Tag Archives: brain

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He’s mad that trusts in the tameness of a wolf

I am an obstetrician, and not a neuropsychiatrist, but I feel a definite uneasiness with the idea of messing with brains –especially from the inside. Talking at it, sure –maybe even tweaking it with medications- but it seems to me there is something… sacrosanct about its boundaries. Something akin to black-boxhood -or pregnant-wombhood, if you will– where we have a knowledge of its inputs and outputs, but the internal mechanisms still too complex and interdependent to be other than interrogated from without.

I suppose I have a fear of the unintended consequences that seem to dog science like afternoon shadows -a glut of caution born of reading about well-meaning enthusiasms in my own field. And yet, although I do not even pretend to such arcane knowledge as might tempt me to meddle with the innards of a clock let alone the complexities of a head, I do watch from afar, albeit through a glass darkly. And I am troubled.

My concern bubbled to the surface with a November 2017 article from Nature that I stumbled upon: https://www.nature.com/news/ai-controlled-brain-implants-for-mood-disorders-tested-in-people-1.23031 I recognize that the report is dated, and merely scratches the surface, but it hinted at things to come. The involvement of DARPA (the Defense Advanced Research Projects Agency of the U.S. military) did little to calm my fears, either –they had apparently ‘begun preliminary trials of ‘closed-loop’ brain implants that use algorithms to detect patterns associated with mood disorders. These devices can shock the brain back to a healthy state without input from a physician.’

‘The general approach —using a brain implant to deliver electric pulses that alter neural activity— is known as deep-brain stimulation. It is used to treat movement disorders such as Parkinson’s disease, but has been less successful when tested against mood disorders… The scientists behind the DARPA-funded projects say that their work might succeed where earlier attempts failed, because they have designed their brain implants specifically to treat mental illness — and to switch on only when needed.’

And how could the device know when to switch on and off? How could it even recognize the complex neural activity in mental illnesses? Well, apparently, an ‘electrical engineer Omid Sani of the University of Southern California in Los Angeles — who is working with Chang’s team [a neuroscientist at UCSF] — showed the first map of how mood is encoded in the brain over time. He and his colleagues worked with six people with epilepsy who had implanted electrodes, tracking their brain activity and moods in detail over the course of one to three weeks. By comparing the two types of information, the researchers could create an algorithm to ‘decode’ that person’s changing moods from their brain activity. Some broad patterns emerged, particularly in brain areas that have previously been associated with mood.’

Perhaps this might be the time to wonder if ‘broad patterns’ can adequately capture the complexities of any mood, let alone a dysphoric one. Another group, this time in Boston, is taking a slightly different approach: ‘Rather than detecting a particular mood or mental illness, they want to map the brain activity associated with behaviours that are present in multiple disorders — such as difficulties with concentration and empathy.’ If anything, that sounds even broader -more unlikely to specifically hit the neural bullseye. But, I know, I know –it’s early yet. The work is just beginning… And yet, if there ever was a methodology more susceptible to causing collateral damage, and unintended, unforeseeable consequences, or one that might fall more afoul of a hospital’s ethics committee, I can’t think of it.

For example, ‘One challenge with stimulating areas of the brain associated with mood … is the possibility of overcorrecting emotions to create extreme happiness that overwhelms all other feelings. Other ethical considerations arise from the fact that the algorithms used in closed-loop stimulation can tell the researchers about the person’s mood, beyond what may be visible from behaviour or facial expressions. While researchers won’t be able to read people’s minds, “we will have access to activity that encodes their feelings,” says  Alik Widge, a neuroengineer and psychiatrist at Harvard University in Cambridge, Massachusetts, and engineering director of the MGH [Massachusetts General Hospital] team.’ Great! I assume they’ve read Orwell, for some tips.

