Biggest extinction in Earth’s history caused by global warming—and how it could happen again

Penn JL et al. Temperature-dependent hypoxia explains biogeography and severity of end-Permian marine mass extinction. Science, December 2018.

Some 252 million years ago, long before dinosaurs, the vast majority of species on Earth were wiped out in the “Great Dying,” the worst mass extinction in our planet’s history. Up to 96% of all marine species and 70% of land animals were killed off during this event. Scientists have been trying to find the cause for this catastrophic event, which marked the end of the Permian period. One study suggested that a type of microbe spouted large amounts of methane into the atmosphere. Other studies suggested the event was triggered by a series of volcanic eruptions that released deadly amount of carbon dioxide into the air and led to cataclysmic ocean acidification. A new research study now claims that the Great Dying was primarily as a result of rapidly increasing temperatures. The researchers examined the marine fossil records and simulated the climate conditions to observe the effects of rising temperatures 252 million years ago. Researchers first ran a climate model with Earth’s configuration during the Permian period, when the tropical ocean temperatures at the surface had reached some 10 degrees Celsius (50 degrees Fahrenheit) higher. The model then reproduced dramatic changes in the oceans; oceans lost about 80 percent of their oxygen and about half the oceans’ seafloor became completely oxygen-free. To investigate the effects of these paleoclimate changes on marine species, the researchers then analyzed the varying oxygen and temperature sensitivities of 61 modern marine species including crustaceans, fish, shellfish, corals and sharks. Their calculations predicted that many marine organisms went extinct under these conditions, especially the organisms that lived far from the tropics were most sensitive to oxygen levels and they were nearly completely wiped out. To test this prediction, researchers analyzed late-Permian fossil distributions from the Paleoceanography Database and confirmed that species far from the equator suffered most during the event. The agreement between the simulations and fossils strongly suggests that climate warming and oxygen loss was a primary cause of the extinction. By 2100, warming in the upper ocean is projected to approach 20 percent of warming in the late Permian, and by the year 2300 it will reach between 35 and 50 percent. This study highlights the potential for a mass extinction arising from a similar mechanism under anthropogenic climate change. It is also a clear warning that Earth is on the path to another devastating mass extinction. According to experts, Earth could already be undergoing a sixth mass extinction that would kill off most animal and plant species. The International Union for the Conservation of Nature predicts that 99.9% of critically endangered species and 67% of endangered species will be lost within the next 100 years.

New target for therapeutic brain stimulation to treat depression found

Rao VR et al. Direct Electrical Stimulation of Lateral Orbitofrontal Cortex Acutely Improves Mood in Individuals with Symptoms of Depression. Current Biology, November 2018.

Researchers have finally found an effective target in the brain for electrical stimulation to improve mood in people suffering from depression. Stimulation of a brain region called the lateral orbitofrontal cortex (OFC) reliably produced acute improvement in mood in patients who suffered from depression. In a recent study, researchers studied 25 patients with epilepsy who had electrodes placed in the brain for medical reasons to locate the origin of their seizures. Many of those patients also suffered from depression, which is often comorbid with epilepsy. With the patients’ consent, researchers took advantage of those electrodes to deliver small electrical pulses to areas of the brain thought to be involved in regulating mood. The researchers focused their attention and the electrical stimulation on the OFC, which is a key hub for mood-related circuitry. Moreover, they specifically induced a pattern of activity in brain regions connected to OFC that was similar to patterns seen when patients naturally experienced positive mood states. The researchers applied these stimulation regimes while collecting verbal mood reports and questionnaire scores. Analyses of these reports revealed that unilateral stimulation of the lateral OFC produced acute, dose-dependent mood-state improvement in subjects with moderate-to-severe baseline depression. There is still substantial work remains to be completed before the deep brain stimulation (DBS) treatments could enter routine clinical practice. One major challenge in this study is to see whether stimulation of OFC produces durable improvement in mood over longer periods of time. Biomedical engineers hope to develop a medical device for patients with treatment-resistant mood disorders that can monitor brain activity in OFC and stimulate only when needed to keep that activity within a healthy range. Ultimately, it would be ideal if activity in mood-related brain circuits could be normalized indefinitely without patients needing to do anything.

