Wednesday, November 12, 2014

Torpor in Space Travel

With existing tested technology the fastest transit time between Earth and Mars is during the perihelion (although Mars has only come within 34.8 million miles in 2003 versus the 33.9 million of the actual perihelion) resulting in a minimum transit estimate of approximately 180 days. Some believe that six months of monotonous space travel would be a significant psychological detriment on the future colonists, thus they recommend investigating a strategy of inducing torpor initiated through a therapeutic hypothermia methodology. Therapeutic hypothermia involves lowering an individual’s body temperature and is commonly reserved for medical emergencies involving cardiac arrest and various embolisms like strokes. It is thought that the decrease in temperature reduces biological metabolism, which reduces tissue damage born from oxidation and excess neuronal excitation triggered by a lack of regulated blood flow. Note that torpor is a state of decreased physiological activity through a reduced body temperature reaching a lower limit of survivable metabolism. Due to these changes torpor is commonly viewed as a state of consciousness distinct from wakefulness, sleep or coma.

The chief method to induce therapeutic hypothermia is a controlled reduction of core temperature through one of three possible methods: 1) invasive cooling usually involving an IV of cooled fluids; 2) conductive cooling where the body is placed in contact with cold compresses, typically cold gel pads and/or wet blankets; 3) convective cooling where specific gases evaporate and pass into the nasal and oral cavity leading to a reduction in body temperature.

Of the three conductive cooling is typically the most widely utilized because of its effectiveness and simplicity. Some researchers have explored new and more direct chemical methods to develop a hibernation state like activating adenosine receptors or using hydrogen sulfide to reduce cellular demand for oxygen.1 Others have thought to induce hibernation through synaptic manipulation, but that method is probably best avoided due to brain plasticity issues, which could result in temporary or permanent brain damage.

While the above methods are viable for inducing therapeutic hypothermia, a significant concern for a “hibernated” space travel strategy is that cooling/cryogenic strategies are in their infancy, thus most therapeutic hypothermia states rarely exceed 24-hrs and the longest is only about 14-days, a long cry from the 180-days of a trip to Mars. In addition to improving cooling methodology, temperature monitoring needs to be improved to incorporate a better realization of core temperature versus localized temperatures from specific measurement points (bladder, rectal, tympanic or esophageal). In general practice these specific measurement points tend to correlate with core temperature, but long-term hypothermia inducement will more than likely require more universal tracking of acute internal temperature changes. In addition to lowering the core body temperature one must neutralize shivering otherwise metabolic rates will not decrease sufficiently to realize the associated therapeutic benefits. Currently shivering is commonly controlled through the application of desflurane, pethidine, and/or meperidine.2

The most obvious non-psychological benefit of placing a colonization crew in torpor is a significant reduction in food/consumables for transit and the potential reduction in overall consumables. The reason that the overall reduction may only be a possibility is determined by whether or not the non-consumption during transit will transfer to “on Mars” consumption. For example suppose 1 ton of food (not mission specific just a number for example purposes) is loaded for a standard non-torpor mission and among the four colonists a total of 4 pounds is consumed daily. Over the course of the trip approximately 760 pounds of food will be consumed leaving 1,240 pounds of food for consumption on Mars. In a torpor mission two strategies are available: 1) only 1,240 pounds of food will be loaded saving 760 pounds for something else or just straight cost savings; 2) 1 ton of food is loaded with no cost savings, but an additional 760 pounds of food will be available for consumption on Mars.

Secondary benefits come from the possible reduction in the required pressurized volume in the living quarters and the elimination of ancillary crew accommodations, which could reduce the size of the transport craft reducing the total cost of the mission or increase the ability to add subsystem redundancy and/or more radiation shielding at similar costs. Basically the chief non-psychological benefit for a torpor mission is a greater flexibility in distributing what types of materials are loaded for a Mars mission and the final mission cost.

While torpor proponents would suggest that there are a few bugs left to work out, but prospects for such a strategy appear viable, in actuality there remain two significant problems that must be overcome before a torpor strategy can be viewed as viable. The first problem, the most pressing, is muscular atrophy born from general space travel and the second problem is overall safety. The principle responsibility of skeletal muscle is to govern movement of all voluntary muscle, including the maintenance of posture. Due to human evolution on Earth skeletal muscle has to move parts of the body against gravity, thus there is a strong relationship between the size and metabolism of skeletal muscle and the gravitational force of the existing environment.

Skeletal muscle is comprised of bundles of muscle fibers, which are large cells formed through the fusion of many individual cells during development. Most skeletal muscles consist of myfibrils, which are cylindrical bundles of either thicker myosin filaments or thinner actin filaments, and form contractile elements (sarcomeres). Sarcomeres are separated into Z discs (the ends) along with A and I bands where A bands are largely comprised of myosin and I bands are largely comprised of actin. Some have additionally defined a buffer zone of sorts (H zone).
The general methodology for muscle contraction is the sliding filament model.

Muscle fibers generate active and passive mechanical forces to overcome gravity to ensure proper posture, movement and biological function. Active muscle tension is derived from muscle contractions leading to shortening of myofiber’s sarcomeres whereas passive tension occurs through sarcomere stretching reducing their level of overlap.3-5 It appears that slow twitch muscle fibers are more susceptible to the change in gravitational force versus fast twitch muscle fibers.6,7 This difference in degradation can be troublesome because not only is slow twitch muscle more associated with posture, but is also associated with muscular endurance. In addition to muscle atrophy there is a serious drop-off (>50%) in protein synthesis rates and a significant loss of calcium balance.8-10 Whether or not this loss of calcium is due to actual direct losses or indirect absorption losses (i.e. a lack of Vitamin D) is unknown.

The change in protein synthesis rate is further compromised by activation of protein degradation rates.11 One of the major pathways responsible for atrophy is the ATP-dependent ubiquitin/proteasome pathway with the most important feature being E3 ubiquitin ligase due to its specificity in targeting certain proteins for elimination.12

Torpor proponents believe that the negative influence of atrophy, which will be much worse for individuals in torpor because of the lack of ability to exercise, can be neutralized through the use of neuromuscular electrical stimulation (NMES). NMES induces muscle contraction using electric impulses born from electrodes on the skin in close proximity to the desired muscle to be stimulated. This system works because the electrical stimulation from the electrodes mimics neuronal stimulation derived from action potentials.

Proponents view NMES as an effective strategy for increasing muscle mass, muscle endurance, maximal voluntary strength, neural drive and oxidative metabolism, which could also increases immune system activity.13 With these changes proponents believe that NMES could have a positive effect on reducing muscular atrophy. While NMES may have the ability to induce these increases relative to not exercising, there are two important questions that have yet to be answered. The first question is whether or not NMES can outperform the current exercise regime utilized by ISS astronauts?

For example in one study despite aerobic exercise for 5 hours per week at moderate intensity and resistance exercise performed 3-6 days per week at 2 hours per day calf muscle volume in astronauts decreased by 13%, peak power decreased by 32%, force-velocity reduced between 20 to 29% and there was a 12 to 17% increased shift between fast twitch muscle to slow twitch muscle.14 This study and others support the idea that current vigorous exercise designs are not sufficient to ward off significant muscle atrophy hence why most ISS habitation is a maximum of six months.

Unfortunately there is little evidence to suggest that NMES is superior to voluntary endurance and strength exercises because there is almost no evidence comparing the two methodologies in well-designed and properly controlled studies. Another concern related to this comparison is the lack of specifics regarding the biological changes that occur when an individual is exposed to long-term NMES. Finally the second important question creates a logical belief that NMES is not equal or greater than normal voluntary exercise.

This second major question is how does NMES affect muscular fatigue? In humans despite using several different stimulation patterns, frequencies under 16 Hz were not strong enough to produce a contraction that extending a quadriceps to at least 40 degrees.15 Therefore, most stimulation methodologies, depending on the overall type of intervention, utilize frequencies between 20-50 Hz.16,17 This magnitude of frequency creates a non-selective, spatially fixed (due to the continuous nature of the pulse) and synchronous motor unit recruitment.18-20 The immediate interesting element is that these characteristics of recruitment are different from that which occurs in voluntary muscle contraction, which is governed by the Henneman’s size principle.21,22

The evolution of muscle firing and recruitment is shown in the size principle where smaller more fatigue-resistant motor units are activated first followed by larger units if necessary; these larger units can also replace de-recruited units that drop out due to fatigue.23 This process creates an efficient firing recruitment system that maximizes muscular endurance and reduces overall fatigue and its negative effects. However, NMES has a more random simultaneous recruitment instead of organized sequential recruitment, which eliminates fatigue-reducing mechanisms. Unfortunately the level of this non-selective recruitment is not uniform, but seems almost dependent on what particular muscle group is being stimulated.24,25 Another concern with this change in recruitment is how non-selective recruitment for approximately 6 months could influence the long-term functionality of normal voluntary movement when NMES is eliminated after arriving on Mars. Basically will there be any long-term negative effects when “retraining” muscles for size recruitment rather than random recruitment?

Also this increased rate of fatigue may explain why fast twitch muscle fiber tends to morph into slow twitch muscle in NMES patients13 as slow twitch muscle is more resistant to fatigue. This conversion is troublesome because as discussed above, for some reason slow twitch muscle tends to be more prone to atrophy versus fast twitch muscle. Thus this muscle conversion could handicap the ability of NMES to ward off muscle atrophy versus voluntary muscle exercises.

A third concern is that surface-stimulating electrodes apply current directly beneath the surface of the electrode. However, because the electrodes are on the surface the currents they produce need to travel through various subcutaneous tissues with a diverse level of resistances. One study calculated that this impulse was only able to reach superficial motor units 10-12 mm deep and had difficulty reaching the larger motor units deeper in tissue.26 Therefore, an increase in pulse width or amplitude would be needed to improve penetration to reach these other motor units. This “incomplete” penetration may also explain the non-selective motor unit recruitment seen from NMES. Another problem with the localized influence of the electrodes in NMES is the potential damaging effect of the isometric contractions. Multiple studies report significant increases in creatine kinase, macrophage infiltration, z-line disruption and increases in muscle soreness.27-30

A fourth possible issue with NMES is the lack of full neuronal activation. With the stimulation origin focused on a single location at a specific muscle group there is the potential for reduced neuronal coordination with other critical systems. For example some believe that one of the keys to effective muscular endurance and overall muscle health is not only consistent muscle exercise, but also the sequence that begets the activation of the muscle including proper interaction between the muscle, the heart and respiratory systems, something that escapes current NMES protocols. Basically for voluntary muscle movement the neuronal signals originate in the brain and are able to coordinate the appropriate timing on heart, respiratory and other important associated systems whereas NMES skips this activation and relies on feedback to start the process.

