- Open Access
This new research cited below suggests that hypercapnia stimulates the locus ceruleus [LC] of the brain stem to activate the stress response. Not the fight or flight response necessarily, but the stress response to described by Desborough. The stress response to dangerous internal conditions inside the body. Conditions like injury, internal bleeding, hypercapnia, hypoxia, infection, physical trauma and surgery. Paula seems to be unable to raise her respiratory rate at rest even if her airways become inflamed. This could be due to problems with the nerves or muscles or bones of the thoracic cage. No one knows. Her lungs seem normal. Her brain stem seems to compensate by manipulating the function of the rest of the body during health and during physical illness , including co-ordination of the other vital signs, circulation of the blood, thermoregulation, behaviour, locomotor activity, feeding activity and sleep activity, accordingly. Most of this is likely orchestrated by the locus ceruleus. And thus, we have found a link between the internal stress response to probable respiratory failure, slow active breathing at rest and cognitive disturbance, all linked to the LC of the brain stem. Fascinating!
Locus Coeruleus as a vigilance centre for active inspiration and expiration in rats. Karolyne S. Magalhães, Pedro F. Spiller, Melina P. da Silva, Luciana B. Kuntze, Julian F. R. Paton, Benedito H. Machado & Davi J. A. Moraes Scientific Reports volume 8, Article number: 15654 (2018).
At rest, inspiration is an active process while expiration is passive. However, high chemical drive (hypercapnia or hypoxia) activates central and peripheral chemoreceptors triggering reflex increases in inspiration and active expiration. The * Locus Coeruleus contains noradrenergic neurons (A6 neurons) that increase their firing frequency when exposed to hypercapnia and hypoxia. Using recently developed neuronal hyperpolarising technology in conscious rats, we tested the hypothesis that A6 neurons are a part of a vigilance centre for controlling breathing under high chemical drive and that this includes recruitment of active inspiration and expiration in readiness for flight or fight. Pharmacogenetic inhibition of A6 neurons was without effect on resting and on peripheral chemoreceptors-evoked inspiratory, expiratory and ventilatory responses. On the other hand, the number of sighs evoked by systemic hypoxia was reduced. In the absence of peripheral chemoreceptors, inhibition of A6 neurons during hypercapnia did not affect sighing, but reduced both the magnitude and incidence of active expiration, and the frequency and amplitude of inspiration. These changes reduced pulmonary ventilation. Our data indicated that A6 neurons exert a CO2-dependent modulation of expiratory drive. The data also demonstrate that A6 neurons contribute to the CO2-evoked increases in the inspiratory motor output and hypoxia-evoked sighing. Locus Coeruleus as a vigilance centre for active inspiration and expiration in rats. Karolyne S. Magalhães, Pedro F. Spiller, Melina P. da Silva, Luciana B. Kuntze, Julian F. R. Paton, Benedito H. Machado & Davi J. A. Moraes Scientific Reports volume 8, Article number: 15654 (2018).
Paula and I turned to Wikipedia [July 2 2020] to learn more about the LC or locus ceruleus. This part of the brain is linked to serious mental illness and may explain why various psychiatric medications [including the SSRI that Paula takes] make a difference to the body.
- The locus ceruleus (LC) contains norepinephrine (NE)-synthesizing neurons that send diffuse projections throughout the CNS. The LC-NE system has a major role in arousal, attention, and stress response. The Locus Ceruleus is a nucleus in the pons of the brainstem and is a part of the reticular activating system.
It is related to many functions via its widespread projections. The LC-NA system modulates cortical, subcortical, cerebellar, brainstem, and spinal cord circuits. Some of the most important functions influenced by this system are:
- Arousal and sleep-wake cycle
- Attention and memory
- Behavioral flexibility, behavioral inhibition and stress (psychological)
- Cognitive control
- Posture and balance
The locus coeruleus may figure in clinical depression, panic disorder, Parkinson’s disease, Alzheimer’s disease and anxiety. Some medications including norepinephrine reuptake inhibitors(reboxetine, atomoxetine), serotonin-norepinephrine reuptake inhibitors (venlafaxine, duloxetine), and norepinephrine-dopamine reuptake inhibitors (bupropion) are believed to show efficacy by acting upon neurons in this area.
Research continues to reveal that norepinephrine (NE) is a critical regulator of numerous activities from stress response, the formation of memory to attention and arousal. Many neuropsychiatric disorders precipitate from alterations to NE modulated neurocircuitry: disorders of affect, anxiety disorders, PTSD, ADHD and Alzheimer’s disease. Alterations in the locus coeruleus (LC) accompany dysregulation of NE function and likely play a key role in the pathophysiology of these neuropsychiatric disorders.
The locus coeruleus is responsible for mediating many of the sympathetic effects during stress. The locus coeruleus is activated by stress, and will respond by increasing norepinephrine secretion, which in turn will alter cognitive function (through the prefrontal cortex), increase motivation (through nucleus accumbens), activate the hypothalamic-pituitary-adrenal axis, and increase the sympathetic discharge/inhibit parasympathetic tone (through the brainstem). Specific to the activation of the hypothalamic-pituitary adrenal axis, norepinephrine will stimulate the secretion of corticotropin-releasing factor from the hypothalamus, that induces adrenocorticotropic hormone release from the anterior pituitary and subsequent cortisol synthesis in the adrenal glands. Norepinephrine released from locus coeruleus will feedback to inhibit its production, and corticotropin-releasing factor will feedback to inhibit its production, while positively feeding to the locus coeruleus to increase norepinephrine production.
The LC’s role in cognitive function in relation to stress is complex and multi-modal. Norepinephrine released from the LC can act on α2 receptors to increase working memory, or an excess of NE may decrease working memory by binding to the lower-affinity α1 receptors.
There, in a nutshell is one of the causes of loss of mind in unpleasant, quiet confusional states we call bipolar depressive attacks.
Loss of mind is a sign of an emergency! Loss of mind most likely signals failure of some key system of the body and needs immediate investigation in order to restore homeostasis [and mind].