we further explore how the relationship between reward and cognitive processing is mediated. We not only assess the integrity of reciprocal neural connections between the lateral PFC and VMPFC brain regions in different experimental contexts but also test whether additional cortical and subcortical regions influence this relationship. Psychophysiological interaction analyses were used as a measure of functional connectivity in order to characterize the influence of both cognitive and motivational variables on connectivity between the lateral PFC and the VMPFC.

These findings provide evidence for a dynamic interplay between lateral PFC and VMPFC regions and are consistent with an emotional gating role for the VMPFC during cognitively demanding tasks. Our findings also support neuropsychological theories of mood disorders, which have long emphasized a dysfunctional relationship between emotion/motivational and cognitive processes in depression.
http://dl.acm.org/citation.cfm?id=1480468

depression that may occur as part of stress system dysfunction

Stress precipitates depression and alters its natural history. Major depression and the stress response share similar phenomena, mediators and circuitries. Thus, many of the features of major depression potentially reflect dysregulations of the stress response. The stress response itself consists of alterations in levels of anxiety, a loss of cognitive and affective flexibility, activation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system, and inhibition of vegetative processes that are likely to impede survival during a life-threatening situation (eg sleep, sexual activity, and endocrine programs for growth and reproduction).
http://www.nature.com/mp/journal/v7/n3/full/4001032a.html

Limbic-cortical dysregulation: a proposed model of depression

A working model of depression implicating failure of the coordinated interactions of a distributed network of limbic-cortical pathways is proposed. Resting state patterns of regional glucose metabolism in idiopathic depressed patients, changes in metabolism with antidepressant treatment, and blood flow changes with induced sadness in healthy subjects were used to test and refine this hypothesis. Dorsal neocortical decreases and ventral paralimbic increases characterize both healthy sadness and depressive illness; concurrent inhibition of overactive paralimbic regionsand normalization of hypofunctioning dorsal cortical sites characterize disease remission. Normal functioning of the rostral anterior cingulate, with its direct connections to these dorsal and ventral areas, is postulated to be additionally required for the observed reciprocal compensatory changes, since pretreatment metabolism in this region uniquely predicts antidepressant treatment response. This model is offered as an adaptable framework to facilitate continued integration of clinical imaging findings with complementary neuroanatomical, neurochemical, andelectrophysiological studies in the investigation of the pathogenesis of affective disorders.
http://neuro.psychiatryonline.org/cgi/content/short/9/3/471

ELECTRICAL STIMULATION OF THE SYMPATHETIC NERVE CHAIN

The present invention provides a method of affecting physiological disorders by stimulating a specific location along the sympathetic nerve chain. Preferably, the present invention provides a method of affecting a variety of physiological disorders or pathological conditions by placing an electrode adjacent to or in communication with at least one ganglion along the sympathetic nerve chain and stimulating the at least one ganglion until the physiological disorder or pathological condition has been affected.

[0009] A number of treatment regiments utilizing electrical stimulation can be employed for a vast array of physiological disorders or pathological conditions associated with the sympathetic and parasympathetic nervous system. Physiological disorders that may be treated include, but are not limited to, hyperhydrosis, complex regional pain syndrome and other pain syndromes such as headaches, cluster headaches, abnormal cardiac sympathetic output, cardiac contractility, excessive blushing condition, hypertension, renal disease, heart failure, angina, hypertension, and intestinal motility disorders, dry eye or mouth disorders, sexual dysfunction, asthma, liver disorders, pancreas disorders, and heart disorders, pulmonary disorders, gastrointestinal disorders, and biliary disorders. The number of disorders to be treated is limited only by the number, variety, and placement of electrodes (or combinations of multiple electrodes) along the sympathetic nervous system.

http://www.faqs.org/patents/app/20110098762

An absence of afferent feedback concerning autonomically generated bodily states was associated with subtle impairments of emotional responses

 Neuroanatomical basis for first- and second-order representations of bodily states

H. D. Critchley1,2, C. J. Mathias2,3 and R. J. Dolan1

nature neuroscience • volume 4 no 2 • february 2001

The use of stellate ganglion block in the treatment of panic/anxiet... - PubMed - NCBI

Pain Pract. 2010 Jul-Aug;10(4):359-65. doi: 10.1111/j.1533-2500.2010.00373.x. Epub 2010 Apr 20.

http://www.ncbi.nlm.nih.gov/pubmed/20412504



Stellate ganglion block used to treat symptoms associated with combat-related post-traumatic stress disorder: a case series of 166 patients.

Mulvaney SW, Lynch JH, Hickey MJ, Rahman-Rawlins T, Schroeder M, Kane S, Lipov E.Mil Med. 2014 Oct; 179(10):1133-40.
In search of an effective treatment for combat-related post-traumatic stress disorder (PTSD): can the stellate ganglion block be the answer?

