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Anesthesiology, Medicine and Literature, Neuroscience

Exploring the conscious (and unconscious) brain in every day life

Exploring the conscious (and unconscious) brain in every day life

line of peopleThe first time I fainted, I was seven. I passed out while racing my fellow second-graders across the playground. One minute, I was leading the pack in the race; the next thing I knew, I was lying in the nurse’s office with adult faces hovering all around me. My parents explained to me that I’d lost consciousness – it was like falling asleep for a minute, they told me.

It frustrated me to no end- even as a seven year old – that I didn’t know where that time had gone. Why couldn’t I remember those moments where I collapsed onto the grass and got scooped up by a petrified teacher? I ended up fainting a handful of times over the next few years (luckily doctors chalked it up to nothing more than dehydration and a genetic propensity to faint), and each time I was reminded of that frustration of not being able to grasp what was going on in my brain during those lost minutes.

As a seven-year-old, I didn’t have the chance to call up scientists and ask them to explain the brain to me, so when I started working on a feature article on consciousness for the latest issue of Stanford Medicine magazine, I was thrilled that maybe I’d get that chance to finally answer those questions that had been lingering in my head for decades. What makes the brain go from awake and aware to such a blank state, and then back again?

But it’s not that simple, I learned: There’s no single switch that flips the brain from conscious to unconscious. In fact, consciousness isn’t an on-off switch at all; it’s a whole spectrum of states. Anesthesiologist Bruce MacIver, PhD, pointed me toward this handy chart that shows different levels of consciousness. Each state of consciousness has its own unique place on two scales: physical arousal and mental awareness. As I looked at it, I realized that my experience with altered consciousness wasn’t just limited to my childhood fainting episodes – we all go in and out of multiple states of consciousness on a daily basis, and not only when we fall asleep and wake up.

“If you’re an elite athlete and you get in that so-called ‘zone,’ that’s an altered state of consciousness,” anesthesiologist Divya Chander, MD, PhD, explained to me. I’m no elite athlete, but after talking to Chander, I suddenly started paying attention to those not infrequent times when I “zone out” while driving or exercising. And when I woke up to a noise in my house on a recent night, I immediately noticed my heightened senses – that alertness is an altered state of consciousness too.

“What I’m always hoping is that hearing about this kind of work makes people ask more questions about what it means when they themselves enter different states,” Chander said to me when we talked. Her message was not lost on me; I’ve become an active observer of my shifts in attention and awareness.

My Stanford Medicine story delves much deeper than these observations of daily life, to look at how and why anesthesiologists are probing what it means to be conscious – and how their research could lead to better anesthetic drugs. But I hope that in addition to conveying the science, it also helps readers realize that subtle changes in consciousness happen in your brain all the time.

As for the questions I had as a seven-year-old, they’re not fully answered, but I’ve only gotten more intrigued to know how the brain mediates consciousness, and more excited to follow where this research goes in the future.

Sarah C.P. Williams is an award-winning science writer based in Hawaii, covering biology, chemistry, translational research, medicine, ecology, technology and anything else that catches her eye.

Previously: Stanford Medicine magazine opens up the world of surgery, Your secret mind: A Stanford psychiatrist discusses tapping the motivational unconscious and Researchers gain new insights into state of anesthesia
lllustration by Jon Han

Neuroscience, Research, Stanford News

Non-invasive technique uses lasers and carbon nanotubes to provide view of blood flow in the brain

Non-invasive technique uses lasers and carbon nanotubes to provide view of blood flow in the brain

When researchers want to explore the brain of living animals, they have two options: surgically remove part of the skull, a procedure that can alter its function or trigger an immune response, or use CT or MRI scans, which isn’t effective for visualizing activity of individual vessels or groups of neurons. But a new approach developed by Stanford chemists holds the promise of offering a third option that is non-invasive and captures “an unprecedented look at blood flowing through a living brain.”