How screen time can disrupt sleep

Mure LS et al. Sustained Melanopsin Photoresponse Is Supported by Specific Roles of β-Arrestin 1 and 2 in Deactivation and Regeneration of Photopigment. Cell Reports, 2018

For most of us, the time spent staring at screens on computers, phones and tablets adds up to many hours in a day and can often disrupt sleep. In a recent work, researchers now have pinpointed how certain cells in the eye process ambient light and reset our internal clocks, the daily cycles of physiological processes known as the circadian rhythm. When these cells are exposed to artificial light late into the night, our internal clocks can get confused, resulting in a host of health issues. A protein called melanopsin in these light-sensitive cells helps them process ambient light. Prolonged exposure to light causes melanopsin to regenerate and continuous regeneration of melanopsin triggers signals to the brain that inform it about ambient light conditions. The brain then uses this information to regulate sleep, alertness, and consciousness. In this study, the researchers turned on the production of melanopsin in retinal cells in mice and found that some of these cells are able to sustain light responses, but others lose sensitivity. Further investigations found that proteins called beta arrestin-1 and beta arrestin-2 help keep the melanopsin sensitive when exposed to light. One arrestin does its conventional job of arresting the response, and the other helps the melanopsin protein reload its retinal light-sensing co-factor. When these two steps are done in quick succession, the cell appears to respond continuously to light. This research uncovers the mechanisms behind how cells being exposed to artificial light confuses the internal body clock, and the ability to regulate sleep. It is hoped that this discovery could lead to new targets that could counter the impact of artificial light, for example by finding ways to influence melanopsin to reset the internal clock. This could lead to new treatments for insomnia, jet lag, and migraines.

The human ear and hearing

The human ear can be divided into several functional sections: the outer ear, the middle ear, the inner ear, and the auditory nerve. Sound goes through a series of changes as it travels through these sections until reaching the brain. The outer ear picks up sound pressure waves, amplifies them and then converts them into mechanical vibrations on the ear drum, which is connected to a series of small bones in the middle ear. These small bones further amplify or diminish the mechanical vibrations in the ear drum and transfer them to the cochlea, a snail-shaped cavity filled with fluid which is located in the inner ear. Change in fluid pressure caused by vibrations within the cochlea lead to changes in the flexible membrane, called the basilar membrane. These changes contain information about the frequency and strength of the sound that has entered the ear. Attached to the basilar membrane are mechanical receptor cells, called hair cells, which are bent according to the deflections of the basilar membrane.The hair cells have hair-like structures. The bending of these hairs assists the release of an electrochemical substance that causes neurons to send electrical signals to the brainstem through the auditory nerve. These signals are in the form of a message (or a code) that the brain understands.

Cochlear Implant (CI) devices

If there is a broken link in any part of the auditory pathway, the brain does not receive any coded signals, and hearing impairment occurs. If a large number of hair cells or auditory neurons in the cochlea have been damaged, then the person is diagnosed as profoundly deaf. The hair cells can be damaged by certain diseases (e.g., meningitis, Meniere’s disease), by congenital disorders, by certain drug treatments, or by other causes. One negative outcome of damaged hair cells is that they can subsequently lead to the degeneration of adjacent auditory neurons. Research has indicated that the most common cause of deafness is the loss of hair cells (>95%) rather than the loss of auditory neurons. This has encouraged scientists to try implanting a device inside the iner ear or cochlea, bypassing the normal hearing mechanism of the ear, to stimulate the remaining auditory neurons directly through electrical signals. These are called Cochlear Implant (CI) devices, which can restore partial hearing in profoundly deaf people . A standard CI system, shown in Figure 1, composes of and performs the following functions: a microphone picks up sound pressure waves and converts these into electrical signals. The signals are sent to the speech processor that is worn by the patient. The speech processor analyzes and encodes these sound signals, sending them back to the external pick-up coil . After passing through a wireless radio link that lies between the external and implanted coils and an implanted electronic devise, coded signals are sent to the implanted array of electrodes in the cochlea to electrically stimulate the remaining auditory neurons , and the brain receives what it interprets to be sound.

