Neuroskeptic - Is It Time To Redraw the Map of the Brain?

A new study published online ahead of print publication in Brain: A Journal of Neurology suggests that our current maps of human brain-lesion deficits are not accurate and need to be reconsidered. Neuroskeptic offered a nice overview of the study, accessible to non-PhD readers. The article is also open access and available online.

I have included the summary from Neuroskeptic and the beginning of the full article - follow the links below to see the original article.

Is It Time To Redraw the Map of the Brain?

By Neuroskeptic | July 1, 2014 

A provocative and important paper just out claims to have identified a pervasive flaw in many attempts to map the function of the human brain.

University College London (UCL) neuroscientists Yee-Haur Mah and colleagues say that in the light of their findings, “current inferences about human brain function and deficits based on lesion mapping must be re-evaluated.”

Lesion mapping is a fundamental tool of modern neuroscience. By observing the particular symptoms (deficits) people develop after suffering damage (lesions) to particular parts of the brain, we can work out what functions those various parts perform. If someone loses their hippocampus, say, and gets amnesia, you might infer that the function of the hippocampus is related to memory – as indeed it is.

However, there’s a problem with this approach, Mah et al say. Conventional lesion mapping treats each point in the brain (voxel) individually, as a possible correlate of a given deficit. This is called a mass univariate approach.

The problem is that the shape and location of brain lesions is not random – some areas are more likely to be affected than others, and the extent of the lesions varies in different places.

What this means is that the presence of damage in a certain voxel may be correlated with damage in other voxels. So damage in a voxel might be correlated with a given deficit, even though it has no role in causing the deficit, just because it tends to be damaged alongside another voxel that really is involved.

Mah et al call this problem ‘parasitic association’. In a large sample of diffusion-weighted MRI scans from 581 stroke patients, the authors show that the co-occurrence of damage across voxels leads to systematic, large biases in mass univariate deficit mapping.

The biases follow a complex geometry throughout the brain: as this lovely (but scary) image shows -

This shows the direction and magnitude of the error that would afflict a standard attempt to localize a hypothetical deficit that was truly associated with points throughout the brain. In some areas, the bias ‘points’ forward, so the deficit would be wrongly mapping as being further forward than it really was. In other places, it points in other direction.

The mean size of the expected error is 1.5 cm, but with a high degree of variability, so it is much worse in some areas.

Worse yet, Mah et al say that in cases where the same deficit can be caused by damage to two, non-adjacent areas, univariate lesion mapping might fail to pinpoint either of them. Instead, it could wrongly implicate a nearby, unrelated area.

The authors conclude that the only way to avoid this problem is by using multivariate statistics to explicitly model voxel interrelationships, e.g. a machine learning approach. This will require large datasets, but they caution that merely having a big sample, without multivariate statistics, would achieve nothing. They conclude on a somewhat downbeat note:

It is outside the scope if this study to determine the optimal multivariate approach: our focus here is on the evidence of the misleading picture the mass-univariate approach has created, and the need to review it wholesale. Taken together, our work demonstrates a way forward to place the study of focal brain lesions on a robust theoretical footing.

I’m not sure the outlook is quite so bleak. It’s a very nice paper, however, Mah et al’s dataset is purely based on stroke patients. Yet there are many other sources of brain lesions that are used for lesion mapping: tumours, infections, and head injuries to name a few.

These kinds of lesions probably throw up parasitic associations as well, however, they might be very different from the kind seen in strokes. This is because strokes, unlike other kinds of lesions, are always centered on blood vessels.

Mah et al note that the bias map they found is clustered around the major cerebral arteries and veins, but the obvious conclusion to draw from this is that it’s only applicable to strokes.

Whether other kinds of lesions produce substantial biases remains to be established. Until we know that, we shouldn’t be rushing to redraw any maps just yet.

Full Citation:
Mah, Y., Husain, M., Rees, G., & Nachev, P. (2014, Jun 28). Human brain lesion-deficit inference remapped. Brain; DOI: 10.1093/brain/awu164

Included here is the abstract and the introduction - follow the link in the title to download the PDF for yourself.

Human brain lesion-deficit inference remapped

Yee-Haur Mah, Masud Husain, Geraint Rees, and Parashkev Nachev

Author Affiliations

1. Institute of Neurology, UCL, London, WC1N 3BG, UK
2. Department of Clinical Neurology, University of Oxford, Oxford OX3 9DU, UK
3. Institute of Cognitive Neuroscience, UCL, London WC1N 3AR, UK
4. Wellcome Trust Centre for Neuroimaging, UCL, London WC1N 3BG, UK