Some have thought to increase the effectiveness of exercise to neutralize atrophy through increasing circulating concentrations of growth hormone, various other steroids and/or insulin-like growth factor 1 (IGF-1), which is the main effector molecule for growth hormone, by either augmenting muscle growth or using proteolytic inhibitors to reduce muscle degradation.14 There are some preliminary studies that demonstrate a synergistic effect between growth hormone and exercise in reducing atrophy, but a lot more work needs to be done to establish a positive correlative protocol. For example chronic delivery of growth hormones and other protein growth factors is troublesome because they have short half-lives and damaging side effects in either large quantities or over long periods of time, which right now is required to augment muscle growth.31,32

When addressing safety a chief concern is about the total time an individual could remain in torpor (approximately 180 days). Some advocate hibernation in shifts where one individual is always awake and switches with another individual every x number of days. Even without a defined length of time for being both awake and in hibernation, the biggest immediate concern with this recommendation is how the body would cope with constantly moving between a hibernated and non-hibernated state. For example how would various enzymes and other proteins, which have a very short temperature range of activation, handle 6-7 cycles of being at 92 degrees C for 21 days and then 98.6 for 7 days? While some could argue that hibernating mammals, like bears, periodically roust themselves safely from torpor during their hibernation cycles before reentering hibernation this argument appears invalid because these creatures have evolved to hone the safe application of this behavior, humans have not.

Also the process of therapeutic hibernation is similar to flying in a plane where the most dangerous aspects are the entrance (takeoff) and awakening (landing); numerous entrances and awakenings from hibernation would only increase the probability of a critical failure resulting in serious health damage or death. Overall at this moment it is difficult to argue in favor of a hibernation “shift” strategy. If one is concerned about relying on 100% automation, it stands to reason that one person should remain active for the entire flight with remaining crewmembers in torpor.

Another question regarding the application of torpor is the loss of in-transit preparation time. While it is ideal that all of the colonists are sufficiently prepared for their specialized tasks when arriving on Mars, there is a significant unknown to how well they would retain this knowledge and training. During the transit, it is reasonable to suggest that most of the time would be spent honing their abilities and skills that will be applied upon arriving on Mars to reduce the probability of critical errors during the colonization process. In a torpor state this additional preparation time is lost. Therefore, it is important to consider how knowledge and skills will be retained both in general and within a torpor state.

While the benefits of placing numerous, if not all, astronauts traveling to Mars in a torpor state for the duration of the transit appear attractive there are two major issues that must be addressed. First, the safety of the methodology must be thoroughly analyzed. On its initial face determining safety may be quite difficult for two reasons: 1) the process of therapeutic hypothermia has only ever been significantly tested on people with severe injuries, not people with high levels of health, a characterization that would comprise all prospective Mars colonists. However, what type of “healthy” individual would volunteer to be placed in a 1-month, 2-month, 3-month, etc. torpor state to determine the positive and negative effects on his/her body? 2) all major testing would more than likely occur on Earth to ward off accidental loss of human life due to the ability to immediately act if anything goes wrong; however, without observing how the body would react in a microgravity environment versus the natural gravity environment of Earth creates holes in the knowledge of how the body changes over time while in hibernation during travel.

Second, it is well known that muscle atrophy is one of the biggest threats to the success of a long-term off-Earth colonization mission. At the moment there is little reason to suspect that NMES will be able to ward off atrophy at a similar level to existing exercise protocols let alone surpass their effectiveness. It does little good to save food and space in transit when colonists will simply suffer major muscle injuries upon waking up and moving around for the first time in half a year. Also the question of erosion of colonist skills is one that must be addressed because it would be unnecessarily risky to expect colonists to re-learn skills after landing on Mars. Overall while the idea of inducing a torpor state in colonists during transit to Mars is an interesting one there are numerous smaller questions as well as a few larger questions that must still be addressed as well as some potential technology hurdles before this strategy can be considered viable.


Citations –

1. Drew, K, et Al. “Central nervous system regulation of mammalian hibernation: implications for metabolic suppression and ischemia tolerance.” J Neurochem. 2007. 102(6): 1713–1726.

2. Sessler, Daniel. “Thermoregulation and Heat Balance.” Therapeutic Hypothermia. Ed. Mayer, Stephen and Sessler, Daniel. Marcel Decker: New York, 2005.

3. Vandenburgh, H, et Al. “Space travel directly induces skeletal muscle atrophy.” FASEB J. 1999. 13:1031-1038.

4. Stewart, D. “The role of tension in muscle growth.” In Regulation of Organ and Tissue Growth (Goss, R. J., ed) 1972. 77–100, Academic Press, New York

5. Goldspink, D, Garlick, P, and McNurlan, M. “Protein turnover measured in vivo and in vitro in muscles undergoing compensatory growth and subsequent denervation atrophy.” Biochem. J. 1983. 210:89–98

6. Narici, M, and de Boer, M. “Disuse of the musculo-skeletal system in space and on earth.” Eur J Appl Physiol. 2011. 111(3):403-20.

7. Fitts, R, Riley, D, and Widrick, J. “Functional and structural adaptations of skeletal muscle to microgravity.” J Exp Biol. 2001. 204(18):3201-8.

8. Schollmeyer, J. “Role of Ca2+ and Ca2+-activated protease in myoblast fusion.” Exp Cell Res. 1986. 162(2):411-22.

9. Barnoy, S, Glaser, T, and Kosower, N. “Calpain and calpastatin in myoblast differentiation and fusion: effects of inhibitors.” Biochim Biophys Acta. 1997. 1358(2):181-8.

10. Haddad, F, et Al. “Atrophy responses to muscle inactivity. I. Cellular markers of protein deficits.” J Appl Physiol. 2003. 95(2):781-90.

11. Sandri M. 2008. Signaling in Muscle Atrophy and Hypertrophy. Physiology 23: 160-170.

12. Bodine, S, and Baehr, L. “Skeletal Muscle Atrophy and the E3 Ubiquitin Ligases, MuRF1 and MAFbx/Atrogin-1.” American Journal of Physiology – Endocrinology and Metabolism. 2014.

13. Maffiuletti, D, et Al. Neuromuscular electrical stimulation training induces atypical adaptations of the human skeletal muscle phenotype: a functional and proteomic analysis. J. Appl. Physiol. 2011. 110:433-450.

14. Trappe, S, et Al. “Exercise In Space: Human Skeletal Muscle After 6 Months Aboard The International Space Station.” Journal of Applied Physiology. 2009. 106:1159-1168.

15. Crevenna, R, et Al. “Neuromuscular electrical stimulation for a patient with metastatic lung cancer–a case report.” Support Care Cancer. 2006. 14:970–973.

16. Chhabra, D, and dos Remedios, CG. “Cofilin, actin and their complex observed in vivo using fluorescence resonance energy transfer.” Biophys J. 2005. 89:1902–1908.

17. Coffey, V, and Hawley, J. “The molecular bases of training adaptation.” Sports Med. 2007. 37:737–763.

18. Gregory, C, and Bickel, C. “Recruitment patterns in human skeletal muscle during electrical stimulation.” Phys Ther. 2005. 85:358–364.

19. Jubeau, M, et Al. “Random motor unit activation by electrostimulation.” Int J Sports Med. 2007. 28(11):901-4.

20. Doucet, B, Lam, A, and Griffin, L. “Neuromuscular electrical stimulation for skeletal muscle function.” Yale Journal of Biology and Medicine. 2012. 85:201-215.

21. Henneman, E, Somjen, G, and Carpenter, D. “Functional significance of cell size in spinal notoneurons.” J Neurophysiol. 1965. 28:560–580.

22. Vanderthommen, M, and Duchateau, J. “Electrical stimulation as a modality to improve performance of the neuromuscular system.” Exerc Sport Sci Rev. 2007. 35(4):180-185.

23. Carpentier, A, Duchateau, J, and Hainaut, K. “Motor unit behaviour and contractile changes during fatigue in the human first dorsal interosseus.” J Physiol. 2001. 534(3):903-12.

24. Bergquist, A, Clair, J, and Collins, D. “Motor unit recruitment when neuromuscular electrical stimulation is applied over a nerve trunk compared with a muscle belly: triceps surae.” J Appl Physiol. 2011. 110(3):627-37.

25. Thomas, C, et Al. “Motor unit activation order during electrically evoked contractions of paralyzed or partially paralyzed muscles.” Muscle Nerve. 2002. 25(6):797-804.

26. Fuglevand, A, et Al. “Detection of motor unit action potentials with surface electrodes: influence of electrode size and spacing.” Biol Cybern. 1992. 67(2):143-53.

27. Aldayel, A, et Al. “Comparison between alternating and pulsed current electrical muscle stimulation for muscle and systemic acute responses.” J Appl Physiol. 2010. 109:735–744.

28. Aldayel, A, et Al. “Less indication of muscle damage in the second than initial electrical muscle stimulation bout consisting of isometric contractions of the knee extensors.” Eur J Appl Physiol. 2010. 108:709–717.

29. Jubeau, M, et Al. “Comparison between voluntary and stimulated contractions of the quadriceps femoris for growth hormone response and muscle damage.” J Appl Physiol. 2008. 104:75–81.

30. Mackey, A, et Al. “Evidence of skeletal muscle damage following electrically stimulated isometric muscle contractions in humans.” J Appl Physiol. 2008. 105:1620–1627.

31. Meling, T, and Nylen, E. “Growth hormone deficiency in adults: a review.” Am. J. Med. Sci. 1996. 311:153–166.

32. Hintz, R. “Current and potential therapeutic uses of growth hormone and insulin-like growth factor I.” Endocrinol. Metabol. Clin. N. Am. 1996. 25:759–773.

Saturday, October 25, 2014

Laundry on Mars

One of the back burner issues involved in the colonization of Mars is how will colonists do laundry? It seems like a rather simple question and a general task that is taken for granted, especially with the convenience of the developed world. However, on Mars heavy conservation of both energy and water will eliminate both conventional machine washing or even hand washing. So with these significant limitations how will Mars colonists clean their clothing?

