It has always fascinated me that disease states can produce stereotypic motor behavior. It has not escaped my notice that the “too little ” motor activity of quiet delirium and the “too much” motor activity of mania and other forms of agitated motor subtypes of delirium are abnormal patterns of motor behavior. Disease states can also produce stereotyped and abnormal speed of stable motor behaviour. We see this in Parkinsonian syndromes [slow and halting motor speed] and we see it in manic states of delirium [abnormally fast motor speed]. We also see this with neuro-active chemicals [abnormal motor behaviour and speed].
Paula and I think that all manic states are chronic stages of hyper-motor delirium. We have not figured out what continuous biochemical or mechanical stimulus is initiating and maintaining this state of motor excitement, no one has. It could be a non progressing cellular swelling and higher than normal intracranial pressure from dysfunction and inhibition of the sodium pump. based on the ouabain animal studies of mania and depression described in the last blog. Although these are helpful studies, inhibition of the sodium pump is common with many illnesses, including many viral and bacterial infections. Mania is one of the hyper locomotor organic outcomes of infection, metabolic problems and poisons [toxins]. [will fill in references soon…….] Mania in bipolar illness is likely to be the same. This suggests that muscles are affected, under certain conditions, when acute or chronic stages of delirium occur. When muscles are affected, then reflex speed and activation can be affected. This can happen to leg and arm muscles, but also to throat and airway and breathing muscles. It is always important to check breathing muscles and changing nervous control by getting vital signs frequently, including the neglected respiratory rate and volume. This will give clues regarding the circulation of blood in the body and the possibility of minor but significant pH changes. Minor pH issues [there is never a minor pH issue] can affect neurotransmitters and enzyme behavior and this can affect the brain and the muscles. Intervention based on knowing what is wrong can be much more effective than the current hit or miss treatments we try currently.
More research regarding pH, breathing muscles and circulation are needed to understand mood disorders, delirium [especially chronic] and dementia-s.
Research papers on the modulation of motor behavior such as the one summarized below, are starting to shine a light on how important it is to understand motor behavior, especially when it becomes abnormal and/or affects their speed. to be continued……
The mesencephalic locomotor region (MLR) [in the brainstem] serves as an interface between higher-order motor systems and lower motor neurons. The excitatory module of the MLR is composed of the pedunculopontine nu- cleus (PPN) and the cuneiform nucleus (CnF), and their activation has been proposed to elicit different modalities of movement. However, how the differences in connectivity and physiological properties explain their contributions to motor activity is not well known. Here we report that CnF glutamatergic neu- rons are more electrophysiologically homogeneous than PPN neurons and have mostly short-range con- nectivity, whereas PPN glutamatergic neurons are heterogeneous and maintain long-range connections, most notably with the basal ganglia. Optogenetic activation of CnF neurons produces short-lasting mus- cle activation, driving involuntary motor activity. In contrast, PPN neuron activation produces long-lasting increases in muscle tone that reduce motor activity and disrupt gait. Our results highlight biophysical and functional attributes among MLR neurons that support their differential contribution to motor behavior. Cell Reports Modulation of motor behavior by the mesencephalic locomotor region Dautan et al., 2021, Cell Reports 36, 109594 August 24, 2021 a 2021 The Author(s). https://doi.org/10.1016/j.celrep.2021.109594
More on the mesencephalic locomotor region (MLR) [in the brainstem].
One brainstem locomotor area from which locomotion can be activated is termed the mesencephalic locomotor region (MLR), which appears to be present in all classes of verte- brates .…….. Moreover, a simple continuous stimulation of this region [the MLR in the brainstem] can elicit locomotion involving the coordinated activation of hundreds of different muscles throughout the body. The more intense the stimulation, the faster the animal will locomote. The MLR projects to reticulospinal neurons in the lower brainstem, which in turn form the major locomotor pathway to the spinal cord. Neurons, Networks, and Motor Behavior Selection and Initiation of Motor Behavior Sten Grillner, Apostolos P. Georgopoulos, and Larry M. Jordan A Bradford Book The MIT Press Cambridge, Massachusetts London, England 1997 Massachusetts Institute of Technology
Stimulation that increases speed and maintenance of locomotor activity and speed includes electrical stimulation, neuroactive substances. pressure …….. Neurons, Networks, and Motor Behavior Selection and Initiation of Motor Behavior Sten Grillner, Apostolos P. Georgopoulos, and Larry M. Jordan A Bradford Book The MIT Press Cambridge, Massachusetts London, England 1997 Massachusetts Institute of Technology
Role of serotonin
Spinal motor neurons, which directly control peripheral muscle activity, are densely innervated by brainstem serotonin neurons. Furthermore, electrophysiological studies have established that serotonin is a potent regulator of motor neuron excitability. Serotonergic Modulation of Spinal Circuits for Flexible Motor Control Fenstermacher, Sara J. New York University, New York, NY, United States https://grantome.com/grant/NIH/K99-NS118052-01
Could Paula’s odd motor pattern of breathing be due to reorganization of the spinal neuronal network due to her anoxic birth and resuscitation?
