Posted by: R. Douglas Fields | May 5, 2015

Watching TV Alters Children’s Brain Structure and Lowers IQ

TV viewing changes brain structure and lowers IQ of children

TV viewing changes brain structure and lowers IQ of children

From the black-and-white days of I Love Lucy to the blue-ray lasers of today’s Game of Thrones in dazzling 3D, parents have worried that television might harm their child’s brain development. Now the answer is plain to see. Brain imaging (MRI) shows anatomical changes inside children’s brains after prolonged TV viewing that would lower verbal IQ.

Neuroscientists in Japan imaged the brains of 290 children between the ages of 5 and 18 years and sorted the data according to how many hours of TV each child had watched. The results showed significant anatomical differences in several brain regions that correlated with the number of hours of TV viewed. These findings were strengthened when the researchers re-examined the same children several years later and were able to see many of these anatomical changes taking place in the children’s brain over time. The more hours of TV children watched, the greater the changes were in brain structure.

The parts of the brain affected are involved in emotional responses, arousal, aggression, and vision. The brain regions that bulked up in children watching more television include gray matter increases in the hypothalamus, septum, sensory motor areas and visual cortex, but also in a frontal lobe region (frontopolar cortex), which is known to lower verbal IQ. Tests confirmed that the children’s verbal IQ had lowered in proportion to the hours of TV watched, ranging from 0 to more than 4 hrs/day. Changes were also observed beneath the cerebral cortex in the brain’s wiring network “white matter regions.” The changes in brain tissue were evident regardless of the sex of the child, age, family income, and many other factors.

The increase in visual cortex is likely caused by exercising vision in TV viewing, but changes in hypothalamus are characteristic of patients with borderline personality disorder, increased aggressiveness and mood disorders. The frontopolar region is active in monitoring and regulating internal mental states, and enlargements in frontopolar cortex are known to be associated with lower verbal IQ. Several previous studies have found lower verbal IQ and increased aggressiveness in proportion to the amount of television children watch. This new research uncovers the biological mechanism for these changes in behavior and drop in intelligence.

The brain alterations could be caused directly by TV viewing, or indirectly by the different life experiences gained through physical and virtual activities while the young brain is maturing. The more time spent sitting on the couch, the less time spent in physical activity, reading, and interacting with friends. Consider that children who watch 4 or more hours of TV a day, spend more than half of their free time watching the tube, assuming they devote 8 hrs for sleep and 8 hours for school. “Guardians of children should consider these effects when children view TV for long periods of time,” the researchers conclude.

Reference
Takeuchi, H., et al., The impact of television viewing on brain structures: Cross-sectional and longitudinal analyses. Cerebral Cortex, May, 2015; 25: 1188-1197.

Posted by: R. Douglas Fields | May 2, 2015

Heisenberg Uncertainty and the Baltimore Riots

tvtruck

Yesterday I encountered a colleague outside the elevator. He was profoundly troubled, as are many, anguished by the violence in Baltimore this week. The looting, burning, and scores of injured from angry youths hurling bricks at police were sparked by the violent death of a black man, Freddie Gray, in police custody.

“I was there yesterday,” I told my concerned colleague.

“What? Where?”

“I went to the CVS Drugstore that was looted and burned,” I replied.

In disbelief he asked, “What was it like?”

“I was too late. All of the DVR’s and other good stuff were already gone,” I said.

My reply can be taken as a crass, inappropriate outburst of dark humor, but there is a deeper message. It is a message that every scientist knows well and grapples with every day–the Heisenberg uncertainty principle. Fundamentally, reporters and scientists are driven by the same passion. Both are engaged in the challenging process of trying to find truth from primary evidence. Thus science and reporting, subject to the same types of errors, sometimes fail for similar reasons.

The facts are that a young black man died a violent cruel death while in police custody. His spine was snapped. He was restrained by handcuffs and leg irons and mortally injured while being transported inside a police wagon in the custody of six police officers. Angry riots erupted in rage against police brutality.

We watched it all live on TV. Hordes of angry black men armed with clubs and stones, facing off against a phalanx of police in black riot gear, wearing modern armor, helmets and shields that harken back to medieval battles between knights of the kingdom and oppressed peasants. We have seen this angry scene thousands of times through thousands of years of human history. As the city of Baltimore burned those of us who remember the horror of the summer of violence that plunged the country into chaos in 1968, were sickened.

“Can’t we all get along?” Rodney King pleaded during riots in Los Angeles in 1992. The black taxi driver was brutally beaten by Los Angeles Police officers after a high-speed chase in 1991. That beating by police was videotaped by a citizen appalled by the brutality erupting on the street beneath his balcony. After a trial that acquitted the police of serious charges, Los Angeles was consumed by riots in which 53 people were killed, 2000 were injured, and the neighborhoods were looted and burned. The military was dispatched to restore order, but many neighborhoods never fully recovered and the violence spread to other cities.

Rodney King’s plea echoed the bewilderment of everyone, and unfortunately the answer to his vexing question cannot be more obvious or more disheartening. Such turmoil and brutality are a deadly consequence of the human mind that within milliseconds of observing another person categorizes the individual into either “us or them.” It happens as quickly and as automatically as the brain attaches the color red or green to an apple. Paradoxically, those automated brain circuits are the essence of human success. They enabled our species to coalesce spontaneously into groups for mutual protection and common purpose, and often to do so through violence. This is the double-edged sword of the human brain. There can be no patriotism without a foreign adversary; no maternal bonding without seeing other babies differently.

The heavy thumping of helicopter blades circling overhead, the smell of charred wood, sirens squealing from every direction, echoing hysterically through the alleyways and streets it is impossible for me to tell where they originate. In a flash a fire truck, police car, or ambulance streaks past, ablaze with flashing red lights, racing toward the violence or away from it to hospitals or police stations.

Stepping into the neighborhood surrounding the CVS drugstore triggers screeching alarms in your brain that raise hair on the back of your neck and make your spine shiver. Groups of men loiter on street corners, drinking oversized cans of malt liquor from rumpled paper bags and smoking. Others pass the day sitting on the stoops of red brick row houses as if discarded. The windows of buildings are boarded with plywood weathered into a furry gray, warped and pealing, the homes and businesses have been abandoned for ages. It is a neighborhood of pawn shops, discount liquor stores, mom and pop corner markets with bars on the doors and windows, of bail bonds and check cashing establishments. Faded tent cities rot under an overpass, cluttered with shopping carts and scavenged junk. It is a perilous place of danger, crime, and drugs. 25 percent of the men are unemployed. They have nothing to do. Nowhere to go. Trapped, they have no way out. Children grow up in squalor and poverty.

All eyes follow me. They are the eyes of black men. I am white. There is not a thing in the world that either of us can do about that. Ours is the biological legacy of genetics; mine following a line of descent from northern Europe, theirs from Africa. It shouldn’t make much difference, but it does.

The violence, though, is not exactly the result of racism; it is the result of tribalism, a human trait that divides the world into us vs them. I suspected as much when I visited the boarded up drugstore, but today we learned that three of the six police officers charged with assaulting Freddie Gray are black. The driver of the police wagon now facing murder charges was a black officer. An unfortunate result of tribalism can be festering pockets of poverty, neglect, hopelessness, divisions between the haves and the have not’s, and instantaneous violence unleashed by brain circuits designed for herding, defense, and mutual cooperation in groups.

But this is not what I wish to explore in this article, which is targeted to those with an interest in science. As we watched the looting streamed live into our homes on TV, what we did not see was the view from the opposite direction. When I visited the burned and boarded up CVS store this week, in the midst of the protests and before the police were charged with the crime, I saw the streets lined with TV vans, satellite dishes, cameramen, soundmen, reporters interviewing men in suits and residents gathered around ogling and curious. Reporters, some of them from foreign countries, positioned carefully so that the camera angle would capture the person being interviewed with a snippet of boarded storefront in frame as the backdrop, carefully avoiding the throngs of other reporters and gawkers loitering around.

A good example is the large photograph on the front page of today’s Washington Post (May 2, 2015). It shows a black woman with orange blond hair standing up through the moon roof of her vehicle jubilantly cheering with her arms outstretched in the air. In her hand, partially cropped from the frame she holds not stones, but rather a cell phone. She is surrounded by others mugging for the camera. I was at that same spot on Wednesday. Look past her and you see not a crowd, but rather people milling about, eyes fixed on their cell phones, and two other cameramen caught in the frame trying to snap the same image that would carry the day’s narrative.

