Archive for the ‘neurosurgery’ Category

They say laughter is the best medicine. But what if laughter is the disease?

For a 6-year-old girl in Bolivia who suffered from uncontrollable and inappropriate bouts of giggles, laughter was a symptom of a serious brain problem. But doctors initially diagnosed the child with “misbehavior.”

“She was considered spoiled, crazy — even devil-possessed,” Dr. José Liders Burgos Zuleta, ofAdvanced Medical Image Centre, in Bolivia, said in a statement.

But Burgos Zuleta discovered that the true cause of the girl’s laughing seizures, medically called gelastic seizures, was a brain tumor.

After the girl underwent a brain scan, the doctors discovered a hamartoma, a small, benign tumor that was pressing against her brain’s temporal lobe.The doctors surgically removed the tumor, and the girl is now healthy, the doctors said.

The girl stopped having the uncontrollable attacks of laughter and now only laughs normally, the doctors said.

Gelastic seizures are a form of epilepsy that is relatively rare, said Dr. Solomon Moshé, a pediatric neurologist at Albert Einstein College of Medicine in New York. The word comes from the Greek word for laughter, “gelos.”

“It’s not necessarily ‘hahaha’ laughing,” Moshé told Live Science. “There’s no happiness in this. Some of the kids may be very scared,” he added.

The seizures are most often caused by tumors in the hypothalamus, especially in kids, although they can also come from tumors in other parts of brain, Moshé said. Although laughter is the main symptom, patients may also have outbursts of crying.

These tumors can cause growth abnormalities if they affect the pituitary gland, he said.

The surgery to remove such brain tumors used to be difficult and dangerous, but a new surgical technique developed within the last 10 years allows doctors to remove them effectively without great risk, Moshé said.

The doctors who treated the girl said their report of her case could raise awareness of the strange condition, so doctors in Latin America can diagnose the true cause of some children’s “behavioral” problems, and refer them to a neurologist.

The case report was published June 16 in the journal ecancermedicalscience.

Thanks to Michael Moore for sharing this with the It’s Interesting community.


Doctors in the US have induced feelings of intense determination in two men by stimulating a part of their brains with gentle electric currents.

The men were having a routine procedure to locate regions in their brains that caused epileptic seizures when they felt their heart rates rise, a sense of foreboding, and an overwhelming desire to persevere against a looming hardship.

The remarkable findings could help researchers develop treatments for depression and other disorders where people are debilitated by a lack of motivation.

One patient said the feeling was like driving a car into a raging storm. When his brain was stimulated, he sensed a shaking in his chest and a surge in his pulse. In six trials, he felt the same sensations time and again.

Comparing the feelings to a frantic drive towards a storm, the patient said: “You’re only halfway there and you have no other way to turn around and go back, you have to keep going forward.”

When asked by doctors to elaborate on whether the feeling was good or bad, he said: “It was more of a positive thing, like push harder, push harder, push harder to try and get through this.”

A second patient had similar feelings when his brain was stimulated in the same region, called the anterior midcingulate cortex (aMCC). He felt worried that something terrible was about to happen, but knew he had to fight and not give up, according to a case study in the journal Neuron.

Both men were having an exploratory procedure to find the focal point in their brains that caused them to suffer epileptic fits. In the procedure, doctors sink fine electrodes deep into different parts of the brain and stimulate them with tiny electrical currents until the patient senses the “aura” that precedes a seizure. Often, seizures can be treated by removing tissue from this part of the brain.

“In the very first patient this was something very unexpected, and we didn’t report it,” said Josef Parvizi at Stanford University in California. But then I was doing functional mapping on the second patient and he suddenly experienced a very similar thing.”

“Its extraordinary that two individuals with very different past experiences respond in a similar way to one or two seconds of very low intensity electricity delivered to the same area of their brain. These patients are normal individuals, they have their IQ, they have their jobs. We are not reporting these findings in sick brains,” Parvizi said.

