Plaques that build up between neurons are a hallmark of Alzheimer's.

Glimmers of Hope Before an Alzheimer’s Epidemic

<p>
 In the war against aging, Alzheimer’s disease is one of our biggest foes. But while we seem to be losing the battle, we may finally have found some chinks in its armor. The most common form of dementia already affects an estimated 5.2 million Americans and 45 million others worldwide, and these numbers are projected to triple by the year 2050 as the baby boomer generation reaches retirement.
</p>
<p>
 Faced with the grim prospect of an Alzheimer’s epidemic, researchers have raced to understand the biology of the disease, and pharmaceutical companies, tempted by the huge profits that an effective treatment would bring, have poured huge amounts of money into researching and developing new drug treatments.
</p>
<p>
 They have developed hundreds of drugs, the vast majority of which have failed when tested in humans. Earlier this year, Genentech, a San Francisco-based biotechnology company, made a big announcement about their latest clinical trial data, at an Alzheimer’s conference.
</p>
<p>
 But the results turned out to be disappointing—overall, these trials failed, too. Their results suggest, however, that early treatments may be effective, and they also emphasize the importance of finding new ways to effectively diagnose the disease as early as possible.
</p>
<div class="related"></div>
<h2>
 A Long Road
</h2>
<p>
 Alois Alzheimer described the first case of the disease that now bears his name in 1906. He noted its pathological hallmarks—the tangles that build up within the neurons of the cerebral cortex and the sticky plaques that accumulate in the spaces around the cells.
</p>
<p>
 By the 1990s, researchers thought they had it all figured out. They had identified the proteins that make up the tangles and plaques—called Tau and amyloid beta, respectively—along with the genes that encode them. They also determined various genetic mutations associated with the disease and found that most of them alter the way in which neurons process these proteins, causing the proteins to fold up incorrectly and clump together, forming “seeds” of the tangles and plaques that can spread between cells.
</p>
<p>
 Animal studies suggested that it was the plaques and not the tangles that kill brain cells in Alzheimer’s. The amyloid protein quickly became a target for new drugs, and researchers began developing drugs that either prevent plaque from forming or break down existing ones. Many of these drugs alleviated memory deficits in genetically-engineered mice carrying known human Alzheimer’s mutations. But when tested in Alzheimer’s patients, however, they failed to slow the rapid decline in memory function characteristic of the disease.
</p>
<div class="pullquote">
<p>
 The discovery of various cellular malfunctions prompted researchers to explore new avenues.
</p>
</div>
<p>
 Proponents of the leading hypothesis—that amyloid plaques cause the disease—claimed that the drugs failed because they weren’t administered early enough, pointing out that the pathological hallmarks appear long before disease symptoms.
</p>
<p>
 But some began to question the amyloid hypothesis, too, and turned to Tau proteins and their tangles as the main culprit. Meanwhile, the discovery of numerous other cellular malfunctions—in the energy-producing mitochondria, for example, and in
 <a href="http://neurophilosophy.files.wordpress.com/2013/04/the-mind-minders.pdf">
  microglia
 </a>
 , the immune cells that normally clean up cellular debris—highlighted a big gap in our understanding of the basic biology of the disease, prompting researchers to explore new avenues.
</p>
<div class="ad"></div>
<p>
 Trial after trial failed, and pharmaceutical companies cut back on their spending, scrapping or halting development of over 100 Alzheimer’s drugs during the 13-year period leading up to 2011. But minor successes in the latest trials offer a glimmer of hope.
</p>
<h2>
 Slowing the Decline
</h2>
<p>
 Genentech presented the results of two phase II clinical trials for crenezumab at the Alzheimer’s Association International Conference (AAIC) in Copenhagen, Denmark, in July. The drug is a genetically-engineered monoclonal antibody that binds to human amyloid beta protein. Originally developed by the Swiss company AC Immune, crenezumab has been licensed to Genentech since 2006. The trials involved a total of 686 patients with mild to moderate Alzheimer’s disease. They were given either small subcutaneous doses of crenezumab, larger intravenous doses of the antibody, or a placebo.