The technique involves injecting water-soluble carbon nanotubes into the subject’s bloodstream, in this case mice, and using near-infrared light to illuminate the brain vasculature and track cerebral blood flow. The work, which was published in Nature Photonics, could be useful in advancing the study of stroke and migraines, as well as Alzheimer’s and Parkinson’s diseases. According to a recent Stanford Report story:

Amazingly, the technique allows scientists to view about three millimeters underneath the scalp and is fine enough to visualize blood coursing through single capillaries only a few microns across, said senior author Hongjie Dai, a professor of chemistry at Stanford. Furthermore, it does not appear to have any adverse affect on innate brain functions.

….

The technique could eventually be used in human clinical trials, Hong said, but will need to be tweaked. First, the light penetration depth needs to be increased to pass deep into the human brain. Second, injecting carbon nanotubes needs approval for clinical application; the scientists are currently investigating alternative fluorescent agents.

Previously: Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact, Peering into the brains of freestyle rappers to better understand creativity and Brain imaging, and the “image management” cells that make it possible

Aging, Genetics, Imaging, Immunology, Mental Health, Neuroscience, Research, Women's Health

Stanford’s brightest lights reveal new insights into early underpinnings of Alzheimer’s

Stanford's brightest lights reveal new insights into early underpinnings of Alzheimer's

manAlzheimer’s disease, whose course ends inexorably in the destruction of memory and reason, is in many respects America’s most debilitating disease.  As I wrote in my article, “Rethinking Alzheimer’s,” just published in our flagship magazine Stanford Medicine:

Barring substantial progress in curing or preventing it, Alzheimer’s will affect 16 million U.S. residents by 2050, according to the Alzheimer’s Association. The group also reports that the disease is now the nation’s most expensive, costing over $200 billion a year. Recent analyses suggest it may be as great a killer as cancer or heart disease.

Alarming as this may be, it isn’t the only news about Alzheimer’s. Some of the news is good.

Serendipity and solid science are prying open the door to a new outlook on what is arguably the primary scourge of old age in the developed world. Researchers have been taking a new tack – actually, more like six or seven new tacks – resulting in surprising discoveries and potentially leading to novel diagnostic and therapeutic approaches.

As my article noted, several Stanford investigators have taken significant steps toward unraveling the tangle of molecular and biochemical threads that underpin Alzheimer’s disease. The challenge: weaving those diverse strands into the coherent fabric we call understanding.

In a sidebar, “Sex and the Single Gene,” I described some new work showing differential effects of a well-known Alzheimer’s-predisposing gene on men versus women – and findings about the possibly divergent impacts of different estrogen-replacement  formulations on the likelihood of contracting dementia.

Coming at it from so many angles, and at such high power, is bound to score a direct hit on this menace eventually. Until then, the word is to stay active, sleep enough and see a lot of your friends.

Previously: The reefer connection: Brain’s “internal marijuana” signaling implicated in very earliest stages of Alzheimer’s pathology, The rechargeable brain: Blood plasma from young mice improves old mice’s memory and learning, Protein known for initiating immune response may set up our brains for neurodegenerative disease, Estradiol – but not Premain – prevents neurodegeneration in woman at heightened dementia risk and Having a copy of ApoE4 gene variant doubles Alzheimer’s risk for women, but not for men
Illustration by Gérard DuBois

Behavioral Science, Chronic Disease, Neuroscience, Pain, Research, Stanford News

Obscure brain chemical indicted in chronic-pain-induced “Why bother?” syndrome

Obscure brain chemical indicted in chronic-pain-induced "Why bother?" syndrome

why botherChronic pain, meaning pain that persists for months and months or even longer (sometimes continuing well past the time when the pain-causing injury has healed), is among the most abundant of all medical afflictions in the developed world. Estimates of the number of people with this condition in the United States alone range from 70 million to 116 million adults – in other words, as much as half the country’s adult population!

No picnic in and of itself, chronic pain piles insult on injury. It differs from a short-term episode of pain not only in its duration, but also in triggering in sufferers a kind of psychic exhaustion best described by the rhetorical question, “Why bother?”

In a new study in Science, a team led by Stanford neuroscientist Rob Malenka, MD, PhD, has identified a particular nerve-cell circuit in the brain that may explain this loss of motivation that chronic pain all too often induces. Using lab mice as test subjects, they showed that mice enduring unremitting pain lost their willingness to perform work in pursuit of normally desirable goals, just as people in chronic pain frequently do.