The men were stimulated with between two and eight milliamps of electrical current, but in tests the doctors administered sham stimulation too. In the sham tests, they told the patients they were about to stimulate the brain, but had switched off the electical supply. In these cases, the men reported no changes to their feelings. The sensation was only induced in a small area of the brain, and vanished when doctors implanted electrodes just five millimetres away.

Parvizi said a crucial follow-up experiment will be to test whether stimulation of the brain region really makes people more determined, or simply creates the sensation of perseverance. If future studies replicate the findings, stimulation of the brain region – perhaps without the need for brain-penetrating electrodes – could be used to help people with severe depression.

The anterior midcingulate cortex seems to be important in helping us select responses and make decisions in light of the feedback we get. Brent Vogt, a neurobiologist at Boston University, said patients with chronic pain and obsessive-compulsive disorder have already been treated by destroying part of the aMCC. “Why not stimulate it? If this would enhance relieving depression, for example, let’s go,” he said.

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.


William Gibson’s popular science fiction tale “Johnny Mnemonic” foresaw sensitive information being carried by microchips in the brain by 2021. A team of American neuroscientists could be making this fantasy world a reality. Their motivation is different but the outcome would be somewhat similar. Hailed as one of 2013’s top ten technological breakthroughs by MIT, the work by the University of Southern California, North Carolina’s Wake Forest University and other partners has actually spanned a decade.

But the U.S.-wide team now thinks that it will see a memory device being implanted in a small number of human volunteers within two years and available to patients in five to 10 years. They can’t quite contain their excitement. “I never thought I’d see this in my lifetime,” said Ted Berger, professor of biomedical engineering at the University of Southern California in Los Angeles. “I might not benefit from it myself but my kids will.”

Rob Hampson, associate professor of physiology and pharmacology at Wake Forest University, agrees. “We keep pushing forward, every time I put an estimate on it, it gets shorter and shorter.”

The scientists — who bring varied skills to the table, including mathematical modeling and psychiatry — believe they have cracked how long-term memories are made, stored and retrieved and how to replicate this process in brains that are damaged, particularly by stroke or localized injury.

Berger said they record a memory being made, in an undamaged area of the brain, then use that data to predict what a damaged area “downstream” should be doing. Electrodes are then used to stimulate the damaged area to replicate the action of the undamaged cells.

They concentrate on the hippocampus — part of the cerebral cortex which sits deep in the brain — where short-term memories become long-term ones. Berger has looked at how electrical signals travel through neurons there to form those long-term memories and has used his expertise in mathematical modeling to mimic these movements using electronics.

Hampson, whose university has done much of the animal studies, adds: “We support and reinforce the signal in the hippocampus but we are moving forward with the idea that if you can study enough of the inputs and outputs to replace the function of the hippocampus, you can bypass the hippocampus.”

The team’s experiments on rats and monkeys have shown that certain brain functions can be replaced with signals via electrodes. You would think that the work of then creating an implant for people and getting such a thing approved would be a Herculean task, but think again.

For 15 years, people have been having brain implants to provide deep brain stimulation to treat epilepsy and Parkinson’s disease — a reported 80,000 people have now had such devices placed in their brains. So many of the hurdles have already been overcome — particularly the “yuck factor” and the fear factor.

“It’s now commonly accepted that humans will have electrodes put in them — it’s done for epilepsy, deep brain stimulation, (that has made it) easier for investigative research, it’s much more acceptable now than five to 10 years ago,” Hampson says.

Much of the work that remains now is in shrinking down the electronics.

“Right now it’s not a device, it’s a fair amount of equipment,”Hampson says. “We’re probably looking at devices in the five to 10 year range for human patients.”

The ultimate goal in memory research would be to treat Alzheimer’s Disease but unlike in stroke or localized brain injury, Alzheimer’s tends to affect many parts of the brain, especially in its later stages, making these implants a less likely option any time soon.

Berger foresees a future, however, where drugs and implants could be used together to treat early dementia. Drugs could be used to enhance the action of cells that surround the most damaged areas, and the team’s memory implant could be used to replace a lot of the lost cells in the center of the damaged area. “I think the best strategy is going to involve both drugs and devices,” he says.

