Sunday, December 9, 2012

Brain Scans Don't Catch The Brain In Action

A visitor to the Wellcome Collection's 2012 exhibition "Brains: The mind as matter" looks at a functional magnetic resonance image (fMRI) showing a human brain as it listens to Stravinsky's "Rite of Spring" and Kant's third Critique.
A visitor to the Wellcome Collection's 2012 exhibition "Brains: The mind as matter" looks at a functional magnetic resonance image (fMRI) showing a human brain as it listens to Stravinsky's "Rite of Spring" and Kant's third Critique.
The backlash has begun! After years of overselling neuroscience and its results in the popular media, we are now finally beginning to hear public voices of dissent. Alissa Quart, writing in The New York Times, warmly sings the song of the backlash, while Gary Marcus, over at, explains that the proliferation of "brain porn" — colorful brain scan images fatuously illustrating articles about you name it — shouldn't obscure the fact that understanding the brain is a worthwhile goal and one that is necessary if we our to understand ourselves.

It would be hard to overstate the extent to which the fervor about the brain-basis of human experience is stoked by the development in the last few years of new technologies for brain imaging.

Until very recently, post-mortem autopsy has been just about the only way to study a person's brain. The brain has remained, for science, a black box. At best we have been able to draw conclusions about its design and functionality by looking at what possessors of brains can say and do. Things are different now, or so it is widely believed. The development of PET, and more recently fMRI, enable us now finally to penetrate the black box.

Not so fast. A functional brain image such as those produced by PET and fMRI no more captures the brain in action than a graph illustrating the percentage of the population who go to church on Sunday captures the people in the act of worship. Brain scan images are graphical renderings of what we hypothesize is going on in the head. There's nothing wrong with such images. In fact, they are valuable tools for carrying on scientific study. But they are not pictures of our brains in action, and so they are positively not images of our minds at work.

To appreciate this, consider that we face a problem from the very beginning about how to decide what neural activity is relevant to a mental phenomenon that we want to understand. Scientists start from the assumption that to a mental task — say the judgment that two given words rhyme — there corresponds a neural process. But how do we decide which neural activity going on inside you when you make a rhyming judgment is the neural activity in which the mental act consists? To do that, we need to have an idea how things would have been in the brain if you hadn't performed the rhyming judgment; that is, we need a baseline against which to judge that the deviation from the baseline corresponds to the mental act. One way to do this is by comparing the image of the brain at rest with the image of the brain making a rhyming judgment. The rhyming judgment presumably depends on the neural activity in virtue of which these two images differ.

But the brain is never at rest! There are stages of sleep when your brain is working harder than it does at most times during the day.

The standard way forward is the method of comparison. For example, suppose you have a bunch of PET images of people listening to recordings of spoken words and then making judgments about whether given pairs of words rhyme. To isolate the area of activation responsible for the rhyming judgment, as distinct from the auditory perception of the spoken words, a standard procedure would be to compare these images with a second set of images of people listening to recordings of spoken words but not making rhyming judgments. Whatever areas are active in the first set of images, but not the second, would be plausible candidates for the place in the brain where the rhyming judgment happens.

But notice: the upshot of all this is not a picture of rhyming perception happening in the brain. It is an argument, and one that could turn to be mistaken.

To give an example of just one assumption at work in the reasoning: the comparison method assumes that there is no feedback between the neural activity that the brain is doing when we make a rhyming judgment and what the brain is doing when we perceive the words. If there were feedback, then it would follow that overlapping regions in the images do not necessarily correspond to a common neural factor that can be factored out. Now, as a matter of fact, it is highly like that there is feedback. There are neural pathways heading back into the brain from the eyes; but there are even more neural pathways heading back out again. And this should not be surprising. Consider how much easier it is to hear a sound that you are expecting than one that you are not expecting. This assumption that there is no feedback in the neural circuitry is the flip side of a different assumption that we can factor the cognitive act itself into (in this example) distinct, modular acts of perceiving the words (on the one hand), and judgments about whether they rhyme (on the other).

That's a substantive empirical claim about the character and composition of cognitive acts themselves and certainly not one that can be simply taken for granted. (I rely here on an excellent older discussion of assumptions in brain imaging: Guy C Van Orden and Kenneth R. Pap's "Functional neuroimages fail to find pieces of the mind in parts of the brain in Philosophy of Science 64, 1997: 85-94.)