Summary

Our knowledge of the anatomical organization of the human brain in health and disease draws heavily on the study of patients with focal brain lesions. Historically the first method of mapping brain function, it is still potentially the most powerful, establishing the necessity of any putative neural substrate for a given function or deficit. Great inferential power, however, carries a crucial vulnerability: without stronger alternatives any consistent error cannot be easily detected. A hitherto unexamined source of such error is the structure of the high-dimensional distribution of patterns of focal damage, especially in ischaemic injury—the commonest aetiology in lesion-deficit studies—where the anatomy is naturally shaped by the architecture of the vascular tree. This distribution is so complex that analysis of lesion data sets of conventional size cannot illuminate its structure, leaving us in the dark about the presence or absence of such error. To examine this crucial question we assembled the largest known set of focal brain lesions (n = 581), derived from unselected patients with acute ischaemic injury (mean age = 62.3 years, standard deviation = 17.8, male:female ratio = 0.547), visualized with diffusion-weighted magnetic resonance imaging, and processed with validated automated lesion segmentation routines. High-dimensional analysis of this data revealed a hidden bias within the multivariate patterns of damage that will consistently distort lesion-deficit maps, displacing inferred critical regions from their true locations, in a manner opaque to replication. Quantifying the size of this mislocalization demonstrates that past lesion-deficit relationships estimated with conventional inferential methodology are likely to be significantly displaced, by a magnitude dependent on the unknown underlying lesion-deficit relationship itself. Past studies therefore cannot be retrospectively corrected, except by new knowledge that would render them redundant. Positively, we show that novel machine learning techniques employing high-dimensional inference can nonetheless accurately converge on the true locus. We conclude that current inferences about human brain function and deficits based on lesion mapping must be re-evaluated with methodology that adequately captures the high-dimensional structure of lesion data.

Introduction

The study of patients with focal brain damage first revealed that the human brain has a functionally specialized architecture (Broca, 1861; Wernicke, 1874). Over the past century and a half such studies have been critical to identifying the distinctive neural substrates of language (Broca, 1861; Wernicke, 1874), memory (Scoville and Milner, 1957), emotion (Adolphs et al., 1995; Calder et al., 2000), perception (Goodale and Milner, 1992), decision-making (Bechara et al., 1994), attention (Egly et al., 1994; Mort et al., 2003), and intelligence (Gla¨ scher et al., 2009), casting light on the anatomical basis of deficits resulting from dysfunction of the brain. Though functional imaging has revolutionized the field of brain function mapping in the last 20 years, the necessity of a brain region for a putative function—arguably the strongest test—can only be established by showing a deficit when the function of the region is disrupted. Inactivating brain areas experimentally cannot easily be done in humans; the special cases of transcranial magnetic and direct current stimulation, though potentially powerful, are restricted temporally to days and anatomically to accessible regions of cortex.

The only comprehensive means of establishing functional necessity thus remains the study of patients with naturally occurring focal brain lesions (Rorden and Karnath, 2004). Though single patients may sometimes be suggestive, robust, population-level inferences about lesion-deficit relationships require aggregation of data from many patients (Karnath et al., 2004). Analogously to functional brain imaging, a statistical test comparing groups of patients with and without a deficit is iteratively applied point-bypoint to brain lesion images parcellated into many volume units (voxels) (Bates et al., 2003; Karnath et al., 2004). Voxels that cross the significance threshold are then taken to identify the functionally critical brain areas whose damage leads to the deficit.

Crucially, this ‘mass-univariate’ approach assumes that the resultant structure-deficit localization is not distorted by co-incidental damage of other, non-critical loci in each patient: in other words, that damage to each voxel is independent of damage to any other. This cannot be assumed in the human brain. Collaterally damaged but functionally irrelevant voxels might be associated with voxels critical for a deficit through an idiosyncrasy of the pathological process—the distribution of the vascular tree, for example—while having no relation to the function of interest. Such associations would lead to a distortion of the inferred anatomical locus.

Importantly, these ‘parasitic’ voxel-voxel associations can be detected only by examining the multivariate pattern of damage across the entire brain, and across the entire group. Studying large numbers of patients with the standard approach simply exacerbates the problem, because such consistent error will also consistently displace inferred critical brain regions from their true locations. Equally, replicating a study with the same number of patients will replicate the error too: observing the same result across different research groups and epochs offers no reassurance. Instead, the pattern of damage must be captured by a high dimensional multivariate distribution that describes how the presence or absence of damage at every voxel within each brain image is related to damage to all other voxels. The presence of ‘parasitic’ voxel-voxel associations would then manifest as a
hidden bias within the multivariate distribution, a complex correlation between individual patterns of damage apparent only in a high-dimensional space and opaque to inspection with simple univariate tools.

To illustrate the problem, consider the 2D synthetic example in Fig. 1, where damage to any part of area ‘A’ alone may disrupt a putative function of interest, but ‘B’ plays no role in this function of interest. If the lesions used to map the functional dependence on A follow a stereotyped pattern where damage to any part of A is systematically associated with collateral damage to the non-critical area B, both areas might appear to be significantly associated even if B is irrelevant to the function of interest. Crucially, if the pattern of the lesions within each patient is such (for reasons to do with factors unconnected to function) that the spatial variability of damage to B is less than to A, B will not only be erroneously determined to be critical but will have a higher significance value for such an association than A. The apparent locus of a lesion function deficit will therefore be displaced from A (the true locus) to B. Thus a hidden bias in the pattern of damage—hidden because it is apparent only when examining the pattern as a whole, in a multivariate way—distorts the spatial inference. 