</p>
<p>
 Overall, the treatment had no significant effect on the participants’ cognitive function or daily functioning, but a subtle effect was observed in a subset of them—it slowed cognitive decline in those with mild Alzheimer’s who were given a large dose.
</p>
<p>
 “It was very informative in identifying the patients who are most responsive to it,” says Carole Ho, a senior group medical director at Genentech. “It’s also important because it shows we can increase the dose safely.”
</p>
<p>
 “We are now taking all the steps to move the trial into phase III, although the decision to proceed has not yet been made,” she adds.
</p>
<p>
 Dean Hartley, director of science initiatives at the
 <a href="http://www.alz.org/">
  Alzheimer’s Association
 </a>
 in Chicago, agrees that the results are promising. “They do suggest that there’s an improvement with these medications if you go earlier enough,” he says, adding that the partial success may encourage drug companies to re-invest in their Alzheimer’s drugs pipeline. “The positive results are important for them to stay engaged.”
</p>
<h2>
 Assessing Inflammation
</h2>
<p>
 Researchers are increasingly recognizing
 <a href="http://journal.frontiersin.org/Journal/10.3389/fnint.2013.00059/full">
  the role inflammation plays in Alzheimer’s
 </a>
 . Inflammation is a normal immune response, and when microglia, the brain’s immune cells, become activated, they are thought to be helpful at first because they normally clear away plaques, dead cells, and other potentially hazardous materials. But then they may become harmful.
</p>
<p>
 Some scientists now believe that not only do over-active microglia begin to damage healthy cells, but that these immune mechanisms also might be the real cause of the disease. Indeed, in some trials, naproxen, a common non-steroidal anti-inflammatory often prescribed for rheumatoid arthritis, slowed cognitive decline in some Alzheimer’s patients. In others, however, the drug hastened the decline.
</p>
<p>
<a href="http://www.ttuhsc.edu/centers/aging/staff/sidobryant.aspx">
  Sid O’Bryant
 </a>
 , an assistant professor at of the University of North Texas Health Science Center in Fort Worth, and his colleagues have identified key inflammatory biomarkers and are profiling the pro-inflammatory molecules in Alzheimer’s patients using protein array technology. O’Bryant also presented data at the AAIC meeting, showing that biomarker profiling may be one way of diagnosing the disease early. Perhaps more promising, it can distinguish between patients who respond well to the anti-inflammatory drugs and those who respond badly.
</p>
<p>
 “We took blood samples from a previously conducted trial of naproxen and celebrex and assayed the pro-inflammatory markers,” O’Bryant says, “and we’ve shown that, in a sub-group of patients, many of these markers are way too high.” These findings support the idea that there are different types of Alzheimer’s disease which could respond differently to varying treatments. They also suggest that identifying these patient sub-groups, or what O’Bryant calls “endophenotypes,” will be an important step in developing personalized treatments for Alzheimer’s and other neurodegenerative diseases.
</p>
<p>
 “We have to get away from the notion that all Alzheimer’s patients are the same,” he says. “Inflammation is very important for about 15% of patients but not for the others, and I think we can break the disease up into about ten different types, but we still don’t target drugs to the individual.”
</p>
<p>
 O’Bryant’s is one of several research groups trying to develop a blood test for Alzheimer’s based on pro-inflammatory and other biomarkers associated with the disease. The work is in the earliest stages, but O’Bryant and various of his collaborators have compiled a set of guidelines for others doing the same thing, to be published later this year. “The field is trying to unify and create standards so we can get consistency across studies,” he says. “I don’t know about a timeframe [for a blood test], but once that starts to move forward systematically, we’ll be closer to getting something into the clinic.”
</p>
<div class="newsletter"></div>
<div class="pullquote">
<p>
 “We have to get away from the notion that all Alzheimer’s patients are the same.”