People do not behave the same in private and in public. If a reporter does not block them off, people will jump into the scene and clown for the camera. Morning news shows exploit this human phenomenon by shooting live weather reports on the streets outside the TV studio in Manhattan so people will mug for the camera and liven up the otherwise boring announcement of temperature and rain fall.

What effect did the media circus have on the youths watching the looting of stores or of protestors assembling, or of youthful gangs collecting into peer groups intent on confrontation with police? The situation sets up a sort of street theater in which people assume roles and act out in the way they see others doing or in the way that aligns them with others to which they aspire to be. The act of trying to capture the events runs the risk of altering them–the Heisenberg uncertainty principle.

Freedom of the press is essential. It is the only real means to find truth in public affairs. It is the only way to shed light on shady dealings, and to counter the inevitable corruption and abuses of power that otherwise overtake government and industry. Without the videos broadcast by the media of Rodney King being beaten and of the violent protests this week in Baltimore, there is no question that injustice and abuse of power would have gone unchecked. But the same conundrum that perplexes scientists applies to reporters.

Heisenberg’s principle cannot be overcome. It can only be recognized. The laser scanning confocal microscope in my laboratory has revealed wonderful insights for me into how living brain cells operate and communicate, but I know and must always be mindful of the fact that the laser beam that illuminates the cell is also stimulating it and changing it. The light illuminating the cell also heats it, blanches it, drives chemical reactions that generate toxic products, and so do the lights of TV cameras on a crowd.

Posted by: R. Douglas Fields | April 26, 2015

The Kathmandu earthquake will alter brain structure of survivors

Brain structure was altered in survivors of Wenchuan earthquake

Brain structure was altered in survivors of Wenchuan earthquake

The disastrous earthquake in Kathmandu has killed hundreds of people and brought grievous tragedy to thousands. Even among the survivors, the earthquake will leave its mark in the form of altered brain structure, according to neuroimaging research performed on survivors of the Wenchuan earthquake of 2008.

Studies by Lui and colleagues on survivors of the 2008 Wenchuan earthquake in China report changes in brain structure that can be seen by MRI. The 7.9 magnitude Wenchuan earthquake (also called Sichuan earthquake) rocked the mountainous central region of Sichuan province in southwestern China on May 12, 2008. 90,000 people died. 375,000 people were injured. Millions of people were rendered homeless.

A 2013 study was performed on 44 survivors, male and female, 25 days after the earthquake and compared to 38 matched controls who had their brains scanned for other reasons prior to the earthquake. The results showed a decrease in gray matter in the insula, hippocampus, and caudate, and an increase in the orpitofrontal cortex (OFC) and parietal cortex.

The OFC is important in modulating emotional responses in the hippocampus, amygdala, ventral striatum and insula. The increase in gray matter is consistent with elevated demands for top-down (that is executive functioning of the cerebral cortex) regulation of threat, fear, and stress circuitry in the limbic system. The increase in parietal cortex has been reported previously in other types of trauma survivors, and this may reflect enhanced neural activity related to the hyper-vigilant state.

The authors suggest that the lower grey matter volume in the insula, striatum, and hippocampus may result from decreased neurogenesis and increased synapse elimination that are seen in studies of experimental animals subjected to chronically elevated stress hormone levels. Acute stress elevates corticotropin-releasing hormone to activate the hypothalamic-pituitary-adrenal axis that is engaged in the “fight-or-flight” response, but prolonged elevation of this stress response is damaging to the brain and body in many respects.

Scientific data on the effects of stress on the human brain are difficult to obtain for ethical reasons, and extrapolating complex cognitive processes of human stresses from animal research is problematic. Studies of people who have survived natural disasters or traumatic events can provide important insights into the effect of stress on human brain structure.

Similar brain changes have been observed in people who have experienced other major life stresses. Studies have reported altered brain structure in patients with PTSD involving regions that function in threat detection and fear, notably the amygdala, hippocampus, and prefrontal cortex (anterior cingulate and medial frontal gyrus). The altered gray matter volume in the prefrontal to limbic and striatal systems found in earthquake survivors are recognized to be involved in emotional and conscious decision making. The striatum and parietal regions are activated in making decisions under time pressure. These regions also undergo changes in people with anxiety disorders, and these brain regions are engaged when processing fear and pain.

The authors conclude that survivors of severe emotional trauma may experience substantial change in brain function and also in the structural anatomy of the prefrontal-limbic, parietal and striatal brain system. These changes are not necessarily pathological. Rather they reflect in part the brain’s remarkable capacity to modify its structure and function rapidly in response to environmental experience. The changes found in earthquake survivor’s brains likely increase the ability of survivors to respond rapidly and appropriately to the danger and trauma. However, if these brain modifications do not return to normal after the threat has passed, this can result in dysfunction. This is well demonstrated by brave military men and women who suffer post-traumatic stress disorder after returning to a safe environment. Similar changes in the brains of people under stress that helped them survive in combat, can become debilitating after returning to civilian life.

References
Cohen, R.A. et al., (2006) Early life stress and morphometry of the adult anterior cingulate cortex and caudate nuclei. Biol. Psychiatry 59: 975-82.
Davidson, R.J. (2000) Dysfunction in the neural circuitry of emotion regulation — a possible prelude to violence. Science 289: 591.
Lui, S. (2009) High-field MRI reveals an acute impact on brain function in survivors of the magnitude 8.0 earthquake in China. Proc. Natl. Acad. Sci. USA 106; 15412-7.
Lui, S., et al., Bran structural plasticity in survivors of a major earthquake. J Psychiatry Neurosci. 2013 Nov;38(6):381-7
McEwen, B.S. (2007) Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol. Rev. 87:873-904.

Posted by: R. Douglas Fields | April 5, 2015

Snakes on the Brain

Pit vipers have infrared vision.  (Photo by author.)

Pit vipers have infrared vision. (Photo by author.)

After repeated encounters with a friendly rattlesnake last week I have snakes on the brain. Serpents are a storehouse of fascinating neuroscience. Infrared vision, venom, fast-twitch muscles to energize its “warning buzzer,” and more…

The western diamondback rattlesnake can rattle its tail at frequencies of 90 Hz and do this continuously for hours. This is about the frequency of sound handled by the subwoofer in your fancy home theater system. Even a piano virtuoso can’t begin to approach this feat of turbocharged muscle contraction executed with ease by the lowly cold-blooded viper. Try it. You’ll find you can tap your finger at a feeble maximum rate of about five taps/sec (5 Hz), and you’ll quickly poop out.

Hi speed rattling

High speed rattling


You may not know that the simple test of finger tapping rate provides revealing insight into your brain function. The maximum rate of finger tapping correlates with IQ. The finger tapping rate also declines with age in parallel with cognitive decline. So how does the rattler shake its tail into a fuzzy blur, you, and envious surf rock guitarist Dick Dale, might ask?

Dick Dale

Dick Dale


The tailshaker muscle is absolutely packed with energy producing mitochondria. This enables the tailshaker muscle to use oxygen at a much faster rate than muscles of other warm or cold-blooded animals. Hummingbirds have shared this design principle to flutter their wings so fast they can hover in place.

Infrared night-vision cameras are the ultimate imaging technological that can peer through walls and see clearly in complete darkness. Recall the ghostly glowing image of the Boston Bomber hidden inside the fiberglass boat shot from a police helicopter’s infrared camera as the SWAT team closed in? Cool technology, but snakes have had this stealthy equipment for eons.

Boston Bomber seen by infrared camera

Boston Bomber seen by infrared camera

Have a look at the lovely face of the rattler who greeted us repeatedly last week in the backcountry of Nevada. Notice those tiny openings below the eyes? Snakes do have nostrils, but snakes “smell” with their tongues (that’s another story). They flick their tongue in the direction of a warm blooded prey item just before striking–something I observed, but my trigger finger was too slow to catch it on camera. The second set of pits on the reptile’s face are unique sense organs that give pit vipers infrared vision and also give them their name “pit vipers.”