Whether or not such a hidden bias exists has not been previously investigated. Here we analyse the largest reported series of focal brain lesions (n = 581) to show that it does exist, and that it compels a revision of previous lesion-deficit relationships within a wholly different inferential framework.

The Woman Who Forgot the Names of Animals (And four other neuroscience patients who changed how we think about the brain, and ourselves)

This is a cool piece from Mother Jones, even if it is essentially a promotion for Sam Keen's new book, The Tale of the Dueling Neurosurgeons: The History of the Human Brain as Revealed by True Stories of Trauma, Madness, and Recovery. It does look like an interesting book.

The Woman Who Forgot the Names of Animals

And four other neuroscience patients who changed how we think about the brain, and ourselves.

By Indre Viskontas and Chris Mooney | Fri Jun. 13, 2014 

 

Angela Waye/Shutterstock

We've all been mesmerized by them—those beautiful brain scan images that make us feel like we're on the cutting edge of scientifically decoding how we think. But as soon as one neuroscience study purports to show which brain region lights up when we are enjoying Coca-Cola, or looking at cute puppies, or thinking we have souls, some other expert claims that "it's just a correlation," and you wonder whether researchers will ever get it right.

Sam Kean 

But there's another approach to understanding how our minds work. In his new book, The Tale of the Dueling Neurosurgeons, Sam Kean tells the story of a handful of patients whose unique brains—rendered that way by surgical procedures, rare diseases, and unfortunate, freak accidents—taught us much more than any set of colorful scans. Kean recounts some of their unforgettable stories on the latest episode of the Inquiring Minds podcast.

"As I was reading these [case studies] I said, 'That's baloney! There's no way that can possibly be true,'" Kean remembers, referring to one particularly surprising case in which a woman's brain injury left her unable to recognize and distinguish between different kinds of animals. "But then I looked into it, and I realized that, not only is it true, it actually reveals some important things about how the brain works."



Here are five patients, from Kean's book, whose stories transformed neuroscience:

1. The man who could not imagine the future: Kent Cochrane (KC), pictured below, was a '70s wild child, playing in a rock band, getting into bar fights, and zooming around Toronto on his motorcycle. But in 1981, a motorcycle accident left him without two critical brain structures. Both of his hippocampi, the parts of the brain that allow us to form new long-term memories for facts and events in our lives, were lost. That's quite different from other amnesiacs, whose damage is either restricted to only one brain hemisphere, or includes large portions of regions outside of the hippocampus.

KC's case was similar to that of Henry Molaison, another famous amnesiac known as HM. HM taught us that conscious memories of things like which street you grew up on (personal semantic information or facts about yourself) and what happened on your prom night (episodic memories for events in your past) are stored independently from other types of nonconscious memories, of things like how to ride a bike or play the guitar. You can lose one type of memory without losing the other. But KC taught us still more: That our ability to imagine the future is tied to our ability to use our memories to reexperience the past.

KC ("Kent Cochrane"), right, with his family. After losing his long-term memory, KC became one of the most famous patients in neuroscience. Cochrane family

"When he lost his past self," says Kean of KC, "he lost all sense of what he was going to do over the next hour, or over the next day, or over the next year. He couldn't project himself forward at all, and kind of realize that he would want to be doing something in a month or a year. He was kind of eternally trapped in the present tense."

Although it might sound obvious now, before KC came along, neuroscientists hadn't realized how closely tied, on a cognitive level, our future is to our past. "But if you think about it, it does make sense," explains Kean, "because the ultimate biological purpose of having a memory isn't just…to make you happy or something like that. The point of a memory is so that you can kind of keep track of what happened in your past, and then apply that to the future."

2. The man whose vocabulary was reduced to one word: In the late 18th century, the idea that different functions of the mind might be tied to specific parts of the brain first gained a foothold. Phrenology, as it came to be called, was based on the notion that bumps in the skull were markers of larger bits of brain, and that these bumps were clues as to what mental talents, or lack thereof, a person might possess. By the 1840s, however, many scientists dismissed phrenology (and rightly so) as rank pseudoscience.

Paul Broca Wikimedia Commons.

So when Paul Broca, a French neuroanatomist, first proposed that there was a specific "language area" in the brain—and did so based on evidence from the brain of a patient nicknamed "Tan"—he was laughed out of a scientific meeting.

Tan—whose story is related in Kean's new book—suffered from epilepsy throughout his childhood. By age 31, he could only respond to questions by repeating the word "tan." Unless, that is, he was enraged. Then, he'd let out a cry of "Sacre nom de Dieu!" a French insult. Yet Tan still seemed to be able to understand spoken language, even if he could not to speak himself. Because his vocabulary was so impoverished, he became an expert at gesturing, expressing himself through mime.

So how was it possible that a man lost his ability to speak words, but not to understand them?

In 1861, gangrene took Tan's life—and Broca got his brain, which he proceeded to study. Broca found a lesion on the left side of the brain, near the front. This turned out to be the "language production" node; it is now known as Broca's area. From Tan and patients like him, neuroscientists thus learned that the speech production and speech comprehension regions of the brain are quite separable—and we need both, functioning properly, to communicate using language.

