A Scientific Study of the Human Mind and the Understanding of Human Behavior through the analysis and research of Meta Psychology.
Monday, September 29, 2008
Heart patients should be screened for depression
After her double bypass, Barbara Forman says, she spent most of her time sitting in a chair, crying.
Depression is about three times more common in heart attack survivors and those hospitalized with heart problems than the general population, according to the recommendations published in the journal Circulation.
The authors said only about half of heart doctors say they treat depression in their patients -- and not all those diagnosed with depression are treated.
"I think we could reduce considerable suffering and improve outcomes," by screening, said Erika Froelicher, professor of nursing at the University of California, San Francisco. "I know we can do more."
While there's no direct evidence that heart patients who are screened fare better, depression can result in poorer outcomes and a poorer quality of life, the panel said. Depressed patients may skip their medications, not change their diet or exercise or take part in rehabilitation programs, they said.
Anyone from cardiologists to nurses to primary care doctors can and should be involved in determining whether a patient is depressed, said Froelicher, who was co-chair of the panel that wrote the recommendations.
The panel suggests that heart patients be screened by first asking two standard questions: In the past two weeks, have you had little interest or pleasure in doing things? Have you felt down, depressed or hopeless?
If the patient answers yes to one or both, a questionnaire is recommended to determine if the patient is depressed and the severity. If depression is indicated, the patient may need to see a professional qualified in treating depression, the panel said, adding that treatment options include antidepressants, seeing a psychotherapist and exercise.
"Some physicians are qualified to treat it -- others may be more comfortable referring the problem to a qualified mental health professional," Froelicher said.
Psychiatrist Michelle Riba said the statement's emphasis on frequent screening is important.
"What you want to see in a particular patient is how they do over time," said Riba, past president of the American Psychiatric Association, which has endorsed the heart association's recommendations.
One doctor said screening isn't enough; patients need close monitoring to make sure they get help.
"A lot of patients with depression don't follow up on it," said Dr. Mary Whooley, a professor of medicine at the University of California, San Francisco, who was not on the panel.
Barbara Forman, 62, struggled with depression after her double bypass about five years ago. She said she spent most of her time at her Englewood, Ohio, home sitting in her chair, frequently crying for no reason. When she did get out, she was often winded, even from a walk up a sidewalk to deliver cupcakes to her grandchild's classroom.
"I'm thinking, is this the way it's going to be for the rest of my life? Since I've had a heart event, is my life over?" she said. "It also made me afraid to do things. I didn't know how a heart attack felt. I would think, 'Is this a heart attack?"'
A couple of months after she got home she called Mended Hearts, a group affiliated with the heart association that provides support to heart patients, and talked to someone who let her know depression was common in heart patients.
Her family doctor sent her to a psychologist, and after some initial reluctance, she started taking an antidepressant. That, along with starting a walking routine and volunteering with Mended Hearts and the heart association, improved her outlook.
"You can't sit in your house and just vegetate," she said. "Over the last 18 months to two years -- It's really gotten better."
Tuesday, September 23, 2008
Part II: Brain Trauma in Iraq
Mixed Signals
On May 20, 2004, Jerry Pendergrass's convoy was ambushed. The National Guard sergeant was standing outside his Humvee when a rocket-propelled grenade landed a few feet behind him and exploded, launching him 15 feet in the air. A few moments later, Pendergrass found himself lying on the ground, shrapnel lodged in his leg and his helmet several yards away. He was conscious but unsure of where he was, classic signs of concussion. Another member of his unit pulled him behind the protective barrier of the disabled Humvee, where they awaited evacuation to a medical checkpoint in a secure zone down the road.
Pendergrass soon returned to duty, ignoring the persistent headaches and the sleep, memory, and balance problems that plagued him after the blast. When his tour was up and he returned home to North Carolina, he took prescription painkillers and drank, trying to wash away both his memories of war and the reality of his health problems. It wasn't until he began a second tour--and was evacuated two months later for spinal damage linked to the earlier blast--that he realized the full extent of his injuries. He was diagnosed with both mild traumatic brain injury and post-traumatic stress disorder (PTSD)--a condition, first defined in Vietnam veterans, that can develop after exposure to a terrifying event. "Big bangs scare the living fart out of me," says Pendergrass, in a conference room at the Lakeview Virginia NeuroCare center in Charlottesville, VA. He seems startled by even small noises, jumping as a nearby copy machine is jostled into action.
Pendergrass has spent the last three months at NeuroCare, which is partnered with the Defense and Veterans Brain Injury Center. The small in-patient clinic, with an adjacent residence for patients, offers intensive therapy and is staffed by occupational and physical therapists, speech and language therapists, and clinical psychologists. Pendergrass is getting psychological counseling for PTSD and rehabilitation for his brain injury.
He expects to return home soon, but his recovery is complicated by his dual diagnosis. In blast-injured soldiers, PTSD and mild brain injury often occur together. The two conditions also share symptoms--including depression, memory and attention deficits, sleep problems, and emotional disturbances--and research suggests that they can aggravate each other. A 1998 study of veterans with PTSD found that those exposed to blasts were more likely to have lingering attention deficits and abnormal brain activity that persisted long after the injury. And a study published earlier this year in the New England Journal of Medicine found that the 15 percent of soldiers who reported having suffered concussions had a much greater risk of developing PTSD: 44 percent of soldiers who had lost consciousness on the battlefield met criteria for PTSD, compared with 16 percent of those in the same brigades who suffered other injuries.
However, the two conditions can have different prognoses. While PTSD is a serious anxiety disorder, it can often be treated effectively with psychological and drug therapies. Patients with moderate to severe TBI have a far grimmer prognosis. Even people with concussions, who often get better on their own, can have enduring damage: symptoms that linger more than six months may be permanent. No drug treatments have proved effective for curing long-term symptoms, and other therapies are limited. For the most part, patients are simply taught new strategies for dealing with their impairments, such as carrying notepads to help them remember important tasks or designating specific spots for their keys.
Determining the true extent of the Iraq War's brain-injury epidemic will require sorting out whether individual patients' persistent symptoms are caused primarily by PTSD or by physical trauma. Statistical analysis from the New England Journal of Medicine study found that lasting symptoms could be attributed largely to PTSD and depression rather than to brain injuries themselves. But the conclusion is controversial. "I think that's minimizing the potential effects of concussion in this equation," says Barth, the University of Virginia neuropsychologist.
The debate over whether the mental wounds of war are biological or psychological has recurred in one form or another in every major war of the last century, ever since powerful explosives became widespread on the battlefield. During World War I, military doctors coined the term "shell shock" to describe the plight of soldiers who stumbled into army hospitals afflicted by dizziness and confusion, uncontrollable twitching, or an inability to speak. At first, doctors attributed the symptoms to brain damage caused by the frequent explosions that characterized the new trench warfare. But as soldiers who had never been exposed to blasts began reporting similar complaints, military psychiatrists started to suspect a sort of combat-triggered hysteria. A labeling system used by the British army at the time suggests the difficulty of distinguishing between the two problems (and the moral opprobrium attached to those whose condition was deemed psychological). Victims were designated either "shell-shock wounded," meaning the symptoms arose after the soldier was shelled, or "shell-shock sick," meaning the symptoms were not linked directly to an explosion. Only those with "wounded" status were awarded pensions and granted the honor of wearing "wound stripes" on their uniforms.