In 1937 Noble and Schmidt put blindfolds on rattlesnakes and found that the blindfolded snakes could magically strike at moving objects very accurately, such as a dead rat or a cloth-wrapped light bulb. Moreover, the snakes had the ability to distinguish between identical warm and cold objects. In 1952, Bullock and Cowles took an electrophysiological approach to understand the function of these pits and uncover how they worked. The scientists surgically exposed the superficial branch of the superior maxillary division of the trigeminal nerve that connects the pit organs to the brain. They suspended the slender nerve on a pair of wire electrodes that were connected to an electronic amplifier powering a loudspeaker. (Try that sometime. I’m leaving out some thrilling procedural details.) What they heard on the loud speaker was a constant barrage of nerve impulses shooting from the sense organ to the brain. The researchers found that when a warm or cold object was held in front of the snake’s face, the firing rate of nerve impulses either suddenly increased or decreased depending on whether the object was slightly warmer or colder than room temperature. An ice cube, for example, held in front of the snake caused the firing rate to instantaneously slow–within 50 ms (5/100s of a second). This response was much too fast to be explained by actual heating or cooling of tissue in the snake’s sense organ. They concluded that these sense organs had to be detecting infrared radiation emitted by warm objects– but how?

(I am fortunate to have had Ted Bullock as one of my mentors when I was a graduate student. His stories of delivery men and secretaries unwittingly walking into the lab and being perplexed by the sudden cacophony of buzzing surrounding them, emanating from burlap bags suspended from the ceiling, are precious. “Rattlesnakes,” he would explain offhandedly to the wide-eyed visitors who immediately departed, propelled by a jolting primal response embedded in the amygdala of human brains by evolution.)

It is difficult to imagine a sensory ability that we humans do not have, but these pit organs likely give the viper a visual sense. The neural pathways from the pit organs connect to the same brain structure as pathways from the snake’s eyes, the optic tectum. Behavioral studies by Bakken and Krochmal in 2007 indicate that the pit organ must be able to respond to temperature changes as minute as 0.001 degree C or less! This is sensitive enough to provide a detailed gray-scale image of objects from the emitted infrared radiation.

In 2002 Terashima and Ogawa reported that capsaicin, the fiery ingredient in hot peppers, caused the nerve terminals in the infrared receptors of snakes to degenerate. This is a clue that the molecular mechanism of detecting warmth somehow shares affinity with how we sense the burn of hot sauce. Indeed, in 2010, Grachevia et al., reported that the molecular basis of infrared detection by pit vipers was provided by an ion channel TRPA1 (transient receptor potential channels). This is a member of a large family of ion channels that give our own heat-sensing neurons the ability to respond to temperature changes and also give us the painful sensation of heat from hot sauce. The researchers discovered this by analyzing the genes expressed in sensory cells in the pit organs. There are many members of the TRP channel family, but more recent studies show that the same TRPA1 ion channel operates as a thermoreceptor in a wide range of animals from mosquitos to rats.

Countermeasures to heat seeking missiles--not news to squirrels

Countermeasures to heat seeking missiles–not news to squirrels


Fighter jets use thermal decoys to confuse heat seeking missiles, but ground squirrels have been using the same cleaver decoy against their venomous predators long before the DoD stumbled upon the same countermeasure. Rundus et al, found that California ground squirrels add an infrared component to their shaking tail when confronted by infrared-sensitive rattlesnakes, but squirrels don’t emit strong infrared signals from their wagging tails when confronted by gopher snakes, which lack the infrared receptors. Using a robotic squirrel to test the rattle snake’s response, the researchers found that when an infrared component was added to the flagging robotic tail, the rattlesnakes shifted from predatory to defensive behavior. This did not happen when the tail was flagged without the added infrared component. That behavior provoked the snake to strike.

Infrared emissions from squirrel tail only when encountering pit vipers, a countermeasure to rattlesnake infrared imaging.  PNAS 2007 104:14382-6.  Fig. 2.

Infrared emissions from squirrel tail only when encountering pit vipers, a countermeasure to rattlesnake infrared imaging. PNAS 2007 104:14382-6. Fig. 2.

Gees, already 1000 words and I’ve hardly gotten started. This story will have to be continued as a sequel–“Snakes on the Brain, Part II.”

Bonus Question: Can someone tell me what species of rattler it is in the photo above?

References

Bakkens, G.S. and Krochmal, A.R. (2007) The imaging properties and sensitivity of the facial pits of pitvipers as determined by optical and heat-transfer analysis. J. Exp. Biol. 210: 2801-10.

Bullock, T.H. and Cowles, R.B. (1952) Physiology of an infrared receptor: The facial pit of pit vipers.

Gracheva E.O., et al., (2010) Molecular basis of infrared detection by snakes. Nature 464: 1006-11.

Nobel, G.K., and Schmidt, A. (1937) Physiology of an infrared receptor: The facial pit of pit vipers. Proc. Am. Phil. Soc. 77: 263.

Rundus, A.S. et al., (2007) Ground squirrels use an infrared signal to deter rattlesnake predation. Proc. Natl. Acad. Sci. USA 104:14372-6.

Schaeffer, P., et al., (1996) Structural correlates of speed and endurance in skeletal muscle: the rattlesnake tailshaker muscle. J. Exp. Biol. 199: 351-8.

Terashima, S. and Ogawa, K., (2002) Degeneration of infrared receptor terminals of snakes caused by capsaicin. Brain Res. 958: 468-71.

Tomoko Aoki, Yoshiyuki Fukuoka (2010) Finger Tapping Ability in Healthy Elderly and Young Adults. Med Sci Sports Exerc. 2010;42(3):449-455

Warner MH, et al., (1987) Relationships between IQ and neuropsychological measures in neuropsychiatric populations: within-laboratory and cross-cultural replications using WAIS and WAIS-R. Clin Exp Neuropsychol. 1987 Oct;9(5):545-62.

Posted by: R. Douglas Fields | March 17, 2015

Big Brains/Little Brain: Whale Brains Provide Clues to Cognition

The cerebellum of whales suggest its role in higher level cognition.  Photo by the author

The cerebellum of whales suggest its role in higher level cognition. Photo by the author

A fascinating report on NPR by science correspondent Jonathan Hamilton yesterday (March 16, 2015) tells the story of Jonathan Keleher, a rare individual born with a major portion of his brain missing: the cerebellum. The name in Latin means “little brain,” because the cerebellum sits separately from the rest of the brain looking something like a woman’s hair bun. Neuroscientists have long understood that the cerebellum is important for controlling bodily movements, by making them more fluid and coordinated, but researchers have also long appreciated that cerebellum does much more. Exactly what these other functions are, have always been a bit mysterious. It is difficult to pinpoint the more hidden functions of the cerebellum, because some of them seem not to involve straight-forward actions that can be easily observed, for example controlling breathing or vision. But this suggests that the little brain is doing something far more complex and interesting.

Whale brains provide interesting insight into the possible functions of the cerebellum beyond its important role in regulating movement. A comparison of cetacean brains supports the growing body of research indicating that the cerebellum contributes to higher level cognitive function. A study by Sam Ridgway and Alicia Hanson compares the brains of two animals with the largest brains on earth: sperm whales and killer whales. (Pause for a minute and consider that last sentence. Having done some anatomical studies on whales as a graduate student, I can say that doing neuroanatomy on an animal that can reach 60 feet in length and 60 tons in weight, is not easy. This is not a job for a scalpel. Electric saws, chisels, and hatchets are the surgical instruments required.) Killer whales are well known from marine aquarium shows, and sperm whales are the enormous beasts harpooned in Herman Melville’s tale of Captain Ahab’s quest. What this study found is that the animal with the biggest brain on the planet (sperm whale) has a smaller cerebellum (proportionately) than a killer whale. In fact, in proportion to the size of the cerebrum, sperm whales have the smallest cerebellum of any mammal on land or sea. Why?

Both killer whales and sperm whales swim in the same way, by undulating their enormous tail (flukes). Both of these whales echolocate. They both have long gestational periods and live long lives. They are closely related animals evolutionarily; both being members of the toothed whales (odontocete). The mass of the killer whale’s cerebellum is 13.7% of its entire brain mass, but the cerebellum of sperm whales is only 7% of its brain mass.