3. The man whose brain was split in two: In the 1940s, neurosurgeons developed a new procedure to treat patients with severe epilepsy. As a last resort when other less invasive treatments were ineffective, they would sever the major fiber tract, known as the corpus callosum, that connects the two hemispheres of the brain. That way, when the sparks of overexcited neurons started in one part of the brain, the seizure was at least confined to that hemisphere, limiting the damage of the electrical storm.

The corpus callosum (in red) Anatomography/Life Science Databases/Wikimedia Commons

But as it happened, the patients involved didn't just have their epilepsy reduced: They also became marvels of science. Because these "split-brain" patients cannot send information from one hemisphere to the other, neuroscientists can learn from them which functions are limited to one side of the brain or the other.

One such patient, with the initials PS, was studied by neuroscientist Michael Gazzaniga. In experiments on PS and other split-brain patients, Gazzaniga devised a clever way of talking to each hemisphere independently. He would flash pictures on different sides of a screen, knowing that the visual system divides the world into two halves, and each hemisphere only sees one of them.

Thus in one experiment, Gazzaniga flashed an image of a snowy scene so that only PS's right hemisphere would perceive it, and an image of a chicken claw so that only his left hemisphere would pick it up. Then, Gazzaniga asked PS to choose, from an array of objects, those relevant to what he had seen. PS's left hand (governed by the right hemisphere) picked up a snow shovel, and his right hand (governed by the left hemisphere) chose a rubber chicken. So far, so good: That makes sense.

But when Gazzaniga asked him why he chose those objects, PS responded, "The chicken claw goes with the chicken, and you need a shovel to clean out the chicken shed," reports Kean. But of course, the shovel actually went with the snow scene. What was happening was that when it came to language, the left hemisphere is dominant. The right hemisphere, by contrast, has a barely functioning language capacity, but can express itself in other ways—by pointing with the left hand, for example, or by drawing or choosing objects with it.

You can watch a video featuring Gazzaniga's work with another split-brain patient here.

Split-brain patients like PS thus unlocked another mystery of the mind; or rather, the two minds. They showed that the two hemispheres store and process different types of information, and that when the connections between the two hemispheres are broken, each one can act independently of the other. For those of us with an intact corpus callosum, however, the hemispheres share information to such a large extent that calling someone "left-brained" or "right-brained" just doesn't make sense. "The idea that the left-brain is logical and controls all language, and the right brain is completely arty and just wants to do those kind of creative things—that's way, way overblown," says Kean.

4. The woman whose brain forgot animals: This is the story that, when Kean first read about it, he "did not believe it at first."

"It was a case of someone who had an injury to the part of their temporal lobe," remembers Kean, "so, on the side of the brain…the temples. And this person lost the ability to recognize all animals." And yet, stunningly, pretty much everything else was fine.

How could that happen? In his book, Kean explains that the woman in question suffered from complications of a herpes virus infection, which in rare cases can spread to the brain's temporal lobes, where we store general information about the world, like our knowledge of the capitals of states and countries. When herpes invades the brain, it can induce a coma and even death. But patients who do recover are sometimes left with very bizarre problems: They can lose the ability to recognize a particular category of things.

That's what happened with the woman who couldn't recognize animals: She could not tell them apart either by sight or sound, even though she could name and recognize other things just fine—the sound of a doorbell versus that of a phone, for instance. "She knew tomatoes are bigger than peas," Kean writes, "but couldn't remember whether goats are taller than raccoons. Along those lines, when scientists sketched out objects that looked like patent-office rejects (e.g., water pitchers with frying-pan handles), she spotted them as fakes. But when they drew polar bears with horse heads and other chimeras, she had no idea whether such things existed."

These patients have what are called category-specific agnosias, or losses of knowledge. And they have taught neuroscientists something critical concerning how we store information about the world: Namely, our brain divides objects into categories, and organizes those categories hierarchically. Thus, in the patient that Kean describes, the "animal" category had been knocked out, but nothing else had been.

That's just the beginning of what can happen to the brain, however. There are other patients who suffer from a disease called semantic dementia. First, they can't tell a robin from a sparrow. Then all birds seem the same. Then, as their brain damage progresses, they can't tell an animal from an inanimate object—until eventually, their speech contains no specific nouns.

5. The king who kept his skull but lost his mind: If you're still not convinced that blows to the head can devastate the brain—even if there are no symptoms of concussion, or exterior damage to the skull—this last case just might make you a serious NFL critic. In 1559, King Henry II of France lost a jousting match after taking a blow to the head. In doing so, he proved unequivocally that an intact skull does not mean that an intact brain resides inside it.

Henry II Wikimedia Commons.

At first, the doctors examining the king were not concerned. "They thought Henry was actually going to be just fine because when they looked at his skull, there was no…big crack on the outside; there wasn't a gory, obvious wound," says Kean. But it took the dueling neurosurgeons in the title of Kean's book to realize the extent of the damage to the king's brain.