It wasn’t that these animals weren’t perfectly capable of carrying out the tasks they’d been trained to do, the researchers showed. Nor was it that they lost their taste for the food pellets which with they were rewarded for successful performance – if you just gave them the food, they ate every bit as much as normal mice did. But they just weren’t willing to work very hard to get it. Their murine morale was shot.

Chalk it up to the action of a mysterious substance used in the brain for god-knows-what. In our release describing the study, I explained:

Galanin is a short signaling-protein snippet secreted by certain cells in various places in the brain. While its presence in the brain has been known for a good 60 years or so, galanin’s role is not well-defined and probably differs widely in different brain structures. There have been hints, though, that galanin activity might play a role in pain. For example, it’s been previously shown in animal models that galanin levels in the brain increase with the persistence of pain.

In a surprising and promising development, the team also found that when they blocked galanin’s action in a particular brain circuit, the mice, while still in as much pain as before, were once again willing to work hard for their supper.

Surprising, because galanin is a mighty obscure brain chemical, and because its role in destroying motivation turns out to be so intimate and specific. Promising, because the discovery suggests that a drug that can inhibit galanin’s activity in just the implicated brain circuit, without messing up whatever this mystery molecule’s more upbeat functions in the brain might be, could someday succeed in bringing back that drive to accomplish things that people in chronic pain all too often lose.

Previously: “Love hormone” may mediate wider range of relationships than previously thought, Revealed: the brain’s molecular mechanism behind why we get the blues, Better than the real thing: How drugs hot-wire our brain’s reward circuitry and Stanford researchers address the complexity of chronic pain
Photo by Doug Waldron

Neuroscience, Parenting, Pediatrics, Research

Can’t remember being a baby? Rapid growth of new neurons in young brains may explain why

Can't remember being a baby? Rapid growth of new neurons in young brains may explain why

baby_073014A close friend once told me that one of her favorite aspects about being a parent is that she could experience what it was like to be a baby and toddler. “As adults, we have no recollection of what it was like to be that young,” she said. “Watching my son grow up offers me a window into that part of my life.”

The inability to remember memories in early childhood is known as “infantile amnesia”. Few adults can remember events in their lifetime that occurred before the age of three. A past study shows that these memories tend to fade away around the age of seven.

But why can’t we remember our days as a crawling, toddling, babbling youngster? Recent research suggests the answer many have to do with how quickly the brain develops during this stage in our lives. According to a Scientific American article published earlier this week:

In a new experiment, the scientists manipulated the rate at which hippocampal neurons grew in young and adult mice. The hippocampus is the region in the brain that records autobiographical events. The young mice with slowed neuron growth had better long-term memory. Conversely, the older mice with increased rates of neuron formation had memory loss.

Based on these results, published in May in the journal Science, [neuroscientists Paul Frankland, PhD, and Sheena Josselyn, PhD] think that rapid neuron growth during early childhood disrupts the brain circuitry that stores old memories, making them inaccessible. Young children also have an underdeveloped prefrontal cortex, another region of the brain that encodes memories, so infantile amnesia may be a combination of these two factors.

Previously: Study finds age at which early-childhood memories fade and Individuals’ extraordinary talent to never forget could offer insights into memory
Photo by D Sharon Pruitt

Autism, Neuroscience, Pediatrics, Research, Stanford News

Finding of reduced brain flexibility adds to Stanford research on how the autistic brain is organized

Finding of reduced brain flexibility adds to Stanford research on how the autistic brain is organized

A Stanford brain-imaging study has just shown that the brains of children with autism are less able to switch from rest to taking on a new task than the brains of typically developing children.

According to the study, which appears this week in the scientific journal Cerebral Cortex, instead of changing to accommodate a job, connectivity in key brain networks of autistic children looks similar to connectivity in the resting brain. The degree of inflexibility was linked to the intensity of children’s autism symptoms: those with less flexibility had more severe restrictive and repetitive behaviors, one of the hallmarks of the developmental disorder.