Unfortunately, the team found that its method can’t help patients with advanced dementia.

“When looking at a patient with mild memory loss, there’s probably enough residual signal to work with, but not when there’s significant memory loss,” Hampson said.

Constantine Lyketsos, professor of psychiatry and behavioral sciences at John Hopkins Medicine in Baltimore which is trialing a deep brain stimulator implant for Alzheimer’s patients was a little skeptical of the other team’s claims.

“The brain has a lot of redundancy, it can function pretty well if loses one or two parts. But memory involves circuits diffusely dispersed throughout the brain so it’s hard to envision.” However, he added that it was more likely to be successful in helping victims of stroke or localized brain injury as indeed its makers are aiming to do.

The UK’s Alzheimer’s Society is cautiously optimistic.

“Finding ways to combat symptoms caused by changes in the brain is an ongoing battle for researchers. An implant like this one is an interesting avenue to explore,” said Doug Brown, director of research and development.

Hampson says the team’s breakthrough is “like the difference between a cane, to help you walk, and a prosthetic limb — it’s two different approaches.”

It will still take time for many people to accept their findings and their claims, he says, but they don’t expect to have a shortage of volunteers stepping forward to try their implant — the project is partly funded by the U.S. military which is looking for help with battlefield injuries.

There are U.S. soldiers coming back from operations with brain trauma and a neurologist at DARPA (the Defense Advanced Research Projects Agency) is asking “what can you do for my boys?” Hampson says.

“That’s what it’s all about.”

The world’s first brain-to-brain connection has given rats the power to communicate by thought alone.

“Many people thought it could never happen,” says Miguel Nicolelis at Duke University in Durham, North Carolina. Although monkeys have been able to control robots with their mind using brain-to-machine interfaces, work by Nicolelis’s team has, for the first time, demonstrated a direct interface between two brains – with the rats able to share both motor and sensory information.

The feat was achieved by first training rats to press one of two levers when an LED above that lever was lit. A correct action opened a hatch containing a drink of water. The rats were then split into two groups, designated as “encoders” and “decoders”.

An array of microelectrodes – each about one-hundredth the width of a human hair – was then implanted in the encoder rats’ primary motor cortex, an area of the brain that processes movement. The team used the implant to record the neuronal activity that occurs just before the rat made a decision in the lever task. They found that pressing the left lever produced a different pattern of activity from pressing the right lever, regardless of which was the correct action.

Next, the team recreated these patterns in decoder rats, using an implant in the same brain area that stimulates neurons rather than recording from them. The decoders received a few training sessions to prime them to pick the correct lever in response to the different patterns of stimulation.

The researchers then wired up the implants of an encoder and a decoder rat. The pair were given the same lever-press task again, but this time only the encoder rats saw the LEDs come on. Brain signals from the encoder rat were recorded just before they pressed the lever and transmitted to the decoder rat. The team found that the decoders, despite having no visual cue, pressed the correct lever between 60 and 72 per cent of the time.

The rats’ ability to cooperate was reinforced by rewarding both rats if the communication resulted in a correct outcome. Such reinforcement led to the transmission of clearer signals, improving the rats’ success rate compared with cases where decoders were given a pre-recorded signal. This was a big surprise, says Nicolelis. “The encoder’s brain activity became more precise. This could have happened because the animal enhanced its attention during the performance of the next trial after a decoder error.”

If the decoders had not been primed to relate specific activity with the left or right lever prior to the being linked with an encoder, the only consequence would be that it would have taken a bit more time for them to learn the task while interacting with the encoder, says Nicolelis. “We simply primed the decoder so that it would get the gist of the task it had to perform.” In unpublished monkey experiments doing a similar task, the team did not need to prime the animals at all.

In a second experiment, rats were trained to explore a hole with their whiskers and indicate if it was narrow or wide by turning to the left or right. Pairs of rats were then connected as before, but this time the implants were placed in their primary somatosensory cortex, an area that processes touch. Decoder rats were able to indicate over 60 per cent of the time the width of a gap that only the encoder rats were exploring.