Looking towards the behavior of astronauts on the International Space Station (ISS) does not provide any immediate assistance. While it is standard procedure for astronauts on the ISS to wear clothing for longer than a 24-hour period, its close proximity to Earth allows for simple clothing replacement during cargo missions with dirty laundry being burnt up during re-entry. This re-supply process is obviously not available for Martian colonists because additional clothing will add weight and cost to the initial launch and in addition to these negative elements will also take months to arrive in any supplementary launches. Another non-helpful aspect is that most conventionally worn clothing by astronauts visiting the ISS is not specialized in any real sense beyond having a reduced number of seams (or being seamless) with Cabelas and Lands End seemingly being the more prominent brands worn.

With the difficulties associated with cleaning and/or providing new clothing after the initial launch some could argue that after the habitat is established clothing may not be necessary. A well-kept habitat would have a comfortable temperature between 65 and 80 degrees F with little humidity. A lack of non-human origin microbes eliminates any direct infection issues. An air lock separates the preparation staging area for extravehicular activities (EVAs) and the remaining living area of the habitat eliminating the incursion of any negative outer environmental elements. Psychological evaluations and training can manage any potential colonist “revulsion” towards interacting with their nude crewmates. However, while the major immediate issues for accepting nudity appear manageable there are a number of smaller issues.

One of the less heralded benefits of clothing is absorption of general excretions like sweat, shed skin cells, etc. Without clothing there is a much higher probability that these excretions are deposited on various solid surfaces within the habitat, which would not be hygienic and could even damage equipment. Also clothing offers a secondary protective barrier to wards off various ailments that could breach the skin like burns or various cuts and scratches. This additional protection would also serve as a valuable psychological assurance when performing maintenance on various life support systems like waste disposal/recycling or when creating new parts in situ within a prospective machine shop. Not many individuals would be comfortable sanding/welding something with only eye protection.

Some rudimentary experiments have been conducted with some more specialized clothing options like the Japanese Space Federation’s “J-wear”, which includes underwear, shirts, pants, and socks made from cotton and polyester and purports to be anti-bacterial, water-absorbent, odor eliminating, antistatic and flame retardant. Most likely this material has these properties because it is doped with titanium oxide (titania or TiO2) and some other additives. However, the actual testing of this material is limited, especially in its publication, so the time frame for the efficacy of these claims is unknown. One “famous” study with a Japanese astronaut on the ISS created some anecdotal evidence that underwear can retain a chiefly non-offensive odor when worn for around one month.

The reason TiO2 is effective at creating the cleaning advantages is because it is a potent photocatalyst that is able to neutralize the staining of almost any organic compound when exposed to ultra violet (UV) radiation. When TiO2 is exposed to and absorbs UV it results in excited electrons on the valence band of TiO2. This excess energy promotes electrons to the conduction band creating new negative electrons and positive holes. In the presence of water the positive hole interacts with the water to form hydrogen gas and hydroxyl radicals. The free negative electron reacts with the newly formed hydroxyl radical to form a super oxide anion, which decomposes organic stains. In addition if TiO2 is doped onto a fabric it creates a protective film that provides a bio-static, super oxidative and hydrophilic barrier.

Photocatalytic effects, as described above, can also kill bacteria due to the large amounts of hydroxyl radicals produced during the reaction steps. These hydroxyl radicals also aid in eliminating odors as they breakdown the molecular bonds that comprise most volatile organic compounds (VOCs). Some have envisioned the further evolution of this process by doping the TiO2 with nitrogen and adding silver iodide to make the process applicable to visible light, but this is not necessary because a small portion of the habitat could inundated with a UV light source to act as a “laundry area” of sorts. Also it is unclear how safe the silver doping would be for excess exposure to silver iodide is toxic when ingested and repeated contact with skin can lead to argyria, which turns one’s skin blue. Therefore, it makes little sense to include silver iodide. Unfortunately efficient operation of photocatalysts, including TiO2 requires water, which will be in short supply on Mars. Therefore, testing would have to be performed to determine the length of time between UV “washes”.

With or without TiO2 doping exposure to UV light should be sufficient to eliminate any bacteria growth born from the bodies of the colonists. Therefore, the biggest issue will be odor. Another strategy to eliminate odors may be to incorporate a “Febreze” strategy. The active ingredient in the household odor eliminating product Febreze is hydroxypropyl beta-cyclodextrin. Various cyclodextrins including beta-cyclodextrin, are produced from starch via enzymatic conversion. These elements can theoretically be produced in situ on Mars, but the difficult element would be converting the beta-cyclodextrin to hydroxypropyl beta-cyclodextrin due to the lack of easily available carbon elements on Mars. Therefore, this type of solution may not be prudent.

Overall it is clear that some area of the habitat will have to be converted into a dark room of sorts with UV lights to act as an area to clean bacteria from clothing. Limiting the influence of odor on the psychological well being of the colonists is the principle question. Some could argue that individuals have a tendency to become accustomed to smells, but that desensitization demands a static element to the odors; it stands to reason that if odors are not managed then they will progressively expand in a negative manner, thus colonists will probably never generate an accustomed affinity. Therefore, an odor elimination strategy will need to be incorporated. Determining between either an “Febreze” chemical strategy versus a photocatalytic strategy will involve identifying the production capacity in situ of the desired odor eliminating chemical and the amount of water that will be required to active that phootcatalytic effect to sufficiently remove odor. This information can be easily determined in a long-term Martian colonization simulation study performed on Earth, which sadly do not yet incorporate such testing.

Tuesday, October 14, 2014

A new tool to help fight against mental illness?

The history of addressing mental illness has been a tumultuous one in the United States. In the past behaving against the norm commonly landed an individual in jail or an asylum, both which existed on the periphery of society, a location that potentially reduced the ability to produce effective treatment. The location was typically not the only element that reduced the viability of effective treatment as a number of asylums were poorly funded and staffed by a number of individuals who appeared to quickly tire of continuous interaction with “non-normal” individuals reducing their vigor for proper treatment both physically and mentally.

In more modern times a “so-called” enlightenment regarding mental illness was born from deinstitutionalization. The “noble” or liberalized story of deinstitutionalization involves the belief that the development of both Medicare and Medicaid as well as various psychotropic medications allows mentally ill patients to function “normally” and live among the community reducing the stigma of having a mental illness, thereby increasing their ability to assimilate and manage their condition(s). However, the more dirtied history of deinstitutionalization is that after the Supreme Court ruling in Souder v. Brennan prohibited mental hospitals from exchanging patient labor for room and board, forcing these institutions to pay for patient labor at minimum wage levels, there was little opposition to implementing the principles of the Community Mental Health Act of 1963 regardless of execution viability. Unfortunately despite the public’s apparent “zest” to integrate mental patients into society, the networked infrastructure that was to support these patients never materialized in a vast majority of places.

Sadly this early failure in the 60s and 70s has yet to be significantly rectified for while the proportion of individuals in public mental hospitals has dropped from 0.338% (558,000/165 million) in 1955 to 0.016% (50,000/313 million) in 2010,1 the Department of Justice estimated in 2006 that at least 24% of inmates in state prisons and 14% of inmates in federal prisons have mental illness and an additional 15% of state inmates and 24% of local/city inmates meet criteria for psychotic disorders.2,3 It stands to reason based on how mental illness is currently treated that this number has only increased into 2014. In addition at least 50% of a number of ex-cons with significant mental illness are rearrested typically through violations of their parole (these individuals have come to be known as “frequent fliers”).1 Incarceration has its own societal stigmas, imagine how difficult successful community treatment could be with both a criminal record and a mental illness.

Deinstitutionalization has also failed to live up to the idealistic diverse and “normal” environment pictured by its supporters in the associated residential “communities”. To most these “communities” have become a de facto urban asylum that again cares little for the recovery or treatment of the patients reducing the probability of any return to genuine normalcy. Some hold out hope that the focus of the American Care Act on result-based outcomes will be an effective panacea to the squalor conditions of a number of these mental illness communities, but whether or not that reality will emerge is difficult to predict due to numerous unknowns and at the moment seems more unlikely than likely.

These environmental factors notwithstanding, one aspect of treatment that is not typically discussed is the idea of an individual focal add-on treatment where an individual that suffers from mental illness attempts to “commandeer” their brain in effort to regain control. Basically one wonders if too much emphasis has been placed on pharmaceutical, talk therapy and, now in modern times, assertive community treatment resulting in the omission of more personal options? Such abandonment is perplexing because these potential methods have almost no side effects and very little financial cost. With this intention to add an extra tool to the toolbox it must be mentioned that general result-based analysis of treatments for mental illness is almost non-existent. Despite advancements in the ability to treat mental illness almost no one actually studies which of these treatments work, both on an absolute (does treatment A work) and relative (does treatment A work better than treatment B) level.4,5 Therefore, these methods would have to be studied and compared against and in cooperation with existing methods.

One example of an individually driven treatment would be an attempt to control the multiple network firing of schizophrenia by engaging in a task requiring overpowering focus to reduce the firing of the other more spontaneous neuronal elements. For example when a schizophrenic begins to hear voices he/she would begin to play a game of chess, start a logic puzzle, a sudoku puzzle, i.e. a task that requires significant focus in order to be successful. One of the keys to this strategy is to identify a simple task/game that requires focus, but also makes an individual content (not necessarily happy). The necessity of contentment is to ensure a lack of frustration thus affording the ability to maintain focus.

Contentment is an element that seems to be pushed to the side when discussing mental illness, with focus instead placed on happiness and unhappiness. Contentment is important because it is less vulnerable to the negative impacts of more extreme emotional states, which can rapidly cascade into opposing elements (i.e. happiness can quickly become unhappiness and visa-versa), but is still emotionally positive enough to spark focus and enjoyment.

Another option could be producing an overpowering focus through visualization. By focusing on a single place of reference an individual would create a positive non-violent altered reality that could control spontaneously produced changes in mood or sensory information. The complexity of elements assigned to enriching and maintaining the visualization could mute the action potentials associated with the spontaneous firings that create symptoms of mental illness.

Another technique, one more recognizable by many for its ability to assist in mental control, is meditation. In recent years meditation has become an interesting subject of contemplation regarding its potential to manage the negative symptoms of mental disease. For the purpose of this brief discussion meditation is regarded as a physiological state invoking physical and mental relaxation with a reduced metabolic activity.6

The state of meditation is achieved through the reduction of thought processes to a single focused internal dialogue in the mind eliminating mental clutter and spontaneous thoughts. Unsurprisingly the elimination of this mental clutter enhances pure awareness and clarity on the single internal dialogue, usually calm central breathing tethered by the single focal word. Theoretically a meditative state could block the occurrence of negative symptoms from mental illness. This possibility is supported by the reported long-term effects seen in meditation practitioners such as: enhanced concentration attention skills, improved self-control and self-monitoring, increased ability to inhibit irrelevant external and internal stimuli, increased positive mood, emotional stability and improved resilience of stress.7 One issue with meditation is that most of the research has been conducted in small groups with few meaningful controls; therefore, outside of very long term practitioners it is difficult to determine when the advantages of consistent meditation will take hold.

