Search Results for: hippo anatomy

Calorie Restriction Slows DNA Methylation in the Hippocampus

DNA methylation is proposed to be a good biomarker of aging, and here researchers show that calorie restriction slows the progression of DNA methylation in the hippocampus - continuing the expected trend of calorie restriction slowing near every identified biological change that occurs with aging: "Aberrant DNA methylation patterns have been linked to molecular and cellular alterations in the aging brain. Caloric restriction (CR) and upregulation of antioxidants have been proposed as interventions to prevent or delay age-related brain pathology. Previously, we have shown in large cohorts of aging mice, that age-related increases in DNA methyltransferase 3a (Dnmt3a) immunoreactivity in the mouse hippocampus were attenuated by CR, but not by overexpression of superoxide dismutase 1 (SOD1). Here, we investigated age-related alterations of 5-methylcytidine (5-mC), a marker of DNA methylation levels, in a hippocampal subregion-specific manner. Examination of 5-mC immunoreactivity in 12- and 24-month-old wild type (WT) mice on control diet, mice overexpressing SOD1 on control diet, wild type mice on CR, and SOD1 mice on CR, indicated an age-related increase in 5-mC immunoreactivity in the hippocampal dentate gyrus, CA3, and CA1-2 regions, which was prevented by CR but not by SOD1 overexpression. ... These findings suggest a crucial role for DNA methylation in hippocampal aging and in the mediation of the beneficial effects of CR on aging."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21764481

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Alternative Reproduction? – Science Based Medicine

I usually start these blog entries with an idea and then see where the research takes me. Certainly I go down many rat holes. Thanks to the recent reversal of reproductive rights by the SCOTUS, with perhaps more to come, I wondered what SCAM alternatives were available when/if reality-based reproductive interventions were no longer an option. I wonder no longer.

There are four aspects of reproduction I will consider, along with some rat holes: contraception, infertility, erectile dysfunction, and pregnancy termination.

As I start this, my assumption was there would be few SCAM approaches to pregnancy prevention, as SCAMs have no efficacy when there is a hard end point to the intervention. There are no SCAM therapies for the infections I see most days as many have almost 100% mortality rates. No one, I would hope, would use a SCAM for the sole treatment of endocarditis or meningitis although there is the occasional person who will rely solely on SCAMs for cancer treatment. It does not end well.

I have told this story before, but I first learned about SCAMs early in my practice when I was called to see a case of wet gangrene of the leg. A young female had a sarcoma of her leg that would have likely been cured with amputation. She chose naturopathy instead and the cancer advanced until most of her leg was cancer, much of it dead and putrefying. That is why they called me, not there was anything I could do. She refused any care (she was admitted because she had passed out) and that night the cancer eroded into an artery and she bled out. That is where I first encountered naturopathy and the first of many cases where cancer denial was an important aspect of the patients care.

Like SCAM cancer therapies, it is obvious when contraception fails. I would think pregnancy would be harder to deny than cancer, but I will not be surprised if the comments have stories that demonstrate otherwise. The if only they had used our SCAM sooner gambit is unlikely to be a convincing argument as to why birth control failed.

Before I wander the SCAMs, though, I wondered how people avoided pregnancy in the era before oral contraceptives. Sure, there are barrier methods, abstinence (like that ever works), and the rhythm method. And you know what we call people who use the rhythm method for contraception? Parents.

If you visit the old towns of the West, it appears that most of the hotels and restaurants were once bordellos. I wonder where they found all the workers for these bordellos. It would seem that most of the female population of the Old West would have to be employed in these houses of ill repute.

But how did the prostitutes, and others, avoid pregnancy? Were there, for lack of a better term, natural forms of birth control? Or were the bordellos filled with their offspring? Besides a variety of barrier methods (half a lemon used as a cervical cap!), the techniques used were not that different than modern SCAM ideas:

Roman women put a leather pouch filled with cats liver on their left foot during sexual intercourse to prevent pregnancy. Some women believed that spitting three times into a frogs mouth was a good method of birth control. European women thought that they could prevent pregnancy by turning backwards a wheel of a mill at midnight. And, in many cultures women constantly wore various necklaces and amulets, which were supposed to have the power of controlling the act of conception. Women were advised to hold their breath and draw their bodies back during sex in order to stop the sperm from entering her body. It was also suggested a woman to jump backwards seven times after sexual intercourse or take something to cause sneezing.

As one website noted:

Until modern contraceptives were invented, women relied on all kinds of ancient birth control methods that had inconsistent results. Some were even dangerous, including the use of heavy metals such as mercury, lead, and arsenic, which did prevent conception but also led to organ failure and brain damage.

I was also amazed to learn that the relationship between ovulation and menses was not discovered until the 1930s, so that method of contraception was unknown for most of human history.

Also used were:

syringes to inject mercury, arsenic, and vinegar into the body to induce abortions or treat diseases.

