Archive for the ‘Neurology’ Category

In a new paper, neurologists Elias D. Granadillo and Mario F. Mendez describe two patients in whom brain disorders led to an unusual symptom: “intractable joking.”

Patient #1 was

A 69-year-old right-handed man presented for a neuropsychiatric evaluation because of a 5-year history of compulsive joking… On interview, the patient reported feeling generally joyful, but his compulsive need to make jokes and create humor had become an issue of contention with his wife. He would wake her up in the middle of the night bursting out in laughter, just to tell her about the jokes he had come up with. At the request of his wife, he started writing down these jokes as a way to avoid waking her. As a result, he brought to our office approximately 50 pages filled with his jokes.

Granadillo and Mendez quote some of the patient’s gags:

Q: What is a pill-popping sexual molester guilty of? A: Rape and pillage.
Q: What did the proctologist say to his therapist? A: All day long I am dealing with assholes.

Went to the Department of Motor Vehicles to get my driver’s license. They gave me an eye exam and here is what they said:
ABCDEFG, HIJKMNLOP, QRS, TUV, WXY and Z; now I know my ABC’s, can I have my license please?

The man’s comedic compulsion was attributed to a stroke, which had damaged part of his left caudate nucleus, although an earlier lesion to the right frontal cortex, caused by a subarachnoid hemorrhage, may have contributed to the pathological punning. Granadillo and Mendez say that a series of medications, including antidepressants, had little impact on his “compulsive need to constantly make and tell jokes.”

Patient #2 was a 57-year old man, who had become “a jokester”, a transformation that had occurred gradually, over a three period. At the same time, the man became excessively forward and disinhibited, making inappropriate actions and remarks. He eventually lost his job after asking “Who the hell chose this God-awful place?”

The patient constantly told jokes and couldn’t stop laughing at them. However, he did not seem to find other people’s jokes funny at all.

The man’s case, however, came to a sad end. His behavior continued to deteriorate and he developed symptoms of Parkinson’s. He died several years later. The diagnosis was Pick’s disease, a rare form of dementia. A post mortem revealed widespread neurodegeneration: “frontotemporal atrophy, severe in the frontal lobes and moderate in the temporal lobes, affecting the right side more than the left” was noted.

Neuroskeptic
« The Myth of “Mind-Altering Parasite” Toxoplasma Gondii?
“Joke Addiction” As A Neurological Symptom
By Neuroskeptic | February 28, 2016 5:51 am
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In a new paper, neurologists Elias D. Granadillo and Mario F. Mendez describe two patients in whom brain disorders led to an unusual symptom: “intractable joking.”

Patient #1 was

A 69-year-old right-handed man presented for a neuropsychiatric evaluation because of a 5-year history of compulsive joking… On interview, the patient reported feeling generally joyful, but his compulsive need to make jokes and create humor had become an issue of contention with his wife. He would wake her up in the middle of the night bursting out in laughter, just to tell her about the jokes he had come up with. At the request of his wife, he started writing down these jokes as a way to avoid waking her. As a result, he brought to our office approximately 50 pages filled with his jokes.

Granadillo and Mendez quote some of the patient’s gags:

Q: What is a pill-popping sexual molester guilty of? A: Rape and pillage.
Q: What did the proctologist say to his therapist? A: All day long I am dealing with assholes.

Went to the Department of Motor Vehicles to get my driver’s license. They gave me an eye exam and here is what they said:
ABCDEFG, HIJKMNLOP, QRS, TUV, WXY and Z; now I know my ABC’s, can I have my license please?

The man’s comedic compulsion was attributed to a stroke, which had damaged part of his left caudate nucleus, although an earlier lesion to the right frontal cortex, caused by a subarachnoid hemorrhage, may have contributed to the pathological punning. Granadillo and Mendez say that a series of medications, including antidepressants, had little impact on his “compulsive need to constantly make and tell jokes.”

granadillo_mendez

Patient #2 was a 57-year old man, who had become “a jokester”, a transformation that had occurred gradually, over a three period. At the same time, the man became excessively forward and disinhibited, making inappropriate actions and remarks. He eventually lost his job after asking “Who the hell chose this God-awful place?”

