Christopher Nolan has always been fascinated by perception and memory, ideas that have defined his films since Following and Memento. With Inception, he’s made a fantastic action film rooted in the human subconscious, and though the technology and premise of the film are stuff of fancy, the story has plenty to teach viewers about the ways our brains really work. Some of the revelations may be old news to those who studied psychology in college, but there’s always more to learn about the fascinating and often unexplored world of dreams. Read on to discover what Inception can teach you about your brain. (Heads up: Plenty of plot spoilers to follow.)
1.Dreaming occurs only in very deep sleep: There are five stages of sleep, each one progressively deeper and stronger. Dreaming happens in the fifth and final stage, known as rapid eye movement (REM) sleep, which kicks in about an hour and a half after you go to sleep. One of the reasons Cobb and the rest of his team use such powerful drugs is that, in order to move through the dream world, they have to go very deep, very quickly, in order to send their brains into REM sleep.
2.You’re pretty much paralyzed while dreaming: One of the key concepts of Inception deals with how people using artificial sleep methods to enter the dream world are essentially left paralyzed while doing so. This is why one member of the team is left behind to watch the others and regulate their activity. The thing is, it’s true. During REM sleep, an amino acid called glycine is released by the brain stem and onto what are called motoneurons, which work to conduct impulses from the spinal cord out to the body. Glycine inhibits their ability, which effectively paralyzes your body during dreaming, likely as an evolutionary way to make sure you don’t physically respond to the images in your head.
3.Dreams are important for your brain: The inhabitants of the world of Inception are often addicted to dreaming, with some of them returning again and again to artificial sleep just to keep dreaming for hours at a time. It’s an interesting interpretation of a very real phenomenon: your brain, some researchers say, needs dreams to function properly. A Harvard psychiatrist published a paper in fall 2009 posits that dreams help the brain get warmed up for the day ahead, with REM sleep and its attendant images the mental equivalent of stretching before exercise. It’s a novel but powerful idea that goes a long toward explaining the benefits and purposes of dreams.
4.Dreams can be controlled: The entire plot of Inception hangs on this one idea. It’s what lets Cobb and his gang do their jobs, allowing them to manipulate and manage dream environments for total strangers. Although the phrase isn’t mentioned in the film, what they’re doing is a version of lucid dreaming. Lucid dreaming is what it sounds like: dreaming with clarity and understanding, in which you are able to react to and control your dream without waking up. It’s an acquired skill that not many have, though researchers have done their best to understand and implement the process. German psychologist Paul Tholey developed what he called the “reflection technique,” which required users to constantly suspect real life to be a dream, hoping that the habit would carry over to the dream state and allow for recognition and control of dreams.
5.You can construct your dreams: It’s one thing to control your dreams lucidly; it’s another to actually create them. Inception revolves around the idea of artificially constructed dream space built by a dream architect responsible for designing safe but believable worlds into which the dreamers can insert themselves. How close is that to reality? Closer than you probably think. Many therapists and researchers use a technique called “dream incubation” as a way to help patients deal with terrifying and traumatic nightmares, and the incubation process works on the brain similar to the rules of Inception. As patients drift off to sleep, they tell themselves to prepare for possible nightmares by having escape routes; someone who dreams of fire might tell themselves that, should the dream occur, they’ll find a fire hose and exit to safety. The process can also work for basic problem-solving, as patients write about a problem before bed and think about it as they go to sleep, often visualizing it in their dreams.
6.“Kicks” are real: The dreamers in Inception are pulled back into consciousness via “kicks,” sudden drops (often from a chair) that startle their body into waking. The kicks are based on hypnic jerks, the twitches that often accompany a sense of falling that occur when someone is drifting off to sleep. Hypnic jerks often wake people up even as they’re falling asleep, thanks to the physical twitch, and it’s this very real brain phenomenon that Inception deftly uses on all its dream levels, requiring everyone to synchronize their kicks and ride a wave of them back up to the real world.