Electrical stimulation of the ear, or CI research, can be traced back to the 1800s. The Italian scientist Alessandro Volta used a battery as a research instrument to demonstrate that electric stimulation could result in a number of human sensations . After connecting a 50- volt battery to his ears, he noted that “…at the moment when the circuit was completed, I received a shock in the head, and some moments after I began to hear a sound, or rather noise in the ears, which I cannot well define: it was a kind of crackling with shocks, as if some paste or tenacious matter had been boiling…”. That electric stimulation of the auditory nerve provides hearing sensation in deaf people was reported more than 100 years after Volta . Electric stimulation in two deaf patients resulting in hearing was reported in 1957. These successes resulted in intensive research into helping deaf people hear in the 1960s and 1970s. One of the early successful single-channel CI devices was developed in the early 1970’s (3MCorp/House) and became the first commercially available CI device approved in the United States in 1984. The University of Utah developed a six electrode implant called the Ineraid or the Symbion device in the early 1990s. It was followed by other devices in Europe, the United States, and Australia.

The present status of Cochlear Implants

Today, around 10% of the population in developed countries suffers from hearing impairment. At present, the number of CI users has reached more than 100,000 worldwide, and is still growing rapidly. Functionally, CI has evolved from the single-electrode device that was used as an aid for lip-reading and

sound awareness to a modern, multielectrode device that can allow an average user to talk on the telephone. Even though significant technological progress has been achieved in the last 50 years, there are still many mysteries about the human hearing process and the parts of the ear. Here, we will compare some aspects of the healthy human ear and CI devices, looking to the future. The human ear operates over a range of sound pressures (its dynamic range) which is greater than one million to one (120dB), with as many as 200 discrete steps in the range. In contrast, today’s CI devices typically provide a dynamic range of three to one (10dB) to ten to one (20dB) with 20 discrete steps. This major difference is mainly due to the fact that the human ear is very adaptive in noisy environments, and is able to suppress noisy background, while picking up and processing appropriate sound signals for better perception. CIs do not differentiate between sounds, but amplify all sounds, which results in poor sound perception. Today, a typical multi-channel CI system uses 16 to 24 electrodes implanted in the cochlea with 8 to 22 signal processing channels. A potential shortcoming of having so many electrodes and channels in current CI technology is the electrical interference of electrodes during simultaneous electrode stimulation. These electrical interactions can disrupt the stimulus waveform prior to neural activity and degrade sound perception. The normal ear contains roughly 3,500 inner hair cells in the cochlea that are tuned to different frequencies from 20 to 20,000 Hz. They are connected to about 35,000 auditory nerves. Hair cells work as signal processing channels, yet each of the inner hair cells has also been wired in a sophisticated and little-understood fashion to 10-20 auditory nerve fibers that carry information to the central nervous system. Since they work in the chemical domain, they do not have the gross interference issues of CI electrodes. While good speech understanding has been achieved by users of modern multi-electrode CIs operating in quiet environments with 70–80% sentence recognition, allowing users to talk on the telephone, the CI devices do not discriminate between noise and the meaningful signals, only achieving speech understanding at between 70% and 80%, which falls to 10% or lower in noisy environments. It is a great challenge for CI users to appreciate music. Some CI listeners reported that they can enjoy music and are able to recognize melodies, but most described musicas sounding unpleasant and noisy, and performance could not be increased with current CI technology. CI users have difficulty in identifying differences in frequencies. Typically, they cannot discriminate any frequency difference for frequencies higher than 500 Hz, while the normal ear can hear up to 20,000 Hz with frequency discrimination between 2 to 3Hz at best. This gross difference is related to the issues surrounding signal processing strategies and electrodes of current CI systems. Predicting post-surgical performance based on presurgical conditions and tests of a CI candidate is still a problem for the physician. The cost of surgery is still high; in the United States, for example, a typical cost is between $40,000 and $75,000. Beyond these issues, the moral, cultural and ethical issues related to CIs are very complex. They are still debated, and are an important part of CI development in the world today. The hair cells in the human ear naturally deteriorate and die as we grow older. This process is typically sped up with exposure to loud noise. In common with all mammals, new hair cell generation in human ears stops right after the birth. However, in fish and amphibians, very similar cells are present and reproduce throughout life. Recently, it was found that hair cells of birds are repaired after being damaged by exposure to noise or ototoxic agents. It was also discovered that hair cells in the mammalian vestibular (balance) organ, very similar to those in the hearing system, can regenerate. These findings, along with other advancements in medical fields, lead to long-term research into different aids for hearing- impaired people. Despite the fact that hearing loss is usually permanent, scientists are optimistic that it may eventually be possible to reverse the damage in the ear by repairing or regenerating the sensory hair cells through gene therapy, stem cell transplantation, or ultimately by replacing the human cochlea with an artificial one. Today, Auditory Brainstem Implants are also being tried on humans for direct brainstem stimulation, bypassing the ears and the auditory nerves. Human beings and most animals on earth are born and equipped with a pair of ears for a good reason: having two ears enhances hearing and sound localization. Scientists are examining whether this is also true for deaf children who receive not one, but two CIs.