Walter Reed's David Moore hopes that new imaging technologies will finally resolve the debate by identifying the subtle neurological damage inflicted by concussion. One promising technology is diffusion tensor imaging (DTI), a variation on traditional magnetic resonance imaging (MRI) that highlights white matter, the long nerve fibers connecting brain cells. Recent studies of people with mild traumatic brain injury (from car accidents, for example) suggest that changes in the organization of the brain's white matter correlate with patients' cognitive deficits. Preliminary evidence suggests that patients who show the greatest disruption of white matter early on also have the poorest outcomes.
In a large, ongoing study at Walter Reed, which Moore is overseeing, researchers will use DTI to compare returning soldiers who have experienced blasts and report the hallmarks of concussion--loss of consciousness or situational awareness--with a military control group reporting no previous brain injuries. The scientists hope the images will help them identify specific brain changes linked to concussion, which will make it easier to diagnose the injury and predict its outcome.
Overwhelmed
Three years after Geoffrey Ling's time in Iraq, his war on brain injury has really just begun. Scientists have preliminary evidence that forces unique to blasts can damage the brain directly, independent of any blunt injuries that the blast might also cause. The key questions, however, remain unanswered. Which aspects of the blast do the most damage? How can the military better protect its personnel? And perhaps most important for legions of soldiers on patrol, can repeated exposure to weak blasts lead to long-lasting brain damage?
The prognosis for soldiers returning home with symptoms of brain damage is not encouraging. Decades of research into civilian head trauma have come to very little; treatments that seemed promising in animal models have turned out to be ineffective in human tests. "It's a completely untapped area of medical development," says trauma surgeon Jon Bowersox. While the military is testing a handful of existing drugs, there's a "time mismatch" when it comes to developing new treatments specifically for traumatic brain injury, Bowersox observes. "The military is interested in developing products they can have out during the current war," he says. "They are not used to the fact that medical development has a longer time line."
Even the few therapies that do exist will be difficult to deliver to everyone who needs them. "What will we do with all these people?" asks Barth. "We're talking about thousands. This is going to overwhelm the VA hospitals." The military is preparing some of those hospitals to better deal with brain injury, hiring neuropsychologists to make diagnoses and other experts to run rehabilitation programs. But resources are limited. At some of the medical centers, "physicians haven't had any training in rehabilitation other than clinical medicine," says Bowersox.
Perhaps the greatest challenge will be to help injured soldiers resume their previous lives. "Young people are not equipped emotionally and financially to handle this," says Marilyn Price Spivack, founder of the Brain Injury Association of Massachusetts, which has recently begun an outreach effort aimed at veterans. "Often they can't go back to their civilian jobs and are very hard to employ."
The goal of facilities like NeuroCare is to return people to service or to their civilian jobs. But even a quick visit with some of the patients shows what a long road that will be for many of them. In the clinic, one patient apologizes as he twitches uncontrollably. Another abruptly leaves the room, suddenly overcome with anxiety. And Pendergrass, who has had serious balance problems since he was injured, is unlikely to be able to return to his previous job hanging power lines. He doesn't yet know what he'll do when he leaves the rehab center.
Emily Singer is TR's biotechnology and life Sciences editor.
Brain Trauma in Iraq
A few days into his tour of duty at the 86th Combat Support Hospital in Baghdad, Colonel Geoffrey Ling, a U.S. Army neurologist, noticed something unusual. Soldiers who had sustained severe head injuries in blasts from improvised explosive devices (IEDs) appeared to be in much worse shape than he would have expected given his experience with patients who had suffered seemingly similar injuries in car accidents and assaults. The brains of the injured soldiers were swollen and appeared "a very angry red," he recalls. Some soldiers were conscious and could talk normally but were stumbling around the hospital, unable to keep their balance. "Their [brain] scans were stone-cold normal, and when you talked to them, they seemed fine," says Ling, who is now a staff physician at Walter Reed Army Medical Center and a program manager in the Defense Sciences Office at the U.S. Defense Advanced Research Projects Agency (DARPA) in Arlington, VA. "But when I started testing them, like asking them to do addition, they were clearly not normal."
By the time Ling arrived in Iraq, in 2005, thousands of U.S. soldiers had experienced IED attacks. While many of them had survived the concussive blasts, Ling and other physicians had begun to notice that a worrisome number were showing signs of brain damage. Ling, who is a neuroscientist as well as a neurologist, was puzzled. "Why does this injury look different?" he wondered. "What is it in the blast that's causing it--the pressure, the noise, the cloud of fume?" After months of treating blast wounds in both American troops and Iraqi security forces, Ling had returned from his tour determined to wage war on brain injury. He knew that the answers to these questions could be crucial to protecting soldiers in the field and screening and treating them when they came home.
Traumatic brain injury has been called the signature injury of the Iraq War, in which increasingly powerful IEDs and rocket-propelled grenades are the insurgents' weapons of choice. Because they produce such powerful blasts, these weapons often cause brain injuries. Meanwhile, thanks to better body armor and rapid access to medical care, many soldiers whose injuries would have been fatal in previous wars are returning alive--but with head trauma. "With IEDs, the insurgents have by dumb luck developed a weapon system that targets our medical weakness: treating brain injury," says Kevin "Kit" Parker, a U.S. Army Reserve captain and assistant professor of biomedical engineering at Harvard University who served in southern Afghanistan in 2002. Doctors do not yet fully understand brain injuries, particularly those caused by blasts, and no effective drug treatments exist. Early evidence suggests that explosions, which account for nearly 80 percent of the brain injuries identified at Walter Reed, cause unique and potentially long-lasting damage.
The extent and impact of the brain-injury epidemic are not yet clear, though the U.S. Congress appropriated $300 million last year for research into traumatic brain injury and post-traumatic stress disorder. The U.S. Department of Defense reports that approximately 30 percent of those evacuated from the battlefield to Walter Reed Army Medical Center have traumatic brain injury (TBI). The problem is probably worse than that: the DOD figure does not include brain injuries in soldiers whose wounds were not severe enough to require evacuation or whose injuries were not identified until after they completed their tours. Post-deployment surveys suggest that 10 to 20 percent of all deployed troops have experienced concussions. At worst, thousands of service members could return home with long-lasting problems, ranging from debilitating cognitive deficits to severe headaches and depression to subtler personality changes and memory deficits.
Military doctors are only beginning to get a grasp on the number of soldiers who have suffered mild traumatic brain injury, the medical term for a concussion. Mild injuries are by far the most common type of brain trauma, but they are more easily missed than moderate and severe injuries (they typically don't show up on standard brain scans), and the lasting effects, especially of repeated concussions, are not yet clear. Surveys of troops to be redeployed in Iraq suggest that 20 to 40 percent still had symptoms of past concussions, including headaches, sleep problems, depression, and memory difficulties. "We don't know what it means in terms of long-term functional ability," says William Perry, past president of the National Academy of Neuropsychology.
An Orange Flash
In November 2004, Stephen Kinney, a U.S. National Guard sergeant from North Chelmsford, MA, was patrolling a main supply route through southern Iraq when a buried artillery shell exploded outside the door of his Humvee. The blast propelled the vehicle into the air, riddling the doors with shrapnel. "All I remember is a big orange flash," says Kinney, who was thrown against the Humvee's radio, then against the ceiling, and briefly lost consciousness.