7.Your brain assembles information while you sleep: The bulk of Inception deals with a plot to plant an idea in Fischer’s subconscious so that, upon waking, he’ll have the urge to do something he previously didn’t want to do. The plot sounds at best like something out of science-fiction, using dreams to plant ideas that come to fruition upon waking. But there’s a nugget of truth in there about how our brains really work while we dream. Neurologists have recently found that sleep might actually be an invaluable part of the problem-solving process, allowing ideas to marinate and letting people see problems in a new light upon waking. A possible incubation period for ideas that happens while dreaming might be able to increase people’s ability to make inferences and connections in their lives by one-third. So if there’s a problem you can’t seem to solve, sleep on it. You just might figure it out.
8.Bad memories can haunt our dreams: Throughout Inception, Cobb is haunted by the memories of his wife, Mal, who killed herself after going crazy while stranded in limbo. Every time he travels down into the subconscious world of dreams, even in someone else’s brain, he’s attacked by a manifestation of his anger and guilt that’s transformed into a murderous version of Mal. He keeps her memory locked up in his subconscious, never healing, and he suffers the consequences when she/it gets out. That kind of thing can happen to you and me, according to researchers. In fact, most of our dreams are negative in some way, functioning as escape hatches for our darkest fears, worries, and memories. New traumas can trigger the release of old, suppressed horrors that make themselves known again in our dreams, as was the case with the man who was abused as a child and found himself reliving the horror in his adult dreams after being burglarized. There are many ways to deal with past problems, whether it’s therapy, dream incubation, or something else, but the lesson from the movie is the one to carry into real life: you have to deal with the bad stuff, or it will tear you apart.
The discovery of the antibiotics by the middle of the 20th century seemed to have doomed the human pathogens. They proved effective against many bacteria and fungi causing hospital infections, like meningitis, pneumonia and scarlet fever, which before were deadly. But antibiotics cannot attack viruses, like HIV or flu virus; many cause allergies and kill many beneficial microorganisms.
The under use of antibiotics (when a patient does not complete treatment because he/she feels better) cause the emergence of resistant strains, as not all the bacteria are killed. Their abuse is also harmful. In livestock they induce an accelerated growth, and this cause an increase in the microbial resistance. This can leave us without antibiotics.
Massive vaccination campaigns eliminated to the end of the 20th century smallpox and today polio leave paralyzed less than 1,000 children annually (in 1988 more than 1,000 per day), and has remained active in less than 10 countries. Sanitation has eliminated cholera, whose bacterium is transmitted through infested water, from many places. Better food, life style, medical care and laws controlling food manipulation have reduced infection diseases in many places.
In the 21st century, there are still infections against which we are defenseless and which, despite all the medical advances, bringing advantages more to developed nations, still kill millions of people every year. Poverty, war, hunger, lack of health infrastructure and sanitation, immigration, trade, globalization contribute to the spread of the diseases. In the last years, outbreaks of ebola, cholera, pest, meningitis, SARS and bird flu have been witnessed. These are infectious diseases that have produced and produce a lot of victims around the world.
(also called bubonic plague) outbroke in Europe in 1347, when a boat coming from Crimea docked at Mesina, Sicily. Besides its load, the ship transported the pest, which soon spread throughout whole Italy. It was like the end of the days for Europe. In four years, this bacterium killed 20 to 30 million Europeans, about one third of the continent’s population. Even the remote Iceland was struck. In the Extreme East, China dwindled from 123 million inhabitants at the beginning of the 13th century to just 65 million during the 14th century, because of the pest and the hunger.
The pest bacterium is transmitted by fleas and usually, the infection jump from rats to humans.
This catastrophe has not match in the human history. 25 to 50 % of the inhabitants of Europe, North Africa and certain Asian areas died then.