The patient constantly told jokes and couldn’t stop laughing at them. However, he did not seem to find other people’s jokes funny at all.

The man’s case, however, came to a sad end. His behavior continued to deteriorate and he developed symptoms of Parkinson’s. He died several years later. The diagnosis was Pick’s disease, a rare form of dementia. A post mortem revealed widespread neurodegeneration: “frontotemporal atrophy, severe in the frontal lobes and moderate in the temporal lobes, affecting the right side more than the left” was noted.

The authors say that both of these patients displayed Witzelsucht, a German term literally meaning ‘joke addiction’. Several cases have been reported in the neurological literature, often associated with damage to the right hemisphere of the brain. Witzelsucht should be distinguished from ‘pathological laughter‘, in which patients start laughing ‘out of the blue’ and the laughter is incongruent with their “mood and emotional experience.” In Witzelsucht, the laughter is genuine: patients really do find their own jokes funny, although they often fail to appreciate those of others.

Granadillo ED, & Mendez MF (2016). Pathological Joking or Witzelsucht Revisited. The Journal of Neuropsychiatry and Clinical Neurosciences PMID: 26900737

by Elizabeth Preston

Amputees often feel eerie sensations from their missing limbs. These “phantom limb” feelings can include pain, itching, tingling, or even a sense of trying to pick something up. Patients who lose an eye may have similar symptoms—with the addition of actual phantoms.

Phantom eye syndrome (PES) had been studied in the past, but University of Liverpool psychologist Laura Hope-Stone and her colleagues recently conducted the largest study of PES specifically in patients who’d lost an eye to cancer.

The researchers sent surveys to 239 patients who’d been treated for uveal melanoma at the Liverpool Ocular Oncology Centre. All of these patients had had one eye surgically removed. Some of their surgeries were only 4 months in the past; others had taken place almost 4 and a half years earlier. Three-quarters of the patients returned the surveys, sharing details about how they were doing in their new monocular lives.

Sixty percent of respondents said they had symptoms of phantom eye syndrome. These symptoms included pain, visual sensations, or the impression of actually seeing with the missing eye.

Patients with visual symptoms most often saw simple shapes and colors. But some people reported more distinct images, “for example, resembling wallpaper, a kaleidoscope, or fireworks, or even specific scenes and people,” the authors write.

Then there were the ghosts.

Some people said they had seen strangers haunting their fields of vision, as in these survey responses:

A survey isn’t a perfect way to measure how common PES is overall. But Hope-Stone says there were enough survey responses to produce helpful data for doctors who treat patients with eye cancer.

“We can now tell whether certain kinds of patients are more likely to have phantom symptoms,” she says. For example, “PES is more common in younger patients, and having pain in the non-existent eye is more likely in patients who are anxious and depressed, although we don’t know why.”

About a fifth of PES patients, understandably, said they were disturbed by their symptoms. A similar number found them “pleasurable,” Hope-Stone says.

Doctors aren’t sure exactly why phantom eye syndrome occurs. Since different patients have different symptoms, Hope-Stone says, “I suspect that…there may be a range of causes.”

For that matter, phantom limbs are still mysterious to doctors too. “Human perception is a complex process,” Hope-Stone explains. Even when our sensory organs are gone—the vision receptors in our eyes, the pain and touch receptors in our hands—the nerves and brain areas that used to talk to those organs keep working just fine. “Interactions between [these systems] may contribute to phantom sensations,” she says, although “the exact mechanisms are unclear.”

Even if they don’t know why it happens, doctors can warn their patients about the kinds of symptoms they’re likely to experience—and the ghosts they might see.

Phantom Eye Patients See and Feel with Missing Eyeballs


Healthy people who are given commonly prescribed mood-altering drugs see significant changes in the degree to which they are willing to tolerate harm against themselves and others, according to a study published Thursday. The research has implications for understanding human morality and decision-making.

