Pathoclisis (from meaning "predisposition" in Ancient Greek)
is the theory that certain specialized parts of the brain are the first to be damaged in the case of disease,
lack of oxygen, or
malnutrition
Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...
. The selective vulnerability of certain neurons can then lead to the expression of pathology.
The APA dictionary of psychology defines pathoclisis as “sensitivity to particular toxins, or the tendency of particular toxins to target certain organs or systems of organ.”
Pathoclisis has been postulated to mediate the sensory effects of a
near-death experience
A near-death experience (NDE) is a profound personal experience associated with death or impending death which researchers claim share similar characteristics. When positive, such experiences may encompass a variety of sensations including detac ...
.
Research
Cécile Vogt-Mugnier
Cécile Vogt-Mugnier (27 March 1875 – 4 May 1962) was a French neurologist from Haute-Savoie. She and her husband Oskar Vogt are known for their extensive cytoarchetectonic studies on the brain.
Professional life
Education and career
Vogt- ...
and her husband
Oskar Vogt
Oskar Vogt (6 April 1870, in Husum – 30 July 1959, in Freiburg im Breisgau) was a German physician and neurologist. He and his wife Cécile Vogt-Mugnier are known for their extensive cytoarchetectonic studies on the brain.
Personal life
He wa ...
came up with the idea of pathoclisis through their research on insects and the human cerebral cortex.
They defined it as the "genomically-determined excessive variability, reaching in intensity the degree of pathological change".
During their work in France and Germany, these prominent scientists of neurological research first experimented on animals, administering
pharmalogical agents and using electricity to observe electrical and functional disturbances. After also experimenting with human brains, their findings presented a case that certain factors influence patterns of pathoclisis in different brain regions.
[Engmann, B. (2014). ''Near-death experiences: Heavenly insight or human illusion?'' Springer International Publishing/Springer Nature. https://doi.org/10.1007/978-3-319-03728-8]
Different types of pathoclisis
Upon their discovery of pathoclisis, Cécile Vogt-Mugnier and her husband Oskar Vogt decided to categorize and classify the disease into many subcategories. One of the main separations was between Soma-pathoclisis and Gene-pathoclisis. “Soma” refers to how vulnerable a section of the brain can be when it comes in contact with a damaging substance or situation, such as
Carbon Monoxide
Carbon monoxide ( chemical formula CO) is a colorless, poisonous, odorless, tasteless, flammable gas that is slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the si ...
, or a lack of oxygen. “Gene” has to do with hereditary genes deteriorating due to an outside circumstance or near-death experience. Upon further research, certain mental disorders were traceable to this affect,
schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wi ...
being one example.
The other division was between General-pathoclisis and Special-pathoclisis. “General” referred to the conclusion that one specific part of the brain could be affected by a multitude of factors including poisonings,
malnutrition
Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...
,
paralysis
Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 5 ...
, lack of nutrients, and even certain types of
dementia
Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
. On the other hand, “Special,” referred to there being a specific connection between the location of deterioration and the factor that caused it. These separate categories were used during the continuation of their pathoclisis research.
Near-death experiences
When close to death, certain parts of the brain may experience a lack of oxygen and through pathoclisis, specific structures of the brain are affected. These structures contribute to the creation of commonly experienced phenomena when near death.
Some
near death experiences
A near-death experience (NDE) is a profound personal experience associated with death or impending death which researchers claim share similar characteristics. When positive, such experiences may encompass a variety of sensations including detac ...
such as seeing light or having out of body experiences have been reported more commonly. This supports the idea of pathoclisis, an effect of being near death that is shared among humans in which some brain structures are more susceptible to malfunction and are affected first with lack of oxygen.
Mechanism
More so than any other organ, the brain is remarkably heterogeneous in its cellular composition.
The wide variety of cell types might thus be the basis for selective vulnerability.
The brain has many structures and pathoclisis implies the tendency for some of these regions to be more vulnerable and become affected first when encountering a lack of oxygen. To comprehend the concept of pathoclisis, it is necessary to understand the temporal sequence that leads to the death of an organ. This sequence is characterized chronologically by; Disturbance of function, small amount of cell loss, large amount cell loss and therefore damage to part of an organ, damage to entirety of an organ, full loss of organ function, organ death.
Regions of the brain that have been found to be most vulnerable to a lack of oxygen or glucose include the
cerebral
Cerebral may refer to:
* Of or relating to the brain
* Cerebrum, the largest and uppermost part of the brain
* Cerebral cortex, the outer layer of the cerebrum
* Retroflex consonant, also referred to as a cerebral consonant, a type of consonant so ...
and
cerebellar cortex
The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebe ...
,
thalamus
The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all direction ...
, structures in the
striatum
The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutamate ...
,
Ammon’s horn, lower olivary body of the
medulla oblongata
The medulla oblongata or simply medulla is a long stem-like structure which makes up the lower part of the brainstem. It is anterior and partially inferior to the cerebellum. It is a cone-shaped neuronal mass responsible for autonomic (involun ...