More concerned about a bruised hip and swollen shoulder than about his head, Kinney never considered the possibility of brain injury. The doctor who treated him at a military field hospital in Iraq didn't ask him about losing consciousness, or about his state of mind after the blast. "There were marines coming in from Fallujah with their arms blown off," says Kinney. "They figured if you weren't bleeding and had all your limbs, you were doing okay."
It wasn't until months after Kinney's return home the following February that he saw a psychiatrist at the local VA hospital and was evaluated for brain injury. He underwent extensive neuropsychiatric testing, which assessed cognitive capacities such as memory, attention, and higher-order reasoning, and he was diagnosed with mild traumatic brain injury. When Kinney returned to his job with the post office, he began to notice problems. He had trouble remembering names and numbers and often forgot whether he had scanned the bar codes on mailboxes along his route, as mail carriers do every 30 to 60 minutes to log their progress. In addition, though he'd been an avid illustrator (while on duty in Iraq he drew a Christmas card depicting a Humvee parked under a decorated palm tree), he hasn't taken up his colored pencils since he returned.
Despite the designation "mild," even a single concussion can produce serious symptoms, including severe headaches, difficulty sleeping, problems with memory and concentration, and even changes in personality. "The spouses say, 'He is totally different--he used to be a quiet guy and now he's agitated,' or 'He used to be energetic and now has no motivation,'" says Jeffrey Barth, a neuropsychologist at the University of Virginia School of Medicine in Charlottesville who has done pioneering work in the study of concussion. "They can also lose the ability to put everything together and to make good judgments." About half of people who suffer concussions quickly recover. But in the rest, symptoms can linger indefinitely. About 10 percent of concussion victims have problems severe enough to interfere with daily life and work. "No one knows how to treat it, how long it lasts, and whether it's safe to leave someone deployed," says Jon Bowersox, chief of surgery at the Cincinnati VA Medical Center and a colonel in the U.S. Air Force Reserve.
Especially worrying is the prospect that troops in Iraq will suffer repeated concussions, reinjuring their brains while they're still in a vulnerable state. For soldiers patrolling highways and guiding convoys, exposure to multiple blasts is a given; some have reported encountering tens of blasts in a day. In rare cases, multiple concussions in quick succession can lead to serious injury. But subtler damage may also accumulate, leading to depression and cognitive decline. "It's still an open question," says Barth. "How many concussions can you have without having a really bad outcome down the road?"
Anatomy of an Explosion
In Iraq, an IED is often buried near a road or hidden in a car and then triggered remotely. Detonating the device sets off a chemical reaction in which anywhere from a few to hundreds of kilograms of explosive expel their energy in a microsecond, compressing the surrounding air into a powerful shock wave. The explosion can also produce an electromagnetic pulse, a wave of electric and magnetic fields that may cause surges in current and voltage. Though blasts and the resulting injuries have been part of warfare for a long time--after the Napoleonic wars, some speculated that people who mysteriously died near firing cannons were injured by excessive vibration in the air--little is known about exactly how a blast wreaks havoc on the brain. (Before newer types of body armor were available, soldiers exposed to blasts often died of lung injury when pressure waves ruptured air-filled tissue; so blast research has largely been concerned with the lungs rather than the brain.)
Most studies of concussion have focused on blunt trauma, as in a blow to the head, not the effects of blasts. To complicate matters, an explosion can cause multiple types of brain injury. For example, when Kinney's Humvee was blown up, his brain endured the type of rapid acceleration and rotational forces typically seen in a car crash. Such forces, which can send the brain bouncing around inside the skull, can twist or tear axons--the long, thin fibers that connect nerve cells--and induce bleeding and swelling in the brain. But Kinney also felt the forces unique to blasts: the massive pressure wave, the electromagnetic pulse, and the light, heat, and sound from the explosion, all of which may ravage the brain in ways that haven't been fully documented.
To better understand what a blast does to the brain, Raul Radovitzky, an associate professor of aeronautics and astronautics at MIT, and David F. Moore, a neurologist at Walter Reed Army Medical Center who has a doctorate in fluid dynamics, developed a software model incorporating both the physics of pressure waves and the variable properties of the brain's tissues. Through magnetic resonance imaging, Moore modeled 11 features of the head, including the skull, the cerebrospinal fluid, the brain's fluid-filled ventricles, the sinuses, the brain's layer of white matter, and even the fat layer surrounding the eyes. The researchers used that information to create a computer model of the head, which they subjected to a simulated blast, observing how energy transferred from the air to the head affects the different structures. The model highlights the parts of the brain that endure the greatest stress and are thus most vulnerable to injury.
A movie of one simulation shows a rainbow-colored pressure wave propagating through a cross-sectional slice of the head, ricocheting off the skull, and rippling through the brain seemingly at random. So far, using values approximating a pressure wave that would damage the lungs, the model indicates that pressure from a blast far exceeds the minimum level thought to induce impact-related brain injuries. The researchers have also determined that tissue interfaces, such as the boundary between bone and brain, reflect the waves, so those areas are at greater risk. The pressure wave appears to enter the brain predominantly through the eyes and sinuses, and to a lesser extent through the skull, an observation that could influence the design of protective gear. Radovitzky and Moore are testing a new version of the model that includes a helmet, to evaluate how well it shields against the blast wave. "Blast protection for the head has not been a consideration in the design of body armor," says Radovitzky. "Maybe a small change to the armor could mediate the damage."
Across the Potomac River at DARPA, Geoffrey Ling has embarked on a similar quest to determine how blasts injure the brain. But unlike Radovitzky and Moore, whose computer model focuses on the pressure wave and its interaction with brain tissue, Ling and his colleagues are using animals, mostly pigs, to study the damage inflicted by each component of the blast: heat, sound, light, pressure wave. "We want to figure out what in that dirty environment causes [the most] injury," Ling says. "Say it's pressure or sound. Then we can go back and look for strategies to defeat them."
The pigs are immobilized in harnesses and then exposed to an explosion powerful enough to cause moderate to severe brain injuries. Since the animals will not be thrown against a wall or hit with debris, the scientists can study the effects of the explosion in isolation. "When exposed to a survivable blast, they have difficulty walking that lasts for days," says Ling. The explosions also disrupt appetite--all symptoms that mimic those reported by soldiers with blast-induced concussions.
But another finding is surprising. Most scientists have assumed that blast-related injury comes from the pressure wave. Preliminary studies from the DARPA program seem to contradict that hypothesis. When pigs were put into a specialized wind tunnel that generates shock waves like those accompanying blasts, the scientists did not see the same neurological effects found in pigs exposed to explosions. "We had to ramp up the pressure significantly before we saw [brain-related problems]," says Ling. "That made us step back and say, maybe it's something else, or not the pressure wave alone."
Radovitzky and Moore say that Ling's findings can't be directly compared with their own. Pigs' skulls are thicker than humans', for instance, so the interaction of the pressure wave and the pigs' brains may be different, too. But the apparent contradiction does illustrate just how difficult it is to understand brain injury.