Much to my amusement, one Boston brothel had:

a homeopathic doctor considered to be crackpotty at the time, according to Beaudry. He prescribed unusual remedies for the women, most likely for treating sexually transmitted diseases and inducing abortions.

He would likely be considered crackpotty today.

One would think, wouldnt one, that if acupuncture is efficacious in aiding in pregnancy and given its numerous alleged salubrious effects on female and male reproductive physiology, acupuncture and traditional Chinese pseudo-medicine could also be used for contraception. I can think of one application where acupuncture might be efficacious, but there are no acupuncture points on the genitals.

While I was not surprised to find zero papers on the Pubmeds on using acupuncture for birth control, I could also not find any with a general Google search.

There are no SCAMs that are touted for contraception. Not acupuncture, not homeopathy, not chiropractic, not naturopathy. No surprise. There would be no way to rationalize away pregnancy.

One site mentioned in passing, stone seed root, thistle, wild carrot seed, and ginger root as potential contraceptives. I would suggest not.

Since, as noted above, the goal is to adjust and harmonize the state of the female body from a holistic approach and there is no useful form of SCAM contraception, the harmonized state appears to be barefoot and pregnant.

Infertility has a complex differential diagnosis with a variety of anatomical and hormonal abnormalities leading to an inability to conceive. It also makes for a huge literature, although like most of the SCAM literature, high-quality studies are few and far between. I am going to discuss a few I find instructive and or amusing.

SCAM providers are fond of claiming that their raison detre is to help return the body to its optimal state of homeostasis or as one review noted, to adjust and harmonize the state of the female body from a holistic approach.

There are a vast number of SCAMs that are used as an adjunctive therapy for infertility. In China, not unsurprisingly, Traditional Chinese Pseudo Medicine, especially acupuncture and moxibustion, are used as primary treatment for infertility. And, as is always the case in studies out of China, the studies are uniformly positive.

It is a massive literature of Tooth Fairy science and I will note here an infertility study that was randomized and double-blind comparing real acupuncture with placebo acupuncture (same thing) in patients undergoing IVF treatment. The results? No difference, really; p=0.038. But what was amusing was that the pregnancy was increased in the placebo group:

The overall pregnancy rate was significantly higher in the placebo acupuncture group than that in the real acupuncture group (55.1 versus 43.8%, respectively).

But there is no real acupuncture, as I have argued before. And their conclusion? Not that doing two interventions with no reality-based reason for efficacy is going to lead to random noise that looks significant. Nope:

Placebo acupuncture was associated with a significantly higher overall pregnancy rate when compared with real acupuncture. Placebo acupuncture may not be inert.

LOL. What is inert is the critical thinking functions of the researchers.

Reading even the meta-analysis is the usual mess, because acupuncture, as always, is a heterogeneous intervention, with traditional, electro, cat gut, and warm being some of the variations used and compared. It is quite the mess for drawing any conclusions about whether a specific intervention is effective. But as I have mentioned before, it is not the specific intervention that is allegedly useful, it is the concept of acupuncture that is allegedly effective.

But if limited to quality studies, the efficacy of acupuncture is not impressive:

There was no statistically significant difference between the acupuncture group and no acupuncture (intervention) controls around the time of embryo transfer (ET; risk ratio, RR, 1.24, 95% confidence interval, CI, 1.02-1.50) or in unblinded trials, trials blinded to physicians and double-blind trials (95% CI 1.26-1.88, 0.82-1.33 and 0.89-1.25, respectively). This was also the case when comparing acupuncture with sham acupuncture controls around the time of ET (RR, 1.03, 95% CI 0.87-1.22) or when restricting to unblinded trials, trials blinded to physicians and double-blind trials (95% CI 0.80-2.02, 0.82-1.18 and 0.77-1.17, respectively).

Much of the primary literature is in China and, for example, I could not find the Chinese Journal of Family Planning and similar journals to see the details about the effects of TCM retention enema on tubal obstructive infertility. Yes. Really.

A warm enema containing Chinese medicine is administered before going to bed to treat fallopian tube adhesion. The drug can be absorbed directly by rectal mucosa, which is beneficial to improve the congestion, edema, adhesion, and hyperplasia of local tissues, and thus restoring the function of the fallopian tube.

What continues to amaze me is how health care professionals, well versed in anatomy, physiology, biochemistry, etc., apply the techniques of reality on fiction. It only happens in medicine. You do not see engineers trying to apply the physics of Warner Brothers cartoons to the building of bridges and tunnels. There is no alternative engineering or aviation but doctors continue to act like acupuncture and other SCAMs are not ludicrous.

Huge numbers of herbal preparations have been tried for male and female infertility, more than I have time to review except to note the efficacy is often secondary endpoints like cervical mucus consistency or sperm motility and concentration, not conception rates.

Chiropractic has been used for infertility but:

There are very few original data articles documenting responses of infertile females treated with spinal manipulation.

And:

In the absence of a robust body of primary data literature, the use of spinal manipulation the management of female infertility should be approached with caution.