"Twisting injuries, where you get hit on the side of your head, and your head kind of jerks one way," explains Kean, "those are especially bad because they end up tearing the seams between neurons—sometimes even tearing neurons themselves—open. And your brain—because of the flood of chemicals that come out of these torn neurons—your brain often has a big, electrical discharge at the same time."

"If the brain starts to swell or blood pools up inside the brain, it's very, very deadly. It will start to crush cells," Kean says. In such a case, a skull fracture might actually help matters by releasing some of the pressure and limiting the damage.

Henry II was not so lucky: The blow to his head caused his brain to swell and eventually hemorrhage, leading to his death—even though not a single shard of the jousting rod that hit him actually penetrated his brain. Henry's doctors could not save him, but future researchers learned from his case just how bad brain injuries can be.

Such, then, are some of the fascinating things we can learn from patients whose brains have been altered, or damaged, in unique ways. But as Kean relates, these patients don't just teach us by virtue of what they have lost. We also have much to learn from what they keep, from the brain functions that still work for them, even after all of their injuries.

Notably, they all seem to keep, at least in some form, their core identities.

"The more cases I looked [at], the more I saw evidence that you really do retain the sense of self," Kean says. "And in some ways…I thought that was kind of comforting, too, because when you're talking about these stories, you have to put yourself in the mind of these people, and think, you know, 'What would I be like if I lost this function of my brain, or, you know, if I turn into a pathological liar or I couldn't recognize my loved ones anymore?' But there are some things you do retain, that you won't lose about yourself."

To listen to the full interview with Sam Kean, you can stream below:

This episode of Inquiring Minds, a podcast hosted by neuroscientist and musician Indre Viskontas and best-selling author Chris Mooney, also features an exclusive brief interview with Neil deGrasse Tyson about the meaning of the just-completed Cosmos series; a discussion of whether the famed and controversial hormone oxytocin might be capable of extending the span of human life; and a breakdown of the physics of how soccer balls travel through the air (just in time for the World Cup).

To catch future shows right when they are released, subscribe to Inquiring Minds via iTunes or RSS. We are also available on Stitcher and on Swell. You can follow the show on Twitter at @inquiringshow and like us on Facebook. Inquiring Minds was also recently singled out as one of the "Best of 2013" on iTunes—you can learn more here.

Indre Viskonta - Inquiring Minds co-host.
Indre Viskontas is a neuroscientist, opera singer, and co-host of the Inquiring Minds podcast. RSS | Twitter

Chris Mooney -Correspondent
Chris Mooney is a science and political journalist, podcaster, and the host of Climate Desk Live. He is the author of four books, including the New York Times bestselling The Republican War on Science. RSS | Twitter

Researchers at the University of Arizona (here in Tucson) have been identifying where language centers lie in the brain and how they can formulate therapies to restore function after those areas are damaged in stroke (or otherwise).

Pélagie Beeson, professor and head of Dept. of Speech Language and Hearing at the University of Arizona, will be speaking tonight as part of the UA College of Science’s series “The Evolving Brain.” These talks are FREE and therefore quite popular - get there early for good seating.

You can teach a damaged brain new tricks

Courtesy UA - Pélagie Beeson, professor and head of Dept. of Speech Language and Hearing at the University of Arizona.

February 11, 2014
By Tom Beal

Like much of what we know about the brain, knowledge of the areas involved in spoken and written language comes mainly from studying the loss of those abilities to trauma or disease.

Pélagie Beeson, who studies the neural substrates of written language, will talk Monday about “The Literate Brain.” She will describe where those language centers lie and how she and her colleagues formulate therapies to restore function after those areas are damaged.

The lecture, part of the UA College of Science’s series “The Evolving Brain,” is at 7 p.m. in Centennial Hall on the University of Arizona Mall. [See below for more info.]

Beeson is a professor and head of the Department of Speech, Language and Hearing Sciences at the University of Arizona, with a joint appointment in the Department of Neurology.

Speech and writing problems usually develop after damage to the left hemisphere of the brain, though a small number of people (usually left-handers) develop those skills in the right hemisphere, she said.

Through years of cataloging symptoms and imaging the brain, specialists such as Beeson and her research group have developed a pretty good understanding of where those centers are and can usually predict, before the brain is imaged, where the damage has occurred, based on symptoms.

Beeson’s Aphasia Research Project sees clients at least six months and sometimes years or decades after loss of speech or writing function.

That six-month period, during which there is ongoing therapy, is also the period in which the brain repairs itself to the extent that it can.

Subjects can continue to improve through behavioral therapy by harnessing other, usually nearby, parts of the brain, to perform functions previously performed by damaged cells, she said.

This is especially true for younger patients, whose “elastic” brains can often develop language capabilities in the right hemisphere, Beeson said. That elasticity vanishes with youth.

Aphasia is the term applied to the acquired impairment of language, usually after stroke or trauma, but sometimes occurring with progressive neurological diseases.

It can be spoken, written or both. The acquired impairment of reading is known as alexia, and the impairment of spelling and writing is called agraphia.

Researchers in the UA’s Aphasia Research Project have developed an algorithm called a “decision tree” that personalizes treatment based on symptoms and performance on a battery of tests.