I am using the rhyming case as an illustrative example. My aim is not to show that there is anything in the least misguided about the method of comparison. What I do want to bring out is that brain scanners don't simply show us what is going on when we listen and judge.

In a way, these considerations about feedback in the brain and cognitive models are only the tip of the iceberg. PET and fMRI have very low spatial and temporal resolution. When you localize events in the brain, using these techniques, you localize them to cubic regions of between 2 and 5 mm, that is, to regions in which there are hundreds of thousands of cells. If there is specialization or differentiation among these cells, that won't show up in the illustration. Nor, for that matter, can we be sure exactly when neural events are happening. Cellular events unfold at the scale of thousandths of a second, but it can take much longer time scales (large portions of a minute) to detect and process signals for making images. For these reasons, scientists have developed techniques of normalizing data.

Typically, data from different subjects is averaged. The averaging process involves the loss of considerable information. After all, brains differ from one another no less than faces do. Just as the average American tax payer has no height and weight, so averaged neural activity has no location in any particular brain. For this reason, scientists project their findings onto an idealized, stock brain. The pictures we see in Nature are not snapshots of a particular person's brain in action.

Finally, putting all this to one side, it is important to be clear that there is no sense in which PET or fMRI illustrations deliver direct information about consciousness or cognition. They do not even deliver direct representations of neural activity. Functional brain imaging systems such as PET and fMRI build images based on the detection of physical magnitudes (such as radio or light waves) that are are believed to be reliably correlated with metabolic activity.

For example, in PET, one injects a positron emitting isotrope into the blood stream; PET detects the emission of gamma rays caused by the collision of positrons and electrons. In this way, the PET image carries indirect information about metabolic activity (based on the direct measurement of a physical magnitude) which is in turn supposed to carry information about neural activity. The latter supposition is not unreasonable. Neural events require oxygen, and so they require blood. The neural activity, in its turn, is supposed to correlate to significant mental activity. Brain scans thus represent the mind at three steps of remove: they represent physical magnitudes correlated to blood flow; the blood flow in turn is correlated to neural activity; the neural activity in turn is supposed to correlate to mental activity.

If all the assumptions are accurate, a brain scan image may contain important information about neural activity related to a cognitive process. But we need to take care not to be misled by the visual, pictorial character of these images. Brain scans are not pictures of cognitive processes in the brain in action.

How to Inspire Your Brain (Part 2)

By Deepak Chopra, MD, FACP and Rudolph E. Tanzi, Ph.D., Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard University, and Director of the Genetics and Aging Research Unit at Massachusetts General Hospital (MGH), co-authors of Super Brain: Unleashing the Explosive Power of Your Mind to Maximize Health, Happiness, and Spiritual Well-being. (Harmony)

 Evidence is gathering by the day that the brain isn't really an object but a continuous and active process. Thoughts and experiences create new pathways in the brain. They even affect the output of genes. What this means for the individual is extremely important. The control center for the brain's constant shaping and reshaping is you, the person who is using the brain. Although there are many brain processes that run on automatic, they too are highly influenced by experiences - that's why, for instance, the automatic rise and fall of blood pressure during the day is highly responsive to all the things that happened to you during the day.
Brain health comes down to a simple-seeming formula: maximize the positive input and minimize the negative input. The result will be positive rather than negative output. To some extent the difference between positive and negative input isn't hard to define:

It's positive to maintain balanced diet, negative to eat an imbalanced one.
It's positive to take regular exercise; it's negative to be sedentary.
It's positive to have good relationships, negative to have stressful ones.

Anyone who has kept pace with the public campaign in prevention can make the list longer; the risk factors for a healthy lifestyle are well known. But this is where the difference between positive and negative get trickier. Information isn't the same as compliance. That Americans are getting more obese and sedentary while consuming massive quantities of sugar and fatty junk food isn't due to lack of information. Non-compliance is about inspiring your brain to function in a better way. This is a role assigned to the mind; the brain can't inspire itself.