It’s one of the great conundrums of Science, though, isn’t it? When one stretches societal orthodoxy, and approaches the edge of the reigning ethical paradigm, how should one proceed? I don’t believe merely assuming that someone else, somewhere else, and sometime else will undoubtedly forge ahead with the same knowledge, is a sufficient reason to proceed. It seems to me that in the current climate of public scientific skepticism, it would be best to tread carefully. Science succeeds best when it is funded, fêted, and understood, not obscured by clouds of suspicion or plagued by doubt -not to mention mistrust. Just look at how genetically modified foods are regarded in many countries. Or vaccinations. Or climate change…

Of course, the rewards of successful and innovative procedures are great, but so is the damage if they fail. A promise broken is more noteworthy, more disconcerting, than a promise never made.

Time for a thought experiment. Suppose I’ve advertised myself as an expert in computer hardware and you come to me with particularly vexing problem that nobody else seemed to be able to fix. You tell me there is a semi-autobiographical novel about your life that you’d been writing in your spare time for years, stored somewhere inside your laptop that you can no longer access. Nothing was backed up elsewhere –you never thought it would be necessary- and now, of course, it’s too late for that. The computer won’t even work, and you’re desperate.

I have a cursory look at the model and the year, and assure you that I know enough about the mechanisms in the computer to get it working again.

So you come back in a couple of weeks to pick it up. “Were you able to fix it?” is the first thing you say when you come in the door.

I smile and nod my head slowly. Sagely. “It was tougher than I thought,” I say. “But I was finally able to get it running again.”

“Yes, but does it work? What about the contents? What about my novel…?”

I try to keep my expression neutral as befits an expert talking to someone who knows nothing about how complex the circuitry in a computer can be. “Well,” I explain, “It was really damaged, you know. I don’t know what you did to it… but a lot of it was beyond repair.”

“But…”

“But I managed to salvage quite a bit of the function. The word processor works now –you can continue writing your novel.”

You look at me with a puzzled expression. “I thought you said you could fix it -the area where my novel is…”

I smile and hand you back the computer. “I did fix it. You can write again -just like before.”

“All that information… all those stories… They’re gone?”

I nod pleasantly, the smile on my face broadening. “But without my work you wouldn’t have had them either, remember. I’ve given you the opportunity to write some more.”

“But… But I was stored in there,” you say, pointing at the laptop in front of you on the counter. “How do I know who I am now?”

“You’re the person who has been given the chance to start again.”

Sometimes that’s enough, I suppose…

 

 

 

 

 

 

 

 

 

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The Unheard Problem with Noise

Life in the city can be noisy. That’s not where I live, so I find my occasionally unavoidable forays into its bowels almost unbearable.

“How can you live like this?” I asked a friend as we sat on the patio of a coffee shop on a downtown street as an ambulance screamed by.

“What do you mean?” she answered, looking at me with puzzled eyes, her coffee on it’s way to her mouth undisturbed.

The noise had been so obviously intrusive and irritating, that words failed me for a moment. I raised my arm and pointed along the busy, cacophonous street.

“All the people, you mean?” She smiled innocently and shrugged. “It’s near lunch time, I guess,” she said, and picked up her coffee for another sip.

I rested my hands on the table to steady them before I made an attempt to lift my own cup. “Don’t you find it rather…” I paused as I searched for the proper word to describe my angst. “… turbulent?” It was probably not the best description, but I still felt agitated.

The smile wavered for a moment as she tried to decipher my question. Then she sighed –or at least seemed to sigh –I couldn’t hear her soft intake of air in the din that vibrated and careened around us as if we were sitting in the middle of a traffic jam at rush hour. “You’ve been away too long, my friend,” she said, shaking her head sadly.

I attempted to return her smile, but I think my lips were quivering too much for it to become the answer she expected. “Doesn’t all the noise bother you Janet?”

She blinked her eyes slowly in reply. It might have been seductive in another setting, but here it only seemed like a rebuke. “You learn to block it out. It’s an urban adaptation…” Her face softened at my obvious discomfort. “To tell you the truth, I don’t think I even hear it anymore unless it’s so loud it scares me…”

That seemed counterproductive to me, but I didn’t say so at the time. Warning signals are surely just that: alarms that are meant to alert those in the vicinity to potential risks. They’re supposed to provoke a reaction. In my case it probably heightened my awareness of the risks of signal fatigue. Of crying wolf too often. Perhaps it also sensitized me to research that recognized this and attempted novel technological solutions: http://www.bbc.com/future/story/20170714-the-brain-hacking-sound-thats-impossible-to-ignore

The alerting signal the article discussed ‘was inspired by neuroscience research on sounds that affect the emotion-processing centres of the brain.’ It was originally used in Malawi, Africa, ‘To alert Malawi locals to HIV tests and health checks from a mobile clinic […].’