Lipov E.Pain Pract. 2010 Jul-Aug; 10(4):265-6.
Stellate ganglion block improves refractory post-traumatic stress disorder and associated memory dysfunction: a case report and systematic literature review.

Lipov EG, Navaie M, Brown PR, Hickey AH, Stedje-Larsen ET, McLay RN.Mil Med. 2013 Feb; 178(2):e260-4.
[Three paradigms in the treatment of posttraumatic stress disorder].

Martényi F.Neuropsychopharmacol Hung. 2005 Mar; 7(1):11-21.

Limbic System: Amygdala (Section 4, Chapter 6) Neuroscience Online: An Electronic Textbook for the Neurosciences | Department of Neurobiology and Anatomy - The University of Texas Medical School at Houston

Limbic System: Amygdala (Section 4, Chapter 6) Neuroscience Online: An Electronic Textbook for the Neurosciences | Department of Neurobiology and Anatomy - The University of Texas Medical School at Houston:



"Amygdala is the integrative center for emotions, emotional behavior, and motivation"

Limited heart rate variability, autonomic nervous system imbalance implicated in the aetiology of CFS

The Conversation: "The stress-response neural systems of chronic fatigue syndrome (CFS) patients remain on high alert even when they sleep, signalling that it’s not safe to relax, researchers have found.

Researchers also discovered that reduced heart rate variability, or changes in heart beat timing, are the best predictors of cognitive disturbances, such as concentration difficulties commonly reported by CFS sufferers. This adds to the growing body of evidence linking autonomic nervous system imbalance to this disorder.

The findings could lead to new ways to improve cognitive difficulties in people with CFS, which remains a poorly understood condition."

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0049518  

ETS results in reduced heart rate variability and alters the ANS (sympathetic and parasympathetic balance). This article might provide some insight into the cases where ETS resulted in a variety of unwelcome and detrimental side-effects, including fatigue, altered cognitive function ('brain fog'), etc.

Sympathetic chain ganglia are responsible for delivering information to the rest of the body regarding stress situations and the fight or flight response

Sympathetic chain ganglia are responsible for delivering information to the rest of the body regarding stress situations and the fight or flight response. These sympathetic ganglia are the structures that are destroyed during a sympathectomy

http://www.ast.org/publications/Journal%20Archive/2009/9_September_2009/CE.pdf

The stellate ganglion has shown to have second and third order neurons that connect with hypothalamus, amygdala, infralimbic, insular and ventromedial temporal cortical regions

Stellate ganglion block: "In the course of mapping the sympathetic nervous system to the related regions of the cerebral cortex, Westerhaus and Loewy used pseudorabies virus injections to identify connections of the stellate ganglion. Pseudorabies virus allows identification of neural pathway connections that are 2–3 synapses from the point of injection of the virus. In this manner, the use of pseudorabies virus injection is used to identify cortical areas connected to the stellate ganglion.

The stellate ganglion has shown to have second and third order neurons that connect with hypothalamus, amygdala, infralimbic, insular and ventromedial temporal cortical regions.

These data provides objective, anatomical support for the stellate ganglion interaction with several key structures known to modulate core body temperature, CRPS and PTSD."



http://flipper.diff.org/app/items/info/7052

"Similar low values are observed in patients with sympathectomy and in patients with tetraplegia"

"Patients with progressive autonomic dysfunction (including diabetes) have little or no increase in plasma noradrenaline and this correlates with their orthostatic intolerance (Bannister, Sever and Gross, 1977). In patients with pure autonomic failure, basal levels of noradrenaline are lower than in normal subjects (Polinsky, 1988). Similar low values are observed in patients with sympathectomy and in patients with tetraplegia. (p.51)

The finger wrinkling response is abolished by upper thoracic sympathectomy. The test is also abnormal in some patients with diabetic autonomic dysfunction, the Guillan-Barre syndrome and other peripheral sympathetic dysfunction in limbs. (p.46)

Other causes of autonomic dysfunction without neurological signs include medications, acute autonomic failure, endocrine disease, surgical sympathectomy . (p.100)

Anhidrosis is the usual effect of destruction of sympathetic supply to the face. However about 35% of patients with sympathetic devervation of the face, acessory fibres (reaching the face through the trigeminal system) become hyperactive and hyperhidrosis occurs, occasionally causing the interesting phenomenon of alternating hyperhidrosis and Horner's Syndrome (Ottomo and Heimburger, 1980). (p.159)



Disorders of the Autonomic Nervous System
By David Robertson, Italo Biaggioni
Edition: illustrated
Published by Informa Health Care, 1995
ISBN 3718651467, 9783718651467"