Finally, encoder rats were held still while their whiskers were stroked with metal bars. The researchers observed patterns of activity in the somatosensory cortex of the decoder rats that matched that of the encoder rats, even though the whiskers of the decoder rats had not been touched.

Pairs of rats were even able to cooperate across continents using cyberspace. Brain signals from an encoder rat at the Edmond and Lily Safra International Institute of Neuroscience of Natal in Brazil were sent to a decoder in Nicolelis’s lab in North Carolina via the internet. Though there was a slight transmission delay, the decoder rat still performed with an accuracy similar to those of rats in closer proximity with encoders.

Christopher James at the University of Warwick, UK, who works on brain-to-machine interfaces for prostheses, says the work is a “wake-up call” for people who haven’t caught up with recent advances in brain research.

We have the technology to create implants for long-term use, he says. What is missing, though, is a full understanding of the brain processes involved. In this case, Nicolelis’s team is “blasting a relatively large area of the brain with a signal they’re not sure is 100 per cent correct,” he says.

That’s because the exact information being communicated between the rats’ brains is not clear. The brain activity of the encoders cannot be transferred precisely to the decoders because that would require matching the patterns neuron for neuron, which is not currently possible. Instead, the two patterns are closely related in terms of their frequency and spatial representation.

“We are still using a sledgehammer to crack a walnut,” says James. “They’re not hearing the voice of God.” But the rats are certainly sending and receiving more than a binary signal that simply points to one or other lever, he says. “I think it will be possible one day to transfer an abstract thought.”

The decoders have to interpret relatively complex brain patterns, says Marshall Shuler at Johns Hopkins University in Baltimore, Maryland. The animals learn the relevance of these new patterns and their brains adapt to the signals. “But the decoders are probably not having the same quality of experience as the encoders,” he says.

Patrick Degenaar at Newcastle University in the UK says that the military might one day be able to deploy genetically modified insects or small mammals that are controlled by the brain signals of a remote human operator. These would be drones that could feed themselves, he says, and could be used for surveillance or even assassination missions. “You’d probably need a flying bug to get near the head [of someone to be targeted],” he says.

Nicolelis is most excited about the future of multiple networked brains. He is currently trialling the implants in monkeys, getting them to work together telepathically to complete a task. For example, each monkey might only have access to part of the information needed to make the right decision in a game. Several monkeys would then need to communicate with each other in order to successfully complete the task.

“In the distant future we may be able to communicate via a brain-net,” says Nicolelis. “I would be very glad if the brain-net my great grandchildren used was due to their great grandfather’s work.”

Journal reference: Nature Scientific Reports, DOI: 10.1038/srep01319


How far should doctors go in attempting to cure addiction? In China, some physicians are taking the most extreme measures. By destroying parts of the brain’s “pleasure centers” in heroin addicts and alcoholics, these neurosurgeons hope to stop drug cravings. But damaging the brain region involved in addictive desires risks permanently ending the entire spectrum of natural longings and emotions, including the ability to feel joy.

In 2004, the Ministry of Health in China banned this procedure due to lack of data on long term outcomes and growing outrage in Western media over ethical issues about whether the patients were fully aware of the risks.

However, some doctors were allowed to continue to perform it for research purposes—and recently, a Western medical journal even published a new study of the results. In 2007, The Wall Street Journal detailed the practice of a physician who claimed he performed 1000 such procedures to treat mental illnesses such as depression, schizophrenia and epilepsy, after the ban in 2004; the surgery for addiction has also since been done on at least that many people.

The November publication has generated a passionate debate in the scientific community over whether such research should be published or kept outside the pages of reputable scientific journals, where it may find undeserved legitimacy and only encourage further questionable science to flourish.

The latest study is the third published since 2003 in Stereotactic and Functional Neurosurgery, which isn’t the only journal chronicling results from the procedure, which is known as ablation of the nucleus accumbens. In October, the journal World Neurosurgery also published results from the same researchers, who are based at Tangdu Hospital in Xi’an.