</p>
</div>
<p>
<a href="http://www.mayo.edu/research/faculty/jack-clifford-r-jr-m-d/bio-00026247">
  Clifford Jack
 </a>
 of the Mayo Clinic in Minnesota and his colleagues are using a similar approach, combining brain imaging with measurements of blood plasma levels of key Alzheimer’s biomarkers, to determine how the biomarkers are related to pathological and behavioral changes. They have developed a theoretical model of biomarker dynamics in Alzheimer’s, and they argue that this could be used to track the progression of the disease.
</p>
<p>
 Several years ago, a string of surprising discoveries revealed more potential drug targets. As the brain develops, it forms its connections by trial and error then prunes back the incorrect ones. In the mature brain, old connections are constantly removed, and new ones formed, in response to experience, a process thought to be critical for learning and memory.
</p>
<p>
 Various groups of researchers then published evidence that
 <a href="http://www.theguardian.com/science/neurophilosophy/2011/aug/19/neuroscience-microglia-synapses">
  microglia eliminate unwanted synapses
 </a>
 in the embryonic brain and, possibly, throughout the mature brain, too. This has led some to speculate that incorrect activation of this process may cause the loss of synaptic connections seen in Alzheimer’s. They are beginning to identify the signaling molecules that target synapses for destruction and initiate the process, and are designing drugs that block, which they aim eventually to test as potential treatments.
</p>
<h2>
 Power of the Antibody
</h2>
<p>
 Meanwhile, Genentech is involved in another large trial designed to test the preventative power of antibodies. Most of the participants in the five-year, $100 million study will belong to a large extended Colombian family containing more than 5,000 members, many of whom carry a genetic mutation that causes them to begin showing cognitive impairments in their mid-40s and full blown dementia by their early 50s.
</p>
<p>
 Some family members carrying the mutation will be given crenezumab every two weeks while others will be given a placebo. Although hereditary forms of Alzheimer’s account for only a small proportion of cases, the trial includes family members who are still decades away from developing the disease. It’s an opportunity that could provide researchers with valuable information about the earliest stages of the disease.
</p>
<p>
 Hartley welcomes these new approaches and emphasizes the vital importance of obtaining more funding for Alzheimer’s research. “We have to expand our horizons,” he says, “and to find an end to this terrible disease we’ll need more research, more clinical trials, and new ideas, so we have to make sure researchers get all the funds they need.”
</p>
<p>
 Image credit: National Institute on Aging
</p>

<p>Recent studies of Alzheimer&#x27;s earliest stages suggest we may finally be closing in on successful treatments.</p>

When Does Consciousness Begin and End?

<p>
</p>
<p>
 In March of this year, the beloved singer-songwriter Joni Mitchell was rushed to the hospital after being found unconscious on the floor in her Bel Air home. Subsequently, long-time friend Leslie Morris filed a petition to become Mitchell’s legal guardian, stating that the singer “remains unconscious and unable to make any responses, and is therefore unable to provide for any of her personal needs.”
</p>
<p>
 Statements issued on Mitchell’s
 <a href="http://jonimitchell.com/">
  official website
 </a>
 deny that Mitchell is in a coma, claiming instead that “she comprehends, she’s alert, and she has her full senses. A full recovery is expected.” But Mitchell’s doctor, the neurosurgeon Paul Vestra, has confirmed that her mental faculties are severely impaired and that she will unlikely be unable to attend the court hearing over guardianship, which is scheduled in July.
</p>
<div class="pullquote">
<p>
 “Consciousness refers to two quite distinct things.”
</p>
</div>
<p>
 The conflicting information about Mitchell’s health status reveals the stigma attached to coma and other conditions in which consciousness is impaired. In such situations, complex ethical questions regarding end-of-life decisions inevitably arise, ones that most societies are still struggling to answer.
</p>
<div class="related"></div>
<p>
 “Clinically, consciousness refers to two quite distinct things—wakefulness and awareness,” explains neuroscientist Adrian Owen of the University of Western Ontario in
 <a href="https://www.youtube.com/watch?v=JeBkUtYvBBM&amp;feature=youtu.be">
  a recent public lecture
 </a>
 . “But the problem for people working on consciousness is that none of us can agree on what it actually means.”