The Journal of Vertebral Subluxation Research (not on Pubmed as Pubmed does not list science fiction) has papers purporting to show benefit of chiropractic in infertile patients. And, to no ones surprise, chiropractors tout the benefits of their interventions on the web.

I can find next to nothing on Pubmed using homeopathy or naturopathy for infertility. Well, for homeopathy preparations it would be exactly nothing.

The acupoints for erectile dysfunction are distant from the problematic organ, in one study being, slightly below the navel, slightly above the hairline at the back of the head, between the inside ankle bone and the achilles tendon, in the inside wrist. And the results?

No definite conclusions can be drawn.

A conclusion supported in the most recent meta-analysis where:

Low quality evidence shows beneficial effect of acupuncture as adjunctive treatment for people mainly with psychogenic ED.

And the best results were:

Acupuncture combined with tadalafil appeared to have better effect on increasing cure rate.

Lol. It takes a Western medicine to get the best results.

There is the also creepy Clinical Holistic Medicine: Holistic Sexology and Acupressure Through the Vagina (Hippocratic Pelvic Massage).

Noted in one clinical study:

The most difficult problem of this procedure seems to be that it makes it very difficult to be sure that the procedure and all the involved steps are always necessary and rational.

Eye roll and head shake.

There is nothing on the PubMeds for using chiropractic, homeopathy or naturopathy for ED, but no shortage of websites promoting their use.

I wondered about homeopathy, so I picked a website at random. The first suggestion is Agnus castus:

This remedy may be helpful if problems with impotence develop after a man has led a life of intense and frequent sexual activity for many years. A cold sensation felt in the genitals is a strong indication for Agnus castus. People who need this remedy are often very anxious about their health and loss of abilities and may have problems with memory and concentration. This remedy is one of the best homeopathic medicine for ED.

Agnus castus is the chaste berry, which one site says:

The fruit has been historically used for reducing sexual desire.

As one site notes:

The leaves of this plant were used to adorn the beds of Greek women during the absence of their husbands so as to prevent any impure thoughts from entering their minds and also by medieval monks to repress sexual desire. In the actual provings the remedy has shown that it does repress sexual instinct and desire.

And:

Agnus castus is indicated for promiscuous young people who have abused their sexual energies through either homosexual or heterosexual multiple contacts and who have contracted repeated venereal infections, especially gonorrhea.

Huh? Homeopathic teaching is that a product that causes the symptoms undergoes serial dilution and succussion to make a more potent medication. Somehow a medication that reduces sexual desire increases libido when homeopathized? Writing these entries leads to some of the weirdest stuff.

While no trials can be identified in the Pubmeds, acupuncture was used for abortions in China although it was unreliable. Cue Louie. Acupuncture does have forbidden points. Specifically if you stimulate:

San Yin Chiao (SP6) in conjunction with He Gu (LI4). The abortion is generally realized within 24 hours.

But thats in humans, in Wistar rats stimulating the forbidden points does nothing:

We found no evidence that acupuncture in LI4-SP6 and sacral points could be harmful to the pregnancy outcome in Wistar rats.

But then, why would it? Was trying to confirm or deny a fiction worth abusing and killing rats? I doubt it.

I have often wondered how they map human acupoints and meridians onto animals; evidently so do acupuncturists in search of One Acupuncture. One Acupuncture to rule them all, One Acupuncture to find them, One Acupuncture to bring them all and in the darkness bind them, I suppose.

Moving toward a neuroanatomically accurate veterinary acupuncture system requires rethinking current atlases and embarking upon a systematic analysis of the human points in terms of where, if at all, corresponding sites exist in the nonhuman.

Good luck with that. Because you might run into issues such as those with Boa constrictors, although why one would want to torture a snake with acupuncture is uncertain.

Thus, the objective of this study was to map and describe the main points of acupuncture in the species Boa constrictor, and their indications to promote the balance of this species. The unprecedented result of the mapping was the discovery of specific acupoints with individual location indications without distribution in specific meridians and dispersedly distributed in the body.

Careful, clever, scientists, they measured the heart rate:

HR was obtained by counting heart rate.

And if you wondered how they found acupuncture points?

Use of the electrostimulator and location of EL points 30 10/100 Hz NKLpoints of Brazilian origin. The EL30 is an electronic device that is intended exclusively for non-invasive applications in the technique called electro-acupuncture. It was conceived as a point detection instrument, where an electrostimulation therapy, used in different media with a purpose of detection and determination of qualities as stimulus conditions for different species and for different points. It was traversed with an exploratory tip of the animals body points to an occurrence of an audible signal indicating the localized point and an impedance. The sensitivity controller has been adjusted to find a better setting.

More animal abuse for no good reason. But I digress. Again.

Consistency not being a strong point in acupuncture, when acupuncture was used as an adjunct to medical abortion they used Hegu (LI 4), Sanyinjiao (SP 6), Neiguan (PC 6) and Kunlun (BL 60). I suspect the increased efficacy was due to BL 60.