Knowing the cause of the pandemic helped: in 1907 an outbreak of bubonic plague in San Francisco produced just several victims, as the authorities started a massive campaign for exterminating the rats, while in 1896 an outbreak in India caused 10 million dead in 12 years, as the cause was not known.
Americas escaped of the Black Death because of the isolation. But when discovered, the smallpox struck. In 1518 an outbreak of smallpox in the Haiti island left just 1,000 of the Native Indians. 100 years after the discovery of America by Columbus, 90 % of its native population have died of smallpox. Mexico passed from 30 million to 3 million inhabitants, Peru from 8 million to 1 million.
About 1,600, when the first European colonists reached Massachusetts, found it practically uninhabited, as smallpox had killed almost all local Indians.
It is believed that along the history, smallpox killed more humans that all the wars of the 20th century together. Since 1914 to 1977 smallpox killed 300 to 500 million people. By 1970, smallpox still killed 2 million people annually, but OMS managed to eradicate the diseases through vaccination and in the last case was found in Somalia, in 1977. This was possible because smallpox transmits only from human to human. At the time of eradication, no effective cure was known against smallpox.
The first ever vaccine was created in 1798 by Edward Jenner and was against smallpox.
infects 2 million people annually and about 12 million diseased are found worldwide, mostly adult men. It is produced by a protozoa (Leishmania) that spreads through the bite of the sand flies (Phlebotomus).
The most severe type is “kala azar” (“black fever” in Hindu), which infects 0.5 million people, and incubation lasts some weeks. The parasite induces skin ulcers which extend all over the body and can produce obstructions or nasal hemorrhage.
It causes severe lesions on the legs and a temporary or definitive physical disability.
Kala azar swells the spleen and the liver and attacks the bony marrow and linph nodules. Without treatment, the parasite kills 75-95 % of the patients.
It is found mainly in Africa, China, India, Latin America, and outbreaks occur sometimes in Mexico and the US.
The best drug is Pentostam. Intravenous Amphotericin B is effective, like the Pendamidine, but there is no vaccine yet.
is found in 500 million people (!) and is caused by a protozoa spread by the female of the Anopheles mosquito. 300 million of these cases are severe. In the east African villages, children are bitten by the Anopheles mosquitoes carrying malaria 50-80 times a month.
It triggers fever, shivering, abundant sweating, articulation pains, severe headache, vomit and extreme weakness, so that the diseased cannot even cry.
Annually, 1.5 million people die of malaria (one million in Africa South of Sahara), a child every 30 seconds. About 120 million people died of malaria since 1914, and the disease is endemic in 101 countries, mainly tropical, in Africa, Asia and America.
It spreads during the rainy season, when the mosquitoes breed. Quinine extracted from the bark of the South American cinchona tree saved millions of malaria diseased. Many treatments have been developed (mefloquine, Halofantrine, Artemisia products) but none has a total effectiveness, as the parasite constantly mutates, and there is no vaccine.
5. Gonorrhea and syphilis
are triggered by two bacteria (Neisseria and Treponema pallida) and are transmitted sexually.
62 million people worldwide are affected, aged mainly 15 to 29 years, all over the planet, especially in urban areas and of low socioeconomic level.
In man, gonorrhea produces urinary incontinence, urethra pain, reddening, penis burning sensation and testicle inflammation. In women, it induces severe pain which reaches the trumps and uterus.
Syphilis induces ulcered lesion (syphilis chancre) at the entrance site. After that, it triggers skin eruptions, fever, hair loss, less severe hepatitis and gential condilloms, but if untreated, the lesions extend to the nervous system, leading to death.
The treatment consists in extremely powerful antibiotics (ceftriaxone, Cefixime, and others) which are also extremely costly.
affects 1 % of the planet’s population and can be produced by viruses or bacteria (like Aeromonas hydrophila).
It produces fever, shiver, sweating, cough with expectoration, muscle, head and thoracic pain, appetite loss, weakness.