In our book Super Brain we focus on how to you can best relate to your brain on the basis of more positive thinking, emotions, attitudes, and beliefs. In that regard we are running counter to the prevailing trend, which sees the brain as an organ that needs to be maintained the way one would maintain the heart of stomach. Of course the brain is an organ, but far more importantly, it serves the mind. Therefore, everything you think, say, and do depends on aligning the brain with your desires, intentions, and the vision you have of your life. The brain keeps a constant feedback loop going with the mind and body; if you were to fall into a coma, it can sustain life.

But only you can sustain meaning and purpose. For all of its brilliant discoveries, neuroscience can't give your brain meaning, and if you feel that you lack purpose, there is no drug or surgery that will bring it back. At present the main breakthroughs in neuroscience are medical. Curing organic disorders like Alzheimer's and depression are urgent goals since they undermine anyone's chance to find meaning and purpose.
But our emphasis is to raise the everyday functioning of the brain to a higher level. The baseline brain, as we call it, passively handles everyone's life given the input that is provided. Super brain, on the other hand, goes beyond the baseline brain to actively optimize what the brain can do - it brings to life hidden potential that exists in everyone's brain. To give a sense of what we mean, here's a quiz to test how much of your brain's potential you are presently using.

Quiz: Baseline Brain versus Super Brain

Look at the following list and place a check beside each sentence that describes your behavior at least some of the time. Don’t be judgmental or hard on yourself. Simply mark the items that honestly seem to apply to you.

I don’t ask myself to behave very differently today than I did yesterday.
I am a creature of habit.
I don’t stimulate my mind with new challenges very often.
I like familiarity. It’s the most comfortable way to live.
I’m not that excited with the work I do.
My relationships follow pretty set patterns.
I should pay more attention to my weight.
I don’t exercise regularly.
I can be impulsive and then regret it later.
I have certain habits I just can’t seem to break.
I look at my past and see major regrets.
I know that I have missed some major opportunities.
I’m only fair at making decisions.
I’m aware of having inner conflicts.
I worry about aging, particularly memory loss.
I’ve had much better times in my life than now.
The future fills me with uncertainty.
I need to be in better control of my life.
I wonder what my purpose in life is.
I wish that my emotions were more valued.
I rarely read inspirational stories, poetry, or scriptures.
I feel that I deserve more appreciation.
I don’t see my life really getting better.
I have a hard time getting a good nights’ sleep every night.
I don’t feel that great about my body.
Total Score __________

Analyzing your score: Every item on the list describes the baseline brain. Its attitudes, beliefs, and habits are self-limiting. They aren’t bad or wrong – this quiz isn’t about judging yourself. It’s about the habitual way that you relate to your brain. The point is to assess where you stand in relation to your hidden potential.
18 – 25 points. You are not sufficiently proactive as you relate to your brain. Much of the time you allow inertia to creep into your daily life. You let old habits and beliefs hold power over you. When something goes wrong, you tend to let it slide. You don’t believe that you can change your life at every moment, significantly. It’s good that you see yourself realistically, because each item that you checked off can be improved, as you will discover reading Super Brain.

11 – 17 points. You know that your life could be better and have a good appreciation of your limitations. You have spent some time trying to change, either through therapy, self-help, or spiritual pursuits. You may consider yourself a seeker. Even if you don’t, you would welcome positive change. Looking back at your past, you know that you had more potential than you have fulfilled so far. It’s good that you are so ready to change. Every page of Super Brain will speak to you personally and help you to get on the path to fulfillment.

5 – 10 points. You are a self-aware person who has been interested in fulfilling your potential for a long time. It’s likely that you are very familiar with therapy or the spiritual path. You value yourself and don’t easily accept limitations. You are ready to turn the rest of your life into a rising arc. You are already so proactive that Super Brain offers fulfillment at an unusually high level. The possibility of reaching higher consciousness and calling on the higher brain to get you there is very real.

0 – 4 points. Either you are astonishingly self-aware or you didn’t take the quiz seriously. Please take it again without fearing that you will make yourself look bad. The quiz is about an objective assessment, not about judging against yourself.

In the next post we'll discuss the implications of turning baseline functioning into higher functioning.