Ling's team will soon begin studying other potential causes of injury, such as electromagnetic pulses (EMPs). If the EMP from a blast is powerful enough, it can interfere with nearby electronic devices. "The brain is an electrical organ," says Ling. "If an EMP pulse can take out a radio, why not short-circuit the brain?"
Meanwhile, the pig studies have shed some light on the biology of blast-related brain injury. Animals subjected to explosions show signs of neurodegeneration: according to Ling, preliminary results suggest that some of the pigs' neural fibers start to break down, triggering cell death primarily in the cerebellum (a brain structure involved in balance and coördination) and the frontal lobes (which play a role in impulse control, judgment, problem solving, complex planning, and motivation). As with the injured soldiers, however, it is not yet clear how the test pigs will fare in the long run--whether they will heal, whether their walking deficits will continue, or whether their initial injuries will set off a spiral of neural degeneration. And perhaps most important, it remains uncertain whether pigs exposed to repeated explosions will suffer exponentially more harm than those whose exposure is more limited.
Ling is overseeing a study of marines being trained to set controlled explosions, which should provide some evidence of the effects of successive but milder blasts. "Because [they] expose themselves repeatedly to blast, we can determine if, in fact, these repeated exposures cause mild TBI," says Ling. The marines will undergo cognitive and neuropsychological testing and intensive brain-imaging studies both before and after their training. And because their blast exposure doesn't occur on the battlefield, they are unlikely to experience the combat stress that can complicate the diagnosis of brain injury.
Mixed Signals
On May 20, 2004, Jerry Pendergrass's convoy was ambushed. The National Guard sergeant was standing outside his Humvee when a rocket-propelled grenade landed a few feet behind him and exploded, launching him 15 feet in the air. A few moments later, Pendergrass found himself lying on the ground, shrapnel lodged in his leg and his helmet several yards away. He was conscious but unsure of where he was, classic signs of concussion. Another member of his unit pulled him behind the protective barrier of the disabled Humvee, where they awaited evacuation to a medical checkpoint in a secure zone down the road.
Pendergrass soon returned to duty, ignoring the persistent headaches and the sleep, memory, and balance problems that plagued him after the blast. When his tour was up and he returned home to North Carolina, he took prescription painkillers and drank, trying to wash away both his memories of war and the reality of his health problems. It wasn't until he began a second tour--and was evacuated two months later for spinal damage linked to the earlier blast--that he realized the full extent of his injuries. He was diagnosed with both mild traumatic brain injury and post-traumatic stress disorder (PTSD)--a condition, first defined in Vietnam veterans, that can develop after exposure to a terrifying event. "Big bangs scare the living fart out of me," says Pendergrass, in a conference room at the Lakeview Virginia NeuroCare center in Charlottesville, VA. He seems startled by even small noises, jumping as a nearby copy machine is jostled into action.
Pendergrass has spent the last three months at NeuroCare, which is partnered with the Defense and Veterans Brain Injury Center. The small in-patient clinic, with an adjacent residence for patients, offers intensive therapy and is staffed by occupational and physical therapists, speech and language therapists, and clinical psychologists. Pendergrass is getting psychological counseling for PTSD and rehabilitation for his brain injury.
He expects to return home soon, but his recovery is complicated by his dual diagnosis. In blast-injured soldiers, PTSD and mild brain injury often occur together. The two conditions also share symptoms--including depression, memory and attention deficits, sleep problems, and emotional disturbances--and research suggests that they can aggravate each other. A 1998 study of veterans with PTSD found that those exposed to blasts were more likely to have lingering attention deficits and abnormal brain activity that persisted long after the injury. And a study published earlier this year in the New England Journal of Medicine found that the 15 percent of soldiers who reported having suffered concussions had a much greater risk of developing PTSD: 44 percent of soldiers who had lost consciousness on the battlefield met criteria for PTSD, compared with 16 percent of those in the same brigades who suffered other injuries.
However, the two conditions can have different prognoses. While PTSD is a serious anxiety disorder, it can often be treated effectively with psychological and drug therapies. Patients with moderate to severe TBI have a far grimmer prognosis. Even people with concussions, who often get better on their own, can have enduring damage: symptoms that linger more than six months may be permanent. No drug treatments have proved effective for curing long-term symptoms, and other therapies are limited. For the most part, patients are simply taught new strategies for dealing with their impairments, such as carrying notepads to help them remember important tasks or designating specific spots for their keys.
Determining the true extent of the Iraq War's brain-injury epidemic will require sorting out whether individual patients' persistent symptoms are caused primarily by PTSD or by physical trauma. Statistical analysis from the New England Journal of Medicine study found that lasting symptoms could be attributed largely to PTSD and depression rather than to brain injuries themselves. But the conclusion is controversial. "I think that's minimizing the potential effects of concussion in this equation," says Barth, the University of Virginia neuropsychologist.
The debate over whether the mental wounds of war are biological or psychological has recurred in one form or another in every major war of the last century, ever since powerful explosives became widespread on the battlefield. During World War I, military doctors coined the term "shell shock" to describe the plight of soldiers who stumbled into army hospitals afflicted by dizziness and confusion, uncontrollable twitching, or an inability to speak. At first, doctors attributed the symptoms to brain damage caused by the frequent explosions that characterized the new trench warfare. But as soldiers who had never been exposed to blasts began reporting similar complaints, military psychiatrists started to suspect a sort of combat-triggered hysteria. A labeling system used by the British army at the time suggests the difficulty of distinguishing between the two problems (and the moral opprobrium attached to those whose condition was deemed psychological). Victims were designated either "shell-shock wounded," meaning the symptoms arose after the soldier was shelled, or "shell-shock sick," meaning the symptoms were not linked directly to an explosion. Only those with "wounded" status were awarded pensions and granted the honor of wearing "wound stripes" on their uniforms.
Walter Reed's David Moore hopes that new imaging technologies will finally resolve the debate by identifying the subtle neurological damage inflicted by concussion. One promising technology is diffusion tensor imaging (DTI), a variation on traditional magnetic resonance imaging (MRI) that highlights white matter, the long nerve fibers connecting brain cells. Recent studies of people with mild traumatic brain injury (from car accidents, for example) suggest that changes in the organization of the brain's white matter correlate with patients' cognitive deficits. Preliminary evidence suggests that patients who show the greatest disruption of white matter early on also have the poorest outcomes.
In a large, ongoing study at Walter Reed, which Moore is overseeing, researchers will use DTI to compare returning soldiers who have experienced blasts and report the hallmarks of concussion--loss of consciousness or situational awareness--with a military control group reporting no previous brain injuries. The scientists hope the images will help them identify specific brain changes linked to concussion, which will make it easier to diagnose the injury and predict its outcome.
Overwhelmed
Three years after Geoffrey Ling's time in Iraq, his war on brain injury has really just begun. Scientists have preliminary evidence that forces unique to blasts can damage the brain directly, independent of any blunt injuries that the blast might also cause. The key questions, however, remain unanswered. Which aspects of the blast do the most damage? How can the military better protect its personnel? And perhaps most important for legions of soldiers on patrol, can repeated exposure to weak blasts lead to long-lasting brain damage?