However, meditation does have its share of more serious potential concerns as there is past evidence that during meditation an individual with a mental illness can have an increased probability of exacerbating short-term (non-permanent) psychosis.8 This increased risk for temporary psychosis could be drawn from the increased anxiousness that is common among individuals with mental illness, which makes meditation in general more difficult, but could also make it more beneficial in the long run. Another concern is that individuals with mental illnesses have motivational issues or even defects, which may make inspiring the discipline for routine focal tasks like meditation more difficult.

Note that these above personal add-on strategies differ from cognitive behavioral therapy because they do not seek to change the long-term thinking paradigms held by a particular individual. Instead these techniques are theoretically thought to act as an acute deterrent to be applied upon the onset of a significant negative aspect of a given mental illness.

On a side note numerous individuals think that education is an important aspect to limiting, or even eliminating, stigmas associated with mental illness, which is a reasonable and accurate assessment. However, no one really seems to suggest a means of applying a mandatory aspect to this education element, which would significantly increase its effectiveness. For example one effective means to addressing public education of mental illness would be for all high school students to take a psychology class that would be required for graduation that covers various mental illnesses in depth. Through this class all high school students would learn rudimentary means to identify symptoms of mental illness, manage it, and how to effectively interact with those who have a mental illness limiting uncomfortable and/or inappropriate moments.

Overall many have professed a concern that mental illness will increase in the future due to increases in population and proportion of occurrence.9 This increase is buffered by the concern that most traditional talk therapy treatment will remain centralized in high population affluent areas of the country. Unfortunately there is no evidence that this unequal distribution of certain psychological services will change, thus placing additional pressure on community environmental therapy and pharmaceuticals. To alleviate this pressure new techniques need to be developed. Understand that these techniques are acute immediate response deterrents and are not meant to replace other therapies; it is to say that one should not say that Johnny no longer needs his anti-psychotics because he plays chess. The above strategies appear to be theoretically viable and worthy of further study to determine whether or not they are empirically viable. If so these individual acute strategies could be important elements in reducing the more severe negative attributes associated with mental illness.

Citations –

1. Edmondson, B. “Crazy enough to care.” The American Scholar. Spring 2012. 46-55.

2. Clayton, A, et Al. “The citizenship project part II: impact of a citizenship intervention on clinical and community outcomes for persons with mental illness and criminal justice involvement.” Am. J. Community Psychol. DOI 10.1007/s10464-012-9549.

3. Department of Justice. Mental health problems of prison and jail inmates. Bureau of Justice Statistics Special Report. (2006). NCJ 213600.

4. Morgan, R, et Al. “Treating offenders with mental illness: a research synthesis.” Law Hum Behav. 2012. 36(1): 37–50.

5. Rice, M, and Harris, G. “The treatment of mentally disordered offenders.” Psychology, Public Policy, and Law. 1997. 3:126–183.

6. Young, J, and Taylor, E. “Meditation as a voluntary hypometabolic state of biological estivation.” News in Physiological Sciences. 2001. 13:149–153.

7. Rubia, K. “The neurobiology of meditation and its clinical effectiveness in psychiatric disorders.” Biological Psychology. 2009. 82:1-11.

8. Walsh, R, and Roche, L. “Precipitation of acute psychotic episodes by intensive meditation in individuals with a history of schizophrenia.” Am J Psychiatry. 1979. 136:1085–6.

9. Mathers, C. and Loncar, D. “Updated projections of global mortality and burden of disease, 2002–2030 data sources, methods and results.” Evidence and Information for Policy. 2005.

Saturday, September 27, 2014

Who’s afraid of a big bad guaranteed basic income?

Note: Reading about the structure and execution of a GBI here would go a significant way to enhancing this particular blog post.

The political trepidation behind the very attempt to legislate a guaranteed basic income (GBI) should be quite surprising, but sadly is not. A GBI should be one of the major goals of the progressive movement, but there has been no effort to achieve it, largely based on the notion that a GBI is thought of as “politically unfeasible”. However, what is interesting from a logical and rational perspective is that there is no direct fundamental reason why a vast majority of United State citizens would object to a GBI regardless of their political, religious or other moral leanings.

For example suppose:

You are a Democrat –

A GBI is generally the Holy Grail with respects to eliminating poverty and hunger. With a GBI poor individuals will be able to create a stable savings account and advance their economic position without the significant threat of falling into the poverty trap. In addition all individuals will be able to afford to attend college, if so desired, creating a more educated and creative society. Individuals that have already attended college would have a greater ability to pay off student loan debt in a timely fashion removing the potential of being financially crippled by consistent payments during hard times. Finally no longer would an individual be handicapped and imprisoned by the poor decisions of their parents for regrettably the economic climate of the United States no longer only demands hard work and reasonable intelligence, but social and political connections.

You are a Republican –

A GBI is an effective means to reduce the level of bureaucracy in the Federal government resulting in the simple and transparent consolidation of all government “safety net” programs which include, but are not limited to: unemployment insurance, general welfare, supplemental nutrition assistance program (SNAP a.k.a. food stamps), school meal programs, low-income housing assistance, home energy bill assistance, refundable portions of the Earned Income Tax Credit and Child Tax Credit, supplemental security income, etc.

There is reason to suspect that the supplementary income provided by a GBI will also increase the probability of marriage and strength family bonds in general. One of major reasons why marriage rates have decreased over the last few decades, especially the last decade, is that most younger individuals are holding off marriage because they do not have the necessary financial resources. Some individuals could argue that small-scale studies disprove this benefit, but that argument misinterprets the results of those studies. Based on logic and the existing marriage climate a GBI should increase marriage probability.

Finally a GBI would significantly enhance market efficiency by increasing the available spending and investment capital in the environment. Not only would individuals have more available money to drive the consumption elements of the economy creating more indirect business opportunities and jobs, individuals would have additional capital that could be utilized to establish their own businesses. Basically instead of relying on venture capitalists or harder to acquire bank loans, which creates market inefficiencies by removing money from the general consumer environment, the money acquired from these businesses stays with the company founders and in the general consumer economy. Keeping more money in this part of the economy will accelerate economic growth. However, if bank loans are needed a GBI would increase credit flow from lending institutions due to increased confidence in repayment.

You are a Libertarian –

A GBI significantly enhances personal freedom by reducing the severity of economic obstacles. Instead of being bound to a job one hates and has little skill at solely because one needs the paycheck to eat, an individual can use the GBI to make decisions not bound by the need for a paycheck. The GBI will accomplish a noted goal, reducing the size of the Federal government. Finally a GBI will further the development of a genuine meritocracy, that winners and losers are determined by talent, hard work, drive, intelligence, etc., instead of a somewhat fixed system where an individual can be consistently placed at a significant disadvantage by elements outside of his/her control.

Regardless of one’s political affiliation a GBI would create a dramatic reduction in lost human potential. For example instead of having an individual who is interested and gifted in engineering, psychology, teaching, law enforcement, etc., bound to a low level undesired service job simply to put food on the table or to help his/her family, this individual will now be able to pursue jobs with their valued skill sets and interests. This rejuvenation of human potential will increase economic efficiency and growth as well as increase physical and mental health.

You are an Environmentalist –

An environmentalist may balk at the above mention of economic growth through additional consumption. However, it is important for environmentalists to recall that a vast majority of “environmentally friendly” energy and transport options are significantly more expensive than their less friendly alternatives; with the additional funds from a GBI individuals will be able to more easily support positive environmental changes increasing the probability for continued economic growth while at the same time reducing the damages born from global warming and other pollution factors.

You are a “Insert Religion Here” –

One of the major tenets of every major religion is to help the poor; supporting and creating a GBI is one of the best strategies for helping the poor. In addition a GBI would free up significant charitable donations to various religious organizations from domestic commitments and allow them to be redistributed to global charitable projects, if so desired. Overall anyone who truly believes in the message of their particular religious faith should support a GBI.

You are in the Upper 15% Income Bracket –

Intuitively one might think that rich individuals, make no mistake those in the top 15% income bracket are rich, would be opposed to a GBI because of the small changes it would make to the tax code resulting in a very slightly reduced direct return. However, a GBI would also significantly increase the amount of disposable income to the general public, which would significantly increase the moneymaking opportunities for rich individuals through investment. It stands to reason that intelligent rich individuals would support a GBI because they could identify the worthwhile new business opportunities in which to invest, either directly or indirectly through stocks, thus increasing their overall wealth as well as improving society in general. Therefore, rich individuals should support a GBI as a means to increase their personal wealth, increase the overall prosperity of the country (enhancing international negotiating power) and reduce market uncertainty and inefficiency increasing overall productivity.

With a vast majority of the public falling into one of the above demographics that would logically support a GBI it is rather peculiar that no reasonable effort has been made by the Federal government to establish one. As stated at the beginning of this thought exercise it appears that preconceived notions about a GBI not being “political feasible” has derailed its viability before even identifying whether or not these preconceived notions are accurate. The interesting thing about this philosophy is how can a piece of legislation be defined as “dead on arrival” if no one actually brings the issue up for discussion? Allowing these assumptions to control the actual perception of various ideas prevents the United States from identifying and establishing quality legislation like a GBI. Overall there is little reason to object to a GBI as long as it is operated transparently and is cost effective for it benefits everyone in society even if some individuals may not immediately realize it.

Tuesday, September 16, 2014

Reducing Concussions in Football?

The awareness and medical implications of concussions in professional sports have increased significantly over the last half-decade, especially in National Football League (NFL). The direct responsibilities of both the NFL and players to manage the concussion question have previously been outlined in the blog here. Unfortunately neither party, especially the players, has administered those responsibilities appropriately. While behavior still needs to be adjusted to reduce concussion probability, there may be biological strategies that can help maximize positive health outcomes for athletes with regards to concussions.

Various concussion research has involved evaluating rugby-based headgear as well as other helmet designs, custom-fitted mouth guards and face shields (in ice hockey).1-4 The general conclusions are that no particular type of headgear, including rugby-based, reduces the probability of acquiring a concussion any more effectively over most other types of helmets and there is no strong evidence that mouth guards or face shields reduce concussions.4,5 In addition significant amounts of research has focused on post-concussion symptoms and recovery. However, less research has been conducted on secondary factors to developing concussions. For example football has changed significantly in many ways since the early professional days in the 50’s and 60’s; one way that could be very relevant to concussion development is the means in which the brain processes and consumes oxygen.