This is the main cause of mortality in the world: it kills 3.5 million people each year. It attacks especially patients with severe immunodepression, those that follow chemotherapy, people who are older than 75, asthmatics, smokers, alcoholics, those with renal insufficiency and children under 2 years of age. It affects especially the poor countries.
Antibiotics work in the case of the bacteria. Therapy includes oxygen, liquids, and physiotherapy.
Patients with a simple pneumonia can cure in 2-3 weeks, but elders or those with debilitating diseases can die of respiratory or cardiorespiratory failure.
The vaccine trimetropin sulfamethoxazole is effective against the most frequent complications.
7. Sleeping sickness
is triggered by the Tripanosoma gambiense and T. rhodesiense, protozoans spread by the tse-tse fly (Glossina). The American variant, T cruzi, is spread by biting bugs and cause the disease called chagas.
The toxins of the parasites affect especially the central nervous system and the heart muscle. It manifests through fever, edemas, sleepiness, and meningitis.
It affects 60 million people, but only 4 million receive treatment, and it kills 150,000 people yearly.
It affects the livestock, being deadly or inducing low fertility, weight and productivity, with severe economical losses. It is found in the habitat of the tse-tse fly: over 10 million square km in 36 African countries. Chagas is found in certain areas of Central and South America.
DFMO, the effective drug, is already not produced. Currently, melarsoprol with arsenic are employed, fact that induces the death of up to 10 % of the patients. Vaccine exists only for the carrying livestock. There are also efforts to eliminate the flies in some areas.
is caused by the Koch bacterium. It is as old as the humankind. TBC was found even in mummies coming from the ancient Egypt and Peru. 2 million people die annually of tuberculosis. About 150 million people are estimated to have died of TBC since 1914.
One third of the people carry the Koch bacterium, which spreads through the air and affects all the body, especially the lungs. It induces prolonged coughing, fever, shivering, bloody expectoration, weight loss, sweating, tiresome, and glossy eyes.
It infects one third of the world population and each year another new 8 million cases appear. Each second a person dies of tuberculosis. It is more aggressive in women and persons between 15 and 45 years old. Mutant strains are resistant to almost all drugs and kill about 50 % of the patients.
It is worldwide spread, but its advance is rampant in Bangladesh, China, Indonesia, Philippines, India and Pakistan, with over half of the new cases.
TBC has a treatment, but it cannot be eradicated because of the emergence of multiresistant strains if the long and costly treatment, of over 6 months, is interrupted sooner than it should. 3-5 % of the new cases are coinfected with HIV.
The vaccine is effective in children, but useless in adults. Current employed drugs are isoniazid, ethambutol and Rifapentin.
is estimated to be found in 46-60 million people and it’s produced by the human immunodeficiency virus (HIV), spread through blood, semen, and vaginal fluids. Some say the virus is still in an early stage.
The symptoms come rather late and start with exhaustion and fever. After that, ganglion inflammation appears along with persistent diarrhea, pneumonia and weight loss. In the final stage, the patient’s state is profoundly altered.
Each minute, five new persons get infected with HIV, and the virus kills young people, found in their productive period. It has killed 25 million people since 1981 and about 3.3 million people with HIV die annually. 68 million people could die between 2000-2020. Africa has lost 20 % of its labor power. Lifespan in Sub-Saharian Africa is now of 47 years old; without the AIDS it would have been 62.
In developed world, 58 % of the new cases are drug addicts who share syringes and 33 % through unprotected sexual contacts, but in undeveloped countries is mainly through unprotected sex and blood transfusions.
28 million of the HIV infected are found in Africa, and 0.5 million in West Europe; 300,000 in Eastern Europe, 600,000 in Eastern Asia and Oceania; 2.6 million in America (mostly South America).