, and in the
occipital lobe
The occipital lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The name derives from its position at the back of the head, from the Latin ''ob'', "behind", and ''caput'', "head".
The occipital lobe is the v ...
.
The gray matter of the
cerebral cortex
The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting o ...
is the first to begin shrinking as aging progresses. Based on MRI studies however, researchers are beginning to realize that this brain aging may not be as random as they had assumed. Seemingly healthy, older individuals are showing signs of cerebral
atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply ...
, which leads to the conclusion that brain deterioration is specific and dependent. The
prefrontal Prefrontal may refer to:
*Prefrontal bone, a skull bone in some tetrapods
*Prefrontal cortex, a region of the brain of a mammal
*Prefrontal scales
The prefrontal scales on snakes and other reptiles are the scales connected to the frontals, toward ...
,
parietal, and
occipital
The occipital bone () is a cranial dermal bone and the main bone of the occiput (back and lower part of the skull). It is trapezoidal in shape and curved on itself like a shallow dish. The occipital bone overlies the occipital lobes of the cere ...
lobes tend to be the first to begin the decline in health. Sections of the brain that deal with higher-order concepts tend to age in line with the body more so than other areas.
A possible explanation for pathoclisis is distribution of
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neur ...
s affects vulnerability. Another hypothesis is that the circulation of certain regions influences their susceptibility to disturbance and damage.
Role in neurodegenerative diseases
Subcortical structures, such as
basal ganglia
The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. In humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an extern ...
and the
brain stem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...
, are particularly vulnerable to ATP depletion, explaining why
parkinsonism
Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), rigidity, and postural instability. These are the four motor symptoms found in Parkinson's disease (PD), after which it is named, dementia with Lewy b ...
and
depressive symptoms
Depression is a mental state of low mood and aversion to activity, which affects more than 280 million people of all ages (about 3.5% of the global population). Classified medically as a mental and behavioral disorder, the experience of ...
are among the earliest symptoms of
vascular dementia
Vascular dementia (VaD) is dementia caused by problems in the supply of blood to the brain, typically a series of minor strokes, leading to worsening cognitive abilities, the decline occurring piecemeal. The term refers to a syndrome consisting ...
,
hypoxia
Hypoxia means a lower than normal level of oxygen, and may refer to:
Reduced or insufficient oxygen
* Hypoxia (environmental), abnormally low oxygen content of the specific environment
* Hypoxia (medical), abnormally low level of oxygen in the tis ...
,
carbon monoxide poisoning
Carbon monoxide poisoning typically occurs from breathing in carbon monoxide (CO) at excessive levels. Symptoms are often described as " flu-like" and commonly include headache, dizziness, weakness, vomiting, chest pain, and confusion. Larg ...
, chronic intoxication by mitochondrial complex I inhibitors (such as
rotenone
Rotenone is an odorless, colorless, crystalline isoflavone used as a broad-spectrum insecticide, piscicide, and pesticide. It occurs naturally in the seeds and stems of several plants, such as the jicama vine plant, and the roots of several member ...
and
annonaceous acetogenins
Acetogenins are a class of polyketide natural products found in plants of the family Annonaceae. They are characterized by linear 32- or 34-carbon chains containing oxygenated functional groups including hydroxyls, ketones, epoxides, tetrahydrof ...
) and
chronic traumatic encephalopathy
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repeated trauma to the head. The encephalopathy symptoms can include behavioral problems, mood problems, and problems with thinking. The disease often gets worse ov ...
.
Especially,
progressive supranuclear palsy
Progressive supranuclear palsy (PSP) is a late-onset degenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty ...
and
corticobasal degeneration
Corticobasal degeneration (CBD) is a rare neurodegenerative disease involving the cerebral cortex and the basal ganglia. CBD symptoms typically begin in people from 50 to 70 years of age, and the average disease duration is six years. It is chara ...
seems to be illnesses resulting from mitochondrial complex I deficiency.
Additionally, hypoxia during childhood seems to be a factor of schizophrenia, due to corticobasal and cerebellar damages to the brain.
Today, the theory of pathoclisis is used in
alzheimer’s
Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As t ...
research, as both relate to the degeneration of the brain and in alzheimer’s certain parts of the brain are affected before others, while some are left unaffected.
It has also been explored in sporadic parkinson's disease, as patients with the disease have shown to have the molecular basis for pathoclisis.
Gender Role
Pathoclisis correlates with the aging process. According to many studies which measure the BMAI, brain matter area index, gender plays a role in how quickly this deterioration process takes place or if it takes place at all. The frontal and temporal lobe atrophy at a faster rate in men than in women. Because of this, the pathoclisis effects of these areas are seen less often in women. The rate of atrophy in the parietal lobe and the cerebellum are the same on average between men and women. However, women are less susceptible to atrophy in these areas. The atrophy of the parietal lobe and cerebellum appears more frequently in older men rather than women. Overall, men are more effected by pathoclisis than women.
References
{{Reflist
Neurophysiology