There are two chief theories that attempt to explain the biological origins of a concussion. First, some believe that the first step involves a significant level of at least one type of force, linear, rotational or angular, that is directly or indirectly applied to the head leading to the disruption of cell membranes in various neurons throughout the brain. This disruption creates an influx of potassium ions to the cells resulting in depolarization and the release of neurotransmitters, usually glutamate.6 The release of glutamate creates a cascade of depolarization among various neuronal networks. Sodium-potassium pumps operate at greater than normal capacity to correct the unnatural and uncontrolled potassium influx, which leads to an energy shortage (excessive consumption of ATP and glucose) resulting in excess lactate accumulation.7-9 All of these elements work in consort to generate neurological imbalance and damage.

Some also believe there is a loss of glucose metabolizing efficiency due to excessive metabolization during the initial stages of the concussion. This loss of metabolizing efficiency is due in part to inefficient lactic acid removal after the concussion event, at least in rodents, which leads to reduced blood flow for a number of days after a concussion event.7,10 Interestingly enough this lack of blood flow could explain why an individual has a higher concussion probability rate (vs. baseline) for a number of days after the initial concussion event because there is less cerebral blood flow and greater ability to produce slosh and other forces. Whether or not calcium accumulation results in cell death through a secondary pathway is unclear.11

Second, some believe that rapid acceleration/deceleration of the brain due to forces and collisions create “slosh” (movement of liquid inside containers that are undergoing motion). Slosh occurs in tissues and fluids with differing densities (white matter, skull, spinal fluid, blood, gray matter, etc.) because they accelerate/decelerate at different rates leading to shearing forces and even hydrodynamic cavitation.12,13 Cavitation is the formation of vapor cavities in liquid born from a rapid change to a lower pressure (below saturated vapor pressure of the liquid). After these cavities are formed an increase in pressure results in their implosion creating shockwaves. These shockwaves create damage throughout the brain.14

Whether or not concussions are driven by functional or structural changes is still an open question. While structural damage has been demonstrated in some brains of humans, commonly resulting in a state similar to Alzheimer’s disease, these changes appear to require numerous concussions over a relatively short period of time (decade or less). Overall it is highly likely that concussions are driven by temporary functional changes, which is why the symptoms are only temporary.

An interesting element about concussions is that both rams and woodpeckers can tolerate head impacts much larger than those that are thought to induce concussions in humans. For example typical football impacts generate 25 to 50-g of force whereas rams ramming each other during demonstrations of supremacy generate 500-g and woodpeckers generate 1200-g numerous times a day.15 This ability to experience head trauma without detrimental outcome is thought to be managed by manipulating intracranial volume and pressure. Both animals have different methodologies behind this ability; rams utilize a carbon dioxide-mediated response to altitude and woodpeckers utilize altered jugular outflow.12,15 These methods create efficient brain compacting, which reduces motion and shearing forces. Clearly altering jugular outflow is not reasonable for humans, but it may be possible to incorporate information from an altitude response to reduce the probability of concussions.

Some of the central features that drive a concussion occur within the skull, which is why no helmet can ever clinically claim to reduce concussions because they cannot directly influence forces inside the cranium. However, playing at an increased altitude (venues at or exceeding 644 ft.) appears to decrease the probability of developing a concussion. A recent study of concussion occurrence in the NFL calculated a 30% reduction at higher altitudes.15 Recall from above that one of the elements that is thought to causes concussions is the brain “sloshing” around creating various forces and cavitation. Clearly one of the methods to reduce the probability of concussions is to increase intracranial volume that would allow the brain to reduce “slosh”.15,16

Some have argued that inadequate adjustment to altitude reduces the ability of players to exert maximum effort thus reducing the amount of force applied when running, blocking and tackling thereby reducing the probability of concussions. However, studies in the past have demonstrated that there is no significant enhancement of fatigue at the 644 ft. threshold; therefore, this “reduced force” reasoning should not be applicable. If concussion probability reduction occurred only at higher altitudes like 2000 ft. then it would be more plausible, but that is not the case.

The protective effect of higher altitudes may directly involve the rate of oxygen flow to the brain. The chief change relative to oxygen at higher altitudes is a drop in oxygen partial pressure throughout the body, especially the brain. For example alveolar oxygen partial pressure drops from 103 to 98 when moving from 0 to 1000 ft.17,18 This reduced partial pressure lowers the available oxygen in the blood for consumption by various organs including the brain. With a greater demand for oxygen cerebral blood flow increases, which increases intracranical volume and decreases the probability of concussion. This relationship between oxygen and altitude could also explain why there is not an empirical linear relationship in the above study between altitude and oxygen for after a certain point players become fatigued by the lack of ambient oxygen and resort to supplementing oxygen consumption with outside sources. This supplementation could explain why Denver, the highest altitude playing field in the NFL, did not have the lowest rate of concussion.15

The relationship between oxygen-related blood flow and concussions also can influence the rate of inertial cavitation. The skull can be considered a rigid vessel with a reduced compliance (due to increased intracranial volume) the probability of inertial cavitation decreases because there is less sudden directional changes in near-by fluids reducing the formation of vapor cavities.13,14,19,20 Therefore, increased cerebral blood flow reduces both the force and the cavitation elements associated with potential concussion progression.

So how is cerebral blood flow controlled naturally? The brain has a much higher metabolic requirement for oxygen than other organs and uses approximately 20% of existing oxygen to maintain normal function. Under normal biological operation blood flow to the brain is constant due to vascular resistance provided by large arteries and parenchymal arterioles and tight gap junctions.21,22 Flow is increased through the dilation of upstream vessels avoiding downstream microvascular pressure.23 Overall blood flow rates are controlled by vasodilation of distal to proximal arterial and myogenic mechanism24 maintaining a cerebral blood flow at approximately 50 mL per 100 g per minute as long as cerebral perfusion pressure (CPP) is between 50-60 and 160 mmHg.25

If CPP falls below 50-60 mmHg cerebral ischemia occurs and the body attempts to compensate by increasing oxygen extraction from blood and increasing blood flow to the brain.26,27 Part of the reason blood flow needs to increase is because the partial pressure of oxygen drops hemoglobin saturation from 100% to 50%.28 There is a rather linear relationship between blood flow and CPP below 50-60 mmHg, but there is little change in metabolism regardless of oxygen partial pressure.28 Under these hypoxic conditions cerebral arteries and arterioles reduce vascular resistance increasing vasodilation and smooth muscle hyperpolarization.

An increase in CO2 concentration has a similar effect to reducing oxygen concentration because of a decrease in oxygen partial pressure. In response cerebral blood flow is increased through similar methods as above (cerebral arteries and arterioles dilation).29 The biological effect of CO2 inhalation is rather significant where a solution of 5% CO2 increases cerebral blood flow by 50% and a 7% CO2 solution increases blood flow by 100%.30 The chief mechanism behind hypercapnic vasodilation is the direct influence of extracellular hydrogen on vascular smooth muscle as changes in CO2 partial pressure along does not change cerebral artery diameter.31,32

With the above information it appears that increasing the ratio of CO2/oxygen in the blood will increase the rate of blood flow to the brain, which will decrease the probability that an individual suffers from a concussion. Outside of playing at altitude what are the methods to increase cerebral blood flow? One long term solution could be breathing conditioning where continuous periods of holding one’s breath would increase CO2 concentration in the blood stream over a very short period of time which could lead to the expansion of carotid arteries increasing blood flow to the brain.

However, breathing conditioning is a long-term solution that many individuals may not have the time or the inclination to undertake, so is there a short-term solution that can temporarily increases cerebral blood flow? One possibility that springs to mind is the consumption of a specific carbonic acid beverage (basically a stronger version of soda/pop). Whether or not this method would be viable is unclear as there is almost no empirical information regarding how the consumption of such a beverage would influence cerebral blood flow or other systems and organs.

Another question is whether or not the use of mouth-to-mask ventilation increases concussion risk by temporarily reducing cerebral blood flow. While there appears to be no direct evidence regarding this question, anecdotal evidence involving the drop-off of concussion reduction at very high altitudes (Mile High Stadium in Denver for example) appears to support this idea.
Basically the technical aspect of this question is how does the brain respond with respects to blood flow to a brief (15-30 seconds) inhalation of 50-100% oxygen and what is the residence time of this response? The answer to this question could change the use of mouth-to-mask ventilation to only emergency situations rather than an augmented pick-me-up after a 26-yard run in order to avoid increasing the chance of a concussion in the next play.

There are numerous behavioral methods to reduce the probability of concussions in football including ensuring that defensive players tackle properly (no leading with the head) and proper neurological evaluation after significant head contact. However, another avenue of concussion prevention has remained generally unexplored. Based on some preliminary evidence it appears that devising a strategy to increase cerebral blood flow to act as a “biological helmet” could go a long way to decreasing the probability of concussion development. The one significant caveat to the development of such a method would be determining any long-term detrimental effects associated with multiple temporary increases to cerebral blood flow. Overall it is important to investigate biological methods as well as material methods and behavioral solutions to prevent concussions in sports.

Citations –

1. McIntosh, A, et Al. “Does padded headgear prevent head injury in rugby union football?” Med Sci Sports Exerc. 2009. 41:306–13.

2. Benson, B, et Al. “Head and neck injuries among ice hockey players wearing full face shields vs half face shields.” JAMA. 1999. 282:2328–32.

3. Newsome, P, Tran, D, and Cooke, M. “The role of the mouthguard in the prevention of
sports-related dental injuries: a review.” Int J Paediatr Dent. 2001. 11:396–404.

4. Benson, B, et Al. “What are the most effective risk-reduction strategies in sport concussion?” Br. J. Sports Med. 2013. 47:321-326.

5. Benson, B, et Al. “Is protective equipment useful in preventing concussion? A systematic review of the literature.” BJSM. 2009. 43:i56–67.

6. Katayama, Y, et Al. “Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury.” J Neurosurg. 1990. 73(6):889–900.

7. Giza, C, and Hovda, D. “The neurometabolic cascade of concussion.” J Athl Train. 2001. 36(3):228–235.

8. Yoshino, A, et Al. “Dynamic changes in local cerebral glucose utilization following cerebral conclusion in rats: evidence of a hyper- and subsequent hypometabolic state.” Brain Res. 1991. 561(1):106–119

9. Andersen, B, and Marmarou, A. “Functional compartmentalization of energy production in neural tissue.” Brain Res. 1992. 585(1–2):190–195.