Antiretrovirals can improve the immunity but its price is too costly for about 95 % of the infected. Only 4 % of the patients in the developing countries receive treatments. This treatment can cost 6-18,000 Euro ($ 8-25,000) and the virus will get resistance to drugs if the treatment is interrupted.
In pregnant women, antiretrovirals during the second and third trimesters of the pregnancy can avoid the child’s infection.
There is no vaccine, and the combination of up to four different drugs is the main principle in stopping the disease. These drugs keep the blood lymphocytes at normal levels, maintaining the virus latent but without its deadly ability.
hit the world in 1918-1919 and killed over 30 million persons, soon after the First World War. Not even the bubonic plague had ever killed so rapidly so many persons. Typhus outbreaks use to accompany war conflicts. A huge typhus pandemic outbroke during the First World War in the eastern Europe. Since 1914, over 20 million people died of typhus.
Every year, hundreds of thousands of people suffer from paralyzed limbs as a result of peripheral nerve injury. Recently, implantation of artificial nerve grafts has become the method of choice for repairing damaged peripheral nerves. Grafts can lead to some degree of functional recovery when a short segment of nerve is damaged. But they are of little use when it comes to regenerating nerves over distances greater than a few millimeters, and such injuries therefore often lead to permanent paralysis.
Now though, surgeons from Germany have made what could be a significant advance in nerve tissue engineering. They have developed artificial nerve grafts made from hollowed-out pig veins filled with spider silk fibres and, in a series of animal experiments, showed that the grafts can enhance the regeneration of peripheral nerves over distances of up to 6cm. Their findings have just been published in the open access journal PLoS One.
Peripheral nerves have a greater regenerative capacity than those in the central nervous system, but regenerating them properly is challenging. The individual nerve fibres must not only regrow into the damaged area, but also find their proper targets. Furthermore, the regenerated nerve will not function properly unless it is populated by Schwann cells, which produce myelin. This fatty tissue is essential for full recovery, as it wraps itself around the nerve fibres at regular intervals (a process called myelination), facilitating the conductance of nervous impulses along their length.
Conventionally, damaged peripheral nerves are treated either by suturing or by implantation of nerve grafts. The two ends of a severed nerve can be surgically re-attached to each other, as long as the nerve is not stretched in the process. This is not possible for gaps longer than about 5mm, in which case a short length of nerve from elsewhere in the patient’s body can be grafted into the damaged area. But this often causes causes pain in the donor area, and it can be difficult to find a nerve segment that has the same diameter as the damaged nerve. Nerves can be obtained from another person, but they can be rejected by the recipient’s immune system, so drugs that suppress the immune response are usually administered.
An alternative approach, which has emerged in the past ten years or so, is the use of artificial nerve grafts made from silicon or synthetic polymers such as polyethylene. These form scaffolds which bridge the gap in the damaged nerve and serve as conduits through which the nerve fibres can regrow. Artificial grafts can lead to some degree of functional recovery, but they can become toxic with time, or they can constrict the nerve.
These problems can potentially be overcome by using nerve grafts made from biodegradable materials. Five years ago, Peter Vogt and his colleagues in the Department of Plastic, Hand and Reconstructive Surgery at Hannover Medical School reported that Schwann cells readily ensheath spider silk fibres when grown on them, and that nerve grafts made of de-cellularized veins filled with spider silk can be maintained in culture for periods of up to a week. More recently, they showed that spider silk vein grafts can be used to regenerate 20mm gap in the sciatic nerve of rats, either alone or when supplemented with Schwann cells.
In the new study, Vogt’s group dissected 6cm lengths from the small veins in pigs’ legs, washed them and stripped away most of the endothelial cells from their inner walls. They then harvested dragline silk from the golden silk spider Nephila clavipes and pulled the silk through the de-cellularized veins, until it filled about one quarter of their diameter. Using adult sheep, the researchers removed a 6cm length of the tibial nerve in the leg. In one group of animals, the gap was bridged with the spider silk constructs; in another, the section of nerve that had been removed was replaced in reverse orientation.