Acupuncturists can get quite wiggens over the forbidden points, going as far as to suggest the auricular acupuncture should be avoided in pregnancy. I would add it should be avoided when not pregnant as well. Several reviews suggest acupuncture is safe in pregnancy when correctly applied, whatever correctly applied might be.

While I can find papers where acupuncture is purported to prevent spontaneous abortion, and I can find nothing to confirm the abortifacient effects of acupuncture.

I can find nothing on using homeopathy, chiropractic or naturopathic techniques to induce abortion, although they allege they can help prevent spontaneous abortion/miscarriage. The one-way street that is SCAM.

Herbs? Theres a problem. I will admit, I am not one for social media. Twitter is a time suck and Facebook opaque and pointless. I certainly do not grok the concept of influencers. So TikTok? So out of my geezer understanding. But, per the Rolling Stone (geezer cred?) TikTok is a popular source for information on DYI abortions using pennyroyal, blue cohosh, and mugwort. Herbs that are not efficacious but are certainly toxic and could be fatal. As one PubMed review noted:

the ingestion of plants to induce abortion involves the risk of severe morbidity and mortality.

Hard to believe, but when it comes to medical advice it is suggested:

not to listen to what you hear on TikTok.

It is a question with no real answer: would a SCAM provider be any better?

It turns out self-managed abortion is not that uncommon, with 7% of US women of reproductive age (kind of redundant, women not in their reproductive age are unlikely to need an abortion) going the DYI route, often with herbs and without success.

With the Handmaidens Tale decision this year, I expect DYI abortions will only increase with resultant morbidity and mortality. Desperate people will do desperate things.

Mark Crislip, MD has been a practicing Infectious Disease specialist in Portland, Oregon, since 1990. He is a founder and the President of the Society for Science-Based Medicinewhere he blogs under the name sbmsdictator.He has been voted a US News and World Report best US doctor, best ID doctor in Portland Magazine multiple times, has multiple teaching awards and, most importantly, the Attending Most Likely To Tell It Like It Is by the medical residents at his hospital.His growing multi-media empire can be found at edgydoc.com.

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Alternative Reproduction? - Science Based Medicine

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Brain-Computer Interfaces Move Forward at the Speed of Musk : Neurology Today – LWW Journals

Article In Brief

A brain-computer interface (BCI), developed by a company tied with Elon Musk, offers an innovative new technology to move the field forward. But independent experts said some of the claims about what that technology can potentially do are somewhat hyperbolic at this stage. Other efforts around BCI are also featured.

It's going to blow your mind, said Elon Musk, the billionaire founder and CEO of Tesla, SpaceX and Neuralink. Speaking via a webcast on August 28, Musk introduced the latest developments, or at least made the latest claims, regarding Neuralink's brain-computer interface (BCI), a computer-based system that measures and analyzes brain activity and then converts signals into commands that are relayed to output devices that carry out the desired action.

The US Food and Drug Administration (FDA), he announced, had given the company a Breakthrough Devices Designation, and good progress, he said, was being made toward clinical trials.

As evidence of that progress, Musk presented what he called the Little Pigs demo. Three pigs in the webcast looked equally healthy, but one of them had been implanted with a device that was wirelessly transmitting neural spikes from the snout area of its brain as it rooted around in a pen.

There's a lot of function that this device could do related to monitoring your health and warning you about a possible heart attack or stroke, and convenience features like playing music, Musk said. It's sort of like if your phone went in your brain.

He predicted that, one day, you will be able to save and replay memories...Over time we could actually give someone super vision. You could have ultraviolet or infrared, or seeing radar, and actually have superhuman vision.

Alas, none of those capabilities has ever been demonstrated by Musk's company or, for that matter, by any scientist or company. Neurologists and neuroscientists who have been laboring in the field for over a decade seek not to endow healthy humans with superpowers, but to help people with neurodegenerative diseases, strokes or traumatic injuries to regain speech and motor functions. Despite that disconnect, however, leaders in the field told Neurology Today that they are impressed by the legitimate progress Neuralink appears to have made.

The company's implantable device, they say, is doing things that none of their own devices have yet achieved: It communicates to a nearby computer wirelessly, rather than through wires; its low-powered battery, also recharges wirelessly, lasts up to a day; it bristles with over a thousand electrodes, compared to a few hundred in traditional arrays; and rather than attaching those electrodes to inflexible shanks, the Neuralink device uses flexible threads so delicate they are implanted by a robotic sewing machine.

If indeed they have made a device that can detect a thousand channels with good fidelity, and it can scan through this wireless technology, that is an important development, said Karunesh Ganguly, MD, PhD, associate professor of neurology at the University of California, San Francisco. At some point, you want to see it peer reviewed to know that what they're identifying as a neuron is actually a neuron. But they do seem to be pushing the technology ahead.