A team of scientists from the University College London (UCL) and Oxford University found that healthy people who were given the serotonin-boosting antidepressant citalopram were willing to pay twice as much to prevent harm to themselves or others, compared to those given a placebo. By contrast, those who were given a dose of the dopamine-enhancing Parkinson’s drug levodopa made more selfish decisions, overcoming an existing tendency to prefer harming themselves over others.

The researchers said their findings, published in the journal Current Biology, provided clues to the neurological and chemical roots of common clinical disorders like psychopathy, which causes people to disregard the emotions of others.

The researchers compared how much pain subjects were willing to anonymously inflict on themselves or other people in exchange for money. Out of 175 subjects, 89 were given citalopram or a placebo and 86 were given levodopa or a placebo.

They were anonymously paired up into decision-makers and receivers, and all subjects were given shocks at their pain threshold. The decision-makers were then allowed to choose a different amount of money in exchange for a different amount of shocks, either to themselves or the receivers.

On average, people who were given a placebo were willing to pay about 35p per shock to prevent harm to themselves and 44p per shock to prevent harm to others. Those who were given citalopram became more averse to harm, paying an average of 60p to avoid harm to themselves and 73p per shock to avoid harm to others. This meant that citalopram users, on average, delivered 30 fewer shocks to themselves and 35 fewer shocks to others.

However, those who were given levodopa became more selfish, showing no difference in the amount they were willing to pay to prevent shocks to themselves or others. On average, they were willing to pay about 35p per shock to prevent harm to themselves or others, meaning that they delivered on average about 10 more shocks to others during the trial than those who took a placebo. They also showed less hesitation about shocking others than those given the placebo.

Similar research conducted by the same team in November found that subjects were willing to spare the stranger pain twice as often as they spared themselves, indicating that they preferred harming themselves over others for profit, a behavior known as “hyper-altruism.”

“Our findings have implications for potential lines of treatment for antisocial behavior, as they help us to understand how serotonin and dopamine affect people’s willingness to harm others for personal gain,” Molly Crockett of UCL, the study’s lead author, said in a press release. “We have shown that commonly-prescribed psychiatric drugs influence moral decisions in healthy people, raising important ethical questions about the use of such drugs.

“It is important to stress, however, that these drugs may have different effects in psychiatric patients compared to healthy people. More research is needed to determine whether these drugs affect moral decisions in people who take them for medical reasons.”

http://www.ibtimes.com/antidepressants-affect-morality-decision-making-new-study-finds-1995363

Just as losing a limb can spare a life, parting with a damaged axon by way of Wallerian degeneration can spare a neuron. A protein called SARM1 acts as the self-destruct button, and now researchers led by Jeffrey Milbrandt of Washington University Medical School in St. Louis believe they have figured out how. They report in the April 24 Science that SARM1 forms dimers that trigger the destruction of NAD+. Basic biochemistry dictates that this enzyme cofactor is essential for cell survival.

ARM1 and NAD+ have emerged as key players in the complex, orderly process underlying Wallerian degeneration. Scientists are still filling in other parts of the pathway. SARM1, short for sterile alpha and TIR motif-containing 1, seems to act as a damage sensor, but researchers are not sure how. Recently, researchers led by Marc Tessier-Lavigne at Rockefeller University, New York, found that SARM1 turns on a mitogen-activated protein (MAP) kinase cascade that is involved. Loss of NAD+ may also contribute to axon degeneration, because its concentration drops in dying axons, and Wlds mutant mice that overproduce an NAD+ synthase have slower Wallerian degeneration.

Now, first author Josiah Gerdts confirms that SARM1 is the self-destruct switch. He engineered a version of the protein with a target sequence for tobacco etch virus (TEV) protease embedded in it. Using a rapamycin-activated form of TEV, he eliminated SARM1 from axons he had sliced off of mouse dorsal root ganglion (DRG) neurons. Without SARM1, the severed axons survived.