Conclusion

The sense of hearing is a gift for human beings which they hold dear and are grateful for, as much as for any of the other senses with which they have been equipped. It is important to strive to find cures for all kind of diseases, yet, more important than the cure is prevention of harm to our body and its amazing senses. Here, we have tried to open a small window onto human hearing, to examine how related impairments are being dealt with through cochlear implant (CI) devices, as well as looking at the issues related to these devices and the future directions of research for restoring hearing to deaf people. It is obvious that we have learned much about human hearing and ear in the past century; yet, this may well be just the tip of the iceberg.

References

1. S.U. Ay, F.-G. Zeng, B.J. Sheu, “ Hearing with bionic ear,” IEEE Circuits & Devices Magazine, Vol. 13, No. 3, pp.18-23, May 1997.

2. F.-G. Zeng, “Trends in cochlear implants,” Trends in Amplification, Vol. 8(1), pp.1-34, 2004.

3. A. Volta, “On the electricity excited by mere contact of conducting substances of different kinds,” Royal Soc. Philos.Trans., vol. 90, pp.403 431, 1800.

4. A.M. Andreev, G.V. Gersuni, A.A.Volokhov, “On the electrical excitability of the human ear: On the effect of alternating currents on the affected auditory apparatus,” Journal of Physiology USSR, Vol. 18, pp.250-265, 1935.

The discipline in which medicine and engineering truly meet and face new challenges is the field of “biomedical engineering,” an emerging discipline that is only a few decades old. In each sub-specialty of biomedical engineering, researchers study the human body, develop new materials and structures using engineering sciences, either as a treatment method for disease (e.g. artificial bone implants, artificial blood, vascular stents, cardiac valves, etc.) or to diagnose them (e.g. imaging methods and other diagnostic instruments in hospitals). Biomedical engineers face the incredible challenge of developing materials and devices that are compatible with biological systems and capable of working inside the human body to substitute bodily functions. Needless to say, the extreme complexity of the human body makes it impossible to mimic the original system or function of the organs in any way. However, even a poor replacement part or a functional improvement provides great benefit to the patients.

One of the most complex systems of the human body is the nervous system, which consists of the central area (the brain and the spinal cord) and the peripheral parts. The branch of biomedical engineering that deals with the nervous system is “neural engineering.” In this article, we will touch upon a specific subject in the broader area of neural engineering, that is, “neural prosthetics.”1 As the name implies, neural prosthetics is an area where engineering knowledge is utilized to treat neural disorders.

The building blocks of the nervous system are called “neurons.” Neurons generate electric pulses to communicate with each other. The fact that these electric pulses can be elicited by artificial means, i.e. by applying small electric currents to the neurons externally, forms the very foundation of the field of neural prosthetics. Neural engineers can input information into the nervous system by taking advantage of this phenomenon, called “neural stimulation.” Likewise, the information content of neuronal activity can be deciphered by recording the electrical pulses from the neurons and interpreting them according to neuronal function. This two way traffic, monitoring and controlling the neural activity, allows researchers in this field to develop methods of treatment for some sensory, motor, and psychological disorders.