More evidence of progress in the BCI field came with a September 7 report by Dr. Ganguly's group in Nature Biotechnology. Unlike other approaches for invasive BCIs, his plug and play system based on electrocorticography (ECoG) has permitted an individual with tetraplegia to maintain control of a computer cursor without daily recalibration and retraining.

While he and other scientists in the BCI field expressed some skepticism about some of the claims made by Neurolink and Musk, they told Neurology Today they appreciate the interest that Neuralink is bringing to the field.

It will be really important, as these technologies become available, hopefully over the next few years, for neurologists to become familiar with how BCI can help the patients they see in their daily practice, said Leigh Hochberg, MD, PhD, FAAN, professor of engineering at Brown University, senior lecturer in neurology at Harvard Medical School, and director of the Center for Neurotechnology and Neurorecovery at Massachusetts General Hospital.

As a neurologist, I am completely focused on developing and testing technology that will help patients I see who have paralyzing disorders to maintain or regain their ability to move and speak.

Companies like Neuralink, he said, are essential to achieving that goal.

At the end of the day, neither universities nor academic medical centers make the final marketed and supported medical devices that become available to patients outside of clinical trials, Dr. Hochberg said. That is always done by a company. The engagement of companies in this field will ultimately benefit our patients.

Although Neuralink has not published a description of its technology in peer-reviewed scientific literature, and neither Musk nor any of the scientists working for him responded to requests for interviews, some detailed descriptions have appeared on the preprint server bioRxiv.

In March of 2019, Philip Sabes, PhD, of the University of California, San Francisco (and a founding team leader at Neuralink) was the lead author of a paper describing the sewing machine his group had developed with funding by the Defense Advanced Research Projects Agency (DARPA).

The fixed, rigid metal arrays used since the 1950s to penetrate the brain, the paper noted, disturbs the vasculature and attracts immune cells. Thinner, more flexible probes, however, would not be stiff enough to insert into the brain directly. Dr. Sabes' solution was to design a system that works like a sewing machine, with stiff needle-like injectors that implant polymer probes with the aid of a neurosurgical robot.

Each of the system's 96 polymer threads, the paper stated, holds 32 electrodes, for a total of 3,072 electrodes. We developed miniaturized custom electronics that allow us to stream full broadband electrophysiology data simultaneously from all these electrodes. We packaged this system for long-term implantation and developed custom online spike detection software that can detect action potentials with low latency.

Five months later, in August of 2019, Musk was listed as the first author of another preprint on bioRxiv that described Sabes' sewing machine as part of Neuralink's BCI platform. We have built arrays of small and flexible electrode threads, Musk's paper stated, with as many as 3,072 electrodes per array distributed across 96 threads.

As described by Musk in his webcast in August, implantation of the company's device will require removal of what he called a coin-sized piece of skull by its robot. Then the device replaces the portion of skull that we removed.

Technological advances already made and anticipated from the Neuralink effort are remarkable and will serve the neuroengineering community well, Lee E. Miller, PhD, Distinguished Professor of Neuroscience at the Feinberg School of Medicine of Northwestern University, said. This scale of private investment of financial and intellectual effort is unprecedented in our field. He added, however, that the company needs to demonstrate that its device is doing what it claims to be doing.

They showed these rasters of brain activity on the webcast, with cool bloopy sounds, he said. For peer review, I would insist on seeing the actual signals they recorded. Although there is no reason to believe it to be the case, they could be recording movement artifacts.

My hunch is that it will not be as expensive as deep brain stimulation for Parkinson's disease, which costs tens of thousands of dollars. But it's going to be more expensive than, say, LASEK surgery.

DR. LEE MILLER

When I was first approached about working on brain-machine interfaces, I thought, This is crazy. But we went farther than we could have reasonably hoped to do. That's why I'm not completely closed to the wildest claims Musk makes. It's not insane that maybe one day we can replay memories.

DR. SLIMAN BENSMAIA

Dr. Miller also took issue with Musk's prediction that a BCI device could eventually cost as little as a few thousand dollars. That's not going to happen any time soon, Dr. Miller said. My hunch is that it will not be as expensive as deep brain stimulation for Parkinson's disease, which costs tens of thousands of dollars. But it's going to be more expensive than, say, LASEK surgery.

He also disagreed with Musk's over-the-top claims about recording and replaying memories.

There's a lot of science in the realm of memory, he said, including Wilder Penfield's decades-old work that appeared to show existing memories being triggered by electrical stimulation of the brain's temporal lobes during neurosurgery.

That's a far cry, however, from suggesting it would ever be possible to record from a particular memory and play it back, Dr. Miller continued. While short-term, working memory very likely is based on reverberating neural activity and amenable to the intriguing hippocampus memory prosthesis that Ted Berger has been working on, long-term memories almost certainly require protein synthesis and structural changes to neurons that couldn't even be recorded, let alone played back. That's pure science fiction, and to suggest otherwise sets up all sorts of false expectations.

