Subjective Cognitive Decline and Disruption of “Voluntary Initiation of Action”.

“The conscious experience of deciding that is associated with the voluntary initiation of action is a key element of everyday life. A central objective in the study of voluntary action has been to identify how changes in neural activity are related to the timing of the conscious decision to act. Investigating this relationship has been particularly challenging since it is difficult to establish the causality of relatively unconstrained associations in a complex system such as the brain. These complexities are further highlighted by the varying contexts for which the decision to initiate movement can be primed, such as interactions between self-paced and stimulus-driven triggers, variations in the complexity of the movement and task-related psychological processes, as well as the involvement of non-motoric, cognitive and motivational processes. The challenge is made even more difficult by a lack of clarity on how to precisely measure the time these kinds of decisions take place. The aim of our review was to evaluate the role of underlying brain processes in the neural control of movement and examine how these underlying processes are temporally related to the conscious experience of deciding and the initiation of voluntary action”. Front. Psychol., 18 December 2018 | Neural Oscillations and the Initiation of Voluntary Movement Samuel Armstrong1Martin V. Sale1,2 and Ross Cunnington1,3*

During Paula’s attack of what was diagnosed then to be major depression, Paula’s ” conscious experience of deciding was very impaired because she could not remember what she wished to do before she could speak of it or implement it. It was horrifying and completely incapacitated her. This was a completely private experience and all she did most of the day [and night] was to try to retain her thought and try to speak her thought and try to initiate an action. For example, she understood that she was neurologically confused and this affected her ability to tell anyone [she could not find the words to explain ] and she wanted to call doctor but she no longer knew how, and then as she was trying to work out these issues…she forgot what she was trying to say or do. It was a nightmare and Paula knew that no one would think to examine her medically, or to obtain her vital signs [including her respiratory rate- which was depressed ] and that no one would understand that this was a treatable syndrome.

Paula had a yearlong attack of major depression with psychomotor slowing 20 years ago. She remembers now that she was quietly confused and cognitively impaired during this attack. She also had difficulty initiating voluntary movements. Her thinking was too disorganized to organize actions with any intention or so it seems to her now. She either sat a lot with a fixed gaze or paced aimlessly.

AND she was able to voluntarily utilize other people’s movements to generate her own, perhaps because of what is explained in the research paper “Structure in Neural Activity during Observed and Executed Movements Is Shared at the Neural Population Level, Not in Single Neurons.” Apparently,  “Even when we don’t move, motor cortex is involved in process- ing observed movements”. 

 When Paula saw her husband get up and out of bed in the morning, she was able to use what she observed to do the same. She knew she got out of bed at the same time as him on work days , before getting sick.  She could no longer easily initiate such an action alone, she needed to piggyback on his voluntary actions to do the same. She recognized that she also needed to get up and get ready, but only when she received cues from observing what he did. Otherwise, she was “as if” frozen and amnesic, not remembering what she should do. Her movements, once started, were perfectly co-ordinated and fluid – not like  Parkinson’s. symptoms. It was as if, in absence of organized thought, she could still kick start what she wished to do by copying other people’s movements, most likely because of the motor cortex involvement in processing observed movement.   This made her actions look fairly normal to others, despite her mental confusion and partial amnesia. Yet she was very incapacitated.

It also made diagnosing her much harder because she was too confused cognitively to tell anyone and it turns out that you can get pretty far by using observational cues to initiate behaviors that you cannot initiate by yourself even though you would like to. She kind of felt internally like an agitated empty-headed zombie, though. 

To summarize, Paula did not move a lot, in part because she was unable to translate her thoughts into motor speech or into motor actions. Her behavioural inhibition was due to her amnesic and disorganized thinking, her empty thoughts providing few instructions to the voluntary muscles, resulting in reduced locomotor activity.

Why? Our hypothesis is that Paula had sudden memory loss for autobiographical information concerning self [acute autobiographical amnesia] during an adaptive response that enhances recovery by conserving energy to combat acute inflammation. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. Both sickness behaviour and autobiographical memory loss are linked to an underlying factor explaining both, we think.

Why? Our hypothesis, based on her very depressed respiratory rate and cognitive decline, is that she was suffering from a dose-related hypercapnia respiratory failure. Because of her abnormal ventilatory system not keeping up with carbon dioxide production by cells. Too much of anything is a poison, a dose-related toxin.

The Dose Makes the Poison”

Nearly 500 years ago, Swiss physician and chemist Paracelsus expressed the basic principle of toxicology: “All things are poison and nothing is without poison; only the dose makes a thing not a poison.” This is often condensed to: “The dose makes the poison.” It means that a substance that contains toxic properties can cause harm only if it occurs in a high enough concentration.

In other words, any chemical—even water and oxygen—can be toxic if too much is ingested or absorbed into the body. The toxicity of a specific substance depends on a variety of factors, including how much of the substance a person is exposed to, how they are exposed, and for how long.

Paula was actually very sick. She needed supportive medical treatment.

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers. * published:  Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways Michael MaesMichael BerkLisa GoehlerCai SongGeorge AndersonPiotr Gałecki & Brian Leonard 

One of the overlooked less well defined triggers is HYPERCAPNIA or a buildup of endogenous and /or exogenous carbon dioxide and the difficulty exhaling enough of it to prevent a buildup of C02 in the blood and tissues of the body causing dose related signs and symptoms of hypercapnia. See the following for what these signs and symptoms might be:

Cytokines have been implicated in the pathology of depression.  It seems that in absence of more information, it is difficult to know what this means since this is a nonspecific physical sign. Front. Psychiatry, 07 February 2019 | Cytokine Research in Depression: Principles, Challenges, and Open Questions Hubertus Himmerich1,2*Olivia Patsalos1Nicole Lichtblau3Mohammad A. A. Ibrahim4 and Bethan Dalton

Respiratory rate and volume are key to the body’s response to physical illness and injury. If this response is abnormal, then the body may need supportive medical help to help fight hidden infection that wouldn’t be a problem otherwise.

Cytokines are regulators of host responses to infection, immune responses, inflammation, and trauma. Some cytokines act to make disease worse (proinflammatory), whereas others serve to reduce inflammation and promote healing (anti-inflammatory). Proinflammatory cytokines Chest  2000 Aug;118(2):503-8. doi: 10.1378/chest.118.2.503. C A Dinarello 

Can levels of respiratory failure type 2 be responsible for some major and bipolar depressions with psychomotor slowing and cognitive decline ? as well as mania with psychomotor excitement and insanity ?

You bet… is otherwise known as delirium, all locomotor subtypes, chronic until infection and alveolar hypoventilation is rescued with modern medical treatments.

I think it is time for a paradigm shift ! If respiratory rates are abnormal in some depressed, amnesic, apathetic and silently confused patients, then we will be able to understand why these patients have such altered behavior and mood. Ventilatory failure, whether mild, moderate or severe is not pleasant- kind of like suffocation at the cellular level, if you will….and not very visible….except for the detection of ventilatory motor defects, putting these patients at risk of serious organic consequences if their biochemical defences become overwhelmed.

All it takes to investigate this hypothesis in non-medicated patients is basic first aid practice and scientific curiosity about the motor act of ventilation and its physical hidden injuries.

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