</p>
<p>
 Owen is less interested in defining consciousness than he is in measuring it. He’s also keen on finding ways to detect hidden signs of consciousness and determining if patients have conscious awareness, exactly what they are aware of, and how much of their mental faculties they retain. Owen’s is one of several research groups that are pioneering new ways of doing this, and although the work is still in its infancy, it is already helping clinicians to diagnose consciousness disorders more accurately.
</p>
<h2>
 Awake, Asleep, or Neither?
</h2>
<p>
 Our understanding of consciousness has been hampered by our historically rudimentary ways of understanding its absence. We can easily determine if someone is awake, because their eyes will probably be open. Wakefulness can also be detected if one’s eyes are closed, because the awake and sleeping brain are each characterised by distinct patterns of brainwaves, which can be recorded with electroencephalography (EEG), using electrodes placed onto the scalp.
</p>
<p>
 Awareness is much harder to detect, because the only way we have of knowing whether or not someone is aware is by asking them. Comatose patients, for example, have their eyes closed at all times, and are neither awake nor aware. Patients in the vegetative state, however, often show signs of wakefulness. “They often open their eyes and look around the room and they have intact sleep-wake cycles,” Owen says, “but they won’t fixate on anything in particular and, importantly, never respond to a command, so they’re often referred to as awake but not aware.”
</p>
<div class="ad"></div>
<p>
 This poses a major problem for clinicians working with patients who have consciousness disorders because, while minimally conscious patients are more likely to recover, they do not show outward signs of awareness. The problems with diagnosis thus make it extremely difficult to identify those whose conditions might improve.
</p>
<p>
 Owen and his colleagues pioneered the use of functional neuroimaging to detect signs of consciousness in patients diagnosed as being in a persistent vegetative state, and to communicate with them. The method was first described in
 <a href="http://www.coma.ulg.ac.be/papers/vs/VS_science2006.pdf">
  a landmark 2006 paper
 </a>
 , and involves scanning patients’ brains while asking them a series of questions that require a “yes or no” answer. Upon entering the scanner, the patients are instructed to imagine playing a game of tennis if they want to answer “yes” or to imagine walking around their apartment if their answer is “no.”
</p>
<p>
 Each task produces different brain activation patterns that be detected by the scanner—one activates the supplementary motor cortex, which is involved in planning movements, and the other activates the hippocampus and surrounding areas, which play critical roles in spatial navigation.
</p>
<div class="pullquote">
<p>
 “One in five of patients in vegetative states are entirely unresponsive but will reliably produce conscious awareness activity patterns in the scanner.”
</p>
</div>
<p>
 Remarkably, Owen and his colleagues found that a significant proportion of apparently vegetative patients can actually follow these commands and respond to the questions by imagining one scenario or the other. The ability to do so indicates that certain of their mental abilities—especially attention, memory, and language comprehension—are intact, and that they are, in fact, aware of what is going on around them.
</p>
<p>
 “All of these things are part and parcel of what we call conscious awareness, things that we all use day every day just to get through our activities,” Owen says. “We’ve seen a lot of patients, all of them diagnosed as being in the vegetative state, and about one in five of them are entirely unresponsive at the bedside but will reliably produce these activity patterns in the scanner.”
</p>
<p>
 On the basis of these results, Owen and his colleagues conclude that around 20% of patients with these disorders are misdiagnosed as being in a persistent vegetative state when they are actually minimally conscious. For many, this is a matter of life or death: Court cases that decide whether hydration and nutrition should be withdrawn from apparently vegetative patients are becoming increasingly common around the world, and such decisions often hinge on the question of whether or not the patient is conscious.
</p>
<p>
 Brain scanning is expensive, and moving patients to have these tests can be hugely problematic, so Owen and his colleagues have developed a
 <a href="http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003887">
  cheaper, portable EEG-based version
 </a>
 of the test. They want to test as many patients as they can, and to that end have built what they call the
 <a href="http://www.owenlab.uwo.ca/faq/the%20eejeep.html">
  EEJeep
 </a>
 , which they use to visit patients in their homes. And they believe that some patients may be unable to follow commands despite retaining some awareness, so have developed
 <a href="http://www.pnas.org/content/111/39/14277.short">
  a “passive” test
 </a>
 based on the shared experience and brain activity people have when watching the same movie together.