SARM1 contains SAM and TIR domains, which promote protein-protein interactions. Previously, Gerdts discovered that the TIR domain was sufficient to induce degeneration, even in healthy axons, but it relied on the SAM region to bring multiple SARM1 molecules together. He hypothesized that axonal SARM1 multimerizes upon axon damage. To test this idea, he used a standard biochemical technique to force the SARM1 TIR domains together. He fused domains to one or another of the rapamycin-binding peptides Frb and Fkbp and expressed them in DRG neurons. When he added rapamycin to the cultures, the Frb and Fkbp snapped the TIR domains together within minutes. As Gerdts had predicted, this destroyed axons, confirming that SARM1 activates via dimerization.

Next, the authors investigated what happens to NAD+ during that process. Using high-performance liquid chromatography, Gerdts measured the concentration of NAD+ in the disembodied axons. Normally, its level dropped by about two-thirds within 15 minutes of severing. In axons from SARM1 knockout mice, however, the NAD+ concentration stayed unchanged. In neurons carrying the forced-dimerization constructs, adding rapamycin was sufficient to knock down NAD+ levels—Gerdts did not even have to cut the axons. Ramping up NAD+ production by overexpressing its synthases, NMNAT and NAMPT, overcame the effects of TIR dimerization, and the axons survived. Gerdts concluded that loss of NAD+ was a crucial, SARM1-controlled step on the way to degeneration.

He still wondered what caused the loss of NAD+. It might be that the axon simply stopped making it, or maybe the Wallerian pathway actively destroyed it. To distinguish between these possibilities, Gerdts added radiolabeled exogenous NAD+ to human embryonic kidney HEK293 cultures expressing the forced-dimerization TIR domains. Rapamycin caused them to rapidly degrade the radioactive NAD+, confirming that the cell actively disposes of it.

Gerdts suspects that with this essential cofactor gone, the axon runs out of energy and can no longer survive. He speculated that the MAP kinase cascade reportedly turned on by SARM1 might lead to NAD+ destruction. Alternatively, SARM1 might induce distinct MAP kinase and NAD+ destruction pathways in parallel, he suggested.

“Demonstrating how NAD+ is actively and locally degraded in the axon is a big advance,” commented Andrew Pieper of the Iowa Carver College of Medicine in Iowa City, who was not involved in the study. Jonathan Gilley and Michael Coleman of the Babraham Institute in Cambridge, U.K., predict that there will be more to the story. They note that a drug called FK866, which prevents NAD+ production, protects axons in some instances. Gerdts suggested that FK866 acts on processes upstream of SARM1, delaying the start of axon degeneration. In contrast, his paper only addressed what happens after SARM1 activates. “It will be fascinating to see how the apparent contradictions raised by this new study will be resolved,” wrote Gilley and Coleman.

Could these findings help researchers looking for ways to prevent neurodegeneration? “The study supports the notion that augmenting NAD+ levels is potentially a valuable approach,” said Pieper. He and his colleagues developed a small molecule that enhances NAD+ synthesis, now under commercial development. It improved symptoms in ALS model mice, and protected neurons in mice mimicking Parkinson’s. NAD+ also activates sirtuin, an enzyme important for longevity and stress resistance as well as learning and memory.

However, both Pieper and Gerdts cautioned that they cannot clearly predict which conditions might benefit from an anti-SARM1 or NAD+-boosting therapy. At this point, Gerdts said, researchers do not fully understand how much axon degeneration contributes to symptoms of diseases like Alzheimer’s and Parkinson’s. He suggested that crossing SARM1 knockout mice with models for various neurodegenerative conditions would indicate how well an anti-Wallerian therapy might work.

—Amber Dance

http://www.alzforum.org/news/research-news/axon-self-destruct-button-triggers-energy-woes

Results of a small study suggest that Parkinson’s patients seem to improve if they think they’re taking a costly medication. The findings have been published online Jan. 28 in Neurology.

