Your Brain and Yourself: Perspectives on Our Golden Age of Neuroscience

Books

Andreasen NC. 2005. The Creative Brain: The Science of Genius. Plume, New York.
Amazon

Andreasen NC. 2004. Brave New Brain: Conquering Mental Illness in the Era of the Genome. Oxford University Press, New York.
Amazon

Gazzaniga MS. 2005. The Ethical Brain. Dana Press, Washington, DC.
Amazon

Nicolelis MAL. 1998. Methods for Neural Ensemble Recordings. CRC Press, Boca Raton.
Amazon

Journal Articles

Extrinsic and intrinsic brain activity

Gusnard DA, Raichle ME. 2001. Searching for a baseline: functional imaging and the resting human brain. Nat. Rev. Neurosci. 2: 685-694.

Raichle ME. 2006. The brain's dark energy. Science 314: 1249-1250.

Raichle ME, Gusnard DA. 2005. Intrinsic brain activity sets the stage for expression of motivated behavior. J. Comp. Neurol. 493: 167-176.

Raichle ME, Mintun MA. 2006. Brain work and brain imaging. Annu. Rev. Neurosci. 29: 449-476.

Brain-machine interfaces

Carmena JM, Lebedev MA, Crist RE, et al. 2003. Learning to control a brain-machine interface for reaching and grasping by primates. PLoS Biol. 1: E42. Full Text

Lebedev MA, Nicolelis MA. 2006. Brain–machine interfaces: past, present and future. Trends Neurosci. 29: 536-546.

Nicolelis MA. 2003. Brain–machine interfaces to restore motor function and probe neural circuits. Nat. Rev. Neurosci. 4: 417-422.

Nicolelis MA. 2001. Actions from thoughts. Nature 409: 183-193.

Nicolelis MA, Chapin JK. 2002. Controlling robots with the mind. Sci. Am. 287: 46-53.

Nicolelis MA, Ribeiro S. 2006. Seeking the neural code. Sci. Am. 295: 70-77.

Neuroscience of individual differences

Magnotta VA, Andreasen NC, Schultz SK, et al. 1999. Quantitative in vivo measurement of gyrification in the human brain: changes associated with aging. Cereb. Cortex 9: 151-160. Full Text

Nopoulos P, Flaum M, O'Leary D, Andreasen NC. 2000. Sexual dimorphism in the human brain: evaluation of tissue volume, tissue composition and surface anatomy using magnetic resonance imaging. Psychiatry Res. 98: 1-13.

White T, Andreasen NC, Nopoulos P. 2002. Brain volumes and surface morphology in monozygotic twins. Cereb. Cortex 12: 486-493. Full Text

Neuroscience and the law

Gazzaniga MS. 2005. What's on your mind? New Sci. 186: 48-50.

Gazzaniga MS. 1998. Brain and conscious experience. Adv. Neurol. 77: 181-192.

Rosen J. 2007. The brain on the stand. The New York Times Magazine (March 11). (subscription required)

The former mining town of Aspen, Colorado sits about 8000 feet above sea level, but during the Aspen Institute's annual Ideas Festival, the local atmosphere becomes even more rarefied. Between formal presentations by the likes of Bill Clinton and Karl Rove, other boldface names wander the Institute's elegantly landscaped grounds engaging in casual chats.

On July 7–8, 2007, the William A. Haseltine Foundation for Medical Sciences and the Arts sponsored a series of high-concept talks about neuroscience for this prestigious gathering. Featuring some of the top scientists in the field, a conference track titled "Your Brain and Yourself" drew large audiences, and for these intelligent but mostly nonscientific attendees, the researchers stepped back from their usual data-driven styles to discuss neuroscience's larger challenges.

Much of the current boom in neuroscience, which conference organizer Eric Haseltine referred to as the field's new "golden age," has been driven by the development of new technologies for peering inside working brains. What we're seeing is at once fascinating, mysterious, and in some cases, more than a little bit frightening. Besides opening the door to potentially revolutionary diagnostic and therapeutic strategies, the new technology could cause a wholesale re-evaluation of some of our most fundamental social beliefs.

Marcus Raichle, an early pioneer in neuroimaging now based at Washington University in St. Louis, provided a brief primer on the primary techniques of modern brain imaging: positron emission tomography (PET) and magnetic resonance imaging (MRI). He then discussed his own work, which has revealed that much of the "noise" neuroscientists have been filtering out of their images actually contains important information.