Defects in the animals’ gait became apparent immediately after the surgery – the hind limb was partially paralyzed and flexed abnormally. But within three weeks there was a significant improvement, with both groups of animals being able to stand properly. By four months, the animals could stand upright on both hind limbs, the hind limbs moved in co-ordination with one another during walking, and there was no obvious difference in strength between the operated and unoperated limbs.
Ten months after surgery, the sheep were killed and their regenerated nerves examined under the microscope. In both groups of animals, the severed nerve fibres had regrown into the nerve grafts to bridge the 6cm gap; Schwann cells had migrated into the grafts and wrapped themselves around the entire length of the regenerated nerves; and the sodium channels required for generating nerve impulses were distributed irregularly along the fibres. This shows that myelination had occurred properly, with the formation of Nodes of Ranvier, the regular gaps in the myelin sheath at which the sodium channels normally cluster. No trace of residual spider silk was detected in the experimental animals, and there was no sign of inflammation at the repair site, indicating that the silk fibres were absorbed subtly without adverse effects.
These findings could have important applications in reconstructive nerve surgery. This is the first time that a large animal model has been used to study nerve regeneration, and the study is the first in which a defect longer than 2cm in length has been successfully repaired. The spider silk constructs enhanced nerve regeneration at least as effectively as the sheeps’ own nerves, and would be advantageous in the clinic, because transplanting large lengths of a patient’s own nerves is unfeasible.
More work will be needed before the technique can be applied to humans. Meanwhile, the regeneration reported here could be further enhanced in a number of ways. The spider silk constructs could, for example, be loaded with substances such as Nerve Growth Factor, or they could be grafted together with Schwann cells, to speed up nerve regrowth. But ultimately, engineering fully functional peripheral nerves will probably require a combination of advanced microsurgery, transplantation of both cells and tissues, advances in materials science and, possibly, gene transfer for the effective delivery of growth factors.
Radtke, C. et al. (2011). Spider Silk Constructs Enhance Axonal Regeneration and Remyelination in Long Nerve Defects in Sheep. PLoS ONE, 6 (2) DOI: 10.1371/journal.pone.0016990.
Formerly only in the domain of fantasy, brain-controlled devices now exist. These complex robotic tools are made possible by past studies of nerve cell communication.
This has implications for the approximately 5.6 million Americans, about 1.9 percent of the population, who are paralyzed. While some treatments focus on ways to repair the damage, other approaches aim to restore some independence by helping patients control a device, such as a robotic arm or computer cursor.
Finding out how the brain controls movement
Every handshake or footstep is the result of the brain exchanging information with an arm or leg. But what if that link is severed? Research shows function may be restored with mechanical limbs. Such brain-machine connections are now possible because of experiments that examined nerve cell communication.
Strength in Numbers of Neurons
In the 1920s, researchers investigating electrical activity in the brain noticed the signals they recorded varied with a person’s behavior. Nerve cells in the brain called neurons communicate with each other via chemicals and bursts or “spikes” of electricity. Using instruments attached to the outside of the scalp, the researchers found evidence that these signals are related to behavior.
(Left: Image Description (above): Microwire arrays such as the one shown have made brain-controlled devices possible. The arrays are implanted into the brain’s motor region to record the electrical signals of individual neurons simultaneously. Credit: Miguel Nicolelis, MD, PhD; Duke University.)
Years later, scientists recorded signals from individual nerve cells by implanting tiny rigid wires in the brains of macaque monkeys. They found each cell in the motor cortex, the brain’s movement control center, responded differently when the monkey moved its arm in certain directions. This led researchers to believe single neurons controlled behavior.
However, subsequent research showed the collective effort of nerve cells working together directs behavior. In the early 1990s, arrays of implanted electrodes with flexible wires allowed researchers to record almost 50 neurons at once in a conscious animal. As the animal moved, each cell’s electrical signal changed and was logged. These studies suggested brain cells compute in clusters, not in isolation. This was a surprising finding.