10. Maugans, T, et Al. “Pediatric Sports-Related Concussion Produces Cerebral Blood Flow Alterations.” Pediatrics. 2012. 129:28-38.

11. Meehan, W, and Bachur, R. “Sport-Related Concussion.” Pediatrics. 2009. 123;114-123.

12. Smith, D, et Al. “Internal jugular vein compres­sion mitigates traumatic axonal injury in a rat model by reducing the intracranial slosh effect.” Neurosurgery. 2012. 70:740-746.

13. Turner, R, et Al. “Effect of slosh mitigation on histo­logic markers of traumatic brain injury: laborato­ry investigation.” J Neurosurg. 2012. 117:1110-1118.

14. Goeller, J, et Al. “Investigation of cavitation as a possible damage mechanism in blast-induced traumatic brain injury.” J Neurotrauma. 2012. 29:1970-1981.

15. Myer, G, et Al. “Rates of concussion are lower in National Football League games played at higher altitudes.” Journal of Orthopaedic & Sports Physical Therapy. 2014. 44(3):164-172.

16. Kurosawa, Y, et al. “Basic study of brain injury mechanism caused by cavitation.” Conf Proc IEEE Eng Med Biol Soc. 2009. 7224-7227.

17. Altitude oxygen calculator. Available at:

18. Kraemer, W, et Al. “Resistance training and youth.” Pedi­atr Exerc Sci. 1989. 1:336-350.

19. Church, C. “A theoretical study of cavitation generated by an extracorporeal shock wave lithotripter.” J Acoust Soc Am. 1989. 86:215-227.

20. Zhong, P, et Al. “Effects of tissue constraint on shock wave-induced bubble expansion in vivo.” J Acoust Soc Am. 1998. 104:3126-3129.

21. Faraci, F, and Heistad, D. “Regulation of large cerebral arteries and cerebral microvascular pressure.” Circ Res. 1990. 66:8–17.

22. Cipolla, M, et Al. “SKCa and IKCa Channels, myogenic tone, and vasodilator responses in middle cerebral arteries and parenchymal arterioles: effect of ischemia and reperfusion.” Stroke. 2009. 40:1451–1457.

23.Kulik, T, et Al. “Regulation of cerebral vasculature in normal and ischemic brain.” Neuropharmacology. 2008. 55:281–288.

24. Iadecola, C, et Al. “Local and propagated vascular responses evoked by focal synaptic activity in cerebellar cortex.” J Neurophysiol. 1997. 78:651–659.

25. Phillips, S, and Whisnant, J. “Hypertension and the brain.” Arch Intern Med. 1992. 152:938–945.

26. Hossmann, K-A. “Viability thresholds and the penumbra of focal ischemia.” Ann Neurol. 1994. 36:557–565.

27. Iadecola, C. Cerebral circulatory dysregulation in ischemia. In Cerebrovascular Diseases, Ginsberg MD, Bogousslavsky J. (Eds.). Cambridge, MA: Blackwell Science, 1998. 319–332.

28. Steiner, L et Al. “Cerebral oxygen vasoreactivity and cerebral tissue oxygen reactivity.” Br J Anaesth. 2003. 90:774–786.

29. Reivich, M. “Arterial PCO2 and cerebral hemodynamics.” Am J Physiol. 1964. 206:25–35.

30. Kety, S, and Schmidt, C. “The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J Clin Invest. 1948; 27:484–492.

31. Kontos, H, Raper, A, and Patterson, J. “Analysis of vasoactivity of local pH, PCO2 and bicarbonate on pial vessels.” Stroke. 1977. 8:358–360.

32. Kontos, H, et Al. “Local mechanism of CO2 action of cat pial arterioles.” Stroke. 1977. 8:226–229.

Tuesday, August 26, 2014

Recovery from Coma?

While the number of individuals suffering from long-term unconscious events (comas and coma similar states) is proportionally small relative to the population, the family members and friends of those in comas frequently suffer from significantly negative financial and psychological effects. One of the more prevalent negative effects is the uncertainty associated with comas. Patients and their loved ones can deal with most diseases and similar conditions because they know the cause, the available treatment options and how long to expect before recovery, if recovery is possible; unfortunately these elements are lacking for those in a coma. In addition most people tend to be optimistic and the idea that a person they care about will never regain consciousness is a significant psychological burden as well as a financial one due to resources required for care. Developing a treatment to increase the probability that one recovers from a coma will not produce the overall medical benefits of a cancer or Alzheimer’s cure, but it will produce a treatment for another serious condition that is sufficiently prevalent.

The classic definition of a coma is an individual who exhibits a complete absence of wakefulness and is unable to consciously feel, speak, hear, or move. Traditionally it is believed that consciousness is maintained through two separate components: the cerebral cortex and the reticular activating system (RAS).1 The cerebral cortex is the outermost layer covering the cerebrum and plays a key role in numerous functions including memory, attention, awareness, language, thought and consciousness. RAS is located within the brainstem in a tight association with the reticular formation (RF) and is composed of two tracts, the ascending and descending tract. The ascending tract is principally comprised of acetylcholine-producing neurons, which focus on arousal sending neuronal signals through the RF, then the thalamus and finally the cerebral cortex. The descending tract feeds into the reticulospinal tract, which acts on motor neurons mainly influencing movement and postural control. Basically RAS coordinates the arousal signal and the cerebral cortex acts upon it.

However, on a biological level simply defining unconsciousness, and indirectly a coma, as “the absence of consciousness” does little to facilitate a treatment. There are different gradients of unconsciousness between blows to the head, focal deficits (blindsight), epilepsy, chloroform and other chemical exposure (like anesthesia) and comas/vegetative states.2 Some believe that comas are an emergency response by the body to brain injury to create a better therapeutic environment for self-recovery. Within the context of this theory any damage that is not permanent should eventually be repaired and increase the probability of a return of consciousness.

The general biological methodology of a coma is that a form of injury damages or kills a certain number of neurons, which reduces their ability to send action potentials to other neurons within the range of their synapse. Without consistent action potential activation the otherwise healthy neurons that previously bound neurotransmitters released from these damaged neurons down-regulate their dendritic and post-synaptic receptors limiting their ability to produce action potentials creating a negative feedback across entire networks of neurons. Natural recovery is thought to occur as the damaged neurons repair themselves and once again start sending action potentials (remember that these neurons are essential for consciousness, so consistent action potential generation is the norm) causing adjacent neurons to up-regulate their receptors “rebooting” the previously lost network. The problem, even if this belief is correct, is that there is no timeline for identifying when that recovery will be completed.

In order to achieve an accurate and consistent assessment of the possibility an individual will regain consciousness from an unconscious state (i.e. maximize treatment expectations) each general stage of unconsciousness must be identified. Consciousness itself is divided into two main features: arousal and awareness with arousal incorporating wakefulness and awareness incorporating acknowledgement of environment and oneself.3,4 Note that arousal is a necessary condition for awareness. For the purpose of this discussion four states will be identified: coma, vegetative state, minimum conscious state (MCS) and locked-in syndrome. Brain death is not considered because there is no reasonable and consistent path to recovery.

A coma is principally defined as the absence of arousal, thus also the lack of awareness and the lack of consciousness. In a coma the patient is unresponsive unable to open his/her eyes. Stimulation does not produce spontaneous periods of arousal.3 A coma requires at least one hour of arousal absence to separate it from concussion or syncope (fainting). Fortunately most individuals tend to move beyond a coma state into either a vegetative state or MCS, but after this progression further advancement is less certain.

A vegetative state is defined as sporadic, yet existing arousal with a complete lack of awareness. The term “vegetative” is typically defined as “living merely a physical life devoid of intellectual activity or social intercourse”.5 This state can be acute, persistent or permanent where a persistent vegetative state is one that is prolonged for at least 1 month after brain damage be it acute traumatic or non-traumatic.6 Not surprisingly permanent vegetative states are believed to be irreversible and require at least 3 months after a non-traumatic brain injury or 12 months after a traumatic one for such classification.

A MCS was created as a form of middle ground between full consciousness and a vegetative state, thus it is defined as an individual who has consistent arousal, but inconsistent awareness. Inconsistent awareness is defined as the temporary ability to follow simple commands, gesture or verbally reply “yes or no”, engage in intelligible speech, or produce purposeful behavior.3 Not surprisingly individuals in a MCS have a much higher probability of returning to full consciousness versus individuals in a vegetative state.

Finally locked-in syndrome is defined through sustained arousal and eye opening with awareness of the environment, but the inability to verbally communicate that awareness due to a form of muscle paralysis. Usually communication with other parties is limited to blinking or rarely appendage movements. Typically locked-in syndrome, unlike vegetative states and MCS, originate from neurological damage to the lower portion of the brain versus upper portions of the brain.3 For example one common method of occurrence is derived from quadriplegia and anarthria due to the disruption of corticospinal and corticobulbar pathways.7 Fortunately locked-in syndrome is easy to diagnose, but there is no real treatment.

Initial assessment of the type of lack of consciousness involves the observation of spontaneous exhibited actions as well as responses to vocal and painful stimuli commonly known as AVPU (alert, vocal stimuli, painful stimuli and unresponsive) scale. However, distinguishing between vegetative and a MCS is the real importance of coma evaluation because it is the difference between these two states that largely determines whether or not one should expect the patient to recover using current treatments. Unfortunately, but not surprisingly, these specific elements of voluntary and reactionary behavior can be easily missed or inappropriately linked or dismissed to consciousness making differentiation between different states tricky. Some previously studies indicate that 37-43% of patients diagnosed with the vegetative state later manifested goal-directed behaviors that could be interpreted as a MCS state.8-10

The Glasgow Coma Scale (GCS) is the most widely used method for diagnosing the type of coma state. The GCS defines severity through visual cues like observing the oculocephalic reflex to test the integrity of the brainstem through witnessing opposing movement between a patient’s eyes and their head.11 If both eyes fail to move in the opposite direction (i.e. head turns left eyes move right) then there is more than likely some damage to the affected side. Caloric reflex tests also produce insight to cortical and brainstem function where eye deviation towards an ear that is injected with cold water is anticipated. If no direct eye movement occurs a high probability exists for brainstem damage and no real probability for recovery.12 For example one study identified 47 of 111 patients with at least 1 absent brainstem reflex (pupillary light responses, corneal reflexes, or oculocephalic reflex) where only 2 eventually had a significant improvement over time.12,13

While GCS is popular some believe that there are better evaluation scales like Full Outline of UnResponsiveness (FOUR), Wessex Head Injury Matrix (WHIM) or Coma Recovery Scale-Revised (CRS-R).14 FOUR focuses on detecting and distinguishing between vegetative state, locked-in syndrome, MCS and brain death through the use of a 17-point scale characterizing motor response, eye response, breathing and brainstem reflexes.15-17 The chief strength of FOUR is that it can be applied to patients with endotracheal tubes where GCS cannot. WHIM focuses on the empirically derived sequence of recovery through a 62-point scale among 6 different categories (communication, attention, social behavior, concentration, visual awareness, and cognition) and can effectively distinguish between different awareness levels from vegetative state, MCS and partial recovery.14,18

CRS-R focuses exclusively on vegetative state and MCS and the prospects of transitioning between those states by evaluating 29 hierarchical items categorized in auditory, visual, oromotor/verbal, communication, motor, and arousal.19,20 Some believe that the statistical nature of CRS-R makes it the superior evaluation scale because score summation among the 29 criteria items can be used to track changes in consciousness over time (i.e. linear estimates of ability over time).