Killer whales are much different from sperm whales in their behavior. Killer whales are the ocean’s top predator, working in organized groups to hunt down a large variety of different fish, birds, and marine mammals, whereas sperm whales graze in the deep ocean on primarily one food source: giant squid and some fish. The authors conclude that the group coordination during hunting by killer whales on a variety of elusive prey requires higher level cognition and creativity to outfox their prey, to communicate and cooperate with other members of their group. This could explain why they have a larger cerebellum proportionately than sperm whales.

The researchers cite other evidence in support of the function of the cerebellum in higher level cognition. The cerebellum increases in size going up the evolutionary tree from monkeys to great apes. Increased cerebellar size is also seen in hominoid evolution. Fossils show that early hominids had a relatively small cerebellum.

Mr. Kehler’s remarkable brain is giving similar insights into the function of this poorly understood part of the brain, but also more. His inspirational story shows how adaptable the human brain can be in some people who are fiercely determined to develop their abilities to the highest level possible.

References:
Hamilton, J (2014) A man’s incomplete brain reveals cerebellum’s role in thought and emotion. NPR, March 16, 2015 http://www.npr.org/templates/transcript/transcript.php?storyid=392789753.

Ridgway, S.H. and Hanson, A.C. (2013) Sperm whales and killer whales with the largest brains of all toothed whales show extreme differences in cerebellum. Brain Behavior and Evolution, 83;266-274.

Posted by: R. Douglas Fields | February 5, 2015

Brian Williams ‘False Memory’–a Neuroscience Perspective

Brian WilliamsNBC News anchor Brian Williams apologized for his erroneous account of being aboard a helicopter forced to make an emergency landing after being hit by enemy fire while reporting on the Iraq war in 2003. Williams blames the fallibility of human recall for the error. How can the neuroscience of memory (and false memory) provide insight?

“I would not have chosen to make this mistake,” Williams told the Washington Post. “I don’t know what screwed up in my mind that caused me to conflate one aircraft with another.”

Williams’ bewilderment is perhaps understandable. We all know that memory is fallible. Eye witness testimony has been shown often to be false, even though the witness firmly believes his or her account of what they personally experienced. Rapists sent to prison on the basis of a victim identifying the attacker without any doubt, have been found to be innocent through DNA evidence years later.

“I spent much of the weekend thinking I’d gone crazy, Williams says in the Washington Post article. “I feel terrible about making this mistake.” This is the same remorse and disbelief that shakes the victim of a rape who is forced by facts to accept that her memory was false.

To understand false memories one must first understand what a memory is and what it is not in terms of brain function. Memory is not a recording. A recording of our day-to-day experiences would be worse than useless; it would be counterproductive. Memories are fabrications, and they have to be.

“That hole [in the helicopter] was made by a rocket-grenade, or RPG. It punched cleanly through the skin of the ship, but amazingly it didn’t detonate.” This account by Williams we now know is entirely false, but consider for a moment the following. What if this picture of the helicopter with a hole pierced through it was indeed a snapshot of a true experience embossed in the mind’s ‘memory bank.” Even if it were accurate, this picture is not a memory. This picture would be much like a single frame snipped out of a movie reel. Without context, sequence, and significance in relation to other experiences, there is no memory of what had transpired.

Consider all the various sights, sounds, tastes, smells, emotions, that must be combined together to form a coherent memory, and assembled in the proper temporal sequence and in meaningful relationships between these new experience and past experiences that are essential to form a coherent memory. These multiple sensory inputs and the other aspects of mental processing required to associate emotions and other events with the new experience, must somehow tie together multiple mental functions taking place all over the brain into one scene, which we call a memory. Memory researchers call this a schema. How this assembly is accomplished is still poorly understood, but this stitching together of a mental scene is the essence of what a memory is.

One of the brain’s remarkable abilities is that it can fill in missing information to connect the dots and form a coherent memory. We can recognize a specific individual from a skilled cartoonist’s squiggly line. This mental filling in is where false memories can begin to form.

Secondly, a memory needs to be continually updated. Of what use is an outdated image of a person in our memory in recognizing that individual now or in the future? Even a picture of a loved one from years ago surprises us because we have completely forgotten that they once looked that way. That memory has been erased. We constantly update memories according to new information, and much of this happens while we sleep. Memories are not recordings; they are fabrications.

Can Williams’ false report be understood in the context of a false memory? Consider that Williams is a reporter. His function and purpose while on the scene in Iraq was to record facts and to do so accurately. There is no opportunity for false memory in this situation. Just as a scientist would never falsify data, because doing so would completely undermine their objective, neither would a reporter. Researchers do sometimes fudge data, but scientists do not. Likewise, there is not and cannot be any false memory in the mind of a reporter.

Reference
Paul Farhi February 4, 2015. Brian Williams admits that his story of coming under fire while in Iraq was false. The Washington Post

http://www.washingtonpost.com/lifestyle/style/brian-williams-admits-that-his-story-of-coming-under-fire-while-in-iraq-was-false/2015/02/04/d7fe32d0-acc0-11e4-9c91-e9d2f9fde644_story.html

Posted by: R. Douglas Fields | January 27, 2015

Synapse Poisons in Croc Bile Beer the Likely Killer in Mozambique

aleOn January 11, 2015 news swept the globe reporting that scores of people died and 200 were sickened by drinking beer poisoned with crocodile bile in Mozambique. Thinking is now shifting to the possibility of poisoned synapses, not reptilian bile as the cause of these deaths.

A horribly tragic incident occurred at a funeral on January 9, 2015 in Mozambique, when people who had come to pay their last respects suffered poisoning from consuming the traditional home-made beer that was served. The mass fatalities of over 70 people devastated families, leaving many children orphans overnight. The toxic substance in the beer is still not known, but the media frenzy is astonishing. Is crocodile bile a deadly poison? How much bile can a person drink anyway? What is it in croc bile that could be so potent, trace amounts too weak to taste could kill and sicken hundreds of people?

Science writer for Forbes, David Kroll, traced the story back to the source. What he found was rumor and superstition, and what is more important, a likely cause of all this death. I refer you to his article for the details of his investigation and the suspicion that croc bile was not likely the poison in this brew.

The cause of these deaths is not yet known, but if it wasn’t croc bile that killed the beer drinkers, let’s have a look at the alternatives being suggested–all of them are related to nervous system function, and along the way delve a bit into the science of homebrew.

Not what made Milwaukee famous

The beverage brewed in Mozambique is a far cry from the Bud Light that most Americans associate with beer. Called pombe, the brew is a mixture of corn, bran, sorghum, and sugar, fermented with a different species of yeast (Schizosaccharomyces pombe) from the Saccharomyces cerevisiae used for making beer and wine. Beer as we know it is made from malted barley and hops. The fermented drink in Mozambique appears to somewhat resemble the corn-based traditional beverage, called chicha, which has been made in South America for centuries.

Professor Javier Carvajal Barriga, a microbiologist at Pontificia Universidad Católica del Ecuador in Quito, Ecuador, has resurrected yeasts from ancient fermentation vessels and other sources all over the world, including fermentation pottery from a pre-Incan tomb. From a fermentation vessel dating from 650 AD, Professor Carvajal Barriga resurrected dormant yeast and discovered an entirely new species, which he named Candida theae. This discovery also provided clues to how the ancient brew was made. Human spit was used to break down the corn starch into sugar that yeast can ferment into alcohol. (Saliva contains the starch digesting enzyme, amylase). His microbiological research also supported what conquistadores recorded about the traditional chicha recipe: that human feces were added to start the pot fermenting.

This is not how beer is made today. Malted barley is used, making spit unnecessary. Malting is a process whereby the grain is moistened and allowed to start sprouting. When a seed sprouts it generates enzymes to break down the starch to sugar, which is the energy store that will feed the sprouting plant. Beer makers hijack Nature’s intentions by roasting the freshly sprouted barley to stop the germination process right after the enzyme is made. Then the brewer adds water to make a porridge that must be held at a precise sequence of temperature steps to coax the enzymes to make sugar from the starch. Yeast can then convert the sugar to alcohol and carbon dioxide. How early humans figured this all out is baffling, but no less amazing than the ingenuity used to make chicha.

So I when I heard of this mass death in Mozambique from poison pombe, I contacted Professor Carvajal Barriga for his insights.