In the study, 12 patients had their movement symptoms evaluated hourly, for about four hours after receiving each of the placebos. On average, patients had bigger short-term improvements in symptoms like tremor and muscle stiffness when they were told they were getting the costlier of two drugs. In reality, both “drugs” were nothing more than saline, given by injection. But the study patients were told that one drug was a new medication priced at $1,500 a dose, while the other cost just $100 — though, the researchers assured them, the medications were expected to have similar effects.

Yet, the researchers found that when patients’ movement symptoms were evaluated in the hours after receiving the fake drugs, they showed greater improvements with the pricey placebo. What’s more, magnetic resonance imaging scans showed differences in the patients’ brain activity, depending on which placebo they’d received. The patients in the study didn’t get as much relief from the two placebos as they did from their regular medication, levodopa. But the magnitude of the expensive placebo’s benefit was about halfway between that of the cheap placebo and levodopa. What’s more, patients’ brain activity on the pricey placebo was similar to what was seen with levodopa.

And this effect is “not exclusive to Parkinson’s,” according to Peter LeWitt, M.D., a neurologist at the Henry Ford West Bloomfield Hospital in Michigan, who wrote an editorial published with the study. Research has documented the placebo effect in various medical conditions, he told HealthDay. “The main message here is that medication effects can be modulated by factors that consumers are not aware of — including perceptions of price.”

http://www.empr.com/pricey-placebo-works-better-than-cheaper-one-in-parkinsons-study/article/395255/?DCMP=EMC-MPR_DailyDose_rd&CPN=edgemont14,emp_lathcp&hmSubId=&hmEmail=5JIkN8Id_eWz7RlW__D9F5p_RUD7HzdI0&dl=0&spMailingID=10518237&spUserID=MTQ4MTYyNjcyNzk2S0&spJobID=462545599&spReportId=NDYyNTQ1NTk5S0

brainy_2758840b

Talking to yourself used to be a strictly private pastime. That’s no longer the case – researchers have eavesdropped on our internal monologue for the first time. The achievement is a step towards helping people who cannot physically speak communicate with the outside world.

“If you’re reading text in a newspaper or a book, you hear a voice in your own head,” says Brian Pasley at the University of California, Berkeley. “We’re trying to decode the brain activity related to that voice to create a medical prosthesis that can allow someone who is paralysed or locked in to speak.”

When you hear someone speak, sound waves activate sensory neurons in your inner ear. These neurons pass information to areas of the brain where different aspects of the sound are extracted and interpreted as words.

In a previous study, Pasley and his colleagues recorded brain activity in people who already had electrodes implanted in their brain to treat epilepsy, while they listened to speech. The team found that certain neurons in the brain’s temporal lobe were only active in response to certain aspects of sound, such as a specific frequency. One set of neurons might only react to sound waves that had a frequency of 1000 hertz, for example, while another set only cares about those at 2000 hertz. Armed with this knowledge, the team built an algorithm that could decode the words heard based on neural activity alone (PLoS Biology, doi.org/fzv269).

The team hypothesised that hearing speech and thinking to oneself might spark some of the same neural signatures in the brain. They supposed that an algorithm trained to identify speech heard out loud might also be able to identify words that are thought.

Mind-reading

To test the idea, they recorded brain activity in another seven people undergoing epilepsy surgery, while they looked at a screen that displayed text from either the Gettysburg Address, John F. Kennedy’s inaugural address or the nursery rhyme Humpty Dumpty.

Each participant was asked to read the text aloud, read it silently in their head and then do nothing. While they read the text out loud, the team worked out which neurons were reacting to what aspects of speech and generated a personalised decoder to interpret this information. The decoder was used to create a spectrogram – a visual representation of the different frequencies of sound waves heard over time. As each frequency correlates to specific sounds in each word spoken, the spectrogram can be used to recreate what had been said. They then applied the decoder to the brain activity that occurred while the participants read the passages silently to themselves.