Functional Magnetic Resonance Imaging of the brain, during which a subject performs reading and writing tasks, further refines the picture of the impairment by allowing researchers to see what parts of the brain “light up” when certain tasks are performed.

Those who suffer a stroke or brain injury have a wide variety of aphasia symptoms — ranging from those who have no understandable speech to those who talk easily and form sentences but “can’t pull up the right word,” Beeson said.

Beeson said she’s never had to advertise for subjects for her research.

She receives a steady stream of referrals from neurologists and therapists in the Tucson area and from elsewhere in the country.

Her department recently kept its No. 5 spot in the annual U.S. News and World Report ranking of speech-language pathology programs.

Part of the center’s charge is to spread the word about new therapies through publishing results and reporting them at conferences, she said.

Promulgation of the latest therapies is part of the charge given by the National Institute on Deafness and Other Communication Disorders, one of the National Institutes of Health, which partly funds the research.

If you go

What: The UA College of Science 2014 lecture series on "The Evolving Brain."
When: Mondays at 7 p.m.
Where: Centennial Hall, 1020 E. University Boulevard 1020 E. University (campus mall east of North Park Ave.)
Admission: Free
Parking: (Fee charged) Tyndall Avenue Garage, between North Tyndall and North Park avenues south of University Boulevard.
Information: Call 520-621-4090621-4090cq

• Feb 17 (Monday): "The Literate Brain" by Pélagie M. Beeson, professor and head of Speech, Language and Hearing Science
• March 3: "The Ancestors in Our Brains" by Dr. Katalin M. Gothard, associate professor of Physiology, Neurobiology, and the Evelyn F. McKnight Brain Institute
• March 10: "More Perfect Than We Think" by William Bialek, the John Archibald Wheeler/Battelle Professor in Physics, Princeton University

Can Images Unlock the Mystery of a Healing Brain?

Maybe. Maybe not. But they can offer pathways for investigation. This article comes from MedPage Today.

Can Images Unlock the Mystery of a Healing Brain?

By Nancy Walsh, Staff Writer, MedPage Today
Published: February 01, 2013

Click the bottom right corner of the video player for full screen

Reports that sophisticated imaging had revealed residual brain activity in former Israeli prime minister Ariel Sharon, who's been comatose for more than 6 years, focused on the spectacular technology involved, but overlooked a more important clinical story -- that some patients with severe brain injury actually do regain some degree of cognitive function.

The concept of the minimally conscious state as a separate entity from the vegetative state has been a crucial diagnostic refinement in recent years, according to Nicholas D. Schiff, MD, who directs the Laboratory of Cognitive Neuromodulation at Weill Cornell Medical College in New York City.

"In the past, these patients were all lumped together, until we started asking the question of why it should matter if some patients appear to have some awareness and ability to track although they can't speak, respond, or organize movements," he said.

"Actually, it turns out that it matters a lot," Schiff told MedPage Today.

Consciousness and Recovery

What the brain imaging studies and neural research have demonstrated is that, in the weeks and months following brain injury, there is a vast difference in evolution of their condition between patients with minimal consciousness and those who are truly vegetative.

"Recent studies have demonstrated that it is important to disentangle both clinical entities as functional neuroimaging studies have shown differences in residual cerebral processing and hence, conscious perception, as well as important differences in outcome," Schiff wrote online in the journal NeuroImage.

What the research has begun to show is that recovery of important neural networks may be an occult process in some patients, with no visible changes in their ability to speak or move, he explained.

In one program that has prospectively followed 400 patients with traumatic brain injury over the course of 5 years, a significant proportion of patients advanced at least to a minimally conscious state despite having initially been at the lowest level of the Glasgow coma scale.

Approximately one-third of the patients regained some degree of independent function, and some even acquired vocational re-entry level of functioning, according to Schiff.

One possible factor in the gradual return of consciousness after injury, sometimes over a long period of time, "is that the normal recovery process ... includes a component of structural remodeling that could plausibly relate to reestablishment of goal-directed behaviors and driving of learning and memory mechanisms," Schiff wrote in the December 2009 issue of Trends in Neurosciences.

Imaging the Broken Brain

Following reports of spontaneous cognitive recovery after brain injury, a group of researchers from Cambridge, England, and Liege, Belgium, conducted a series of experiments in which they attempted to identify the level of awareness and the ability to communicate in 54 patients with severe brain injury.

Functional MRI tests in healthy controls have shown that the same areas of the brain activated by motor and spatial tasks can also have increased blood flow when the person imagines doing an activity such as playing tennis or walking through a house.

First, the researchers requested that the patients, while in the MRI scanner, imagine performing those activities.

For patients whose functional brain scans revealed increased intensity in the motor cortex or parahippocampal gyrus, the researchers then increased the complexity of the task, asking a series of autobiographical questions that would have yes or no answers, such as if the patient had a brother named Tom.

To answer yes, patients were instructed to imagine playing tennis, and to answer no, to imagine walking through the house.

The hypothesis was that the motor area of the brain would light up with an affirmative response, while the parahippocampal area that reflects spatial function would show increased signal intensity with a negative reply.