The authors, led by Guodong Gao, claim that the surgery is “a feasible method for alleviating psychological dependence on opiate drugs.” At the same time, they report that more than half of the 60 patients had lasting side effects, including memory problems and loss of motivation. Within five years, 53% had relapsed and were addicted again to opiates, leaving 47% drug free.

(MORE: Addicted: Why We Get Hooked)

Conventional treatment only results in significant recovery in about 30-40% of cases, so the procedure apparently improves on that, but experts do not believe that such a small increase in benefit is worth the tremendous risk the surgery poses.  Even the most successful brain surgeries carry risk of infection, disability and death since opening the skull and cutting brain tissue for any reason is both dangerous and unpredictable. And the Chinese researchers report that 21% of the patients they studied experienced memory deficits after the surgery and 18% had “weakened motivation,” including at least one report of lack of sexual desire. The authors claim, however, that “all of these patients reported that their [adverse results] were tolerable.” In addition, 53% of patients had a change in personality, but the authors describe the majority of these changes as “mildness oriented,” presumably meaning that they became more compliant. Around 7%, however, became more impulsive.

The surgery is actually performed while patients are awake in order to minimize the chances of destroying regions necessary for sensation, consciousness or movement.  Surgeons use heat to kill cells in small sections of both sides of the brain’s nucleus accumbens.  That region is saturated with neurons containing dopamine and endogenous opioids, which are involved in pleasure and desire related both to drugs and to ordinary experiences like eating, love and sex.

(MORE: A Drug to End Drug Addiction)

In the U.S. and the U.K., reports the Wall Street Journal, around two dozen stereotactic ablations are performed each year, but only in the most intractable cases of depression and obsessive-compulsive disorder and after extensive review by institutional review boards and intensive discussions with the patient, who must acknowledge the risks. Often, a different brain region is targeted, not the nucleus accumbens. Given the unpredictable and potentially harmful consequences of the procedure, experts are united in their condemnation of using the technique to treat addictions. “To lesion this region that is thought to be involved in all types of motivation and pleasure risks crippling a human being,” says Dr. Charles O’Brien, head of the Center for Studies of Addiction at the University of Pennsylvania.

David Linden, professor of neuroscience at Johns Hopkins and author of a recent book about the brain’s pleasure systems calls the surgery “horribly misguided.”  He says “This treatment will almost certainly render the subjects unable to feel pleasure from a wide range of experiences, not just drugs of abuse.”

But some neurosurgeons see it differently. Dr. John Adler, professor emeritus of neurosurgery at Stanford University, collaborated with the Chinese researchers on the publication and is listed as a co-author.  While he does not advocate the surgery and did not perform it, he believes it can provide valuable information about how the nucleus accumbens works, and how best to attempt to manipulate it. “I do think it’s worth learning from,” he says. ” As far as I’m concerned, ablation of the nucleus accumbens makes no sense for anyone.  There’s a very high complication rate. [But] reporting it doesn’t mean endorsing it. While we should have legitimate ethical concerns about anything like this, it is a bigger travesty to put our heads in the sand and not be willing to publish it,” he says.

(MORE: Anesthesia Study Opens Window Into Consciousness)

Dr. Casey Halpern, a neurosurgery resident at the University of Pennsylvania makes a similar case. He notes that German surgeons have performed experimental surgery involving placing electrodes in the same region to treat the extreme lack of pleasure and motivation associated with otherwise intractable depression.  “That had a 60% success rate, much better than [drugs like Prozac],” he says. Along with colleagues from the University of Magdeburg in Germany, Halpern has just published a paper in the Proceedings of the New York Academy of Sciences calling for careful experimental use of DBS in the nucleus accumbens to treat addictions, which have failed repeatedly to respond to other approaches. The paper cites the Chinese surgery data and notes that addiction itself carries a high mortality risk.