</p>
<h2>
 Defining Consciousness
</h2>
<p>
 Despite these important advances, this research tells us very little about what consciousness actually is, or about how the brain generates it. Consciousness is at once familiar to us all, and deeply mysterious. We are all familiar with the content of our consciousness, and how those contents change as time passes, and we all lose consciousness every night when we go to sleep, only to regain it in the morning. Yet, neuroscientists and philosophers alike are still struggling to find an adequate definition of consciousness.
</p>
<p>
 When brain scanning technologies first emerged in the 1990s, some researchers began using them to identify the neural correlates of consciousness—activity patterns in specific parts of the brain that are associated with certain aspects of awareness—but this did not explain the relationship between brain activity and experience or why we only become aware of some aspects of the brain’s workings but not others.
</p>
<div class="newsletter"></div>
<p>
 Neuroscientists are increasingly viewing the brain as a complex network of inter-connected modules, and so there is growing interest in mapping the long-range neural pathways linking them. They have also come to believe that the synchronized activity of large groups of brain cells—which produces brain waves—is important for information processing and that the synchronization or de-coupling of brain wave frequencies between inter-connected brain regions is likely important for the flow of information between them.
</p>
<p>
 But many say that we still have no real understanding of consciousness. “I often hear that we haven’t made much progress and still don’t know what we’re talking about,” says Anil Seth, director of the Sackler Centre for Consciousness Studies at the University of Sussex, “but I think that’s simply wrong, because we’ve seen huge developments in understanding.”
</p>
<p>
 One such development is
 <a href="http://www.biolbull.org/content/215/3/216.full">
  integrated information theory
 </a>
 (IIT), developed by neuroscientist Giulio Tononi of the University of Wisconsin-Madison, which explains consciousness in terms of the amount of information that is shared amongst brain regions. IIT states that consciousness is graded, and equates the amount of information being integrated with the level of conscious experience, such that conscious awareness increases with the amount of integration taking place. It predicts that
 <a href="http://rstb.royalsocietypublishing.org/content/370/1668/20140167">
  any sufficiently complex system
 </a>
 that integrates information could have “bits of consciousness.”
</p>
<p>
 Thus, most animals are conscious to a greater or lesser extent, and the internet, with its billions of interconnected computers worldwide, could conceivably be conscious in some sense. Yet a supercomputer simulation of the human brain, which is only partly integrated, could not.
</p>
<p>
 “This is an interesting theory that allows us to make all sorts predictions,” Seth says. For example, it predicts that general anesthetics make us lose consciousness by reducing information integration in the brain to below a certain critical level and that integration is reduced or otherwise disrupted in consciousness disorders. Both of these predictions turn out to be accurate.
</p>
<div class="pullquote">
<p>
 Any sufficiently complex system that integrates information could have “bits of consciousness.”
</p>
</div>
<p>
 Marcello Massimini of the University of Milan and his colleagues developed a test based on Tononi’s theory. It involves using transcranial magnetic stimulation to interfere with the brain’s electrical activity and then measuring the complexity of the brain’s response. Massimini and his colleagues have performed the test on healthy participants while they are awake, asleep, and at different levels of sedation by anesthetic, as well as in comatose, vegetative, and minimally conscious patients. They’ve shown that it can
 <a href="http://stm.sciencemag.org/content/5/198/198ra105.abstract">
  reliably determine the level of consciousness
 </a>
 in each of these states.
</p>
<p>
 Similarly, researchers in France have devised a way to measure how much information is being shared between pairs of scalp electrodes during EEG sessions. Using it to record brainwaves both in patients with consciousness disorders and in healthy controls, they found that unconscious patients’ brains do indeed exhibit lower levels of what they called “
 <a href="http://www.sciencedirect.com/science/article/pii/S0960982213009366">
  global information sharing
 </a>
 ” than those of the others.