Among the 54 patients, five were able to "willfully modulate their brain activity," in response to the task instructions -- in effect, correctly answering the questions, wrote Martin M. Monti, PhD, now of the University of California Los Angeles.

This proved that "in a minority of cases, patients who meet the behavioral criteria for a vegetative state have residual cognitive function and even conscious awareness," Monti and colleagues reported in the Feb. 18, 2010 issue of New England Journal of Medicine.

But functional MRI is expensive and not always accessible, so another group tested 16 apparently vegetative patients using easily available electroencephalography (EEG) techniques and found that three were able to provide appropriate responses to commands that they imagine moving their hands and feet.

The EEG results were equivalent to what is seen for healthy controls, Adrian M. Owen, PhD, of the University of Western Ontario, and colleagues reported in Nov. 10, 2011 issue of The Lancet.

In effect, all these researchers were having simple conversations with their patients, Michael S. Beauchamp, PhD, of the department of neurobiology and anatomy at the University of Texas in Houston, told MedPage Today.

The Need for Assessment

Although the spectacular achievements being seen with neuroimaging have been garnering headlines, Schiff argued that another important need is far from being met.

"What's missing is an articulated framework for tracking patients and translating what we're learning from the research side into a system of care where they are reassessed over time," he toldMedPage Today.

Right now a person who is severely brain injured typically leaves the hospital with a diagnosis of vegetative state. There is no ICD code for minimally conscious state, no registry to follow these patients, and there is no requirement that the person undergo follow-up examinations.

The heightened understanding that the brain can undergo recovery has not been incorporated into the system, according to Schiff. Follow-up assessments are not reimbursed by insurance companies, and there aren't even many centers that provide these services.

The real hindrance has been this structural flaw in the system, he stated.

Thus far the only progress has been made by the defense department, which has proposed -- although not yet implemented -- the establishment of polytrauma centers, where brain injured veterans will be provided with reassessment of levels of consciousness to allow for adjustments in treatment, Schiff explained.

"As of now, it's very much the case that people just keep the diagnosis they were given when they leave the hospital," he said.

That may not be of tremendous concern for a patient who has been comatose for 5 or 10 years. "But certainly a person who is minimally conscious after a couple of months can have a very wide range of outcomes, including some that might not be acceptable to many patients and others that would be acceptable to all," he said.

Beauchamp concurred with the importance of differentiating patients who have no residual brain activity from those who may improve over time, particularly with regard to their treatment.

"If someone is truly brain dead, and there's no brain activity at all, it's probably not worth investing tremendous time and effort in attempting to rehabilitate them. But if there is some brain function and they just have not been able to let you know, you would definitely want to try to help them," he said.

And while it may be only up to 10% of comatose patients who have this minimal consciousness, it would be a tremendous service to provide more aggressive treatment to the one patient in 10 who does have potential for recovery, Beauchamp told MedPage Today.

Limitations and Next Steps

As to the implications of the brain scan results on prime minister Sharon, both Schiff and Beauchamp agreed that, while the specifics of the tests have not been publicly revealed, it seems unlikely that the treatment team found the types of responses seen in the published imaging studies, where patients were able to follow commands and perform other complex tasks.

Imaging studies have also demonstrated that patients who are vegetative can have a considerable amount of ambiguous brain activity, such as apparently responding to one's name or to a familiar face.

"The researchers who tested Sharon said they saw a response to his son's voice, but that's a lot simpler than being able to answer a yes or no question," Beauchamp said.

"They were very careful not to speculate about any possibility of recovery," he added.

"Animal studies also show that there is quite a lot of highly differentiated activity in the brain occurring without any conscious processing," Schiff noted.

Accordingly, imaging tests such as those given Sharon are really not ready for prime time in the clinic, according to Schiff.

In fact, they will probably not ever be useful as screening tests, because they aren't sufficiently sensitive. The false-negative rate is much too high, he said.

The most important role for brain imaging in these patients is for confirming the presence of consciousness. "When the technology works it's an unambiguous rule-in test," Schiff said.

That imaging tests remain imperfect tools for assessing consciousness was echoed by Stuart Hameroff, MD, director of the Center for Consciousness Studies at the University of Arizona in Tucson.

"Imaging studies don't tell us about awareness, they tell us about neuronal activity, behavior, and perception, which may be conscious or nonconscious," Hameroff told MedPage Today.

"Most people would say that consciousness is an emergent effect happening at a higher level of complexity, but my personal belief is that consciousness happens at a deeper level, inside the neuron, and is perhaps even a quantum effect," he said in an interview.

What's most needed now is the adoption of a variety of tools not only including ever-advancing imaging technology but also skilled clinical examinations being done on a regular basis, to identify misdiagnoses and signs of recovery and adjust treatment as needed, according to Schiff.

"We are trying to fundamentally understand what's happening when recovery occurs in a severely structurally damaged brain and to develop models of the underlying physiology, and then to develop rational therapies for those patients we can help," he concluded.