Sliman Bensmaia, PhD, the James and Karen Frank Family Professor of Organismal Biology and Anatomy at the University of Chicago, runs a laboratory there devoted to research in somatosensory neuroscience and prosthetics. Earlier this year, before COVID-19 restrictions began, he visited the Neuralink offices and gave a talk.

There's a team of really great people working there, and the device they have come up with is really remarkable, Dr. Bensmaia said. The device that I work with, that almost everyone works with, the only device that has been used in humans so far, is the Utah array, made of metal microelectrodes. It's like a mini bed of nails that you press into the brain. Of course the brain doesn't like that, and the electrodes don't last. So the fact that Neuralink has these thin, flexible fibers should cause much less damage. And they have a lot more electrical contacts. The question is how robust and stable it will be. Will it last for decades? But it's pretty cool. It's way further along now than it was just six months ago when I visited them.

Despite all that, Dr. Bensmaia added, Then there is Musk and the way he talks about it. Some of the stuff he says is outrageous. It might be possible to achieve some of the things he's talking about one day, but it won't happen for a very long time.

Even so, he said, the progress made in the field in recent years is already beyond anything he thought possible in such a short time.

I participated in DARPA's Revolutionizing Prosthetics program, he said. When I was first approached about working on brain-machine interfaces, I thought, This is crazy. But we went farther than we could have reasonably hoped to do. That's why I'm not completely closed to the wildest claims Musk makes. It's not insane that maybe one day we can replay memories.

In fact, a 2018 paper published in the Journal of Neural Engineering described a study involving epilepsy patients with surgically implanted electrodes near the hippocampus whose electrical spikes were recorded and analyzed while they performed a memorization task. When scientists stimulated the CA1 region by playing back the sequence of neural firing made when the subjects correctly remembered a preliminary set of memorizing tasks, their performance on subsequent memorization tasks improved by 35 percent.)

Dr. Hochberg leads the BrainGate consortium, which includes researchers from Massachusetts General Hospital, Brown University, the Providence VA Medical Center, Stanford University and Case Western Reserve.

Over the past few years, in our published research, the participants in our trial who had very little or no movement of their arm or hand have been able to control an unmodified tablet computer for email, for texting, for controlling their music players, Dr. Hochberg said.

I used to say it would take decades before a BCI is available to people outside of research trials that could offer a true clinical benefit. I now think we are just a few years away. Right now these systems often require the oversight or engagement of a trained technician to start the system and calibrate it at the beginning of each day. We need it to work 24 hours a day, seven days a week, in the absence of any technical oversight. On all those merits, we are on track to achieve that goal with a flexible, powerful and reliable system.

Because Mass General has a clinical research support agreement with Neuralink, Dr. Hochberg said he should not speak specifically about the company. But, he said, I'm excited by the entrants of multiple companies to the BCI field. The engagement of companies will ultimately benefit our patients who have neurological disease or injury.

As for those neurologists who remain leery of a field in which companies like Neuralink are publishing accounts of apparent gains in preprints posted without peer review, a University of Toronto fellow said, essentially, this is a sign of things to come in this burgeoning world of technology.

What we are seeing is a shift to Silicon Valley-style neurotechnology companies that attract venture capital and a lot of talent quickly, said Graeme Moffat, PhD, a former managing editor of Frontiers in Neuroscience who now also runs a company developing non-invasive brain imaging devices.

The pace of iteration in fields that adopt this approachseveral new electronics designs every year and regular software updatesis too fast for journal review cycles. We'll see papers on the long term effects of new BCIs on the brain, but the peer-reviewed scholarly literature is just unsuited to reflecting the rapid innovation in devices like those that Neuralink is building.

Dr. Ganguly has received a one-time consulting fee from Lightside Medical, a medical incubator company. Dr. Stavisky is a scientific advisor to Vorso Corporation and Broad Mind Inc. and has equity in both companies. Dr. Angle owns stock and is employed by Paradromics. Drs. Miller, Bensmaia, and Moffat had no disclosures.

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Forget the GreeksIs This the World’s Oldest Anatomical Text? – Daily Beast

If you were to take a class on anatomy in med school you would probably be told that the history of anatomy really begins in the Renaissance, when doctors and other luminaries like Leonardo da Vinci first started dissecting human bodies and documenting their findings. You might also learn that prior to this point, doctors worked with the anatomical theories of the ancient Greeks and Romans, whose knowledge was gleaned mostly from the bodies of animals and external observation. The ancient Egyptians, who are well known for cutting up dead bodies, might get a look in, but that would likely be it.

But, now, a new study claims that an ancient manuscript unearthed in a tomb in Southern China may well be the worlds oldest anatomical atlas. The article not only promises to revolutionize our understanding of the history of medicine, it also sheds light on the history and scientific foundations of acupuncture.