Despite the neural activity from imagined or actual speech differing slightly, the decoder was able to reconstruct which words several of the volunteers were thinking, using neural activity alone (Frontiers in Neuroengineering, doi.org/whb).

The algorithm isn’t perfect, says Stephanie Martin, who worked on the study with Pasley. “We got significant results but it’s not good enough yet to build a device.”

In practice, if the decoder is to be used by people who are unable to speak it would have to be trained on what they hear rather than their own speech. “We don’t think it would be an issue to train the decoder on heard speech because they share overlapping brain areas,” says Martin.

The team is now fine-tuning their algorithms, by looking at the neural activity associated with speaking rate and different pronunciations of the same word, for example. “The bar is very high,” says Pasley. “Its preliminary data, and we’re still working on making it better.”

The team have also turned their hand to predicting what songs a person is listening to by playing lots of Pink Floyd to volunteers, and then working out which neurons respond to what aspects of the music. “Sound is sound,” says Pasley. “It all helps us understand different aspects of how the brain processes it.”

“Ultimately, if we understand covert speech well enough, we’ll be able to create a medical prosthesis that could help someone who is paralysed, or locked in and can’t speak,” he says.

Several other researchers are also investigating ways to read the human mind. Some can tell what pictures a person is looking at, others have worked out what neural activity represents certain concepts in the brain, and one team has even produced crude reproductions of movie clips that someone is watching just by analysing their brain activity. So is it possible to put it all together to create one multisensory mind-reading device?

In theory, yes, says Martin, but it would be extraordinarily complicated. She says you would need a huge amount of data for each thing you are trying to predict. “It would be really interesting to look into. It would allow us to predict what people are doing or thinking,” she says. “But we need individual decoders that work really well before combining different senses.”

http://www.newscientist.com/article/mg22429934.000-brain-decoder-can-eavesdrop-on-your-inner-voice.html

Everyone knows it’s easier to learn about a topic you’re curious about. Now, a new study reveals what’s going on in the brain during that process, revealing that such curiosity may give a person a memory boost.

When participants in the study were feeling curious, they were better at remembering information even about unrelated topics, and brain scans showed activity in areas linked to reward and memory.

The results, detailed October 2 in the journal Neuron, hint at ways to improve learning and memory in both healthy people and those with neurological disorders, the researchers said.

“Curiosity may put the brain in a state that allows it to learn and retain any kind of information, like a vortex that sucks in what you are motivated to learn, and also everything around it,” Matthias Gruber, a memory researcher at the University of California, Davis, said in a statement. “These findings suggest ways to enhance learning in the classroom and other settings.”

Gruber and his colleagues put people in a magnetic resonance imaging (MRI) scanner and showed them a series of trivia questions, asking them to rate their curiosity about the answers to those questions. Later, the participants were shown selected trivia questions, then a picture of a neutral face during a 14-second delay, followed by the answer. Afterward, the participants were given a surprise memory test of the faces, and then a memory test of the trivia answers.

Not surprisingly, the study researchers found that people remembered more information about the trivia when they were curious about the trivia answers. But unexpectedly, when the participants were curious, they were also better at remembering the faces, an entirely unrelated task. Participants who were curious were also more likley than others to remember both the trivia information and unrelated faces a day later, the researchers found.

The brain scans showed that, compared with when their curiosity wasn’t piqued, when people were curious, they showed more activation of brain circuits in the nucleus accumbens, an area involved in reward. These same circuits, mediated by the neurochemical messenger dopamine, are involved in forms of external motivation, such as food, sex or drug addiction.

Finally, being curious while learning seemed to produce a spike of activity in the hippocampus, an area involved in forming new memories, and strengthened the link between memory and reward brain circuits.

The study’s findings not only highlight the importance of curiosity for learning in healthy people, but could also give insight into neurological conditions. For example, as people age, their dopamine circuits tend to deteriorate, so understanding how curiosity affects these circuits could help scientists develop treatments for patients with memory disorders, the researchers said.

http://www.livescience.com/48121-curiosity-boosts-memory-learning.html