The problem there, as here, was the brain’s tendency to adapt to frequently discordant and unpleasant ambient noise –blocking it from conscious awareness, in effect. It ‘was inspired by the neuroscience research of Luc Arnal at the University of Geneva. Arnal had investigated what neural connections are activated when humans hear a sound that is particularly difficult to ignore: screaming. Scans revealed that, when we hear the characteristically rough, distressing sound of a scream, the amygdala – which processes fear reactions – is activated in our brains. “What I found is that this roughness doesn’t go through the same neural pathways used by speech,” he says.

It means that screams don’t just get our attention, they immediately prompt us to react in some way. We’re stimulated to actually do something. […] Arnal had previously suggested that this insight could be used to design better alarms and sirens that don’t just make us freeze when we hear them, but actually invoke a more constructive reaction.’

An American artist, Jake Harper, had previously recorded  the music of a local band in Malawi and edited it into a form that ‘sounds like nothing you’d recognise from a street elsewhere in the world. Strangely unlike a conventional emergency services siren, instead it is a discordant mashup of musical fragments and intermittent white noise.’

‘Harper spent months experimenting with audio software to try and come up with a noise that sounded man-made enough to distinguish it from human or animal voices in the bush, but which was also not overly harsh or distressing. Getting the balance right – appealing to the emotion-processing parts of the brain without inducing fear or shock – was tough. The results were encouraging. Harper says that on average, a mobile clinic would test 40 people per day for HIV. “During the trial we had 160 people come to get tested,” he says.’

For Arnal, ‘that succeeds in meeting the three key goals here: produce a sound that grabs people’s attention; avoid distressing them; make sure it is distinguishable from non-manmade sounds in the environment.’

‘Our understanding of how audio influences human psychology has evolved greatly in recent years, according to Annett Schirmer at the Chinese University of Hong Kong. For example, studies have shown that people’s neural activity can be co-ordinated with the help of external rhythms. This is exactly the sort of effect you would expect from, say, factory or farm labourers working in time to a song – or the effect of cohesion observed in musicians performing together.

“Music stimulation entrains certain mental processes and aligns them between individuals […]” However, she warns there is also a dark side to using music to alter behaviour.

“Shops use music to make customers stay longer or increase the likelihood that they purchase things,” she notes.’

This is exciting stuff for sure. As Arnal observes, ‘In the future, sound that provokes responses deep in our brains could be more thoughtfully designed into the built environment.’ But we humans are an adaptive lot. We quickly learn to ignore sounds that might have been initially distressing when we first heard them. Apart from the morbid curiosity aroused by it, an ambulance wailing past soon loses its relevance if there is no one nearby who needs it. And if it becomes a too frequent and unwelcome guest, surely the doors to our ears would quickly become unwilling to allow it entrance. I’m not advocating for the Luddites, though, just for an appreciation of Darwin.

Or, perhaps, for the sentiment of Oliver Wendell Holmes as he observed in one of his poems: And silence, like a poultice, comes to heal the blows of sound.

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Gender and Stress

Even the most ardent proponents of gender parity will admit that equality of opportunity does not imply equality of physiology. ‘The worst form of inequality is to try to make unequal things equal,’ as Aristotle said. Homogeneous –likeness, if you will- is not necessarily homogenous (a biological term meaning structurally similar due to common ancestry). Admittedly a semantically fraught distinction, it nonetheless suggests that there may well be differences that do not transcend gender.