“I’m really surprised by this news of poisonous beer,” Carvajal Barriga says. In the middle ages they used rats, cats, a number of flowers and other elements like fungi to give magical properties to their brews. Some of those primitive beers would have been poisonous as well.”

When I visited his lab in Quito in 2012, we shared a wonderful Belgian style ale that Carvajal Barriga had brewed from yeast he resurrected from an ancient oak vat that had held the first beer brewed in America. I remember him telling me how plants or mushrooms with psychoactive properties often would be added to the ancient chicha. (He could see this, by identifying species of yeasts in the ancient fermentation vessel that are associated with these other plants.) The ancient brew masters resorted to this because the species of yeast that they had to work with is killed by relatively low alcohol concentrations. So, unable to achieve the alcohol content of the beer we enjoy today, (outside the state of Utah), the bier meisters would toss in other substances to give the brew more of a kick.

“The poisoning in Mozambique may be due to chemicals added to the beer via flowers or even microtoxins produced by molds living on cereals,” he suggests.

This is the same theory considered by Kroll in his Forbes article; specifically, the possibility that the foxglove plant might have been added to the Mozambique brew. Foxglove is the source of digitalis, a drug used for regulating heartbeat. The plant compound acts on the vagus nerve, part of the parasympathetic nervous system regulating heartbeat, and also acts directly on cardiac muscle, by changing the concentration of sodium ions inside these nervous system cells. The cellular voltage produced by neurons and muscle cells results from an imbalance in charged ions across the cell membrane–just as voltage is produced in a battery. Digitalis inhibits a membrane pump (sodium-potassium ATPase) that pushes sodium ions out of the cell and sucks potassium ions into the cell. When the pump is impaired by digitalis, sodium ions seep back in and the cellular voltage drops. This has a number of consequences, most importantly, changing the amount of calcium ions inside the cell. Calcium ions control many vital cellular processes, including the firing of synapses (i.e., release of neurotransmitter).

Poisoning synapses

Mass deaths at social gatherings often result from food poisoning, frequently caused by clostridial toxins made by bacteria found naturally in the soil, for example botulinum toxin. Botulinum toxin is one of the most deadly toxins known to man. The reason for this is that this toxin attacks the fundamental mechanism of communication in the brain–synaptic transmission.

When a nerve impulse reaches a nerve terminal, voltage-sensitive channels in the neuronal membrane open briefly and admit a spurt of calcium ions. These ions activate a protein called synaptotagmin, which is part of a complex machinery of molecules that tether synaptic vesicles next to the cell membrane of the nerve terminal. Synaptic vesicles are like submicroscopic “water balloons” filled with neurotransmitters, small molecules of various types that carry messages between neurons. When stimulated by an electrical impulse, this molecular machinery causes the synaptic vesicles to fuse to the cell membrane and rapidly dump its contents out of the neuron to stimulate receptors on the next neuron in the circuit.

Botulinum toxin (and tetanus toxin), cut the synaptic vesicle release proteins, thereby blocking synaptic transmission. (Either the synaptic proteins synaptobrevin, SNAP-25, or syntaxin can be attacked, depending on the specific type of Botulinum toxin.) The consequences of cutting communication lines in the nervous system are catastrophic, and food poisoning from clostricial toxins can kill quickly.

But beer is not often a source of food poisoning. This is because the process of brewing beer, unlike the process of making wine, requires prolonged boiling. Even a dead rat would become sterilized in the process of brewing beer. The poisoning in Mozambique most likely attacked synapses, but in a different manner.

Organophosphates

The extraordinary potency of clostridial toxins inspired the creation of man-made neurotoxins that work in a similar way for use in warfare against other people (nerve gas) or against insects (pesticides). At this point, this explanation seems the most likely cause of the mass death among the beer drinkers in Mozambique, according to the Forbes article. The brew was concocted in large barrels. If these or other utensils used in brewing, had been recycled from drums with pesticide residue in them, even low levels of organophosphates could have proven fatal.

Organophosphate pesticides work by inhibiting neurotransmission at synapses that use the nerurotransmitter acetylcholine to communicate. This includes the synapses called neuromuscular junctions that control our muscle contractions. Once acetylcholine is released from the nerve terminal and activates the muscle, the chemical signal to contract muscles must be terminated. This is accomplished by an enzyme in the synapse (acetylcholinesterase), which rapidly breaks down acetylcholine. Organophosphate pesticides and Sarin nerve gas prevent this enzyme from working. Unable to control muscles for breathing and other essential bodily functions that are controlled by synapses using acetylcholine, the victim (bug or enemy) dies quickly and quite miserably.

This brings the Mozambique tragedy close to home. An FDA analysis determined that 49% of fruit, 29% of vegetables, and 26% of grain products produced in the United States have pesticide residue. 50% of shallow water wells have pesticide contamination at detectable levels. Children are especially vulnerable to pesticide exposure because their smaller bodies make the same amount of pesticide on one apple a much higher dose than for an adult. Also, children crawl on the floor, play in dirt and put things in their mouths, increasing their exposure to pesticides. Organophosphate pesticide levels in people living in agricultural areas are higher than in people living in urban areas, but in a large sample of children between ages 8-15 in the general population, the level of pesticide residue in urine samples correlates directly with a risk for attention deficit hyperactivity disorder (ADHD).

In a 2012 review article in the journal Pediatrics the authors conclude that organophosphate exposures that are being experience by US children in the general population may have adverse neurodeveopmental consequences. The consequences of organophosphate exposure to the fetus and young children are known to include decreased IQ, ADHD, neurodevelopmental disorders, and cancer. For example, a study of Latino farm worker families from agricultural regions showed that organophosphate levels in urine from pregnant women were associated with lower IQ in their children at 7 years of age. Finally, many veterans of the Gulf War suffered chronic illness, which appears to be related to low-level exposure to Sarin gas and organophosphate pesticides they were exposed to on the battlefield.

We can only hope that the cause of the poisoning in Mozambique can be found, and that we learn from the tragedy.

Figure Caption An ale made by infusion mash of English pale malted barley, crystal and dextrin malt, and Monteuka, Nelson Sauvin and Green Bullet hops from New Zealand and Nottingham Ale yeast.

References

Fields, RD (2012) Raising the Dead: New Species of Life Resurrected from Ancient Andean Tomb Scientific American on-line February, 19, 2012 http://www.scientificamerican.com/article/new-species-resurrected-ancient-andean-tomb/

Kroll, David, (2015) Did crocodile bile really kill 73 people in Mozambique. Forbes January 12, 2015 http://www.forbes.com/sites/davidkroll/2015/01/12/what-is-crocodile-bile-and-is-it-really-poisonous/

Kroll, David, (2015) Crocodile Bile Expert Suspects Toxic Pesticide In Mozambique Tainted Beer Tragedy Forbes, January 14, 2015

http://www.forbes.com/sites/davidkroll/2015/01/14/crocodile-bile-or-toxic-pesticide-mozambique-death-toll-at-73-from-tainted-beer/

Roberts, JR and Karr CJ Pesticide Exposure in Children Pediatrics 130: e1765, 2012

US FDA Center for Food Safety and Applied Nutrition. Pesticide residue monitoring program http://www.fda.gov/Food/FoodborneIllnessContaminants/Pesticides/UCM2006797.htm

Posted by: R. Douglas Fields | January 14, 2015

Neuroscience of ‘Under the Skin,’ Starring Scarlett Johansson

UnderSkin (2)In the eerie science fiction film, Under the Skin, starring Scarlett Johansson as an alien vixen clothed in human skin, roaming the earth in search of single men for nefarious purposes, a turning point comes when she offers a hooded man on a dark road a ride in her vehicle. When the man takes off his hood we see his shockingly disfigured face. It is not make up. The disfigurement is caused by a genetic condition, neurofibromatosis, affecting actor Adam Pearson. Pearson’s brother has the same disorder, but no disfigurement. Instead he suffers memory problems. The film is a head scratcher–in the best possible way–but neurofibromatosis is not. Let’s have a look.

When Adam Pearson was a school boy he was often taunted as “Elephant Man” by bullies. In fact, one prevailing theory is that the real Elephant Man, Joseph Merrick, suffered from neurofibromatosis. A new paper by Huntley, Hodder and Ramachandran, in the journal Gene, gives a vivid account of the discovery of the Elephant Man in Victorian England, and recounts the scientific sleuthing over the last 125 years to identify the medical condition that caused Merrick to have skin and body features resembling an elephant.