From our press release on the research:

“We wanted to test the idea that a flexible brain is necessary for flexible behaviors,” said Lucina Uddin, PhD, a lead author of the study. “What we found was that across a set of brain connections known to be important for switching between different tasks, children with autism showed reduced ‘brain flexibility’ compared with typically developing peers.” Uddin, who is now an assistant professor of psychology at the University of Miami, was a postdoctoral scholar at Stanford when the research was conducted.

“The fact that we can tie this neurophysiological brain-state inflexibility to behavioral inflexibility is an important finding because it gives us clues about what kinds of processes go awry in autism,” said Vinod Menon, PhD, the Rachel L. and Walter F. Nichols, MD, professor of psychiatry and behavioral sciences at Stanford and the senior author of the study.

The study is the first to examine unusual patterns of connectivity in the brains of children with autism while they are performing tasks; Menon’s team has previously published research on connectivity between different regions of the autistic brain at rest. Some regions of the autistic brain are over-connected to each other, that work has shown, and the degree of over-connection is linked to children’s social deficits, perhaps in part because it interferes with their ability to derive pleasure from human voices. Menon’s lab has also explored how differences in the organization of the autistic brain may contribute to better math performance in some people with autism.

“We’re making progress in identifying a brain basis of autism, and we’re starting to get traction in pinpointing systems and signaling mechanisms that are not functioning properly,” Menon told me. “This is giving us a better handle both in thinking about treatment and in looking at change or plasticity in the brain.”

Previously: Greater hyperconnectivity in the autistic brain contributes to greater social deficits, Unusual brain organization found in autistic kids who best peers at math and Stanford study reveals why human voices are less rewarding for kids with autism

In the News, Neuroscience, Research, Stanford News

A spotlight on Stanford scientists’ use of deep-brain stimulation to eavesdrop on problem neural circuits

A spotlight on Stanford scientists' use of deep-brain stimulation to eavesdrop on problem neural circuits

Earlier this week, KTVU-TV aired a segment highlighting Stanford scientists’ ongoing research using deep-brain stimulation to control Parkinson’s patients’ tremors and record brain activity. A patient interviewed for the piece said the treatment “made a huge difference in my life” and called it “revolutionary.” More from the piece:

The new stimulator nicknamed “brain radio” is developed by Medtronic and tested by [Stanford neurologist Helen Bronte-Stewart, MD, and colleagues.]

“We can for the first time record the neural activity in the brain directly from the deep brain stimulator in somebody’s chest,” she said.

Despite decades of research, doctors have only a sketchy ideas of how the brain works, but now using Medtronic’s device they are for the first time opening a window into the human brain.

“I would think there will be developments that we don’t really know about right now that will come from some of the things we find out as we do this research,” said Bronte-Stewart.

Previously: Stanford conducts first U.S. implantation of deep-brain-stimulation device that monitors, records brain activity

Neuroscience, Research

Talk from the hand: the role of gesture in verbal communication

handAnother reason to revitalize commedia dell’arte: Gestures help us decipher meaning in communication. Okay, I might have made a leap from one Italian study’s conclusions, and the research could have broader implications, but the 16th century multiform theater genre incorporating pantomime to distinguish characters and advance plot came to my mind first.

For the recent study, published in Frontiers in Psychology, scientists conducted two experiments examining how spontaneous gestures that accompany speech carry information that conveys meaning, like intonation and rhythm of oral language. The International School of Advanced Studies researchers found that the sight of gestures combined with the sound of speech created a whole-body system of communication in which movement played an important role in helping listeners understand language that was unclear either because its sounds were unintelligible or the sentence could have more than one possible meaning. Twenty Italian speakers participated.

The authors write in the study:

Our results demonstrate that the prosody that characterizes speech is not a modality specific phenomenon: it is also perceived in the spontaneous gestures that accompany speech. We draw the conclusion that spontaneous gestures and speech form a single communication system where the suprasegmental aspects of spoken language are mapped to the motor-programs responsible for the production of both speech sounds and hand gestures.