For example, there seems to be a sexual discrepancy in the acquisition of post-traumatic stress disorder (PTSD)  http://www.bbc.com/news/health-37936514 -women tend to be more vulnerable to its development than men. A research team from Stanford University published a study in Depression and Anxiety (the official journal of the Anxiety and Depression Association of America) and it suggests that ‘[…] girls who develop PTSD may actually be suffering from a faster than normal ageing of one part of the insula – an area of the brain which processes feelings and pain. […]the insula, was found to be particularly small in girls who had suffered trauma. But in traumatized boys, the insula was larger than usual. This could explain why girls are more likely than boys to develop post-traumatic stress disorder (PTSD), the researchers said. The insula, or insular cortex, is a diverse and complex area, located deep within the brain which has many connections. As well as processing emotions, it plays an important role in detecting cues from other parts of the body. […]This shows that the insula is changed by exposure to acute or long-term stress and plays a key role in the development of PTSD.’ And as I quoted, the changes seem to be different in the two sexes.

The point of all this somewhat detailed background, is to submit that, as the study suggests, ‘it is possible that boys and girls could exhibit different trauma symptoms and that they might benefit from different approaches to treatment.’ Perhaps a sensitive counsellor would recognize this as the sessions continued, but it’s helpful to have some corroboratory evidence to justify any proposed changes.

I have to say that I was woefully ignorant of any sex difference in the development of PTSD. I’m embarrassed to admit that, if anything, I thought of it as largely a male condition –perhaps because of its association with war, and combat -traditionally at least, arenas of male predominance. But of course that is naïve. PTSD is not something confined to combat; it can be equally prevalent in other situations of distress or upheaval. Trauma is trauma, and long term issues can result from such things as natural disasters, car crashes, and certainly sexual or physical assaults, to name only a few. Because the symptoms can be confusing or even disguised, the diagnosis is best left to qualified practitioners, and yet I can’t help but wonder if a greater and more sensitive awareness of the possibility of the condition might encourage more sufferers to seek professional help.

As a gynaecologist, I feel uncomfortable and indeed far out of my depth in discussing most issues pertaining to PTSD, and yet thinking back over my years in practice, it seems to me that I may have suspected something of the sort, but lacked both the vocabulary and training to assign it a label –especially in those women I saw for conditions they suspected may have been attributable to previous sexual abuse: fears that they occasionally admitted to re-experiencing in unrelated events; things about which they still had nightmares; situations that led to unprovoked irritability and anger.

PTSD, by whatever name, has no doubt afflicted humans from time immemorial. Male hubris dictated that it be disguised or denied no doubt –it was a sign of weakness- and therefore unlikely to be mentioned in contemporary accounts. But signs of its presence occasionally snuck into mainstream literature -Shakespeare’s Henry IV being a likely candidate, for example. Perhaps more germane to my specialty, however, was the recognition of the lasting effects of trauma on people other than those involved in traditional conflict: women. The US Department of Veteran’s Affairs in its National Center for PTSD pamphlet states: ‘Most early information on trauma and PTSD came from studies of male Veterans, mostly Vietnam Veterans. Researchers began to study the effects of sexual assault and found that women’s reactions were similar to male combat Veterans. Women’s experiences of trauma can also cause PTSD.’ In fact they maintain that ‘The most common trauma for women is sexual assault or child sexual abuse.’ http://www.ptsd.va.gov/public/PTSD-overview/women/women-trauma-and-ptsd.asp

For too long have the lasting effects of sexual assault been ignored, or at best, trivialized and examined through male eyes in a still-male world. I don’t mean to sound like an overzealous feminist who pins all problems on male dominance, but I think age and a career spent in women’s health grants me a unique –if still masculine- perspective. As with all things, specialists run the risk of deconstruction, overanalyzing the events often with the consequent subversion of their apparent significance -almost a form of historical revisionism, an unintentionally biased and often contextually barren interpretation. One bridge, when crossed by a thousand people, becomes a thousand bridges –we all see the world through our own experiences, our own expectations, our own prejudices.

I think the fact that we can now demonstrate that there are valid reasons to question those often unconscious assumptions is a cause for hope. Much as we have finally realized that the results of many studies carried out only using men cannot necessarily be mindlessly extrapolated to women, so it is becoming increasingly apparent that trauma and its effects may also be non-generalizable. Although not its prisoners, we are after all, creatures of a chromosomal lottery, divergent physiologies, and certainly of different past experiences, so why wouldn’t there be a spectrum of responses to stress?