Some of the most successful neural prosthetic applications have been in deep brain stimulation in Parkinson’s disease,

cochlear prosthesis in hearing impairment, bladder emptying and respiration in spinal cord injury, and vagus nerve (10th cranial nerve) stimulation in epilepsy and psychological depression. These are neural prostheses that are readily available as a treatment method for the given ailments. There is a whole host of others that are in the research and development phase. We will review a couple of examples.

In certain diseases of the inner ear hearing is lost as a result of damage to the hair cells inside the cochlea. In normal cochlea the sound information reaches these hair cells after traveling through the ear drum (tympanic membrane) and the structures of the middle ear, causing them to vibrate. This vibration of the hair cells is mechanically transported to the spiral ganglion cells that form the hearing (auditory) nerve. The hearing nerve carries the sound information to the brain in the form of electric pulses. The ganglion cells are healthy and functional even if the entire population of hair cells has been lost as a result of disease. Neural engineers take advantage of the fact that the spiral ganglion cells (which normally accept input from the hair cells) can be electrically stimulated, thus mimicking the function of the hair cells and producing the sensation of sound.2 During a simple surgical operation, the surgeon inserts an electrode into the ear canal which spirals into the lumen of the cochlea so that the sites where the electric current emits from the electrode are adjacent to the spiral ganglion cells (Figure 1). To summarize the principle of the operation; the audio signals are captured by a microphone, processed, converted into electric pulses (A in Figure 1), and transmitted to the implant over a transmitting antenna (B in Figure 1), or headpiece, held in place by magnets. The implant (C in Figure 1) applies the signals to the ganglion cells in the cochlea through tiny electrodes (D in Figure 1). The hearing nerve (auditory nerve) carries the sound information to the brain, where it is “heard.”

Even though the human spiral ganglion has tens of thousands of nerve cells that provide a rich sense of hearing, the cochlear implant, using only six stimulation contacts, can produce auditory perception with sufficient fidelity to enable a deaf individual to use an ordinary telephone.3 Individuals with cochlear implants can also improve their hearing with practice. Thousands of patients have been implanted with cochlear prostheses to date, including children.

The second neural prosthesis application we will review is the retinal prosthesis, which, unlike the cochlear implants, is still in the research phase. Retinitis pigmentosa and age-related macular degeneration both lead to photoreceptor degeneration in the eye and result in a significant visual deficit or blindness.4 A growing body of research supports the feasibility of replacing the function of the photoreceptors with an electronic device. 5–7 A retinal prosthesis is analogous to the cochlear implant in many ways. In a healthy retina, the photoreceptors initiate a neural signal in response to light. In a retinal prosthesis, electrical pulses are utilized to initiate a neural response in the remaining cells of the retina, the bipolar and ganglion cells. It is hypothesized that the perception of shapes and images will be possible through pattern stimulation of the retina. Initial results are encouraging, but the quality of vision that can be attained with this approach is still a question to be answered. A conceptual retinal prosthesis system is shown in Figure 2. The system consists of an external unit coupled to an implanted stimulator with a wireless link. A video camera in the external unit captures an image and converts it to digital data. The implanted unit receives the signal, recovers power and data from the signal, and generates the stimulating current. The stimulus pattern is applied to the retina via the electrode array, which contains distinct electrodes that interface at many locations on the retinal surface. Recent implants in human subjects suggest the feasibility of this approach where individuals attain perception of bright dots in the visual field called ‘phosphenes.’ Furthermore, blind subjects are able to perceive edges when a few of these bright dots are lined up in their visual field.

Figure 3: A conceptual diagram of a Brain-Computer Interface for high level spinal cord injury or patients with ‘locked-in syndrome’ (adapted from Wolpaw et al., see note 9). The recorded neural activity from the motor cortex is processed and converted into command signals to control, for instance, a wheelchair, or to generate electrical signals to activate hand muscles for grasping an object.