Although basic tools had been developed to tap into the brain’s electrical signals, the full potential of that discovery was still unknown. Researchers needed a way to apply those extracted signals to restore motor function; they needed an interface between neurons and artificial devices.
Animals control machines with their brains
Researchers worked to create a system that could continuously tap into diverse populations of neurons, convert their signals into commands a robot could understand, and then immediately transmit those commands to the machine. Basic science research in animals helped identify three essential components to a brain-machine interface: simply thinking of an action activates motor-control neurons; the signals from hundreds but not thousands of motor neurons are needed to imitate natural movement; and sensory feedback is necessary for proper control of a brain-directed prosthetic.
Movement Without Flexing a Muscle
Remarkably, researchers found that thinking about a motion activates neurons in the same pattern that actually making the movement does. In one early experiment, a rat was trained to expect a reward when it pressed a lever. Researchers then disconnected the lever from the reward and equipped the rat with an electrode array that collected and processed data from about 50 neurons in the motor cortex involved in lever pressing. Even then, the rat still attained the reward, despite never physically touching the lever.
(Left: A simplified schematic shows how signals from nerve cells in the brain’s motor cortex can control a prosthetic device. Electrical communications between neurons are recorded, processed through a machine interface, and used to control a motorized arm. Credit: Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Neuroscience 4(5):417–422, © 2003.)
Scientists then attempted to design a robotic arm that mimicked the motions of a monkey’s arm. The researchers found that to accurately reproduce motion, they had to record many, but not all neurons involved in arm movement. They sampled 50 to 100 neurons throughout the arm sensation and movement control areas in a monkey’s brain at any given time. Signals from those neurons were processed and rerouted to control a robotic arm. When the monkey
reached for a piece of fruit, so did the machine. This finding suggests that people who are injured or ill can still make use of brain-directed prosthetics even with nerve cell loss.
(Left: Basic science research in animals has led to important advances in technologies like brain-controlled machines that could help individuals with central nervous system disorders. A rhesus monkey feeds itself by operating a prosthetic arm through a brain-machine interface. Credit: Motorlab, University of Pittsburgh School of Medicine.)
Also during these landmark experiments, researchers found when they displayed a visual indicator of a neuron’s activity, a monkey could learn to move its limbs to control the cell firing rate. This discovery suggested that, with training and proper sensory feedback, people could learn to control brain signals to operate complex robotic devices. In this way, machines could act in lieu, not in imitation, of a hand or an arm.
New solutions for paralyzed people
Thanks to the success of animal studies, pieces are in place to apply brain-machine systems to the most complex organ: the human brain. Human tests of brain-controlled prosthetics have already begun. In carefully monitored clinical trials, paralyzed people have had sensors surgically implanted in their brains to allow them to move a glass of water or use a computer.
Building a Better Machine
Privately held companies are teaming up with government agencies and academic institutions to develop viable brain-operated robotic devices and computers. In one early trial, a participant controlled a cursor on a computer screen, an activity he had been unable to do since an accident severely damaged his spinal cord. One paralyzed volunteer with an implant recently demonstrated her ability to move a robotic arm with her thoughts. The woman directed the arm to pick up a glass and set it back down.
Similar systems also have given new voices to people unable to speak. The most well-known user of communication technology is the physicist Stephen Hawking, who has a slowly progressing form of amyotrophic lateral sclerosis. Although Hawking uses two fingers to construct sentences on a speech-capable computer, researchers aim to develop such communication systems to act on thought only.
(Left: Basic science research in animals has led to important advances in technologies like brain-controlled machines that could help individuals with central nervous system disorders. A rhesus monkey feeds itself by operating a prosthetic arm through a brain-machine interface. Credit: Motorlab, University of Pittsburgh School of Medicine.)