The prognosis for soldiers returning home with symptoms of brain damage is not encouraging. Decades of research into civilian head trauma have come to very little; treatments that seemed promising in animal models have turned out to be ineffective in human tests. "It's a completely untapped area of medical development," says trauma surgeon Jon Bowersox. While the military is testing a handful of existing drugs, there's a "time mismatch" when it comes to developing new treatments specifically for traumatic brain injury, Bowersox observes. "The military is interested in developing products they can have out during the current war," he says. "They are not used to the fact that medical development has a longer time line."
Even the few therapies that do exist will be difficult to deliver to everyone who needs them. "What will we do with all these people?" asks Barth. "We're talking about thousands. This is going to overwhelm the VA hospitals." The military is preparing some of those hospitals to better deal with brain injury, hiring neuropsychologists to make diagnoses and other experts to run rehabilitation programs. But resources are limited. At some of the medical centers, "physicians haven't had any training in rehabilitation other than clinical medicine," says Bowersox.
Perhaps the greatest challenge will be to help injured soldiers resume their previous lives. "Young people are not equipped emotionally and financially to handle this," says Marilyn Price Spivack, founder of the Brain Injury Association of Massachusetts, which has recently begun an outreach effort aimed at veterans. "Often they can't go back to their civilian jobs and are very hard to employ."
The goal of facilities like NeuroCare is to return people to service or to their civilian jobs. But even a quick visit with some of the patients shows what a long road that will be for many of them. In the clinic, one patient apologizes as he twitches uncontrollably. Another abruptly leaves the room, suddenly overcome with anxiety. And Pendergrass, who has had serious balance problems since he was injured, is unlikely to be able to return to his previous job hanging power lines. He doesn't yet know what he'll do when he leaves the rehab center.
The Unobservable Mind One of Britain's leading philosophers is skeptical that neurobiology can tell us anything about self-consciousness.
Consciousness is more familiar to us than any other feature of our world, since it is the route by which anything at all becomes familiar. But this is what makes consciousness so hard to pinpoint. Look for it wherever you like, you encounter only its objects -- a face, a dream, a memory, a color, a pain, a melody, a problem, but nowhere the consciousness that shines on them. Trying to grasp it is like trying to observe your own observing, as though you were to look with your own eyes at your own eyes without using a mirror. Not surprisingly, therefore, the thought of consciousness gives rise to peculiar metaphysical anxieties, which we try to allay with images of the soul, the mind, the self, the "subject of consciousness," the inner entity that thinks and sees and feels and that is the real me inside. But these traditional "solutions" merely duplicate the problem. We cast no light on the consciousness of a human being simply by redescribing it as the consciousness of some inner homunculus -- be it a soul, a mind, or a self. On the contrary, by placing that homunculus in some private, inaccessible, and possibly immaterial realm, we merely compound the mystery.
Putting the point in that way makes it clear that, in the first instance at least, the problem of consciousness is a philosophical, not a scientific, problem. It cannot be solved by studying the empirical data, since consciousness (as normally understood) isn't one of them. We can observe brain processes, neurons, ganglions, synapses, and all the other intricate matter of the brain, but we cannot observe consciousness. I can observe you observing, but what I observe is not that peculiar thing that you know from within and that is present, in some sense, only to you. At least, so it would seem; if this is some kind of mistake, it is a philosophical and not a scientific argument that will tell us so.
This appropriation of the question by philosophy is apt to make scientists impatient. Surely, they will argue, if consciousness is real it must be part of the real world -- the world of space and time, which we observe with our senses and explain by science. But what part? First-person reports of conscious states are radically affected by brain damage, and the behavior that leads us to describe others as conscious originates in the nervous system, whose functions seem to be largely controlled by the brain. Common sense and scientific inference therefore both point to the brain as the seat of consciousness. So, scientists argue, let's study the brain and find out exactly which of its processes correspond to our conscious mental states. That way, they suggest, we will find out what consciousness is.
But will we? Unfortunately, the philosophical problem comes back at us in another form. How exactly do we discover a correspondence between consciousness and a brain process, given that consciousness is not something that we observe? And suppose we overcome that difficulty and produce a theory correlating conscious mental states with specific neurological events. This means that we have discovered what consciousness is only if we can advance from correspondence to identity. And that is precisely what so many philosophers doubt we can do. True, there are some who defend the view that conscious states are identical with brain processes, but they defend it on philosophical, not scientific, grounds. And their view is open to radical objections: for example, how can a state of one thing (a person) be identical with a process in another (a brain)?
If the neurobiologist Christof Koch, professor of cognitive and behavioral biology at Caltech, enters this territory with some trepidation, he nevertheless hopes to take possession of it in the name of science. The task, he believes, is to avoid getting lost in definitions and conceptual puzzles and instead to discover the "neuronal correlates of consciousness." He at once narrows that target, however, to "the minimal set of neuronal events and mechanisms jointly sufficient for a specific conscious percept." In other words, the object of study is not consciousness as such but "specific conscious percepts," in particular those involved in visual perception. Koch's ambition, nevertheless, is to integrate the analysis of vision into the more general program that he developed with the late Francis Crick, one of the discoverers of the structure of DNA, who contributes the foreword to the book. That program is to explain how consciousness evolved and identify the processes in the brain that carry it. The book gives a fairly comprehensive account of what neurobiology has to say about the higher functions of the brain. It is not surprising, therefore, that the writing is densely scientific and heavily referenced, with many digressions. But proceeding on the supposition that the science is correct, what do we make of the title? Does neurobiology in the style of Crick and Koch really take us further in the "quest for consciousness"? Or is it simply amassing more and more information about the brain, without telling us how brain and mind are connected?
First Person Singular
One of the problems, which constantly intrudes on Koch's argument but is never resolved, is that conscious mental states do not belong to a single category. We assume that all sensations are conscious (there is no such thing, for example, as unconscious toothache), that there is both conscious and unconscious thought, and that while desire may be unconscious, intention never is. But what do conscious mental states have in common? At times Koch seems to suggest that they are all "felt" by the subject, or that they each possess a particular subjective quality or "quale" that is observable only to the subject. But we don't feel our thoughts, and there is no subjective quale that distinguishes the belief that two plus two is four from the belief that three plus three is six, or the intention to sit down to supper from the intention to eat a steak. In the case of language-using creatures, we distinguish conscious from unconscious mental states through the "first-person" perspective. A state is conscious if the subject can truly confess to it, without having to carry out an investigation and on no basis other than understanding the words that he uses. Hence in other places Koch seems to take the first-person case as characteristic of consciousness, a procedure that deprives him of a clear basis for attributing consciousness to animals, who never confess to their mental states because they never confess to anything. This is serious, since the science on which Koch draws derives from examining the brains of mice and monkeys.
Crucial to the Koch-Crick approach is a thought experiment involving the idea of the unconscious zombie. This is a creature all of whose behavior issues by reflex action, mediated by the cortex, but who is not conscious of what he is doing. This creature feels nothing, has no inner "qualia" and -- presumably -- no first-person awareness of his own mental states. So what else does he lack? Or can he be exactly like us and lack only those things? Koch is of the view that a zombie would lack the capacity to plan for the future or to deal with multicontingency situations where complex choices must be made. Plotting, planning, and deciding, he says, are among the important functions of consciousness and point to a Darwinian explanation of why consciousness exists.