The background noise in the regions controlling our hands, for example, is synchronized, suggesting that it may set the time code for coordinated movements. "So the background ... for how this system is working is already in synch, it isn't waiting to be turned on," says Raichle, adding that in general, "the brain isn't activated and turned on—it's modulated, and it's always on."

Miguel Nicolelis, a neurobiologist at Duke University, discussed his team's recent success in decoding the signals the brain uses to drive movements. After teaching a monkey to play a simple video game using a joystick, the scientists can replace the joystick with a hardwired brain-to-computer interface, allowing the animal to control the game directly with its mind.

The investigators are now working on a system that allows the monkey to control a pair of robotic legs. Ultimately, such an arrangement could potentially drive walking prosthetics for human amputees and paraplegics.

Eric Haseltine and Bob Woodruff discussed the brain's remarkable capacity for healing and rewiring, and what that tells us about the durable nature of consciousness. During this session, Haseltine interviewed Woodruff, an ABC news anchorman who had a harrowing encounter with an improvised explosive device in Iraq in 2006. After more than a month in a coma, Woodruff awoke with his identity—and little else—intact. Missing a substantial portion of his brain, he was nonetheless able to relearn such basic skills as walking, speaking, and writing.

Haseltine, whose interesting resume includes stints as a neuroscientist, a Walt Disney "imagineer," and a top-ranking U.S. intelligence official, also hosted an interactive session in which audience members explored the darker side of their own consciousness. After giving the group a cognitive test to reveal unconscious racial bias, Haseltine confessed that, like most other white Americans, he had also gotten a disturbing score on the test.

"I realized that I had some blind spots," says Haseltine, who adds that after he became aware of the issue, he was able to change his perspective consciously. "The personal successes that I'm most proud of only came after I was able to do that, so this stuff really matters," he says.

Nancy Andreasen, a prominent neuropsychiatrist, took up a few other unsettling aspects of neuroscience, all unified by the theme of individual differences. While the uniqueness of each human brain is widely celebrated, it is also the source of substantial trouble, especially when minds become ill. Citing data on the genetic linkage of different illnesses, Andreasen highlights both the need for more work on neurogenetics and the importance of keeping that work in perspective.  "Genes don't control our destiny," she argues. "If they did, it would be very unfortunate, but they do play a very big role in diseases and in normal brain development and function."

Jeffrey Rosen, an attorney by training, discussed the emerging—and disquieting—legal view of neuroscience. Citing the 2005 U.S. Supreme Court decision in Roper v. Simmons as a watershed moment in "neurolaw," he argues persuasively that the courts are blazing new precedents in this area even before scientists, ethicists, and the public have had a chance to consider the ramifications.

Pointing out that historically, American courts have abetted such ethical disasters as McCarthyism and eugenics, Rosen issues a call for action. "When I look at the history of the privacy debates over the course of the 19th and 20th centuries, I'm struck by how little salvation has come from the courts and how much from the political system," he says.

Michael Gazzaniga of the University of California, Santa Barbara, took up the same theme from a neuroscientist's perspective. Pointing to a growing body of data, he explains that neuroscience is quickly eroding the fundamental legal construct of a rational man, acting of his own free will. Instead, our brains appear to reach conclusions first, and construct rationalizations after the fact. At the same time, neuroscientists are developing a new generation of lie detection tests that could undermine our basic notions of guilt and innocence.

Nobody expects the complex challenges of neurolaw, or any of the other issues discussed at the conference, to be solved in a few days.  But as the debates and discussions continued to buzz beneath the aspen trees, it was clear that neuroscience had grabbed the attention of people in high places.

Alan Dove is a science writer and reporter for Nature Medicine, Nature Biotechnology, and Bioscience Technology. He also teaches at the NYU School of Journalism, and blogs at http://dovdox.com.

Speakers:
Marcus E. Raichle, Washington University in St. Louis School of Medicine
Miguel Angelo Laporta Nicolelis, Duke University

Highlights

• Conventional neuroimaging studies focus on changes in brain activity as subjects perform specific tasks, but often ignore underlying, intrinsic activity that accounts for the vast majority of the brain's energy usage.
• The "noise" that most neuroscientists subtract when they analyze brain images may actually contain important information.
• New, computational brain-machine interfaces can process brain signals to enable monkeys to operate robotic arms and legs.
• Preliminary tests of similar interfaces in humans suggest that such technologies might one day be used to create prostheses capable of restoring motor abilities to people with disabling neurological injuries and diseases.