So far individuals have largely received implants that physically plug into machines. Although implants are most effective at reading brain signals, non-invasive interfaces for humans are in development to avoid risk of infection and tissue damage. Even small advances are huge improvements for people who are “locked in” to their bodies due to paralysis.
New Scale of Science
Brain-machine research has given scientists new insight into how the brain works. Before such research, scientists were uncertain how strokes or injuries alter the brain’s ability to control the body. Now, thanks to brain-machine connections that track neuron activity in exquisite detail, scientists know that if a lost connection is restored, the brain may still be able to relay motor commands. This finding has profound implications for both machine-assisted recovery and spinal cord repair.
Source: Society for Neuroscience
Frontotemporal dementia is caused by a breakdown of nerve cells in the frontal and temporal region of the brain (fronto-temporal lobe), which leads to, among other symptoms, a change in personality and behavior. The cause of some forms of frontotemporal dementia is a genetically determined reduction of a hormone-like growth factor, progranulin. Scientists around Dr. Anja Capell and Prof. Christian Haass have now shown that various drugs that are already on the market to treat malaria, angina pectoris or heart rhythm disturbances can increase the production of progranulin. Accordingly, these drugs are good candidates for treatment of this specific form of frontotemporal dementia.
The work has been published in the online edition of the scientific journal Journal of Neuroscience on February 2nd, 2011.
Progranulin is needed in the human brain as a protective factor for sensitive nerve cells, too little progranulin therefore results in a progressive neuronal cell death. As for almost every other gene, there are also two copies of the progranulin gene in the cell. In patients with progranulin dependent frontotemporal dementia, one of the two copies is defective, leading to a 50% reduction in progranulin levels. To rescue the lack of progranulin, the Munich researchers tested various substances for their ability to stimulate the remaining progranulin production and identified a drug called bafilomycin (BafA1). They then examined the molecular mechanism underlying the impact of BafA1 on progranulin more closely. Growth factors such as progranulin are produced in cellular membrane inclusions, known as vesicles. BafA1 has an alkalizing effect on these vesicles: After administration of BafA1 the interior of the vesicles is less acidic — and this increases the production of progranulin.
Impact of Baf1A and chloroquine on progranulin levels. (Credit: C. Haass)
This observation encouraged the researchers to investigate further alkalizing substances for their ability to raise progranulin levels. Among the substances that passed the test were three drugs that are already on the market to treat various diseases: a medication for angina pectoris (bepridil), one for heart rhythm problems (amiodarone) and the widely used malaria drug chloroquine. Chloroquine increased the progranulin level not only in experiments with mouse cells to normal, but also in cells from patients with the defective progranulin gene.
In a clinical study in collaboration with the University of London, the team of Prof. Haass and Dr. Capell will now investigate whether chloroquine actually helps against progranulin dependent frontotemporal dementia. The human studies can be started very soon, as chloroquine has been used on countless patients, so that serious side effects are not to be expected. Even though the Munich scientists are optimistic, Prof. Haass warns against exaggerated hopes. “Experience shows that the step from cell and animal models to the patient is always connected with considerable difficulties. It will take several years until we know, whether chloroquine can be used as therapy for progranulin dependent frontotemporal dementia,” says Haass.
1. A. Capell, S. Liebscher, K. Fellerer, N. Brouwers, M. Willem, S. Lammich, I. Gijselinck, T. Bittner, A. M. Carlson, F. Sasse, B. Kunze, H. Steinmetz, R. Jansen, D. Dormann, K. Sleegers, M. Cruts, J. Herms, C. Van Broeckhoven, C. Haass. Rescue of Progranulin Deficiency Associated with Frontotemporal Lobar Degeneration by Alkalizing Reagents and Inhibition of Vacuolar ATPase. Journal of Neuroscience, 2011; 31 (5): 1885 DOI: 10.1523/JNEUROSCI.5757-10.2011