DBS, however, is quite different from ablation.  Although it involves the risk of any brain surgery, the stimulation itself can be turned off if there are negative side effects, while surgical destruction of brain tissue is irreversible. That permanence—along with several other major concerns — has ethicists and addiction researchers calling for a stop to the ablation surgeries, and for journals to refuse to publish related studies.

Harriet Washington, author of Medical Apartheid:  The Dark History of Medical Experimentation on Black Americans from Colonial Times to the Present, argues that by publishing the results of unethical studies, scientists are condoning the questionable conditions under which the trials are conducted. “When medical journals publish research that violates the profession’sethical guidelines, this serves not only to sanction such abuses, but to encourage them,” she says. “In doing so, this practice encourages a relaxing of moral standards that threatens all patients and subjects, but especially  the medically vulnerable.”

(MORE: Real-Time Video: First Look at a Brain Losing Consciousness Under Anesthesia)

Shi-Min Fang, a Chinese biochemist who became a freelance journalist and recently won the journal Nature‘s Maddox prize for his exposes of widespread fraud in Chinese research, has revealed some of the subpar scientific practices behind research conducted in China, facing death threats and, as the New York Times reported, a beating with a hammer. He agrees that publishing such research only perpetuates the unethical practices. Asked by TIME to comment on the addiction surgery studies, Fang writes that publishing the research, particularly in western journals, “would encourage further unethical research, particularly in China where rewards for publication in international journals are high.”

While he doesn’t have the expertise to comment specifically on the ablation data, he says “the results of clinical research in China are very often fabricated. I suspect that the approvals by Ethics Committee mentioned in these papers were made up to meet publication requirement. I also doubt if the patients were really informed in detail about the nature of the study.” Fang also notes that two of the co-authors of the paper are advertising on the internet in Chinese, offering the surgery at a cost of 35,000 renminbi, about $5,600.  That’s more than the average annual income in China, which is about $5,000.

Given the available evidence, in fact, it’s hard to find a scientific justification for even studying the technique in people at all. Carl Hart, associate professor of psychology at Columbia University and author of the leading college textbook on psychoactive drugs, says animal studies suggest the approach may ultimately fail as an effective treatment for addiction; a 1984 experiment, for example, showed that destroying the nucleus accumbens in rats does not permanently stop them from taking opioids like heroin and later research found that it similarly doesn’t work for curbing cocaine cravings. Those results alone should discourage further work in humans. “These data are clear,” he says, “If you are going to take this drastic step, you damn well better know all of the animal literature.” [Disclosure:  Hart and I have worked on a book project together].

(MORE: Top 10 Medical Breakthroughs of 2012)

Moreover, in China, where addiction is so demonized that execution has been seen as an appropriate punishment and where the most effective known treatment for heroin addiction— methadone or buprenorphine maintenance— is illegal, it’s highly unlikely that addicted people could give genuinely informed consent for any brain surgery, let alone one that risks losing the ability to feel pleasure. And even if all of the relevant research suggested that ablating the nucleus accumbens prevented animals from seeking drugs, it would be hard to tell from rats or even primates whether the change was due to an overall reduction in motivation and pleasure or to a beneficial reduction in desiring just the drug itself.

There is no question that addiction can be difficult to treat, and in the most severe cases, where patients have suffered decades of relapses and failed all available treatments multiple times, it may make sense to consider treatments that carry significant risks, just as such dangers are accepted in fighting suicidal depression or cancer.  But in the ablation surgery studies, some of the participants were reportedly as young as 19 years old and had only been addicted for three years.  Addiction research strongly suggests that such patients are likely to recover even without treatment, making the risk-benefit ratio clearly unacceptable.

The controversy highlights the tension between the push for innovation and the reality of risk. Rules on informed consent didn’t arise from fears about theoretical abuses:  they were a response to the real scientific horrors of the Holocaust. And ethical considerations become especially important when treating a condition like addiction, which is still seen by many not as an illness but as a moral problem to be solved by punishment.  Scientific innovation is the goal, but at what price?
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Thanks to Dr. Lutter for bringing this to the attention of the It’s Interesting community.