In an article inThe Anatomical Record, Vivien Shaw and Isabelle Winder of Bangor University, UK, and Rui Diogo of Howard University published their findings about the Mawangdui manuscripts, a collection of philosophical and medical texts from Changsha in the Hunan province of South Central China. The texts are written on silk and were placed in the tomb of Chancellor Li Cang and his family before it was sealed in 168 BCE. They were rediscovered in the 1970s, but the previously unknown medical texts were somewhat overshadowed by the presence of other important discoveries, like the oldest copy of the I Ching. Because of this, Shaw, Winder, and Diogo are the first to treat these medical texts as evidence of ancient anatomy.

The Mawangduitexts, the authors argue, were written in the second-third century BCE and are roughly contemporaneous with now-lost Greek dissection-based anatomical texts. Of course, the approach taken in these Chinese texts is very different than the one we see in their Greek counterparts. Vivien Shaw said, they looked at the body from the viewpoint of traditional Chinese Medicine, which is based on the philosophical concept of complementary opposites of yin and yang, familiar to those in the west who follow eastern spiritualism.

The Mawangduitexts organize the body into eleven pathways, each of which has particular kinds of disease associated with it. Some of these, Isabel Winder said, map onto later acupuncture meridians, even though acupuncture and acupuncture points are nowhere mentioned. Historians had some evidence for the acupuncture meridians from other ancient Chinese texts, but those texts date to the third century CE and are, thus, roughly four hundred years younger than the ones from Mawangdui.

Their findings, said Shaw, not only re-write a key part of Chinese history and affirm that the Han dynasty was a period of widespread intellectual growth, they also provide medical foundations for acupuncture and change our understanding of how it originally worked.

We believe, she said, that our interpretation of the text challenges the widespread belief that there is no scientific foundation for the anatomy of acupuncture, by showing that the earliest physicians writing about meridians were in fact describing the physical body. Modern acupuncture, Shaw added, is grounded in the belief that it is the function of the meridian points thats important. Originally, however, it seems that Chinese anatomists were interested in mapping the structure of the body. In other words, and regardless of whether or not we think these descriptions of the body are accurate, they are scientific. This means that acupuncture, which is often dismissed as more spiritual than scientific, is grounded in a carefully worked out ancient map of the body that was based on scientific observation.

The reason that the Mawangdui texts have been overlooked as an anatomical resource is because they date from a period when the principles of Confucianism were very much in vogue. Han-era China was governed by Confucian law, which maintained stability and structure through the maintenance of a rigid social structure. One element of this social hierarchy was what is called filial piety, in which children must respect and honor their parents. Venerating ones ancestors did not include cutting up your dead parents. As Isabel Winder, one of the authors of the article, said Confucian cultural practices shunned dissection. However, [the evidence leads us to conclude] that dissection was involved and that the authors [of these texts] would have had access to the bodies of criminals.

This brings us to one of the grizzly secrets of the study of anatomy: to be any good at it you have to be examining actual human bodies. At the time, this was not just a Chinese practice. Herophilus of Chalcedon and his younger contemporary Erasistratus of Ceos, Greek-speaking doctors and medical authors working in Alexandria, Egypt in the first half of the third century BCE, were also dissecting cadavers on a routine basis. As in China (and, later, in 16th 19th century Britain), the bodies used for these experiments were those of criminals. Shortly after Herophilus and Erasistratus died, however, dissection fell into disuse. Though there were some rogue doctors who seem to have been dissecting bodies on the sly it wasnt until the 14th century, when the Italian Mondino de Luzzi publicly performed the first sanctioned dissection in a millennium, that it would begin again in earnest.

While dissection vastly improved medical sciences understanding of the workings of the human body, this doesnt mean that those performing these experiments always accurately described what was in front of them. Leonardo da Vincis scientific drawings of the human body are widely admired for their accuracy, but he sometimes followed tradition rather than the evidence, depicting, as Roy Porter has written in his book The Greatest Benefit to Mankind, a five lobed liver. The human liver only has four lobes; the five-lobe theory was based on the dissection of dogs and pigs and goes back to Hippocrates. We should not assume, therefore, that dissection always deepens and improves medical understanding. It took two hundred years and the creative vision of 16th century anatomist Andreas Vesalius for many ancient medical theories to be questioned and revised.

In between the 3rd century BCE and the rediscovery of dissection in the 14th, European doctors were reliant on the works of famous Greek-speaking doctors Aristotle and Galen, who had only dissected animals. Galen had experience treating gladiators and would have seen the kinds of wounds that would have afforded the opportunity peek inside the body, but there was nothing exhaustive about his exploration of the human body. As a result, all kinds of errorsthe five-lobed liver sketched by Da Vinci, for examplecrept into Western medicine. So, if youre thinking that Chinese medicine sounds unscientific and esoteric, bear in mind that for this 1200-year period of European history you may as well have been seeing a vet.

One of the major contributions of this study is the way that it challenges Eurocentric histories of science and medicine. Rui Diogo, whose lab helped perform the research, told The Daily Beast, that too often textbooks and scientific publications rehearse narratives in which white Europeans (from the Greeks and Romans onwards) make the big discoveries and non-European cultures contribute nothing more than translations of Greek texts or esoteric unscientific knowledge. Discoveries like this one show both that there was a vibrant scientific culture in places like India, China, and Persia and also that medical schemes often dismissed as esoteric have real scientific foundations.