However, like GCS these other evaluation scales have their own drawbacks. One of the biggest drawbacks for CRS-R is its limited diagnostic utility due to its lack of diagnostic criteria.11,21 Basically CRS-R develops a diagnosis directly from the rating system. WHIM seems to have a problem measuring recovery as its progression via WHIM is probabilistic and lacking in precision.14 FOUR and GCS have problems measuring the importance of visual fixation.14 This mischaracterization of visual fixation can lead to a misdiagnosis rate of 24% for FOUR and 38% for GCS respectively, typically defining a patient as having a vegetative state versus MCS.22 Elements surrounding the mischaracterization of visual cues in general seem to be the factor that produces the most misdiagnosis.23

It is also widely regarded that recovery from unconsciousness is extremely unlikely in the absence of pupillary light responses, corneal reflexes or bilaterially absent cortical N20 responses 72 hours after unconsciousness.12 Absence of somatosensory-evoked potentials (SEP) after CPR is also a reliable predictor for negative coma outcomes.24,25 A little more controversial is that some believe that high (> 33 ug/liter) neuron-specific enolase (NSE) serum levels also effectively predict low recovery probabilities, but this correlation is questionable in its significance as recovery has been seen in patients with 90+ ug/liter values.26,27 The debate involving the prediction reliability of NSE serum levels is further clouded by the lack of a standard measurement methodology (different laboratories use different methods to determine NSE levels) and outside factors like hemolysis, which increases NSE levels, but does not affect brain function.28,29

One of the problems with evaluating the reliability of biological tests or even the aforementioned scales is the concept of “self-fulfilling prophecy”. For a number of individuals there is a subconscious intent to restrict treatment for patients with characteristics that indicate a low recovery probability, thereby creating a positive feedback loop that further lowers their ability to recover. This problem is compounded by the double-edged sword of experimental testing between required resources and the significance of the result.

For a study to draw significant conclusions there needs to be a large enough number of patients in order to account for outliers; however, the more patients that are enrolled in the study increases the resources required and the overall costs of the study both in manpower and money. Coma studies also have the problem of a lack of reproducibility due to the unique nature behind the origins of the coma both in the event(s) leading to their loss of consciousness and the biological changes that produced it. Overall the best hope is to simply conduct double blind studies separating those doing the initial and future probability evaluations from those applying the actual treatments.

Not surprisingly the advent of modern technology has lead to the use of imaging modalities to attempt to evaluate unconsciousness on a more tiered level. The two most popular strategies to measure consciousness, both in conscious and unconscious patients, are functional magnetic resonance imaging (fMRI) and electro-encephalography (EEG)/magneto-encephalography (MEG).30 Note that some researchers produce a wSMI, which is an analysis technique to determine the shared information between multiple, usually two, EEG signals.31 Both EEG and fMRI information is typically compiled during visual (usually with a bright light), auditory or pain stimulation as well as command following instructions, all of which are designed to produce strong conscious processing reactions. Event-related potentials (ERPs) can also provide insight into improper brain function as they have short latency periods typically reflect activation in low-level sensory receptive structures of the brain.34

Not surprisingly an increasing wSMI (greater synchrony between EEGs) is directly proportional to an increasing probability for coma recovery.30 Increases across centroposterior areas and across medium and long interchannel distances appear especially predictive.31 Another advantage of wSMI over EEGs alone is the comparison reduces the probability of common source artifacts that could create erroneous conclusions about conscious standing.30 EEGs are typically favored versus fMRI due to cost and required procedure.35,36

The advancement of modern imaging technology has provided improvements in navigating the nuances of characterizing a patient as either in a vegetative state or a MCS in that across various studies anywhere from 24%-33% of patients that were originally classified in a vegetative state were reclassified as being in a MCS after EEG analysis.30,35 However, whether or not this new diagnosis was due to missed behavior signs signifying consciousness or a secondary VS subset where neuronal patterns change before outward behavior changes is unclear. This secondary explanation does make sense because neuronal plasticity leads to brain repair from traumatic damage, which would manifest internally before reestablishing external conscious behaviors.
Overall both the inclusion of behavior measures as well as neuroimaging will increase diagnostic accuracy and increase successful treatment probability.

One of the possibly tricky issues surrounding the evaluation of potential conscious signals is that subconscious/non-conscious processing is more advanced than historically thought. For example the brain can subconsciously recognize certain abstractions in pictures, words and faces,37,38 interpret the relationship between similar words,39,40 and the social context of certain objects like money.41-43 There are even questions regarding whether long-distance synchrony can be produced between prefrontal and occipital cortex through long-term potentiation under unconscious conditions.44,45 Fortunately these subconscious triggers rarely manifest into actionable streams, so while subconscious activity can produce behavior priming and small levels of activity in certain networks the rate of their existence is ephemeral. Therefore, despite these concerns, attributing general consciousness cues to conscious brain activity in a currently unactionable state appears more appropriate than attributing these signals to subconscious brain activity.

Another question when using neuroimaging to diagnosis a state of unconsciousness is when it is ideal to measure the “signal of consciousness”. There is a question to whether or not it is best to focus on early or late neuronal responses to sensory stimulation; i.e. how long does it take before the brain produces a conscious response and is everything else signal chatter?46-50 This question is largely contingent on if conscious action can emerge solely from regional reverberating activity and can skip integration or processing. This concern becomes somewhat academic because neuroimaging a patient in a coma-like state typically collects numerous samples to accurately determine whether or not consciousness was demonstrated; therefore, checking late signals should be preferred due to the belief that a majority of conscious thought does require integration. Also integration is essential for consistency of awareness and significant prospects for recovery.

As previously alluded to when determining an existing conscious state the most important distinction is between a vegetative state and a MCS. Both states demonstrate a similar form of preserved arousal, but MCS patients have an additional layer of intentional behavior associated awareness accompanying this arousal. The problem is whether this intentional behavior is absent or the patient is unable to communicate it to the testers. fMRI data has detected blood flow patterns characteristic of consciousness in some vegetative patients.35,36 Both stand-alone EEG and wSMI have also produced certain patterns characterizing consciousness in vegetative patients.51,52 Taking consideration of the above concern regarding unconscious processing, these results could imply that there needs to be an intermediate stage between vegetative and MCS. However, even if this intermediate stage does exist the question is what does it change regarding treatment and conscious awareness?

Another characteristic feature that is used to distinguish vegetative and MCS patients is an EEG of MCS patients typically have increased alpha (at parietal and occipital sources) and theta wave number and a reduced delta wave frequency.30,53 Alpha waves are neural oscillations at a frequency between 7.5 to 12.5 Hz. They originate from the occipital lobe, or possibly the thalamus, when a subject is awake, but resting with closed eyes. Alpha waves are reduced when the subject has open eyes or is asleep. Biologically during alpha wave activity it appears that areas of the cortex not in use are inhibited and there is a non-visual network coordination and communication.54 A second form of alpha wave occurs during REM sleep originating from the frontal lobe area of the brain and has a generally unknown influence, but is thought to have an inverse relationship to REM sleep pressure.54

Delta waves are neural oscillations typically at a frequency between 0 to 4 Hz although some narrow that range to between 0.5 to 2 Hz. They are the slowest waves, but have the highest amplitude and are a common occurrence during deep stages 3 and 4 of sleep (a.k.a. slow-wave sleep (SWS)). Delta waves also indicate an unconscious state with an enhancement of information iteration, which is why this state is thought to increase the probability that declarative and explicit memories are formed.

Theta waves are neural oscillations at a frequency between 4 to 7 Hz. There are two types of theta waves: hippocampal and cortical. Hippocampal are more common to non-human mammals while cortical are more common to humans. Hippocampal theta waves occur through the medial septal area and flow to both the hippocampus and neocortex.55 These waves are related to learning and memory formation and could be related to arousal, sensorimotor processing or even environmental position.56

Interestingly most theta waves involve GABAergic or glutaminergic signals to drive inhibition and excitation versus cholinergic signals.57 Cortical theta waves are common in young children, but lessen in frequency and potency with age occurring later only during meditative or drowsy states. Theta frequencies are especially important as they are thought to mediate a serial stream of consciousness from the fronto-parietal networks.58-60 For a vegetative state these changes are not surprising as increases in low-frequency oscillations like delta waves are classical elements of deep sleep or coma.

One of the key newer elements in judging coma recovery probability is the influence of the posterior cingulated cortex (PCC). The PCC is the central node in the default mode network (DMN) model and along with the precuneus appears to govern wakefulness and awareness, especially relative to anesthetized and various coma-like states.58 Correlation of mesioparietal activity occurs in the PCC as well as pain and episodic memory retrieval.58,59,61 The DMN is quick to activate and deactivate when thoughts are internally directed

Note that the DMN is the active regions of the brain during periods that lack specific attention or focus (i.e. daydreaming, etc.). Its typical characteristic is coherent neuronal oscillations under 0.1 Hz. DMN may also drive self-referential thought and is at optimal function when an individual’s eyes are closed.63 This self-referential thought can manifest in spontaneous inspiration that embodies creativity. It also could have some connection to tying an emotion to a given memory or event. However, the DMN is criticized for its inability to effectively explain the large amounts of processing that occur in a “resting” brain.62

Not surprisingly as one of the critical elements to wakefulness the PCC is one of the most metabolically active regions in the brain with blood flow and consumption rates significantly higher than other brain regions.63 Aside from driving consciousness the PCC is also important to spatial memory, autobiographical memory, configural learning and maintenance of discriminative avoidance learning.31 There is some debate on the role of PCC in triggering internal and external attention and thereby controlling arousal and focus making the PCC a dynamic network over a static brain element.63

A strong associated activation element with the PCC is the precuneus, which is located near the two cerebral hemispheres between the somatosensory cortex and forward of the cuneus. Historically little information has been collected on the precuneus because of its position in the brain, in part it was previously thought to be a homogeneous structure, but now is known to have three subdivisions.64 The precuneus in posterior areas aids episodic and source memory while a second subdivision aids visuospatial imagery. This aid has sometimes been described as “providing context clues” for the hippocampus in memory retrieval.64

With regards to consciousness, similar to the PCC, the precuneus has much higher average metabolic levels and is “deactivated” or compromised during SWS, loss of conscious events during epilepsy, specific brain lesions and vegetative states.63,64 One means to drive rapid activation of the precuneus is to induced language learning through brief flashes attaining supraliminal instead of subliminal characterization.