Both cochlear and retinal implants are sensory prostheses, i.e. aids for sensory impairments. Another family of neural prostheses deals with motor impairments. Severe motor disability results from high level spinal cord injuries (quadriplegia) where most of the body is paralyzed, sparing only some face, neck, and shoulder muscles. Quadriplegic individuals are in extreme need of a means to control their environment; they need to be in control of their wheelchairs, bed, the room temperature, lights, TV, etc. Because of the level of paralysis it is impossible for them to generate any control signal, except perhaps by sipping or puffing on the end of a tube, which produces a very poor control signal. In the case of a ‘locked-in syndrome’ the condition of the patient is even more serious, with only some functions remaining in the facial muscles. The term ‘brain-computer interface’ has been coined to refer to attempts whereby the motor output of the brain is recorded and interpreted to generate the control signals needed by these patients (Figure 3,9). The ultimate objective of this research will be accomplished when the patients are able to control anything they need to control in their environment, including a computer. The brain-computer interfaces vary in the invasiveness of the approach. The least invasive methods utilize the electroencephalogram (EEG) signals recorded from the scalp. Unfortunately, the signal quality is poor and only ‘on/off’ type of command signals can be generated using this method. In the most invasive, yet most successful applications, an array of electrodes is implanted directly into the motor cortex of the brain at a depth of a couple of millimeters. The recorded signals contain volitional information as the patient makes intentions to move their arms or legs. These signals can be controlled by the patient, and they can in turn be used to control their environment. The current level of success in this type of BCI allows the user to have three dimensional control of a robot arm. This is of invaluable benefit to a quadriplegic individual.

Concluding Remarks: Reflections on Divine Wisdom

Even the subtlest parts of the nervous system are extremely complex. Just to name a few examples, from the highest centers in the brain down to the skeletal muscles in a descending order; the neural circuits of the short-term memory in the hippocampus, fine motor control circuits of the cerebellum, central pattern generators in the spinal cord, and even the control of skeletal muscles in graceful movements of the limbs are impossible to reproduce by artificial means. The Seal of Divine Design is clearly visible in these neural systems, as they are far more complex, far more compact, and far more functionally efficient than any system engineered by mankind. If anything, the growing experience in neurosciences teaches us that the vertebrate nervous system is full of wonders of engineering design. Therefore, it is a great blessing to be a student of both neurosciences and engineering disciplines. This bestows neural engineers with a unique perspective to understand the beauty embroidered into the human nervous system and contemplate on the Divine Wisdom. In spiritual terms, we may think of the human nervous system as a window opening to the works of Divine Wisdom, with manifestations of His Beautiful Names at the brightest level. It is an overwhelming joy to be able to open this window a crack, once in a while, and take a little peek.

References

1. Wise, K.D. ‘Silicon microsystems for neuroscience and neural prostheses,’ IEEE Engineering in Medicine and Biology Society Magazine, vol. 25, no. 5, pp. 22- 29, Sept.-Oct., 2005.
2. G.E. Loeb, ‘Cochlear prosthetics,’ Annu. Rev. Neurosci., vol. 13, pp. 357–371, 1990.
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4. E.L. Berson, ‘Retinitis pigmentosa. The friedenwald lecture,’ Invest Ophthalmol. Vis .Sci., vol. 34, no. 5, pp. 1659–1676, Apr. 1993.
5. E. Zrenner, ‘Will retinal implants restore vision?,’ Science, vol. 295, no. 5557, pp. 1022–1025, Feb. 2002.
6. J.F. Rizzo III, J. Wyatt, J. Lowenstein, S. Kelly, and D. Shire, ‘Perceptual efficacy of electrical stimulation of human retina with a microelectrode array during short term surgical trials,’ Invest. Ophthalmol. Vis. Sci., vol. 44, no. 12, pp. 5362–5369, 2003.
7. M.S. Humayun, J. Weiland, G. Fujii, R.J. Greenberg, R. Williamson , J. Little, B. Mech, V. Cimmarusti, G. van Boemel, G. Dagnelie, and E. de Juan, Jr., ‘Visual perception in a blind subject with a chronic microelectronic retinal prosthesis,’ Vision Res., vol. 43, no. 24, pp. 2573–2581, 2003.
8. Weiland, J.D. and Humayun, M.S., ‘A biomimetric retinal stimulation array,’ IEEE Engineering in Medicine and Biology Society Magazine, vol. 25, no. 5, pp. 14-21, Sept.-Oct., 2005.
9. Wolpaw J.R. et al., ‘Brain-computer interfaces for communication and control,’ Clinical Neurophysiolology, vol. 113(6), pp. 767-791, 2002.