“In human communication, voice is not sufficient: even the torso and in particular hand movements are involved, as are facial expressions,” said study author Marina Nespor, PhD, in a release.

Previously: Abstract gestures help children absorb math lessons, study finds
Photo by Eddi 07 – free stock

Behavioral Science, Neuroscience, Stanford News

Real time view of changing minds

Real time view of changing minds

There at this morning’s meeting was a large box of donuts which I had absolutely no intention of eating. None. Until I changed my mind.

What happened this morning was probably a little more complex than the simple changes of mind that Stanford Neurosciences Institute director William Newsome studies, what with the delicious smell of chocolate and a quick realization that perhaps a lunchtime run could be squeezed into my day.

Newsome has focused on recording the activity of individual neurons in animals making simple decisions, like indicating which way a dot is moving on a screen. He and his team then statistically analyze the results of many such recordings of individual neurons. These studies have gone a long way toward revealing the activity of neurons in different parts of the brain but can miss some of the fine scale dynamics that take place during the decision-making process. Recently, new probes have been developed that allow scientists to record the activity of many neurons at the same time.

Using such a probe, Newsome and his team recorded groups of neurons in animals making simple decisions, and could track in real time the patterns of how the neurons fired as the animals made a decision and changed their minds. They published their results in Current Biology. A press release from New York University quotes co-first author on the paper Roozbeh Kiani (a former postdoctoral scholar in Newsome’s lab):

“Looking at one neuron at a time is ‘noisy’: results vary from trial to trial so you cannot get a clear picture of this complex activity. By recording multiple neurons at the same time, you can take out this noise and get a more robust picture of the underlying dynamics.”

The team was able to watch the neurons firing in real time, and detect a pattern indicating which decision the animal was going to make. They could also tell when the animal changed its mind, for example as a result of a stronger signal on the screen or to more time to make a decision. What I found interesting is that in most cases when the animals changed their minds it was to correct their initial decision.

What does all this suggest about my donut splurge? Maybe that given enough time I was able to correct my initial decision of self-control to the right one – of deliciousness.

Previously: Co-leader of Obama’s BRAIN Initiative to direct Stanford’s interdisciplinary neuroscience institute

Bioengineering, Neuroscience, Sports, Stanford News

Mouthguard technology by Stanford bioengineers could improve concussion measurement

Mouthguard technology by Stanford bioengineers could improve concussion measurement

head impactPerhaps you’ve heard of helmet sensors to alert emergency contacts if a rider falls from a bicycle. Now, Stanford bioengineers are working with mouthguards that measure and report head impacts in football players in real time, and the research could have implications for understanding the forces of head traumas from more common accidents.

Stanford News reports:

For the past few years, David Camarillo, an assistant professor of bioengineering, and his colleagues have been supplying Stanford football players with special mouthguards equipped with accelerometers that measure the impacts players sustain during a practice or game. Previous studies have suggested a correlation between the severity of brain injuries and the biomechanics associated with skull movement from an impact.

Camarillo’s group uses a sensor-laden mouthguard because it can directly measure skull accelerations – by attaching to the top row of teeth – which is difficult to achieve with sensors attached to the skin or other tissues. So far, the researchers have recorded thousands of these impacts, and have found that players’ heads frequently sustain accelerations of 10 g forces, and, in rarer instances, as much as 100 g forces. By comparison, space shuttle astronauts experience a maximum of 3 g forces on launch and reentry.

Camarillo, PhD, and colleagues including bioengindeering doctoral student Lyndia Wu are enhancing the technology and refining the data collected, detecting head impacts in a lab test-dummy with 99 percent accuracy.  They’ve recently published a paper on their work in IEEE Transactions on Biomedical Engineering.

“Our football team has been extremely cooperative and interested in helping solve this problem,” Camarillo told writer Bjorn Carey. “What we are learning from them will help lead to technologies that will one day make bike riding and driving in your car safer too.”

Previously: Is repetitive heading in soccer a health hazard?Now that’s using your head: Bike-helmet monitor alerts emergency contacts after a crash and Stanford researchers working to combat concussions in football
Photo by Linda A. Cicero/Stanford News Service

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