Such an argument will help in the "quest for consciousness" only if we can show how "feeling," "qualia," and the "first-person case" are connected to plotting and planning. If the connection is only contingent, then a zombie could possess all the functions of consciousness without the feelings. If the connection is necessary, then it must be established in some way other than by scientific inference. As it is, the reader is left at the end of Koch's book with the puzzle with which it began: granted that there are neuronal correlates of consciousness, what exactly are they correlated with? And what exactly do we mean by "correlation"?
To answer that question, I would suggest first that we dismiss the idea of purely subjective "qualia." The belief that these essentially private features of mental states exist, and that they form the introspectible essence of whatever possesses them, is grounded in a confusion, one that Wittgenstein tried to sweep away in his arguments against the possibility of a private language. When you judge that I am in pain, it is on the basis of my circumstances and behavior, and you could be wrong. When I ascribe a pain to myself, I don't use any such evidence. I don't find out that I am in pain by observation, nor can I be wrong. But that is not because there is some other fact about my pain, accessible only to me, which I consult in order to establish what I am feeling. For if there were this inner private quality, I could misperceive it; I could get it wrong, and I would have to find out whether I am in pain. To describe my inner state, I would also have to invent a language, intelligible only to me -- and that, Wittgenstein plausibly argues, is impossible. The conclusion to draw is that I ascribe pain to myself not on the basis of some inner quale but on no basis at all.
Of course, there is a difference between knowing what pain is and knowing what pain is like. But to know what it is like is not to know some additional inner fact about it, but simply to have felt it. We are dealing with familiarity rather than information. While one philosopher -- Thomas Nagel, a professor at New York University and author of The View from Nowhere, a fascinating study of subjectivity -- has placed great emphasis on the "what it's like" idea, suggesting that it describes a distinctive mark of conscious experience, the idea remains opaque to further analysis. "What it's like" is not a proxy for a description but a refusal to describe. We can spell it out, if at all, only in metaphors. Q: "What's it like, darling, when I touch you there?" A: "Like the taste of marmalade, harmonized by late Stravinsky."
Similarly, we are not going to get very far in understanding consciousness if we concentrate on the idea of "feeling" things. For there are conscious mental states that have nothing to do with feeling. We feel our sensations and emotions, certainly, just as we feel our desires. All of those mental states would once have been classified as passions, as opposed to mental actions -- thought, judgement, intention, deduction -- which are not felt but done. I can deliberately think of Mary, judge a picture, make a decision or a calculation, even imagine a centaur, but not deliberately have a pain in the finger, a fear of spiders, or a desire for more cake. Even if I could have a pain by willing it, or if I manage to suppress my desires, this does not mean that pains and desires are actions, but only that they are passions that I can affect through mental discipline, as a yogi might reduce his heart rate. Moreover, there are psychologists and philosophers who seem quite happy with the idea of "unconscious feelings." We may balk at the expression, but we know what they mean. It is possible to feel something without being conscious of the feeling. Feeling is a mark of consciousness only if we interpret "feeling" as "awareness." But what is it to be aware of something? Well, to be conscious of it.
Emergent Properties
How do we fight ourselves free from this tangle of circular definitions and misleading pictures? Two ideas seem to me especially helpful in explaining our sense of consciousness as a realm apart. The first is that of an emergent property. Mental states generally, and conscious states in particular, can be seen as emergent states of organisms. A useful analogy is the face in a picture. When a painter applies paint to a canvas, she creates a physical object by purely physical means. This object is composed of areas and lines of paint, arranged on a surface that we can regard, for the sake of argument, as two dimensional. When we look at the painting, we see a flat surface, and we see those areas and lines of paint, and also the surface that contains them. But that is not all we see. We also see a face that looks out at us with smiling eyes. In one sense, the face is a property of the canvas, over and above the blobs of paint; you can observe the blobs and not see the face, and vice versa. And the face is really there: someone who does not see it is not seeing correctly. On the other hand, there is a sense in which the face is not an additional property of the canvas, for as soon as the lines and blobs are there, so is the face. Nothing more needs to be added in order to generate the face -- and if nothing more needs to be added, the face is surely nothing more. Moreover, every process that produces just these blobs of paint, arranged in just this way, will produce just this face -- even if the artist herself is unaware of the face. (Imagine how you would design a machine for producing Mona Lisas.)
Maybe consciousness is an emergent property in that sense: not something over and above the life and behavior in which we observe it, but not reducible to them either.
The second helpful thought is one first given prominence by Kant and thereafter emphasized by Fichte, Hegel, Schopenhauer, and a whole stream of thinkers down to Heidegger, Sartre, and Thomas Nagel. The idea is to draw a distinction between the subject and the object of consciousness, and to recognize the peculiar metaphysical (Wittgenstein would say grammatical) status of the subject. As a conscious subject, I have a point of view on the world. The world seems a certain way to me, and this seeming defines my unique perspective. Every conscious being has such a perspective, since that is what it means to be a subject rather than a mere object. When I give a scientific account of the world, however, I am describing objects only. I am describing the way things are, and the causal laws that explain them. This description is given from no particular perspective. It does not contain words like "here," "now," and "I"; and while it is meant to explain the way things seem, it does so by giving a theory of how they are. In short, the subject is in principle unobservable to science, not because it exists in another realm but because it is not part of the empirical world. It lies on the edge of things, like a horizon, and could never be grasped "from the other side," the side of subjectivity itself. Is it a real part of the real world? The question begins to look as though it has been wrongly phrased. I refer to myself, but this does not mean that there is a self that I refer to. I act for the sake of my friend, but there is no such thing as a sake for which I am acting. (The parallel illustrates Wittgenstein's view of these puzzles as essentially grammatical.)
We can relate to conscious creatures in ways that we cannot relate to objects. Their behavior is the outcome of the way things seem to them and can therefore be altered by altering the way things seem. Giving them "food for thought" or -- in the case of more primitive animals -- "food for perception" and "food for belief," we also bend them to our purposes. Because they feel pleasure and pain, they can be rewarded and punished and so taught to behave in new ways. Everybody who has trained a dog or a horse in even the simplest task knows that consciousness is an essential intermediary in achieving the final result, and that there is nothing puzzling about this at all: consciousness is as much a part of the behavioral repertoire of the animal as eating and excreting. It consists in a set of functional connections between world and behavior, of a kind that leads us to identify a "point of view," a "way things seem" that distinguishes the creature with which we are dealing. This point of view is also the quickest and easiest channel to the springs of its behavior.
In referring to behavior, we don't have to accept the old behaviorist theory that mental predicates can simply be reduced to behavioral syndromes. When we interpret behavior as the expression of a conscious state, we are expressly situating it in an intuitively understood nexus of causal relations. The behavior of a man in pain is only superficially like the behavior of an actor who is pretending to be in pain. The sufferer really cannot stand on his injured leg, and the leg really is injured; the actor's behavior is voluntary, the sufferer's involuntary. And so on. All those judgments are hypotheses concerning the functional connections between world and behavior, and they form parts of a spontaneous theory that some philosophers have called "folk psychology."