Enough about you

In recent years, the field of neuroscience, driven by a bumper crop of powerful new imaging technologies, has risen to a level of cultural prominence few scientific endeavors achieve. Newscasters and editors of popular scientific magazines never tire of stories about scientists diagnosing mental illnesses definitively, confirming or refuting some long-held cultural belief, or uncovering a new strategy to treat widespread neurological diseases such as Alzheimer's or Parkinson's. The beautiful full-color brain scans that inevitably accompany these discoveries are one reason for their popularity—they look great on a magazine page—but perhaps the biggest reason for neuroscience's appeal is simple human egotism.

"When I wrote for Discover magazine, we discovered ... that readers loved learning about the brain, but what they really loved most was learning about their brain," says Eric Haseltine, who organized the appropriately titled "Your Brain and Yourself" track at the 2007 Aspen Ideas Festival in Aspen, Colorado. Synthetic chemistry may drive the development of new drugs, and nuclear physics may revolutionize electronic engineering, but neither one helps us talk about ourselves.

Attendees of this conference track not only learned new ways to think about thinking, they also heard many of the world's top neuroscientists ponder where these thoughts are leading us.

Tuning in the noise

Marcus Raichle, one of the inventors of modern brain imaging, began his presentation with a primer on the two main techniques that now dominate the field: positron emission tomography (PET) and functional magnetic resonance imaging (fMRI).

In PET, subjects are injected with a harmless radiolabeled dye, usually fluorodeoxyglucose, and a scanning system detects its uptake in the brain. MRI, in contrast, uses the magnetic resonance of the molecules already in the brain to paint a picture of blood flow to different areas. As blood flow and glucose utilization change in different brain regions, the amount of oxygen fluctuates accordingly. This blood oxygen level dependent (BOLD) change underlies most modern fMRI studies.

The raw data from a typical PET or fMRI study produce images showing lots of activity throughout the brain. To focus on the most important areas, researchers superimpose scans from a subject performing a particular task over scans of the same subject at rest, and then use software to subtract the "noise" and highlight only the areas that differed.

Identity may lie in the brain's background noise.

While this focus on specific areas has produced important breakthroughs, Raichle argues that the "noise" researchers are filtering out may actually contain important information. "The underlying issue here is that most of what you're looking at is a teeny fraction of what's there," says Raichle.

Drawing an analogy with astronomy, Raichle explains that new neuroimaging techniques operate much like the Hubble space telescope, looking at an enormous field of information from which researchers can study only isolated fragments. Just as the universe appears to be full of "dark energy," whose existence astronomers can only intuit, the brain's activity appears to be dominated by yet-unseen processes.

The brain makes up just 2% of an adult's body weight, but consumes 20% of the body's energy, an equation that wouldn't make much evolutionary sense if only a few patches of the cerebrum need to be active at any time. To explore this conundrum, Raichle and a few other neuroscientists have been looking beyond the evoked activity of the brain and into its intrinsic activity—they're listening to the noise.

What they're hearing so far is tantalizing. In one experiment, for example, researchers looked at the brain areas that show decreased activity in subjects who are focusing so intently on a task that they have become "lost in their work." The resulting images highlight areas involved in memory, emotional salience, and self-referential judgments, suggesting that the intrinsic activity of these areas in resting subjects form an important part of their identities.

In another experiment, scientists found ongoing fluctuations in the BOLD signal in patients who were lying still. A closer look revealed that this seemingly random noise was actually synchronized between the two sides of the brain. "So the background ... for how this system is working is already in synch, it isn't waiting to be turned on," says Raichle, adding that in general, "the brain isn't activated and turned on—it's modulated, and it's always on."

Monkey think, monkey do

Duke University's Miguel Nicolelis explained how he and his colleagues have begun to understand some of the brain's modulations. The team's principal goal is to learn how to decode specific types of brain signals, such as those that drive limb movement, and use that information to develop bionic prostheses for amputees and paralyzed patients. It sounds like science fiction, but the researchers seem very close to achieving it.