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Forget the GreeksIs This the World's Oldest Anatomical Text? - Daily Beast

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New cell therapy improves memory and stops seizures after brain injury – Drug Target Review

A recent study has shown that transplanting new inhibitory neurons may repair damaged brain circuits.

A breakthrough cell therapy to improve memory and prevent seizures in mice following traumatic brain injury (TBI) has been developed by researchers.

In the study, the research team from the University of California, US transplanted embryonic progenitor cells capable of generating inhibitory interneurons (a specific type of nerve cell that controls the activity of brain circuits) into the brains of mice with traumatic brain injury, targeting the hippocampus.

These are transplanted inhibitory neurons (green) successfully incorporated into the hippocampus of a mouse with traumatic brain injury (credit: UCI School of Medicine).

The researchers discovered that the transplanted neurons migrated into the injury where they formed new connections with the injured brain cells and thrived long term. Within a month after the treatment, the mice models showed signs of memory improvement.

The cell transplants also prevented the mice from developing epilepsy, which affected more than half of the mice who were not treated with new interneurons.

Inhibitory neurons are critically involved in many aspects of memory, and they are extremely vulnerable to dying after a brain injury, said Robert Hunt, PhD, assistant professor of anatomy and neurobiology at UCI School of Medicine who led the study. While we cannot stop interneurons from dying, it was exciting to find that we can replace them and rebuild their circuits.

To further test their observations, the team silenced the transplanted neurons with a drug, which caused the memory problems to return.

It was exciting to see the animals memory problems come back after we silenced the transplanted cells, because it showed that the new neurons really were the reason for the memory improvement, added Bingyao Zhu, a junior specialist and first author of the study.

So far, nobody has been able to convincingly create the same types of interneurons from human pluripotent stem cells, Hunt concluded. But I think were close to being able to do this.

The study was published in Nature Communications.

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New cell therapy improves memory and stops seizures after brain injury - Drug Target Review

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New Cell Therapy Improves Memory and Stops Seizures Following TBI – University Herald

Irvine, Calif. - November 14, 2019 - Researchers from the University of California, Irvine developed a breakthrough cell therapy to improve memory and prevent seizures in mice following traumatic brain injury. The study, titled "Transplanted interneurons improve memory precision after traumatic brain injury," was published today inNature Communications.

Traumatic brain injuries affect 2 million Americans each year and cause cell death and inflammation in the brain. People who experience a head injury often suffer from lifelong memory loss and can develop epilepsy.

In the study, the UCI team transplanted embryonic progenitor cells capable of generating inhibitory interneurons, a specific type of nerve cell that controls the activity of brain circuits, into the brains of mice with traumatic brain injury. They targeted the hippocampus, a brain region responsible for learning and memory.

The researchers discovered that the transplanted neurons migrated into the injury where they formed new connections with the injured brain cells and thrived long term. Within a month after treatment, the mice showed signs of memory improvement, such as being able to tell the difference between a box where they had an unpleasant experience from one where they did not. They were able to do this just as well as mice that never had a brain injury. The cell transplants also prevented the mice from developing epilepsy, which affected more than half of the mice who were not treated with new interneurons.

"Inhibitory neurons are critically involved in many aspects of memory, and they are extremely vulnerable to dying after a brain injury," said Robert Hunt, PhD, assistant professor of anatomy and neurobiology at UCI School of Medicine who led the study. "While we cannot stop interneurons from dying, it was exciting to find that we can replace them and rebuild their circuits."

This is not the first time Hunt and his team has used interneuron transplantation therapy to restore memory in mice. In 2018, the UCI team used a similar approach, delivered the same way but to newborn mice, to improve memory of mice with a genetic disorder.

Still, this was an exciting advance for the researchers. "The idea to regrow neurons that die off after a brain injury is something that neuroscientists have been trying to do for a long time," Hunt said. "But often, the transplanted cells don't survive, or they aren't able to migrate or develop into functional neurons."

To further test their observations, Hunt and his team silenced the transplanted neurons with a drug, which caused the memory problems to return.

"It was exciting to see the animals' memory problems come back after we silenced the transplanted cells, because it showed that the new neurons really were the reason for the memory improvement," said Bingyao Zhu, a junior specialist and first author of the study.

Currently, there are no treatments for people who experience a head injury. If the results in mice can be replicated in humans, it could have a tremendous impact for patients. The next step is to create interneurons from human stem cells.

"So far, nobody has been able to convincingly create the same types of interneurons from human pluripotent stem cells," Hunt said. "But I think we're close to being able to do this."

Jisu Eom, an undergraduate researcher, also contributed to this study. Funding was provided by the National Institutes of Health.

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New Cell Therapy Improves Memory and Stops Seizures Following TBI - University Herald

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