Now, there are certainly "neuronal correlates" of consciousness, so understood: namely, all the electrical processes that are necessary to generate conscious behavior (among which, according to Koch, gamma waves -- oscillations recorded by an electroencephalogram in the 30- to 70-hertz domain -- are particularly important). Some animals exhibit these processes; some (insects, for instance) don't. To discover the source of these processes is, in a sense, to discover the seat of consciousness in the brain. But does this bring us any nearer to knowing what consciousness is? Suppose you came across a person who behaved and talked as you did, who related to you in all the ways that people relate to each other, and who one day -- to your astonishment -- unzipped the top of his head to reveal nothing save a dead kitten and a ball of string. Scientifically impossible, perhaps. But logically possible, and giving no grounds at all to deny that this person was conscious.
The Unselfconscious Dog
To put the point another way, consciousness is an emergent property of organisms. But it emerges from the total behavioral and neurological repertoire, not from brain processes considered in themselves -- just as the face in the painting emerges from the whole array of colored patches, not from the canvas that supports them, considered in itself. Of course, you cannot have the behavior without the brain, just as you can't have the painting without the canvas. In that sense there will be neuronal correlates of consciousness. But the discovery of these correlates does not tell us what consciousness is, nor does it solve the mystery of the subject, nor the equally perplexing mystery of the first-person case.
There is a difficulty that I have avoided, and which Koch too avoids, though incidental remarks show that he is aware of it. This difficulty arises from two radical ontological divisions in the realm of the mental. First, there is the division that separates conscious from unconscious creatures. We attribute perception of a kind to mussels and oysters -- but are they conscious? Should we feel remorse when we pry open the oyster and sting its wounds with lemon juice? We are inclined to say that such organisms are too primitive to admit the application of concepts like those of feeling, belief, and desire. Maybe that goes for insects, too, however much we may admire their amazing social organization and perceptual powers.
Secondly, there is the division that separates merely conscious creatures from self-conscious creatures like us. Only the second have a genuine "first-person" perspective, from which to distinguish how things seem to me from how they seem to you. The creature with "I" thoughts has an ability to relate to its kind that sets it apart from the rest of nature, and many thinkers (Kant and Hegel among them) believe that it is this fact, not the fact of consciousness per se, that creates all the mysteries of the human condition. Although dogs are conscious, they do not reflect on their own consciousness as we do: they live, as Schopenhauer put it, in "a world of perception," their thoughts and desires turned outwards to the perceivable world.
The difficulty is this: we want to say of human beings that their self-consciousness is a systematic attribute of their mental life, which affects everything that they think and feel. We want to say of dogs that their consciousness is a systematic attribute of their mental life too, since it distinguishes them categorically from mollusks and beetles. Yet similar mental states seem to exist at all three levels. The beetle sees things; so does the dog; so does the person. How is it that one and the same mental process -- visual perception -- can exist in three different ontological predicaments, so to speak: as a reflex link between visual input and behavioral output, as a conscious perception, and as part of the continuous and distinguishing sense of self?
That question has led some writers (the neuroscientist Antonio Damasio in his book Looking for Spinoza, for instance) to think of consciousness and self-consciousness as monitoring processes -- a move that comes dangerously close to the old homunculus fallacy. It is not as though my mind were just like a dog's, only with a self observing it, or a dog's just like an insect's, only with an internal monitor. Consciousness and self-consciousness are holistic properties, which emerge from the totality of a creature's physiognomy and behavior. We may discover organizations in the brain and nervous system that are biologically necessary for these features. But those "neuronal correlates" are no more likely to cast light on the mysteries of consciousness than the back of Leonardo's Mona Lisa can explain the mystery of her smile.
The conclusion to which I am tempted is not that there is no such thing as consciousness, but that there is nothing that consciousness is, just as there is no physical object that actually is Mona Lisa's smile.
Roger Scruton is visiting professor in the Department of Philosophy, Birkbeck College, London, and the author of more than 20 books, including Modern Philosophy and England: an Elegy. He farms in Wiltshire, England.
Copyright Technology Review 2005.
Facebook Profiles Can Be Used To Detect Narcissism
“We found that people who are narcissistic use Facebook in a self-promoting way that can be identified by others,” said lead author Laura Buffardi, a doctoral student in psychology who co-authored the study with associate professor W. Keith Campbell.
The researchers, whose results appear in the October issue of the journal Personality and Social Psychology Bulletin, gave personality questionnaires to nearly 130 Facebook users, analyzed the content of the pages and had untrained strangers view the pages and rate their impression of the owner’s narcissism.
The researchers found that the number of Facebook friends and wallposts that individuals have on their profile pages correlates with narcissism. Buffardi said this is consistent with how narcissists behave in the real-world, with numerous yet shallow relationships. Narcissists are also more likely to choose glamorous, self-promoting pictures for their main profile photos, she said, while others are more likely to use snapshots.
Untrained observers were able to detect narcissism, too. The researchers found that the observers used three characteristics – quantity of social interaction, attractiveness of the individual and the degree of self promotion in the main photo – to form an impression of the individual’s personality. “People aren’t perfect in their assessments,” Buffardi said, “but our results show they’re somewhat accurate in their judgments.”
Narcissism is a trait of particular interest, Campbell said, because it hampers the ability form healthy, long-term relationships. “Narcissists might initially be seen as charming, but they end up using people for their own advantage,” Campbell said. “They hurt the people around them and they hurt themselves in the long run.”
The tremendous growth of social networking sites – Facebook now has 100 million users, for example – has led psychologists to explore how personality traits are expressed online. Buffardi and Campbell chose Facebook because it’s the most popular networking site among college students and because it has a fixed format that makes it easier for researchers to compare user pages.
Some researchers in the past have found that personal Web pages are more popular among narcissists, but Campbell said there’s no evidence that Facebook users are more narcissistic than others.
“Nearly all of our students use Facebook, and it seems to be a normal part of people’s social interactions,” Campbell said. “It just turns out that narcissists are using Facebook the same way they use their other relationships – for self promotion with an emphasis on quantity of over quality.”
Still, he points out that because narcissists tend to have more contacts on Facebook, any given Facebook user is likely to have an online friend population with a higher proportion of narcissists than in the real world. Right now it’s too early to predict if or how the norms of online self-promotion will change, Campbell said, since the study of social networking sites is still in its infancy.
“We’ve undergone a social change in the last four or five years and now almost every student manages their relationships through Facebook – something that few older people do,” Campbell said. “It’s a completely new social world that we’re just beginning to understand.”
Monday, September 22, 2008
Benefit Of Combination Therapy For Alzheimer's Disease Confirmed
Results from the first long-term study of the real-world use of Alzheimer's drugs, published by researchers from Massachusetts General Hospital in the July/September issue of Alzheimer Disease and Associated Disorders, support a level of effectiveness that may not be immediately apparent to patients or their family members.
"There has been the impression that these drugs only work for some patients and for a limited amount of time," says Alireza Atri, MD, PhD, of the MGH Department of Neurology, lead author of the current study. "One of the problems in judging these drugs has been that patients naturally continue to decline, which can make them think the drugs have stopped working. But our study, which has some unique strengths, indicates that treatment does have long-term benefit."
Two types of medications have received FDA approval for Alzheimer's treatment. Cholinesterase inhibitors have been available since the mid-1990s and act by inhibiting the breakdown of the neurotransmitter acetylcholine. The drug memantine, which received FDA approval in 2003, is the first of a second class of agents that modulate the actions of the amino acid glutamate and is often used in combination with cholinesterase inhibitors (CIs).