Preserved Self-Awareness following Extensive Bilateral Brain Damage to the Insula, Anterior Cingulate, and Medial Prefrontal Cortices

Whenever we think we have it figured out - in this case the "it" is self-awareness - we find something that totally disrupts what we think we know. This research article tells the story of Patient R, who had lost considerable brain tissue following a viral infection, including the chunks of the brain's three 'self-awareness' regions - the insular cortex, anterior cingulated cortex, and medial prefrontal cortex.

The patient, despite these brain tissue losses, still maintains a fairly solid self-awareness, although he experiences amnesia that impacts his narrative sense of self.

New Scientist offered a nice summary:

Location of the mind remains a mystery

• August 2012 by Douglas Heaven
• For similar stories, visit the The Human Brain Topic Guide

Where does the mind reside? It's a question that's occupied the best brains for thousands of years. Now, a patient who is self-aware – despite lacking three regions of the brain thought to be essential for self-awareness – demonstrates that the mind remains as elusive as ever.

The finding suggests that mental functions might not be tied to fixed brain regions. Instead, the mind might be more like a virtual machine running on distributed computers, with brain resources allocated in a flexible manner, says David Rudrauf at the University of Iowa in Iowa City, who led the study of the patient.

Recent advances in functional neuroimaging – a technique that measures brain activity in the hope of finding correlations between mental functions and specific regions of the brain – have led to a wealth of studies that map particular functions onto regions.

Previous neuroimaging studies had suggested that three regions – the insular cortex, anterior cingulated cortex and medial prefrontal cortex – are critical for self-awareness. But for Rudrauf the question wasn't settled.

So when his team heard about patient R, who had lost brain tissue including the chunks of the three 'self-awareness' regions following a viral infection, they immediately thought he could help set the record straight.

Not a zombie

According to the models based on neuroimaging, says Rudrauf, "patients with no insula should be like zombies".

But patient R displays a strong concept of selfhood. Rudrauf's team confirmed this by checking whether he could recognise himself in photographs and by performing the tickle test – based on the observation that you can't tickle yourself. They concluded that many aspects of R's self-awareness remained unaffected. "Having interacted with him it was clear from the get go that there was no way that [the theories based on neuroimaging] could be true," says Rudrauf.

However, R does have severe amnesia, which prevents him from learning new information, and he struggles with social interaction.

Self-awareness and other high-level cognitive functions probably do not relate to the brain in a simple way, says Rudrauf. "They involve layers of abstraction and mechanisms that cannot be explained by standard functional-neuroanatomy." He suggests that there are fundamental mechanisms yet to be discovered. "We would all like simple answers to complicated questions, and we tend to oversimplify our conceptions about the brain and the mind," he says.

Linda Clare, a psychologist at Bangor University, UK, is also not surprised by the finding. "Awareness has many manifestations," she says. "It's not just a matter of a few brain cells."

Journal Reference: 

Philippi CL, Feinstein JS, Khalsa SS, Damasio A, Tranel D, et al. (2012). Preserved Self-Awareness following Extensive Bilateral Brain Damage to the Insula, Anterior Cingulate, and Medial Prefrontal Cortices. PLoS ONE, 7(8): e38413. doi:10.1371/journal.pone.0038413

PLOS ONE is open access, so the article is freely available online. Here is the abstract:

Preserved Self-Awareness following Extensive Bilateral Brain Damage to the Insula, Anterior Cingulate, and Medial Prefrontal Cortices

Carissa L. Philippi^1#, Justin S. Feinstein^1#*, Sahib S. Khalsa², Antonio Damasio³, Daniel Tranel¹, Gregory Landini⁴, Kenneth Williford⁵, David Rudrauf^1#*

1 Division of Behavioral Neurology and Cognitive Neuroscience, Department of Neurology, University of Iowa, Iowa City, Iowa, United States of America, 2 Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California, United States of America, 3 Brain and Creativity Institute and Dornsife Cognitive Neuroscience Imaging Center, University of Southern California, Los Angeles, California, United States of America, 4 Department of Philosophy, University of Iowa, Iowa City, Iowa, United States of America, 5 Department of Philosophy, University of Texas Arlington, Arlington, Texas, United States of America

Abstract

It has been proposed that self-awareness (SA), a multifaceted phenomenon central to human consciousness, depends critically on specific brain regions, namely the insular cortex, the anterior cingulate cortex (ACC), and the medial prefrontal cortex (mPFC). Such a proposal predicts that damage to these regions should disrupt or even abolish SA. We tested this prediction in a rare neurological patient with extensive bilateral brain damage encompassing the insula, ACC, mPFC, and the medial temporal lobes. In spite of severe amnesia, which partially affected his “autobiographical self”, the patient's SA remained fundamentally intact. His Core SA, including basic self-recognition and sense of self-agency, was preserved. His Extended SA and Introspective SA were also largely intact, as he has a stable self-concept and intact higher-order metacognitive abilities. The results suggest that the insular cortex, ACC and mPFC are not required for most aspects of SA. Our findings are compatible with the hypothesis that SA is likely to emerge from more distributed interactions among brain networks including those in the brainstem, thalamus, and posteromedial cortices.