The idea that the PCC and precuneus are focal points of importance for consciousness also makes sense within the context of corticocortical and thalamocortical degradation, including among medium spiny neurons,65 for these two areas have been functionally linked to thalamus nuclei.66,67 This influence on the synchronization of these cortical networks also appears to correlate to global workspace theory (GWT).68

GWT is a theory designed to describe how the conscious and unconscious mind interact to produce cognitive thought and was first applied to the concept of working memory. Most analogize GWT with a play at a theater where the active consciousness is the actor currently speaking (i.e. the “spotlight” of attention, which has limited reach/range)while other actors compete for the spotlight.69 The seating in the theater along with the attending audience represents the unconscious mind, aware of what is consciously occurring, but not providing any direct influence to the behavior of the actors and of great capacity. Finally the non-actors like the director, stage hands, etc. act like executive processes in that they influence actor behavior, but are not directly witnessed.69 One of the major boons of GWT is that it successfully models certain characteristics of consciousness like managing novel situations, working with capacity limits, and incorporating unconscious processes to conscious processes, a characteristic seen in brain elements like how the dorsal cortical stream influences the visual system.69

This model also applies a competition-cooperation parameter to form a “stream of consciousness” where if two elements are received within 100 ms of each other they will be sensory cooperative vs. being sensory competitive, i.e. when the video and audio of a movie are in or out of synch. Alpha, theta and gamma brain waves correspond to this 100 ms threshold whereas ERPs are in the 200-300 ms domain.70 Most argue that the “stream of consciousness” is not an actual stream with events falling perfectly in place with one another, but instead are “edited” together by conscious and unconscious processes similar to how a movie is put together after various scenes and takes. Overall the chief problem with the GWT is that it does not actually explain consciousness, but instead places boundary conditions on theories that do attempt to explain consciousness.71

One of the initial strategies to increase the probability of recovering from a coma, regardless of its specific classification, involves application of mild hypothermia after patient stabilization, especially those suffering from loss of consciousness related to cardiac arrest. The patient’s body is cooled intravascularly at 32-34 degrees C for 24 hours, which typically lowers core body temperature by 2-3 degrees C.12 Fortunately this strategy has become commonplace for many patients, thus reducing the worst-case scenarios for most individuals who lose consciousness in the long-term.72,73 While the specifics of why hypothermia is a successful deterrent of increased future neuronal damage is unclear, there are theories, which involve the reduction of both electrophysiologic and homeostatic energy use,74 reduction of extracellular concentration of excitatory neurotransmitters like glutamate,75 or the reduction of the post-traumatic inflammatory response.76,77

It must be noted that even when individuals recover from comas or coma-like conditions there will be a transition period where the individual will have reduced cognitive and physical ability. Most individuals who recover from comas required physical therapy, speech therapy and some psychological counseling before they are able to continue with their normal lives, that is assuming that they are able to recover fully at all.

Regarding the treatment of any neurological condition some will note the potential of Deep Brain Stimulation (DBS). DBS involves attaching electrodes to specific portions of the brain and applying an electric current in an attempt to initiate excitatory action potentials, typically in the forebrain neurons. It has already drawn interest in treating degenerative neurological conditions like Parkinson’s and dystonia along with psychiatric disorders like depression, obsessive compulsive disorder and various additions.78 The one major general drawback to DBS is that it is an invasive procedure that comes with standard surgical risks and potential complications.

With regards to the ability of DBS to treat coma and coma-like patients the results are not overwhelmingly positive. Most DBS successes are single isolated MCS patients with no positive correlative trend for improved recovery time.65 While DBS does produce behavioral arousal including widening of the palpebral fissure, increased heart rate and blood pressure along with scattered fragmentary movements these improvements are not sustained.65,79 In vegetative state patients there is almost no positive benefit as DBS triggers a local and slow response that does not facilitate synchronization.

Some may argue that the Yamamoto 2010 study demonstrated a significant impact of DBS on vegetative state patients. However, this study appeared to have some serious sampling bias, especially in the old control group where none of the untreated patients recovered from their vegetative states, which mitigates its usefulness.65,80 The second major problem for the credibility of this study is that a number of the “biggest gainers” from the DBS actually had MCS at the beginning of the DBS treatment.81

The reason reclassification of vegetative state patients as MCS patients is a big concern is that the probability that an individual spontaneously regains consciousness from a MCS is thought to be much higher than a vegetative state. For example about 80% of patients in a MCS after 6 months recover spontaneously after 10 months.82,83 Therefore, there is confusion regarding whether or not the patients naturally recovered or recovered due to DBS.

To be fair populating and controlling a significant study to determine improvements in recovery times for coma patients is difficult. Currently there has been only one such clinical trial involving 200 patients and 200 controls spread over 11 participating institutions and 7 years of data collection.65,84 However, currently there is no evidence that DBS facilitates a significant increased probability of recovery for coma patients that are not already significantly through the process of recovery.65

In addition to DBS, there has been exploration regarding pharmaceutical agents for increasing the probability of coma recovery that has produced inconsistent results from L-dopa, Amantadine, and Zolpidem (Ambient).65,84,85 Amantadine is a mixture of a dopaminergic agonist and NMDA antagonist, which seems to have a strong influence on medium spiny neurons triggering greater action potential firing, which then leads to greater mesial cortical neuron firing stimulating conscious activation.65,84 L-dopa is the precursor to the neurotransmitter dopamine, which supposedly acts on neurons in the striatum and frontal cortex to stimulate action potentials. Zolpidem is an alpha-subtype selective positive allosteric modulator of GABA-A receptors. This pathway interaction seems perplexing to why it could help coma patients, but there is a thought that increased GABA-A activity can inhibit the inhibition of thalamocortical outflow, which can increase awakefulness.85 However, none of these methods appear to be consistent enough to be an effective treatment for coma.

As noted above with DBS, one of the major treatments for individuals in a coma or coma-like condition is brain stimulation. Interestingly enough there is significant evidence that focus/attention can be produced even in an unconscious individual.86,87 One common experiment demonstrating this point is orthogonally manipulating visibility and attention through the use of masked images at the edge of conscious perception (some conscious other subconsciously presented).88 From these types of experiments it was theorized that attention over visibility modulated early occipital activity where visibility over attention modulated late temporal and parieto-frontal activity.88 However, there is a changing structure to when the brain reacts to the external stimuli and when the individual becomes conscious of it.89,90

In addition it is recognized that conscious realization of a stimulus requires exceeding a threshold that separates subliminal and supraliminal processing. Exceeding this threshold demands the consistent accumulation of sensory evidence. However, the brain does have a limited capacity to process external stimuli, which is one of the reasons why multi-tasking produces a significant reduction in efficiency between the applied events. Conscious processing of one element creates a bottleneck resulting in either significant reduction of secondary element processing (psychological refractory period (PRP)) or inhibition of the origin of the secondary element (attentional blink or inattentive blindness).91 There is also competition between different stimuli during processing which can make it less likely that any conscious realization occurs.

Finally the adult brain has significant plasticity to allow for repair, but must be primed to truly maximize the efficiency of that repair. This priming element should explain why a number of individuals do not recover from coma states. Similar to the common psychological adage of “use it or lose it” coma/coma-like patients need to “use it” to drive repair recovery. At a biological level this concept involves the activation of positive feedback systems for given neurological pathways, which reinforce certain neurological thoughts/actions versus the termination of neurological pathways that are not utilized or oppose these thoughts/actions. Taking all of these elements into account and tying it to what is known about the PCC and precuneus and their roles in consciousness another potential stimulation strategy emerges.

The first step is to initiate a visual signal cascade to trigger arousal and focus in the patient. This initiation could trigger through the use of a stroboscope (preferable) or general strobe light, which uses high frequency light pulses at various phases and speeds to produce excitatory reactions in the visual processing regions of the brain. Whether or not sounds should also be included in the stroboscope application is questionable. On one hand it can be argued that the addition of sounds should increase arousal probability and recognition of changes in the environment. On the other hand the addition of sound may create some connective confusion, as noted above, and limit the overall efficiency of producing arousal synchronization.

The second step is to request the patient visualize a significant emotional moment in the past. One of the key operational characteristics of the PCC is that it acts as a central integration center for episodic memory, especially those with emotional overtones. Asking the patient to recall, through visualization, an emotional memory should facilitate significant activation of the PCC and trigger the initialization of consciousness recollection, which could initiate further downstream elements of consciousness.

A third optional step would be to ask the patient to visualize themselves on a field running to catch a football or baseball. This visualization should trigger visuospatial areas of the brain, which would aid in triggering precuneus activity. After a seven-minute period (starting with step 1: 2 minutes, step 2: 3 minutes, step 3: 2 minutes), the stimulation is ended and repeated again multiple times after a ten-minute break. The exact amount is unknown but for the moment three times in an hour period over a 24-hour period seems intuitively appropriate.

The above treatment is simply thought to be a potential new therapy option based on understanding the general biological elements associated with how the body retains remedial consciousness. Currently there is no empirical evidence to support the capability of the proposed theory to aid coma recovery beyond the visual activation elements associated with a stroboscope. However, it stands to reason that testing this method should be rather simple due to the lack of known negative elements like invasive surgery or pharmaceutical side effects. One possible side effect could be an increased probability to invoke a seizure due to the action of the stroboscope, but this possibility appears incredibly unlikely. Overall there are certainly no guarantees that this new proposed method will develop into an effective treatment for vegetative state and MCS patients, but there appears to be little reason not to attempt to study its effectiveness.

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