The business end of Nicolelis's technique is an array of tiny wire filaments that can be implanted in an animal or human brain. Each filament samples a single cell, and the arrays can record the activity of 300–500 cells in a monkey, or 50 cells in a human. Sending the signals into an audio circuit and a pair of speakers, the scientists can "listen to a neural orchestra of a conscious human brain that is talking to you," says Nicolelis.

After enjoying a few neural symphonies, the investigators fed the signals from the motor control area of a monkey's brain into a digital signal processing algorithm, and began analyzing the data while the animal played a simple video game. In the game, the monkey uses a joystick to move a cursor and hit a target that appears in random locations on a video screen. Each successful hit yields a fruit juice reward, and the monkey appears to enjoy playing. "She can stay in this game for hours and drink the entire allotment of liquid [for the day]," says Nicolelis.

A monkey can control a robot arm using only its brain.

Meanwhile, a cluster of computers processes the monkey's brain signals, eventually developing an optimal model of the motor signals controlling the joystick. Having reverse-engineered the appropriate hardware driver, the researchers moved the monkey's joystick to another room, where a robotic arm controlled the stick in response to the monkey's brain signals. After a short learning period, the monkey began playing the game successfully by controlling the robotic arm with her brain. "She ... realized that she had to win by thinking, something that doesn't happen very often in our society," says Nicolelis.

Interestingly, muscle monitors reveal that the monkey's actual arm no longer makes joystick-like movements when the animal is using its mind to control the cursor. Indeed, in video footage from the experiment, the monkey appears to use both hands for scratching, gesturing, and other unrelated tasks while controlling the game mentally. In effect, the monkey has acquired a third, robotic arm.

The team is now working on decoding the motor signals that drive a more complex behavior: walking. With the brain signals of a monkey walking on a treadmill in their laboratory in North Carolina, the investigators can drive a bipedal robot on a treadmill in Kyoto, via the Internet. Nicolelis says the walking algorithm is currently about 90% accurate.

With some modifications, a similar system could eventually operate prosthetic limbs in humans, who appear to use similar motor control signals. In one recent study, for example, the researchers found that conscious patients undergoing brain surgery can play a video game similar to the one the monkey played, using nothing but brain signals fed through the same algorithm that worked in the monkey study.

Speakers:
Bob Woodruff, ABC News
Eric Haseltine, The William A. Haseltine Foundation for Medical Sciences and the Arts
Nancy Andreasen, University of Iowa

Highlights

• Rates of traumatic brain injury in American soldiers returning from Iraq and Afghanistan are much higher than have been reported in official records, and pose a challenge to the current U.S. healthcare system.
• The great diversity in individual human brains has implications for personality.
• Even people who consider themselves progressive harbor unconscious racial biases.
• Brains with higher IQ consume less energy to solve a given problem than brains with lower IQ.

The durable and dark mind

Eric Haseltine gave two presentations during the conference, the first of which featured a patient who, if a few rocks had flown differently, might have needed one of Nicolelis's new devices. Instead, Bob Woodruff, an anchorman for ABC News, was able to tell the tale of the remarkable recovery that followed his harrowing January 2006 encounter with an improvised explosive device (IED) in Taji, a city about 12 miles north of Baghdad.

"Because air comes out in advance of this IED ... when the rocks finally followed behind the burst of the air, I was already out and unconscious," says Woodruff. After being airlifted to a military hospital, Woodruff received a series of critical treatments from medics well-versed in handling traumatic brain injury (TBI). Still, he remained in a coma for 36 days, and on waking, it was clear his brain had suffered serious damage. In the ensuing months, he painstakingly relearned such basic skills as walking, speaking, and writing.

Interviewing Woodruff onstage after he told his story, Haseltine cut directly to the fundamental issue of consciousness. "We all have a sense of ourselves ... Did that change at all, do you feel like a different person?" he asks.

"I don't know. That's a good question. I think that's something we'll see more and more as we go forward," says Woodruff, but he adds that a few aspects of his thinking have clearly changed: his wife tells him he's nicer since the incident than he was before, and, like many survivors of battlefield trauma, he feels a strange sense of guilt. "I feel guilt about what I put my family through, and I also feel guilt about what's happened to other people," he says. That latter feeling drives Woodruff's new campaign to get better treatment for veterans returning from Iraq and Afghanistan with traumatic brain injury, a population of wounded warriors that now numbers at least in the tens of thousands.