So, is there a ‘man-cold’? Well, maybe… I know that’s the kind I get, anyway.

 

 

 

 

 

 

 

 

 

 

 

Folk wisdom sometimes gets it right: there is a man-cold… Well, maybe.

 

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A Flicker of Hope

It’s interesting what catches our attention when we surf the apps on our smartphones nowadays. Some of the more provocative articles have dubious sources, of course, but with a little digging the original study can often be found and the claims checked. The problem, however, is that even these results need to be reproducible in case either the methodology or the results were unreliable –and also the conclusions drawn from them. That’s why it’s often unwise to believe everything you see reported –or, on the other side, to report everything you want to believe… Fear and Hope are wonderful incentives, and so the issues in the study need to be thoroughly researched and vetted for bias and innuendo and references to the original study need to be included.

Perhaps because I am now retired, any article about time-related changes catches my eye more easily. So I find myself particularly interested in studies that suggest progress is being made -not with respect to age itself, but more the evolving process of aging: the gerund. It was with considerable interest that I read the BBC news on the use of flashing light therapy for Alzheimer’s http://www.bbc.com/news/health-38220670

I also attempted to read the original paper from MIT (entitled Gamma frequency entrainment attenuates amyloid load and modifies microglia) published in the December 2016  issue, of the journal Nature should you wish to struggle though it, but I have to confess that for me, even the title was difficult…

At any rate, the article suggested that flashing light in the eyes of mice that were genetically engineered to have Alzheimer’s-type damage in their brain, ‘encouraged protective cells to gobble up the harmful proteins that accumulate in the brain in this type of dementia. The perfect rate of flashes was 40 per second – a barely perceptible flicker, four times as fast as a disco strobe.’ And ‘Build-up of beta amyloid protein is one of the earliest changes seen in the brain in Alzheimer’s disease. It clumps together to form sticky plaques and is thought to cause nerve cell death and memory loss.’ Research has focused on ways to prevent this plaque formation using drugs, but with limited success so far. If a non-invasive method like a flickering light can activate the immune system to do it by itself, so much the better. ‘The researchers say the light works by recruiting the help of resident immune cells called microglia. Microglia are scavengers. They eat and clear harmful or threatening pathogens -in this instance, beta amyloid. It is hoped that clearing beta amyloid and stopping more plaques from forming could halt Alzheimer’s and its symptoms.’ Fine with me.

I did, however, initially wonder about how bothersome the flickering would be –news reports on television usually caution their audience whenever even flash photography is found in the report, presumably because of the risk of triggering epileptic seizures. But, as the article discussed: ‘For the patient, it should be entirely painless and non-invasive “We can use a very low intensity, very ambient soft light. You can hardly see the flicker itself. The set-up is not offensive at all,” they said, stressing it should be safe and would not trigger epilepsy in people who were susceptible.’ Better and better! It’s just preliminary stuff, of course, but at least it opens up new pathways and ideas for further research.

As if even reading about the concept was in itself therapeutic, the article immediately triggered what, at first blush, would seem to be a non-sequitur memory of a patient I saw many years ago. The issue as I recall was not so much about mental aberration -although the patient herself was apparently suffering from paranoid schizophrenia- but more about her speculation on the possible effects of flickering light on mental function.

I was, I think, in my first year of residency training in the gynaecology program and was doing a rotation in one of the older teaching hospitals in the city. In those days, things were very busy on the wards and so our tasks were apportioned according to our seniority, the senior residents doing the lion’s share of new consultations, while we juniors were given those jobs that, while important, required less experience -pap smears, usually.

My senior’s name was Sara, I remember, and she decided I should be the one to go to the psychiatric ward to do a pap smear on one of their more ‘unusual patients’ as she said to tease me.

“What do you mean ‘unusual’?” I asked. Sara didn’t like to go onto that ward, for some reason, so she usually made some excuse.

She stared at me for a moment before answering, I remember. “Oh, you know, she has paranoid delusions and hallucinates, or something…” But it was clear that Sara really had no idea why our department had been asked to do the pap, nor had she any intention of doing it herself.