Joseph Merrick was a single-case study presented to the Royal London Hospital in 1884 at the age of 21. Merrick, from Leister England, was discovered at a Freak Show by Sir Frederick Treves, Surgeon to Queen Victoria. The doctor did not routinely seek such entertainment; he went there specifically to see a man on exhibition advertised as having the features of an elephant. Treves paid a shilling to have a private viewing after hours. Sir Treves’ examination documented that Merrick had a large number of disfiguring growths all over his body that made it difficult for the man to speak, sleep or walk. Many of his bones were misshapen and his skull was grossly enlarged, and malformed. Sir Treves described Merrick as “the most disgusting specimen of humanity that I have ever seen.” (Read that with a proper British accent for full effect.)

Soon after the paper describing the case of the Elephant Man was published in 1885 in the journal Trans. Pathol. Soc. London, “A Case of Congenital Deformity,” Freak Shows in Jolly Old London were outlawed. Adding to that tragedy, Merrick was robbed of his life savings by his show manager and he ended up stranded at the Liverpool Street Station, homeless, penniless, and unable to make himself understood because of his speech impediment. The police brought him to Sir Treves, who appealed to the good-hearted public for assistance in a letter to the Times. Within one week he collected enough money to support Merrick the rest of his life at the hospital.

For the rest of the fascinating story of the real Elephant Man, and a recent determination of the medical condition that afflicted Merrick, I highly recommend this new article in the journal Gene. Spoiler alert: the authors conclude that Merrick did not have neurofibromatosis, but instead suffered from a condition called Proteus Syndrome, which is caused by a mutation in the gene PTEN.

Neurofibromatosis is a genetic disorder that causes tumors to grow in the nervous system. I actually published a small paper on neurofibromatosis from research in my lab, which is as close as I expect I will ever get to Scarlett Johansson.

In your dreams, buddy.

In your dreams, buddy.

The tumors in nerves cause disfigurement. As you would expect, they often cause a wide range of neurological problems, from hearing loss to learning impairment, depending on where the tumors grow and interrupt normal communication through nerve axons.

Neurofibromatosis 1 (NF1) causes harmless spots on the skin and tumors under the skin anywhere on the body. Bone growth is often deformed, for example by bowed lower legs or a curved spine. Mild learning disabilities are common, as well as attention-deficit/hyperactivity disorder (ADHD), but not in all cases. The head is typically larger than normal. So there are indeed several similarities to the features exhibited by the Elephant Man, but these are only superficially similar to neurofibromatosis.

Neurofibromatosis 2 (NF2) also causes nerve tumors by unregulated growth of Schwann cells, the glial cell of the peripheral nervous system. Schwann cells form the myelin sheath that is essential for rapid impulse conduction through axons in peripheral nerves. Other Schwann cells encase bundles of slender axons that conduct impulses slowly because they lack the myelin insulation. Hearing loss and balance problems are a common but the tumors can grow in many different nerves causing a wide range of symptoms.

The NF1 gene is on chromosome 17. It normally makes the protein neurofibromin, which helps regulate cell growth. NF2 is caused by the NF2 gene located on chromosome 22. This gene produces the protein merlin, which also controls cell growth.

In either case, you need to inherit only one copy of the mutant gene to get the disorder (autosomal dominant), which means that if you have neurofibromatosis there is a 50:50 probability that your offspring will inherit the disease.

“My kids are going to be genetically awesome anyway,” Pearson says displaying the spunk that has made him a successful actor in a major film. “Now that I’ve appeared nude with Scarlett, I want to be a Bond Villain,” he says. Pearson is also a supporter of the charity Changing Faces which supports people who have medical conditions or injuries that affect their appearance by helping them cope with life. Fundamentally, the coping techniques are to help such people deal with other people’s prejudices and societal reactions to those who are disfigured by burns, injuries, or genetic deformities.

In the movie, the moment when the female alien in human skin meets the character played by Adam Pearson the plot turns, because like the alien herself, the real person who is Adam Pearson, is to be found under the skin.

***Coda***

After my scathing reviews* debunking the inane science fiction movie Lucy, starring Scarlett Johansson, it is nice to have this opportunity to endorse Under the Skin. People either love or hate Under the Skin. This can be explained by the fact that Lucy is a movie, but Under the Skin is a film. A film is a work of art. Art presents captivating and thought-provoking images and performances, left to interpretation by the viewer. Art transcends language in illuminating humankind and the natural world. Under the Skin exposes core issues of sex, gender roles, what it is to be human, and inhuman, but it does it in a way that requires the viewer to bring to the performance their own elusive perceptions, intrinsic beliefs, and fantasies that lie beneath the surface of thought.

For a good review of this film I recommend:

Seitz, M.A. (2014) Under the Skin Movie Review. http://www.rogerebert.como/reviews/under-the-skin-2014

* Fields, R.D. (2014) Cinema Peer Review: Douglas Fields Reviews ‘Lucy’ World Science Festival, July 29, 2014 http://www.worldsciencefestival.com/2014/07/cinema-peer-review-lucy/

*Fields, R.D. Lucy Debunked, Science Friday, August 8, 2014 http://www.sciencefriday.com/guests/r-douglas-fields.html#page/full-width-list/1

References

Changing Faces http://www\changingfaces.org.uk

Day Elizabeth (2014) How Scarlett Johansson helped me challenge disfigurement stigma. The Guardian, April 12, 2014.

Huntley, C., Hodder, A., and Ramachandran (2015) Clinical and historical aspects of the Elephant Man: Exploring the facts and the myths. Gene 555:63-65.

Pearson, A. (2014) ‘Now that I’ve appeared nude with Scarlett, I want to be a Bond villian’: TV’s Beauty and the Beast star hopes to beat prejudice after big-screen debut. Daily Mail, March 29, 2014.

Posted by: R. Douglas Fields | December 21, 2014

The Absurdity of “Medical Marijuana”

marijuana leafMarijuana use is legal in many states for medical purposes, most of them dealing with neurological conditions (pain, epilepsy, tremor, multiple sclerosis, and many others). From the perspective of a neuroscientist researcher, the situation with respect to “medical marijuana” is absurd.

I watched as the young woman inhaled the pungent smoke deeply into her lungs and held it for a second. Clouds of blue-gray smoke exploded from her mouth and nose in a series of short violent coughs. “Sorry, this strain is kind of harsh,” she said.

Rebecca, a bright graduate student at one of the nation’s leading universities, was eager to demonstrate to me the immediate medical benefit marijuana provided her. Out of respect for her privacy, I will not delve into the specific neurological condition Rebecca had discovered was improved by the use of marijuana; moreover, the issue here is much larger than any one condition. The issue is the absurdity of current regulations on medical marijuana and the profound injury these laws are causing thousands of people, while fortifying a wall of ignorance that neuroscientists cannot easily surmount.

Rebecca has a legal prescription to use medical marijuana for her condition, which she administers by vaporizer. The condition Rebecca is using medical marijuana to treat by self-medication is chronic, serious, and there is no drug available to treat it. Rebecca has scoured the medical and neuroscience literature, and collected compelling scientific evidence for the possible benefit of marijuana for this condition, based on the expression of CB1 and CB2 cannabinoid receptors in the appropriate neural circuits involved. (These are the receptors on cell membranes that are stimulated by the active components in marijuana.) The problem is that the legal restrictions on studying marijuana in people are so arduous or impenetrable, that performing the simple experiments that would advance scientific knowledge and could lead to powerful new treatments for disease are nearly impossible.

Thankfully the horrors of the past when medical experiments were sometimes performed on people without their full knowledge and consent are gone. (In most countries.) All research involving human subjects in the United States must be reviewed and approved in advance by an independent review board that carefully weighs the risks and benefits to ensure that the experiments are ethical, scientifically warranted, and conducted properly to protect the health and interests of the person volunteering to participate in the study. This is a rigorous process and it should be.

The problem is that the laws regulating marijuana in some states, as well as federal laws, make it impossible or nearly impossible to do research on the biology of marijuana and its potential medical benefits. The PhD advisor of a graduate student I know laughed at him when he proposed to study the neuroscience of marijuana addiction in rats, because it would be so difficult to obtain the active ingredient in marijuana (THC) for experimental research. The mentor advised his student that he would be far better off to change his research to study cocaine. He did so.