How to Inspire Your Brain

By Deepak Chopra, MD, FACP and Rudolph E. Tanzi, Ph.D., Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard University, and Director of the Genetics and Aging Research Unit at Massachusetts General Hospital (MGH), co-authors of Super Brain: Unleashing the Explosive Power of Your Mind to Maximize Health, Happiness, and Spiritual Well-being (Harmony)

We've entered a golden age for brain research, but all these new findings haven't trickled down to the individual. Yet there are broad discoveries that make it possible to everyone to improve their brains. Let me state these succinctly:

• Your brain is constantly renewing itself.
• Your brain can heal its wounds form the past.
• Experience changes the brain every day.
• The input you give your brain causes it to form new neural pathways.
• The more positive the input, the better your brain will function.

In a new book, Super Brain, I and my co-author, Prof. Rudolf Tanzi of Harvard Medical School, expand upon the neuroscience behind these broad findings. The old view of the brain as fixed for life, constantly losing neurons and declining in function, has been all but abolished. The new brain is a process, not a thing, and the process heads in the direction you point it in. A Buddhist monk meditating on compassion develops the brain circuitry that brings compassion into reality. Depending on the input it receives, you can create a compassionate brain, an artistic brain, a wise brain, or any other kind.

However, as Prof. Tanzi and I see it, the agent that makes these possibilities become real is the mind. The brain doesn't create its own destiny. Genetics delivers the brain in a functioning state so that the nervous system can regulate itself and the whole body. It doesn't take your intervention to balance hormone levels, regulate heartbeat, or do a thousand other autonomic functions. But the newest part of the brain, the neocortex, is where the field of possibilities actually lies. Here is where decisions are made, where we discriminate, worship, assess, control, and evolve.

If you think of everyday experience as input for your brain, and your actions and thoughts as output, a feedback loop is formed. The old cliché about computer software -- garbage in, garbage out - applies to all feedback loops. Toxic experiences shape the brain quite differently from healthy ones. This seems like common sense, but neuroscience has joined forces with genetics to reveal that right down to the level of DNA, the feedback loop that embraces mind and body is profoundly changed by the input processed by the brain.

Our aim was to cut to the chase. If input is everything, then happiness and well-being are created by giving the brain positive input. Without realizing it, you are here to inspire your brain to be the best it can be. This is much more than positive thinking, which is often too superficial and masks underlying negativity. The input that inspires the brain includes a wide array of things. Everyone wants to experience positive feelings (love, hope, optimism, appreciation, approval) without knowing how to get them. For all the theories that proliferate about happiness, from the brain's perspective, the formula is to maximize the positive messages being received by the cortex and minimize the negative ones.

What this implies isn't a brave new world of thought control or pretending that life is rosy. Life will always present challenges, setbacks, and crises. The point is to create a matrix that will allow you to best adapt to both sides, the light and the dark, of experience. In our book, we were particularly focused on a setup that would take people into old age with a brain that remains dynamic and resilient.

Here is our recommendation, having considered the most up-to-date neuroscience.

Matrix for a Positive Lifestyle
• Have good friends.
• Don't isolate yourself.
• Sustain a lifelong companionship with a spouse or partner.
• Engage socially in worthwhile projects.
• Be close with people who have a good lifestyle - habits are contagious.
• Follow a purpose in life.
• Leave time for play and relaxation.
• Keep up satisfying sexual activity.
Address issues around anger.
Practice stress management.
• Deal with the reactive mind's harmful effects: When you have a negative reaction, stop, stand back, take a few deep breaths, and observe how you're feeling.

Your brain will thrive in such a matrix, even as life brings its ups and downs. But by the same token, the brain can't arrive at any of these things on its own. You are the leader of your brain. I'll expand on this theme in the next post, since the whole issue of feedback loops turns out to be vital for all kinds of brain functions, including memory and the prevention of feared disorders like Alzheimer's.

'Chemo Brain' May Start Before Breast Cancer Tx

SAN ANTONIO -- "Chemo brain" is a real phenomenon among breast cancer patients, but it appears to start long before women undergo adjuvant chemotherapy, a researcher said here.

A study using functional MRI (fMRI) suggested that a month before chemotherapy was slated to start, women already experienced deficits in working memory, according to Bernadine Cimprich, PhD, RN, of the University of Michigan School of Nursing in Ann Arbor, Mich.