Continuing the focus on consciousness, Haseltine then took center stage to present some of his own work on the problem. "Consciousness is a very difficult thing to study, because it really is so many different things," says Haseltine.

Consciousness is remarkably durable, but hard to study.

Rather than try to dissect the problem piecemeal, Haseltine prefers to explore its overall effects. After showing a series of slides demonstrating different sorts of optical and auditory illusions, for example, he explained the theme underlying all of them. "Our brains perceive what they expect to see, and do not perceive what they do not expect to see," he says.

In an interactive presentation the following morning, Haseltine picked up the same theme, but explored some of its darker implications. Audience members at that event took a pair of deceptively simple cognitive tests. The first asked a series of questions about individual preferences, then converted that information into a score measuring different types of intelligence. The second test used a matching game to probe a more ominous aspect of consciousness: racial bias.

After the racial bias quiz, Haseltine confessed that "when I took this test, it bothered the heck out of me." Like nearly all white Americans, he scored as having a substantial unconscious bias associating "white" with "good" and "black" with "bad." As a high-ranking U.S. intelligence officer, he wondered if this clouded his professional judgment.

"I realized that I had some blind spots," says Haseltine, who adds that after he became aware of the issue, he was able to change his perspective consciously. "The personal successes that I'm most proud of only came after I was able to do that, so this stuff really matters," he says.

Summarizing the underlying theme of the two tests, Haseltine explained that they emphasize the importance of diversity, first in the different forms of intelligence within our own brains, and then in the different perspectives of other brains.

Identical, but different

Nancy Andreasen also discussed the diversity of individual brains, but from clinical psychiatric perspectives. While Andreasen, one of the few female recipients of the National Medal of Science, is widely recognized as an expert on schizophrenia, her work actually encompasses a broad swath of modern neuroscience.

In one set of studies, Andreasen and her colleagues have focused on differences between the brains of identical twins. Because the twins share genomes, any differences in brain structure or function are very likely to have come from developmental or environmental influences. Brain scans of one pair of twins, Donna and Deanna, reveal slight differences in the folding patterns of their cerebral cortexes. There are also differences in function: Donna's IQ is slightly higher. "So there are small structural differences between these two twins, and there are also physiological differences," says Andreasen.

The brain scans also show physical evidence of the difference in IQ's. When the two women perform a problem-solving exercise, Deanna's brain shows more blood flow into specific brain regions than Donna's. That suggests that a higher IQ means that the brain doesn't have to work as hard to solve the problem.

Higher-IQ brains solve problems more efficiently.

Twins are also useful for determining the importance of genetics in different diseases; combining data from identical twins, who share 100% of their genomic DNA, with data from non-identical twins, who share 50%, yields a concordance score that researchers can compare across different diseases. Breast cancer shows about the same concordance in identical and non-identical twins, but rheumatoid arthritis shows a large difference between the two types of twins, suggesting that the former is largely environmental, while the latter has an important genetic component.

Mental illnesses, including schizophrenia, Alzheimer's disease, and autism, tend to have stronger genetic concordances than physical illnesses. "Genes don't control our destiny—if they did, it would be very unfortunate, but they do play a very big role in diseases and in normal brain development and function," says Andreasen.

The investigators are also looking at a more controversial set of brain differences: those between men and women. So far, researchers have found that women lose cortical gray matter more slowly than men as they age, but individual differences in brain aging may mask this effect in many people. Andreasen also cautions against reading too much into observed gender differences, such as the scarcity of women in the highest levels of scientific research. "We've had centuries in which women were discriminated against for entry into college, medical school, and professions of all kinds. It's really important that we don't overestimate [biological] gender differences," she says.

Speakers:
Jeffrey Rosen, George Washington University
Michael Gazzaniga, University of California, Santa Barbara

Highlights

• Courts are already using neuroscience evidence in the courtroom, setting disturbing precedents.
• Much of the current neuroscientific evidence being used in courts probably doesn't belong there.
• Findings from neuroscience could have implications for our understanding of volition, free will, and how we understand personal responsibility.
• Some have postulated that the tools of neuroscience could have potential applications in lie detection and in predicting the likelihood of criminal behavior in specific individuals.
• Multidisciplinary efforts are underway to assess what current neuroscience theory tells us, and how it might properly inform legal practice.