A colleague of mine, a well-known expert on hippocampal synaptic function, became interested in what appeared to be a possible significant role of CB1 cannabinoid receptors on neurons in regulating development of a particular type of neural circuit. “Getting the clearance to work with THC was impossible,” he told me. The studies he proposed were on experimental rats not people, which is far less arduous than obtaining permission to do experiments on people. Undaunted, the researcher found a synthetic analog of THC that was unregulated, but was actually far more potent than THC, and he began his studies with this compound. Such cleaver circumvention of the restrictive laws on cannabinoids in experimental research are rarely possible. Moreover, any results obtained will have to be tested eventually with real marijuana, a plant that contains 60 different cannabinoids in various mixtures and concentrations that vary greatly in different plant strains.

In Rebecca’s case, the ethical issues related to studying the neurological effects of marijuana would seem much less problematic, because she has a legal prescription to use marijuana for her condition. The research would not subject her to additional risk; it would simply examine the biological effects on the patient of the currently prescribed medication. However, the researcher with the expertise to examine the effects of marijuana on her condition works at a University in another state where marijuana possession is a crime. The researcher has vigorously pursued the appropriate avenues to undertake this experiment, but it is not possible. The time and effort to gain approval to do the research are insurmountable obstacles, given the investigator’s other research responsibilities. Moreover, the judgment of officials familiar with such approvals are that regardless of the scientific merit and ethical justification for doing the research, marijuana is illegal in that state. The research could not be done there. Similarly, federal law criminalizes marijuana use, even for medical purposes, and most biomedical research is funded by federal grants.

A recent survey of the medical literature on the benefits of marijuana for the wide range of neurological conditions (published this year in the journal Neurology) found 34 studies performed between the years 1948 and 2013 that met their criteria for inclusion. Stop right there. 34 studies! Only 34 studies were found for the enormous range of neurological conditions where activation of CB1 and CB2 receptors in the brain by compounds in marijuana could have an effect? There are 32,836 studies in the scientific literature on “health and tobacco.” There are 87,735 studies on “health and alcohol” in the medical literature (PubMed search). The authors reviewing the scientific literature on marijuana found only a total of 1729 studies in the literature, but only 34 studies since the Truman Administration met the criteria to be useful for inclusion in an analysis of the efficacy of medical marijuana on neurological conditions. The criteria for inclusion required that the studies were well-designed, randomized, with placebo-controls, performed on humans; not anecdotal reports,human studies without controls or animals studies.

It is not the scientific rationale for possible effects of marijuana on neurological conditions that can account for the lack of research: the effects of marijuana on the central nervous system are obvious and potent. It is not a lack of interest among researchers in studying how CB1 and CB2 receptors regulate development and function of the brain, and how this new knowledge could lead to new drugs for treating disease and human suffering. The difference is that alcohol and tobacco are legal; marijuana is not.

Tobacco, alcohol, and morphine, are all plant products, just like aspirin. All life on this planet shares a common system of biochemistry. Compounds in plants have powerful effects on the human body, some are poisonous toxins and some are priceless cures. Plants have yielded a treasure trove of potent new drugs that have treated or cured diseases throughout human history, and eased human suffering. New drugs have been developed from plants that have changed the world. Oral contraceptives were developed from a jungle plant, leading to a technological development that has helped countless women with many medical conditions and transformed the lives of women and society by putting women in control of the biological systems at work in their own bodies. But marijuana is off limits.

Science is strangled by a government-imposed catch-22 that restricts access to marijuana on the basis that there is insufficient evidence supporting its medical benefits and safety, while blocking the research that would provide such information.

So we have this absurd situation where the use of medical marijuana is legal in 22 states, yet the scientific research that would uncover the molecular mechanisms by which this plant can treat a wide range of medical conditions is impossibly difficult to perform. In states where the drug is illegal, research is all but impossible. Businessmen decry onerous government regulations that hamper commerce and diminish financial profit, but there the losses are investor’s dollars not people’s lives to disease.

With 60 known cannabinoids in this plant, and the mixture and potency varying widely among strains and from batch-to-batch, patients are left to self-experimentation to find a strain that works for them. Is it Super Silver Haze, White Widow, Skywalker, or God’s Gift? Who knows? The patient is compelled by law to engage in desperate self-experimentation of the sort that would never be approved by an Institutional Review Board examining a proposed scientific study.

Meanwhile there are countless natural products approved for use and promoted for medical benefits that have dubious efficacy or scientific foundation– chondroitin sulfate, Gingko, green tea, resveratrol in red grapes, vitamins of every type and in endless combinations–but cannabis is banned, paradoxically precisely because the compounds in it do have obvious and potent effects on the CNS.

Rebecca discovered the beneficial effect of marijuana on her medical condition by chance in using marijuana recreationally, but she does not want to be dependent on it for her medical needs. There are far too many obvious adverse effects. Any potent drug has adverse effects, but without knowing exactly what compound or combination of compounds in marijuana are helping and which are hurting, and without the necessary scientific research to understand the biological facts that would accelerate the development of potent, effective, and safe new drugs, she has no choice. What she wants is to help scientists discover how this drug is working for her, and help them to develop the right drug that will work but not leave her stoned or at risk from other dangerous compounds in marijuana and the very real harmful effects of cannabis if used incorrectly.

So here we are in the 21st century condemned like cavemen to eat leaves or smoke them for medical uses because the legal regulations restricting access to this particular plant for scientific research are so arduous, for political reasons, that we are constrained by law to the practices of witch doctors.

Reference

Koppel, R.S. et al., (2014) Systematic review: Efficacy and safety of medical marijuana in selected neurological disorders. Neurology, 82, 1556-1563.

Posted by: R. Douglas Fields | December 8, 2014

How is the brain like a guitar? Hint: It is all about rhythm

guitarbearclawtop Typically we are introduced to the nervous system by analogy to an electrical circuit, like a door bell or a telephone line carrying a signal rapidly over long distance to activate a specific process. Never mind that electrical impulses are not transmitted through nerve axons anything like electrons flowing through a copper wire, this electronic circuit analogy is useful up to a point. If you want to understand how the brain works at a more complex level, you are going to need a new analogy, and if you play an acoustic guitar you’ll find it under your fingertips.

Dr. Hans Berger, working at the Psychiatric Clinic at the University of Jena, Germany in the 1920’s was the first person to discover that the human brain radiated waves of electrical energy that could be picked up by electrodes on the scalp. He performed his experiments in secret on hospital patients and on his own son in a small building separated from the rest of the hospital. Initially he believed that he had detected the physical basis for mental telepathy. He told no one in the scientific community about his mysterious findings until after five years of secret experiments.

Fundamentally, Berger, whose daily life was devoted to caring for people with mental illness, was searching for a physical basis for brain function. This was a leap of insight decades beyond his contemporaries. The idea that the human mind and mental illnesses have a physical basis of operation that could be reduced to physical principals and understood by approaching the operation of the mind in the same way a physicist would approach any other phenomenon in nature–by physical measurement–was well outside the realm of thinking among his colleagues in psychiatry.

His brutal approach of stabbing a thermometer deep into the brain of his patients who had survived gunshot wounds leaving holes in the skull, and then provoking various emotional and sensory stimuli to see whether their brain tissue changed its temperature in the process of mental function raises ethical questions by today’s standards. His patients must have had no real understanding of what was being done to them or why, and an attempt to monitor the intricate workings of the human brain in the same way one might use a candy thermometer to monitor the process of making fudge, seems naive in retrospect. However, Berger did not have the advantage of our vantage point. In applying the crude tools available in his day, thermometers and the newly developed electronic amplifier, Berger was doing precisely the same thing that cutting edge neuroscientists today are doing with functional magnetic resonance imaging (fMRI), which allows us to see inside the brain at work and pinpoint where, when, and how its different parts operate. Berger was a man whose scientific ideas were a century ahead of the technology needed to study them.

Brainwaves had been detected in animals, but not in humans before Berger’s experiments. What he observed by attaching electrodes to the scalp and feeding the signals into an electronic amplifier was that the human brain’s electrical activity was not entirely confined to transmission through the wire-like axons connecting neurons into circuits. Instead, the electrical energy of neurons radiated out of the skull like the electromagnetic field radiating from a broadcast antenna or for that matter from any electrical circuit. This is something we all have experienced in hearing the annoying hum of 60 cycle electromagnetic interference that radiates from our electronic devices when it is picked up and amplified unintentionally by sensitive electronic instruments.