Women diagnosed with breast cancer, but who were slated just for radiation therapy, did better on memory tests performed during fMRI scanning while women without cancer did even better, Cimprich told reporters at the San Antonio Breast Cancer Symposium.

And across all the groups in the study, greater fatigue was associated with poorer test performance and more self-reported cognitive problems over time, Cimprich said.

The findings suggest that "chemo brain" is not the best way of thinking about what Cimprich called "cancer-related cognitive dysfunction."

Instead, the effect is probably due at least partly to the stress and fatigue associated with a cancer diagnosis and could be alleviated by interventions aimed at reducing fatigue, she suggested.

For this prospective study, the researchers enrolled 65 women with stages 0 through IIIa breast cancer, as well as 32 healthy, age-matched controls. Among the patients, 28 women were scheduled for adjuvant chemotherapy and 37 were to have radiotherapy alone for localized breast cancer.

Participants in the chemotherapy group performed a verbal working memory task with varying levels of difficulty during functional MRI scanning after surgery, a month before chemotherapy, and second time a month after chemotherapy.

The radiation patients had their testing after surgery, about a month before starting radiation, and again 5 months later, corresponding roughly to the length of the chemotherapy in the other group.

The healthy controls had their fMRI scans done after a negative mammogram and again 5 months later.
All the participants provided self-reports of cognitive function and fatigue at the same time points.

The chemotherapy group, she said, reported significantly greater severity of fatigue (P<0 .05=".05" and="and" b="b" less="less" on="on" performed="performed" the="the" verbal="verbal" well="well">memory
task at the first test.
Indeed, "the patient groups, as a whole, showed less activation [in the target region] than controls," she said, but the radiotherapy group was intermediate between controls and chemotherapy patients.

Greater fatigue was correlated with poorer performance on the memory task, regardless of group, she noted.

On the other hand, there were few differences in the brain scans taken at the second time point, largely because the chemotherapy patients had recovered much of their ability, Cimprich said.

Kent Osborne, MD, of Baylor College of Medicine in Houston, called the findings "very interesting," adding that, in his own practice, he has "often wondered if [chemo brain is] "as much related to the worry, anxiety, and stress at to the treatment itself." Osborne moderated the SABCS press conference.

Brain Abnormalities Linked to Comorbid ADHD in Bipolar Disorder

Brain Abnormalities Linked to Comorbid ADHD in Bipolar DisorderBrain structure abnormalities discovered through magnetic resonance imaging (MRI) in bipolar patients may have been wrongly attributed to the disorder.

They may actually be linked to the patient with bipolar disorder also having an attention-deficit hyperactivity disorder (ADHD), according to new research.

Because of the similarities and frequent coexistence of these two conditions, the ability to separate their symptoms and obtain an accurate diagnosis between the two has been a persistent challenge.

ADHD is a frequent diagnosis in individuals with bipolar disorder, with a comorbidity — co-existing together — prevalence of 5-20 percent.  This is often overlooked, though, when looking at brain imaging data.
For the study, researchers from the University of California at Los Angeles set out to unravel how ADHD and bipolar disorder individually contributed to brain abnormalities found during MRI.

They recruited 85 participants, of whom 17 had bipolar disorder only, 19 had ADHD only, 18 had both bipolar disorder and ADHD, and 31 had no mental disorder. All patients with bipolar disorder were in a non-depressed state at the time of imaging and were not taking lithium.

Researchers used MRI to measure participants’ cortical thickness. Analysis of the prefrontal cortex and anterior cingulate cortex showed that overall cortical thickness was lessened in patients with bipolar disorder both with and without comorbid ADHD.

However, the effect of bipolar disorder on cortical thickness was different in patients with and without ADHD in the right orbitofrontal cortex and the left subgenual cingulate.

In the right orbitofrontal cortex, bipolar disorder was associated with significant cortical thinning only when there was no ADHD diagnosis; furthermore, in the left subgenual cingulate, the presence of ADHD eliminated the cortical thinning associated with bipolar disorder compared to controls.

The effects of bipolar disorder and ADHD in these regions were found to be connected, “resulting in a unique phenotypic signature for the comorbid diagnostic group,” write the researchers in the journal Bipolar Disorders.