</p>
<p>
 These methods could potentially be developed into cheap bedside tests that allow for more accurate diagnosis of consciousness disorders. Broader access to portable EEG tests promises to revolutionize how these patients are diagnosed and cared for.
</p>
<p>
 “We’ve made a great deal of progress and discovered a lot, but it’s a very hard problem, and it’s not going to just go away so easily,” Seth says. As new ways of measuring consciousness are developed further, we will become better equipped to deal with its disorders. And although we may still be a long way from understanding consciousness, by studying its various forms, we now seem to have a loose grasp of it.
</p>
<p>
 Photo credit annedde/iStockphoto
</p>

<p>By studying different states of awareness, we’re narrowing in on what it means to be conscious.</p>

Can Neuroscience Determine Guilt or Innocence?

<section class="entry-content instapaper_body clearfix" itemprop="articleBody">
<div class="add-container clearfix" id="add-block-placer">
</div>
<p>
  In July 2009, a 59-year-old Welshman named Brian Thomas strangled his wife Christine to death in the middle of the night while the couple were vacationing in their camper van. There was no question he did it, but he was acquitted of murder the following year and walked away from his trial a free man.
 </p>
<p>
  A retired steelworker and father-of-two, Thomas was, by all accounts, a devoted and loving husband. He also suffered from a variety of ailments. As the jury at Swansea Crown Court heard, he had a chronic sleep disorder called automatism ever since childhood, and he had been taking three different prescription drugs to treat his depression and hand tremors, a symptom of his Parkinson’s disease. He stopped taking them before the vacation because he believed that they reduced his sex drive.
 </p>
<figure class="richtext-image full-width">
<img alt="" class="richtext-image full-width" src="https://www.pbs.org/wgbh/nova/media/images/parkinsons-connectome.width-990_vtcuvER.jpg"/>
<figcaption>An illustration of the connections within a brain affected by Parkinson's disease
        
    </figcaption>
</figure>
<p>
  Thomas was, however, unaware that sudden withdrawal from the antidepressant can cause vivid dreaming or that the Parkinson’s drug inhibits rapid-eye-movement sleep, during which dreaming occurs. On that fateful July night, he had a violent nightmare, possibly triggered by an earlier encounter with a group of troublesome teenagers. As the couple lay asleep in bed, he dreamt that a man who had broken into the van and was attacking his wife, and he grappled with him. When he awoke, he saw Christine lying dead, realized what he had done, then called the police to report the killing.
 </p>
<p>
  Although extraordinary, the case is not unique. In September of last year, for example, a Swedish man named Mikael Halvarsson was convicted of rape but his charges were overturned. The appeals court heard that he suffered from sexomnia, a rare condition related to sleepwalking, which causes people to engage in sexual behavior while they sleep. Because of this, it was ruled that Halvarsson—like Thomas before him—should not be held responsible for his actions.
 </p>
<p>
  Criminal trials often require proof of a guilty mind, or the intention to act. Neuroscience is slowly changing the way we view ourselves, and some worry that using it to explain human behavior is beginning to erode the idea that we have free will and to absolve us of moral responsibility. Neuropsychologists and members of the legal profession gathered at a
  <a href="http://www.swansea.ac.uk/law/news/mindsbrainsandlawamultidisciplinaryconferenceonlawandneuroscience.php">
   multidisciplinary conference
  </a>
  at Swansea University late last year to discuss how brain research is beginning influence the criminal justice system. While adoption of neuroscience in the courtroom has been gradual, there’s increasing evidence that it will underpin many legal proceedings in the near future.
 </p>
<h2>
  Blaming the Brain
 </h2>
<p>
  The seemingly improbable argument that “my brain made me do it” does sometimes stand up. There is, for example, the widely reported case of the man with a frontal lobe tumor
  <a href="http://archneur.jamanetwork.com/article.aspx?articleid=783830">
   that turned him into a pedophile
  </a>
  , and we now know that the drugs used to treat Parkinson’s disease can cause
  <a href="http://archinte.jamanetwork.com/article.aspx?articleid=1916909#Introduction">
   compulsive behaviors
  </a>
  such as over-eating, hyper-sexuality, and gambling and shopping addiction due to their effects on the brain’s reward system.