Thought crimes and misdemeanors

While cautions like Andreasen's were scattered throughout the conference presentations, the two speakers who began and concluded the neuroscience-oriented track focused on a much more ominous and imminent challenge. The word "neurolaw" remains on the periphery of public consciousness, but a disturbing series of recent scientific and legal developments could soon change that.

Legal scholar Jeffrey Rosen set the tone during a well-attended breakfast session. According to Rosen, as neuroscientists discover more about the formation of intent and the brain's processing of higher concepts, such as morality, lawyers and courts have taken a keen interest.

He cites the 2005 U.S. Supreme Court decision in Roper v. Simmons as a watershed moment. In that case, a majority of justices overturned a death penalty conviction of a minor, partly based on research showing that the human brain is not fully myelinated before age 18, and is therefore incapable of fully adult morality. In another development, several recent neuroscience experiments have shown that a person's intent to do something actually forms before the subject is even aware of it, undermining the fundamental concept of free will. "Maybe we will have to re-examine the whole idea that we're intentional, thinking human beings ... rather than automatons who are driven here by forces beyond our control," says Rosen.

We make decisions before we understand them.

Michael Gazzaniga, delivering the final talk of the conference, echoed the same theme. He cites several studies, including one in which researchers were able to identify a subject's intention to choose a particular response about 300 milliseconds before the patient actually responded. "We're running sort of on tape delay with what the brain is actually doing," says Gazzaniga, adding that "by the time you know something consciously, your brain has already done the work."

In Gazzaniga's own work, so-called split-brain patients—people with epilepsy who undergo a procedure to sever the connections between the two halves of their brains to prevent seizures—reveal an even more disturbing phenomenon. The patients can match pictures of different objects correctly when using either eye, but the stories they concoct to explain their choices differ radically.

In one experiment, a patient looked at a picture of a chicken on his right-hand side, and a picture of a house covered in show on his left. He was then presented with a series of additional pictures to match with what he was seeing. His right hand pointed to a chicken foot, and his left hand to a shovel. The choices made sense, but the explanation was somewhat surprising.

"His left hemisphere, that's doing the talking, says 'the chicken goes with the chicken claw,' and then he's looking down at his left hand, and he says, 'and you need a shovel to clean out the chicken shit.'" The right hemisphere had in fact seen and processed the snow scene, and presumably matched it with the snow shovel, but the patient could not articulate the logic of that choice because the two sides of his brain were not connected. He automatically concocted a different explanation.

The amusing response conceals a thorny problem: the brain appears to be making a decision unconsciously, then inventing a rationale for it after the fact. If we can't control our decisions, should the law hold us accountable for them? Throughout their talks, Rosen and Gazzaniga explored multiple facets of this issue, ranging from the possibility of exonerating defendants on the basis of minor brain abnormalities, to using neuroimaging technologies as lie-detection tools, to the spectre of squads of "thought police" preventively detaining citizens whose brain scans reveal guilty knowledge or predelictions for crime.

Will we jail suspects because of their thoughts?

Pointing out that historically, American courts have abetted such ethical disasters as McCarthyism and eugenics, Rosen issued a call for action. "When I look at the history of the privacy debates over the course of the 19th and 20th century, I'm struck by how little salvation has come from the courts and how much from the political system," he says.

Gazzaniga not only concurs, but is also taking concrete steps to push the debate forward. In a new initiative sponsored by the MacArthur Foundation, which will be launched formally in October, neuroscientists like Gazzaniga will collaborate with prominent judges, lawyers, and ethicists to place neurolaw on a solid philosophical base.

Despite the ominous possibilities of neurolaw, conference attendees were visibly excited about the promise of neuroscience, and continued discussing the presentations over their lunches and dinners. Whether the golden age of neuroscience leads to medical breakthroughs, social disruptions, or both, one thing is certain: we won't soon tire of talking about it.

Should courts be admitting neuroscientific evidence, or is the science still too new?

Will a "guilty knowledge" test become the definitive lie-detector?

How many additional limbs can the brain's body image incorporate?

Is the "noise" in neuroimaging experiments actually where consciousness resides?

To what extent can we override our subconscious racial biases?

Has neuroscience effectively disproven the existence of free will?