I was beginning to suspect this was merely another sluff. Sara fancied herself a consultant now and able to delegate things she didn’t want to do. “But if she’s paranoid and hallucinates, wouldn’t it be better if the doctor doing the pap smear was female?”

Her expression turned angry at that point, and I recall her almost attacking me with her eyes. “Oh for god’s sake, there’ll be a nurse there with you the whole time… Or maybe they said two…” she added, uncertainty softening her glare, but not her resolve to send me to that ward.

I showed up at the psychiatric area and was allowed in only after identifying myself via the phone just outside the door. Then I was led to the brightly lit nursing station, and a rather large matronly nurse handed me the chart of the woman needing the pap.

“She hasn’t had a pap smear in years,” the nurse said in a soft voice, so it couldn’t be heard in the corridor outside of the station. “And her voices told her she has cervix cancer…”

“Her voices?” I should have been more professional, but I was already feeling a bit apprehensive about being inside a locked ward. “I mean, shouldn’t we wait until she’s feeling a bit better before we…”

“We can’t seem to find any good medication for her yet,” the nurse interrupted. “The doctor thought that we could at least calm her by checking her cervix.”

Greta –I still remember her name- was already in the examination room, sitting in her gown on a little table that had a set of rickety old metal stirrups at one end. They’d apparently had to borrow everything from another ward for the job. As soon as I entered with the nurse, Greta examined me from top to bottom with suspicious eyes.

“You’re a man,” she said before we were even introduced.

The nurse, whose name I forget, walked over to Greta and held her hand. “You remember we talked about this, Greta,” she said in the same soft voice she’d used before. “And you said it was okay…”

Greta nodded, smiled and lay back to put her feet in the stirrups. “They said I should show you my cervix,” she said, the italics staring at me between her knees. “Not the one with cancer, though…  I’m supposed to keep that one hidden.”

“Her voices,” the nurse quickly whispered in my ear as I sat on a little stool they’d also borrowed for the occasion along with a light on a long, flexible metal pole. It looked as old as the stirrups.

I got the speculum and the pap smear paraphernalia ready as the nurse readied the light. The bulb kept flickering, though. I fiddled with the bulb to see if it was loose, but it seemed tight enough. And it was obviously plugged into the wall. On, off, on, off… the light was beginning to annoy me. I snapped the switch a few times, but still, it insisted on flickering. On, off, on, off…

“I’ve got a flashlight,” the nurse said, but when she turned it on, it was so weak, I knew I wouldn’t be able to see cervix high up in the vagina with it.

“Well, maybe I can do the pap smear with the flickering light,” I said and shrugged.

Suddenly Greta raised her head and stared at me again. “Sometimes the prongs don’t make good contact in the wall. Everything’s so old in this place,” she added, shaking her head. “Take the plug out and squeeze the prongs.”

By this time I had the speculum in my hand, so I nodded to the nurse to try Greta’s suggestion. Sure enough, squeezing the prongs stopped the flickering.

Greta was still staring at me through her legs. “I may be crazy, doctor, but I’m not stupid…”

I put the speculum down on the medical tray I had on my lap. I sensed Greta wanted to explain something. “It’s a signal, you know.” I didn’t think I should reply. “The light’s always trying to tell you something –sometimes it’s angry, but more often it’s just trying to help…” Her feet still in the stirrups, she raised herself onto one elbow and continued. “It gets right into the brain to help, you know. It doesn’t stay there long enough, though, and that’s why it has to keep going in and out, in and out… And each time it tries, it flickers…” Then she stopped talking for a moment and stared at the nurse with an amazed expression on her face. “That’s what the doctors should be trying –not all those horrible pills…”

Maybe that incident stands out because it was the first pap smear I’d ever done. I don’t remember the result in Greta’s case –I was near the end of my rotation in that hospital- but I do remember Sara asking me what I’d done with that patient.

“Why?” I asked, afraid Greta had accused me of doing something improper.

“The ward told me that your patient seemed much calmer after you left and she apparently kept telling everybody you’d come up with a new treatment, or something…” And then I remember Sara smiling condescendingly at me, as if to say that junior residents could never do anything of the sort.