 </p>
<p>
  Sometimes, though, it does not. Diminished capacity can sometimes lead to harsher punishment. “By giving us a better understanding of the mind, I think neuroscience will actually expand the scope of responsibility,” says
  <a href="http://www.commonlaw.uottawa.ca/index.php?option=com_contact&amp;contact_id=1&amp;task=view&amp;lang=fr">
   Jennifer Chandler
  </a>
  , an associate professor of law at the University of Ottawa.
 </p>
<p>
  She cites examples of how someone with diminished capacity could nonetheless be seen to be responsible for their criminal acts in the eyes of the law, such as a patient with schizophrenia who acted violently or someone with narcolepsy or epilepsy who kills or harms others in a car accident after failing to take their medication. In cases such as these, the defendant is considered to have some insight into and control over their actions. They know the potential consequences of not taking their medication and so could be considered negligent for failing to avoid the foreseeable risk of harm.
 </p>
<p>
  “Responsibility might become a kind of prior negligent failure to avert later actions,” Chandler says. “We may find ways to hold incapable people responsible by looking back to earlier times when they seemed capable and made risky decisions that contributed to their incapacity and dangerous behavior later on.”
 </p>
<h2>
  Trauma’s Role
 </h2>
<p>
<a href="http://psychology.exeter.ac.uk/staff/?web_id=huw_williams">
   Huw Williams
  </a>
  , associate professor of clinical neuropsychology at the University of Exeter, emphasizes that criminal behavior is often associated with traumatic brain injury (TBI). TBI is a major cause of death and disability, and often occurs because of repeated blows to the head which causes lesions as brain’s delicate tissues slide past each other. This often affects the dorsolateral prefrontal cortex, a region which plays an important role in so-called executive functions, leading to changes in mood, thought processes, decision-making, and social behavior.
 </p>
<aside class="pulledquote">
  “The medical needs of prisoners with TBI aren’t being met.”
 </aside>
<p>
  TBI is much more prevalent
  <a href="http://journals.lww.com/headtraumarehab/Fulltext/2012/05000/Prevalence_of_Traumatic_Brain_Injury_Among.12.aspx">
   among prisoners
  </a>
  than within the general population, and prisoners with TBI are at
  <a href="http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001150">
   increased risk
  </a>
  of committing violent crime. Young people are especially vulnerable. Williams’ own research shows that
  <a href="http://www.tandfonline.com/doi/abs/10.1080/09602011.2010.519613#.VJNmGFesVtJ">
   11- to 19-year-old male offenders
  </a>
  with TBI have more convictions and are more than twice as likely than others to commit a serious violent crime. They are at greater risk for substance abuse and
  <a href="http://neuro.psychiatryonline.org/doi/full/10.1176/appi.neuropsych.12010011">
   mental health problems
  </a>
  . Furthermore, TBI is not only associated with a younger age of imprisonment, but it also makes people more likely to re-offend later on.
 </p>
<p>
  It’s impossible to know if TBI actually causes criminal behavior rather than just being correlated with it as there are likely to be many other factors that complicate matters. For example, Attention Deficit Hyperactivity Disorder (ADHD) is associated with criminality, but ADHD medications
  <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1203241#t=article">
   reduce the rate of criminality
  </a>
  in patients. It could even be a two-way relationship, such that injury increases the risk of violence, which in turn causes additional injury that further impacts behavior in a vicious cycle.
 </p>
<p>
  This all has implications for sentencing and for rehabilitation. “The medical needs of prisoners with TBI aren’t being met,” Williams says. “Children, in particular, are most likely to be injured but least likely to get the help and support they need.” In
  <a href="http://www.barrowcadbury.org.uk/wp-content/uploads/2012/11/Repairing-Shattered-Lives_Report.pdf">
   a recent report
  </a>
  , Williams makes a number of recommendations. There should, he says, be standardized assessments of young people entering the criminal justice system, especially before sentencing, to better identify those young offenders who are most at risk. Prison staff and others within the criminal justice should be made aware of the prevalence of brain injury in the prison population and should liaise with mental health experts to monitor offenders. He also recommends that judges take any history of brain injury into account when handing down sentences.