Psychiatric hospital in Jena, Germany where Hans Berger first recorded human brain waves

Psychiatric hospital in Jena, Germany where Hans Berger first recorded human brain waves

Moreover, Berger discovered that the electromagnetic energy emanating from the human scalp progressed in waves of certain characteristic frequencies that changed with mental state. The 8-12 Hz brainwaves that he measured, originally called Berger waves and now called alpha waves, swelled in his son’s brain as he sat quietly in that laboratory with his eyes closed, but when his son opened his eyes, his brainwaves abruptly changed. The alpha waves subsided like ocean waves squelched by rain on a windless sea.

Today we know that the electrodes on the scalp are intercepting the combined activity of millions of neurons in the surface layers of the brain, the cerebral cortex, each one sending signals to another neuron in complex circuits. Like the noise of a crowd in a baseball stadium, these electroencephalogram (EEG) recordings are the combined output of all the individual conversations and exclamations going on in the crowd of neurons beneath our skull. These conversations and exclamations wax and wane and sometimes burst with synchronized cheers in response to something that has stimulated them all. But why the oscillations at such characteristic frequencies?

Human brain waves first recorded by Hans Berger

Human brain waves first recorded by Hans Berger

Scientists soon discovered that there are several different characteristic frequencies of brainwave oscillations; each one accompanies different types of mental activities, including attention, consciousness, arousal, meditation, and many other cognitive processes. The question is whether these waves of electrical energy have any function or are simply an epiphenomenon, like the roar of an engine which changes with different states of activity, but the engine’s sound has no impact on the operation of the engine. To glimpse the answer to this question, which is at the forefront of current research in neuroscience, consider the guitar.

The difference between the rich and responsive sound of a classical guitar and the twang of a banjo has nothing to do with the action of the strings that generate the sound when they are plucked. The difference is in the resonance of the guitar’s body, which not only amplifies the sound of the strings vibrating, it blends all the sounds the strings can create into a harmonious and vibrant acoustic radiation. Some frequencies of sound combine and are thus amplified, and others are cancelled out because the two frequencies of oscillation are out of phase, dampening out the sound of the string at that frequency. In the same way that noise-cancelling headphones block out sound by generating the same waveform out of phase to cancel it, that particular frequency generated when the string is plucked makes no sound. If it did, the sound would create an annoying noise because it is not a frequency compatible with the musical scale.

Luthiers, who build acoustic stringed instruments like guitars and violins, are masters at crafting all the wooden components that go into constructing the instrument such that the instrument as a whole resonates harmoniously at just the right combination of frequencies, while dampening the sounds that interfere with the optimal operation of the instrument. The luthier achieves this result by carefully evaluating the weight, dimensions, and stiffness of all the wooden components that go into making the guitar, shaving them down to precise thickness and dimensions such that he or she can consistently produce a beautifully sounding and responsive instrument. This cannot be done by following a blueprint, because every piece of wood is slightly different in weight, stiffness, grain tightness and orientation. Different types of woods vibrate at different frequencies and reflect or absorb sound waves slightly differently. There are far too many variables to consider, which is why making fine guitars is an art, not a science.

Shaving the top braces of an acoustic guitar

Shaving the top braces of an acoustic guitar

The luthier fusses carefully over the top surface of the guitar, because this plate of wood acts like a speaker cone to radiate the sound, while the back and sides of the guitar operate like the speaker cabinet to further modify and direct the sound energy. The luthier will brace the top with slips of wood and shave them with a chisel to force it to vibrate in very precise ways that will combine all of the bass and treble sounds desired into a harmonious tone. He will shave the top plate of wood down carefully with a hand plane and test the acoustic effect periodically by lifting the plate to his ear by pinching it between thumb and finger, and tapping it briskly with his knuckle. A good sound board will ring with a complex and brilliant sound when it is tapped, so this process of carefully thinning down the wood is called “tap tuning.”

As the luthier carefully shaves the top thinner the tap tone lowers in frequency because the stiffness of the wooden plate is being reduced gradually, making it better at vibrating at low frequencies and worse at vibrating at high frequencies. The decision of when to stop thinning the top is critical and somewhat mysterious, because it is not a precise frequency that the luthier’s ear is listening for; it is a certain rich complexity of tones radiating with clarity and brilliance. If the top plate is thinned too much, it suddenly becomes useless. Knowing when to stop thinning is what separates the master luthier from a furniture maker.

Guitar resonating at 220Hz

Guitar resonating at 220Hz

Guitar resonating at 600 Hz.

Guitar resonating at 600 Hz.

It is possible to see the acoustic action of a guitar top by scattering glitter over its surface and playing specific frequencies of sound through a loudspeaker. Sweeping slowly from low frequency to higher frequency the glitter covering the top suddenly begins to vibrate and dance over the surface. Suddenly at a certain frequency of sound, all the particles of glitter dancing on the surface suddenly form a tight circle. This indicates that the entire top of the guitar is waving up and down, throwing the glitter off the vibrating surface and into the stationary borders, or node. This is the fundamental frequency of the guitar’s top. When the strings generate this frequency the guitar will broadcast a strong, loud tone at this frequency–the lowest frequency the guitar can generate effectively.

Now as the luthier slowly sweeps the sound from the loudspeaker to a higher frequency, the glitter suddenly begins to dance again, and like band members at halftime the glitter comes together, re-arranges, and forms two circles on the top of the guitar as shown in the accompanying photo. The guitar top is now vibrating at higher frequency such that the left and right sides of the guitar top are each oscillating simultaneously. This only occurs at this precise higher frequency. This same process will occur at other specific resonant frequencies making the guitar vibrate in different ways and revealed by different geometric patterns of glitter formed on its vibrating surface.

Now imagine that the top of this guitar in the figure accompanying this article were the top of your brain: the cerebral cortex. If the population of neurons in the sheet of brain cells in our cerebral cortex were firing at this specific frequency what would happen? Both parts of the cerebral cortex, separated by long distances, would suddenly begin to function in synchrony, just like the left and right sides of the guitar top shown above vibrating in synchrony at 600 Hz. This is what brainwaves do. Neurons fire electrical impulses when the voltage of their cell membrane reaches a specific threshold. If the membrane voltage is fluctuating up and down slightly below the threshold for generating an electrical impulse, a signal that arrives when that neuron is close to threshold will make it fire an electrical impulse, but the same signal that arrives when the oscillating voltage is at its trough would fail to reach threshold and the neuron would remain silent. Thus, brainwaves can couple activity of large population of neurons into functional groups, just as ocean waves move all boats at anchor in a harbor in synchrony even though they are not directly tethered to each other. In this way, the transmission and operation of neurons in the brain become coupled into functional assemblies.

Such oscillation is what couples activity of neural circuits into groups, providing a way to couple neural circuits together over long distances so that they operate simultaneously, even though they are not directly tethered together. This resonance is what combines mental activities together and tunes our level of attention and other mental states. Consider, for example, how all the diverse aspects of an experience, sights, sounds, emotions, time and place, somehow get coupled together to form a memory. Without the simultaneous activity of all the neurons in different regions of the cerebral cortex all firing together, the scene (or schema) evoked by a memory could not develop. This is much like the unique sound of say, a C# minor chord, making the entire guitar operate as a system to evoke a rich and specific tone that evokes a very specific emotional and cognitive response in our brain when we hear it.

More to explore
1. For an excellent book on brain waves see: Buzaki, Rhythms of the Brain, Oxford University Press, 2011.

2. I was able to visit Hans Berger’s laboratory and go through his notebooks in researching the chapter on his research for my book The Other Brain, where interested readers can find more on Hans Berger and brainwaves. http://theotherbrainbook.com.

3. Those interested in guitar building may find this article written for the Washington Post Sunday Magazine of interest. The title of the article is “The Last Guitar,” but it was changed by the publisher to “Guitar Hero.” http://www.washingtonpost.com/wp-dyn/content/article/2007/09/04/AR2007090401785.html

The guitar images accompanying this article are from the author’s workshop.

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