Following spinal cord injury (SCI) a series of anatomical and functional plastic changes occur in the spinal cord, including reorganization of the spinal neuronal network, alteration of properties of interneurons and motoneurons as well as up- or down-regulation of different neurotransmitter receptors. In mammalian spinal cord, one of the important neurotransmitters, serotonin (5-HT), plays an essential role in modulating sensory, motor and autonomic functions. Normal Distribution and Plasticity of Serotonin Receptors after Spinal Cord Injury and Their Impacts on Motor Outputs Mengliang Zhang , in Recovery of Motor Function Following Spinal Cord Injury Edited by Heidi Fuller and Monte Gates 2016
What does serotonin have to do with moving muscles? [we are talking about intact muscle, not injured muscles or spinal cords here].
Most people associate serotonin with anxiety and depression, but it turns out that serotonin is released all throughout the brain and the spinal cord and can potently change the activity of the circuits that control movement. That’s because serotonin is a neuromodulator: It has the ability to change the rhythm or behavior of single cells in the nervous system. The neuron might fire once every second, and when you add serotonin, it fires 10 times every second. So when serotonin changes the activity of motor neurons that are contacting muscle, you change the contraction rate of the muscle. Uncovering Serotonin Secrets in Muscle Movement Neuroscientist Sara Fenstermacher of the Simons Society of Fellows explores how the chemical affects motor neurons and why its receptors exist in the spinal cord By John Pavlus November 8, 2018 Simon Foundation.
When we talk of motor speed and activity in bipolar illness, we are talking about the changes to the spinal neurons, not the brain. This is why we do not see seizure with excitement of neurons but we see differences to motor activity and to motor speed.
It is fascinating really.
What does Paula’s respiratory depression have to do with changes to motor activity during or after illness such as infection? I think that it may be very relevant. It turns out that the spinal cord, has sensors that detect pH changes and act to restore pH to physiological levels by reducing motor activity. I suspect that under some circumstances these same sensors can act to restore pH by increasing motor activity and if need be, by increasing the speed of motor activity. The reason this happened in people like Paula is because of their fixed and abnormal range of breathing,[too slow, too fast] resulting in regular assistance from the spinal motor system to help manage pH in illness challenging pH further. to be continued………..
For survival of the organism, acid-base homeostasis is vital [1, 2]. The respiratory and renal systems are central to this control. Here we describe a novel mechanism, intrinsic to the spinal cord, with sensors that detect pH changes and act to restore pH to physiological levels by reducing motor activity. This pH sensor consists of somatostatin-expressing cerebrospinal fluid-contacting (CSF-c) neurons, which target the locomotor network. They have a low level of activity at pH 7.4. However, at both alkaline and acidic pH, the activity of the individual CSF-c neuron is markedly enhanced through the action of two separate channel subtypes. The alkaline response depends on PKD2L1 channels that have a large conductance and an equilibrium potential around 0 mV, both characteristics of mouse PKD2L1 channels [3-5]. The acidic response is due to an activation of ASIC3 . The discharge pattern of the CSF-c neurons is U-shaped with a minimum frequency around pH 7.4 and a marked increase already at slightly lower and higher pH. During ongoing locomotor activity in the isolated spinal cord, both an increase and as a decrease of pH will reduce the locomotor burst rate. A somatostatin antagonist blocks these effects, suggesting that CSF-c neurons are responsible for the suppression of locomotor activity. CSF-c neurons thus represent a novel innate homeostatic mechanism, designed to sense any deviation from physiological pH and to respond by causing a depression of the motor activity. Because CSF-c neurons are found in all vertebrates, their pH-sensing function is most likely conserved. The Spinal Cord Has an Intrinsic System for the Control of pH r Biol 2016 Apr 28. Elham Jalalvand 1, Brita Robertson 1, Hervé Tostivint 2, Peter Wallén 1, Sten Grillner 3 PMID: 27133867 DOI: 10.1016/j.cub.2016.03.048
ReviewModulation of pH by neuronal activity
Available online 5 March 2003.
Although the requirement for a strict regulation of pH in the brain is frequently emphasized, recent studies indicate that neuronal activity gives rise to significant changes in intracellular and extracellular pH. Given the sensitivity of many ion channels to hydrogen ions, this modulation of local pH might influence brain function, particularly where pH shifts are sufficiently large and rapid. Studies using pH-sensitive microelectrodes have demonstrated marked cellular and regional variability of activity-dependent pH shifts, and have begun to uncover several of their underlying mechanisms. Accumulating evidence suggests that regional and subcellular pH dynamics are governed by the respective localization of glial cells, ligand-gated ion channels, and extracellular and intracellular carbonic anhydrase. Modulation of pH by neuronal activity M.Cheslera K.Kailab https://doi.org/10.1016/0166-2236(92)90191-AGet rights and content
In Paula’s case, the reason why the effects of PCO2 and pH are stable and result in abnormal brain function and motor speed and activity…..is because the breathing range is both stable yet abnormal…and insufficient when the person is exposed to various physical stressors.
Breathing and invisible [unless you look carefully] deficits are key to pH difficulties, especially during physical and mechanical stress.
to be continued….
Different levels of Cell Swelling . 2016 May 23;26(10):1346-51.
Cell swelling occurs when the cell loses its ability to precisely control the influx of sodium (Na+) ions and water and efflux of potassium (K+) ions to the cytosol. Practice of Toxicologic Pathology Matthew A. Wallig, Evan B. Janovitz, in Haschek and Rousseaux’s Handbook of Toxicologic Pathology (Third Edition), 2013 https://www.sciencedirect.com/topics/neuroscience/cell-swelling
still working on this post………