 </p>
<h2>
  Developmental Nuance
 </h2>
<p>
  Yet even in the absence of brain injury, new findings about
  <a href="http://www.nimh.nih.gov/health/publications/the-teen-brain-still-under-construction/index.shtml">
   the teenage brain
  </a>
  are already leading some to re-think how young offenders are punished. In England and Wales, the age of criminal responsibility is 10 years, and in the United States, it is 17. Until relatively recently, neuroscientists believed that brain development is complete by about 16 years of age. We now know, however, that while the brain does indeed reach its full size at around that age, its development is far from complete.
 </p>
<p>
  The frontal lobes continue to mature until
  <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892678/">
   well into the late 20s
  </a>
  , and possibly into the third decade of life. The neural circuits involved in functions such as impulse control and decision-making are therefore the very last to mature, and their development is not complete until well beyond what is traditionally thought of as adolescence. What’s more, the reward circuitry in teenagers’ brains
  <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075496/">
   is hypersensitive
  </a>
  . Together, these findings help to explain what we think of as stereotypical adolescent behavior: taking risks, making bad decisions, and trying hard to impress to their friends.
 </p>
<p>
  “Neuroscience holds significant potential to change how young offenders are treated and suggests that we need to take a far more nuanced approach to responsibility,” says
  <a href="http://www.swansea.ac.uk/staff/law/bebhinndonnelly/">
   Bebhinn Donnelly-Lazarov
  </a>
  , a reader in law at Swansea University who organized the conference. “Someone in their early 20s does not lack responsibility in the way that a child does, but we need to recognize that their brain development is still on-going.”
 </p>
<h2>
  Matters of Interpretation
 </h2>
<p>
  Courts of law are already beginning to take these matters into consideration. Brain-based explanations of behavior eventually lead to improvements in the treatment of the criminally insane.
 </p>
<p>
  Traditionally, the verdict of not guilty by reason of insanity is used very rarely, and courts have discretionary power over what then happens to such defendants. The insanity defense covers a wide variety of conditions, from sleep-walking to diabetes and epilepsy. Defendants whose behavior can be attributed to these conditions can be labeled as insane, but with this label comes a great deal of stigma.
 </p>
<aside class="pulledquote">
  Questions of guilt and innocence may at some stage in the future hinge on neuroscientific evidence.
 </aside>
<p>
  “Neuroscience could be of considerable value in determining whether defendants are truly insane,” Donnely-Lazarov continues. “It should cause the law to move away from these stigmatizing labels such that the law may defer to medical concepts instead of legal ones to define responsibility.”
 </p>
<p>
  This raises yet more difficult problems, however, regarding how medical data are interpreted and used. Questions of guilt and innocence may at some stage in the future hinge on neuroscientific evidence, but currently there are major problems with how neuroscientists interpret such data, and those in the criminal justice who might use the information are usually not qualified to evaluate it properly.
 </p>
<p>
  It’s unlikely that neuroscience will lead to sweeping reforms in the legal process. Instead, changes will probably occur piecemeal, as our knowledge of the brain advances, and as unusual cases that set new precedents emerge. “Law is a rule-based system, and as such changes in rules of law are needed to accommodate new information,” says Donnelly-Lazarov. “Prosecutors are becoming increasingly willing to consider neuroscientific evidence, so we need to exercise great caution in how we integrate this information as evidence.”
 </p>
<p>
  “We’re very far away from criminal statutes saying that a defendant’s brain is in some particular state, but neuroscience will be integrated into the practice of law incrementally and naturally.”
 </p>
</section>
<p>
 Image credit: Jared Tanner/University of Florida/NIH
</p>

As our understanding of the human brain grows more sophisticated, it is changing how courts determine culpability.

Mo Costandi

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