"Clinical trials that drug companies conduct for FDA approval only last six months and enroll patients according to very specific criteria," Atri explains. "Only large-population studies can really tell us how these drugs work for the full range of patients in real-life situations." The researchers were able to conduct such a study by analyzing data on patients treated at the MGH Memory Disorders Unit since 1990, including 144 who did not receive any pharmaceutical treatment, 122 treated with a CI alone and 116 who received both a CI and memantine. As part of their regular treatment, every six months patients received standardized assessments of both cognitive abilities and how well they carried out daily activities.
The results showed significant differences in the rate of symptom progression among all three groups – with the smallest level of decline in those receiving combination therapy. While there was an average of two and a half years' worth of data on the study participants, the researchers analyzed the information with a statistical model that predicted probable outcomes for up to four years.
Although the model's projection of future benefits is conservative, it predicted that the longer patients kept receiving combination therapy, the smaller their rate of decline would become, suggesting that treatment might even protect brain cells from further damage, a possibility needing further investigation.
"Finding something that could actually modify the course of the disease is the Holy Grail of Alzheimer's treatment, but we really don't know if that is happening or what the mechanism behind these effects might be," Atri explains. "What we can say now is that providers should help patients understand that the benefits of these drugs are long term and may not be apparent in the first months of treatment. Even if a patient's symptoms get worse, that doesn't mean the drug isn't working, since the decline probably would have been much greater without therapy." Atri is an instructor in Neurology at Harvard Medical School (HMS) and associate director of the Center for Translational Cognitive Neuroscience at the Veterans Administration Hospital in Bedford, Mass.
John Growdon, MD – director of the MGH Memory Disorders Unit, professor of Neurology at HMS, and senior author of the paper – explains, "The results of this study should change the way we treat patients with Alzheimer's disease. Cholinesterase inhibitors are approved for use in mild to moderate dementia, while memantine has been approved for advanced dementia. But it looks like there is an advantage in prescribing both drugs as initial treatment."
The study was entirely supported by grants from the National Institute on Aging and the Massachusetts Alzheimer's Disease Research Center; there was no involvement or support from the pharmaceutical industry. Additional co-authors of the report are Lynn Shaughnessy, Massachusetts School of Professional Psychology, and Joseph Locascio, PhD, MGH Neurology.
Friday, September 19, 2008
What Happens When We Die?
A fellow at New York's Weill Cornell Medical Center, Dr. Sam Parnia is one of the world's leading experts on the scientific study of death. Last week, Parnia and his colleagues at the Human Consciousness Project announced their first major undertaking: a 3-year exploration of the biology behind "out-of-body" experiences. The study, known as AWARE (AWAreness during REsuscitation), involves the collaboration of 25 major medical centers through Europe, Canada and the U.S., and will examine some 1,500 survivors of cardiac arrest. TIME spoke with Parnia about the project's origins, its skeptics, and the difference between the mind and the brain.
What sort of methods will this project use to try and verify people's claims of "near-death" experience?
When your heart stops beating, there is no blood getting to your brain. And so what happens is that within about ten seconds, brain activity ceases —as you would imagine. Yet paradoxically, ten or 20 percent of people who are then brought back to life from that period, which may be a few minutes or over an hour, will report having consciousness. So the key thing here is, are these real, or is it some sort of illusion? So the only way to tell is to have pictures only visible from the ceiling and nowhere else, because they claim they can see everything from the ceiling. So if we then get a series of 200 or 300 people who all were clinically dead, and yet they're able to come back and tell us what we were doing and were able see those pictures, that confirms consciousness really was continuing even though the brain wasn't functioning.
How does this project relate to society's perception of death?
People commonly perceive death as being a moment — you're either dead or you're alive. And that's a social definition we have. But the clinical definition we use is when the heart stops beating, the lungs stop working, and as a consequence the brain itself stops working. When doctors shine a light into someone's pupil, it's to demonstrate that there is no reflex present. The eye reflex is mediated by the brain stem and that's the area that keeps us alive; if that doesn't work then that means that the brain itself isn't working. At that point, I'll call a nurse into the room so I can certify that this patient is dead. Fifty years ago, people couldn't survive after that.
How is technology challenging the perception that death is a moment?
Nowadays, we have technology that's improved so that we can bring people back to life. In fact, there are drugs being developed right now — who knows if they'll ever make it to the market — that may actually slow down the process of brain-cell injury and death. Imagine, you fast-forward to ten years down the line and you've given a patient whose heart has just stopped this amazing drug, and actually what it does is it slows everything down so that the things that would've happened over an hour, now happen over two days. As medicine progresses, we will end up with lots and lots of ethical questions.
But what is happening to the individual at that time, what's really going on? Because there is a lack of blood flow, the cells go into a kind of a frenzy to keep themselves alive. And within about 5 minutes or so they start to damage or change. After an hour or so the damage is so great that even if we restart the heart again and pump blood, the person can no longer be viable because the cells have just been changed too much. And then the cells continue to change so that within a couple of days the body actually decomposes. So it's not a moment, it's a process that actually begins when the heart stops and culminates in the complete loss of the body, the decompositions of all the cells. However, ultimately what matters is, What's going on to a person's mind? What happens to the human mind and consciousness during death? Does that cease immediately as soon as the heart stops? Does it cease activity within the first 2 seconds, the first 2 minutes? Because we know that cells are continuously changing at that time. Does it stop after ten minutes, after half an hour, after an hour? And at this point we don't know.
What was your first interview like with someone who had reported an out-of-body experience?
Eye-opening and very humbling. Because what you see is that, first of all, they are completely genuine people who are not looking for any kind of fame or attention. In many cases they haven't even told anybody else about it because they're afraid of what people will think of them. I have about five hundred or so cases of people that I've interviewed since I first started out more than ten years ago. It's the consistency of the experiences, the reality of what they were describing. I managed to speak to doctors and nurses who had been present who said these patients had told them exactly what had happened and they couldn't explain it. I actually documented a few of those in my book What Happens When We Die because I wanted people to get both angles —not just the patients' side but also get the doctors' side — and see how it feels for the doctors to have a patient come back and tell them what was going on. There was a cardiologist that I spoke with who said he hasn't told anyone else about it because he has no explanation for how this patient could have been able to describe in detail what he had said and done. He was so freaked out by it that he just decided not to think about it anymore.
Why do you think there is such resistance to studies like yours?
Because we're pushing through the boundaries of science, working against assumptions and perceptions that have been fixed. A lot of people hold this idea that well, when you die you die, that's it. Death is a moment, you know you're either dead or you're alive. All these things are not scientifically valid but they're social perceptions. If you look back at the end of the 19th century, physicists at that time had been working with Newtonian laws of motion and they really felt they had all the answers to everything that was out there in the universe. When we look at the world around us, Newtonian physics is perfectly sufficient. It explains most things that we deal with. But then it was discovered that actually when you look at motion at really small levels —beyond the level of the atoms — Newton's laws no longer apply. A new physics was needed, hence, we eventually ended up with quantum physics. It caused a lot of controversy, even Einstein himself didn't believe in it.
Now, if you look at the mind, consciousness, and the brain, the assumption that the mind and brain are the same thing is fine for most circumstances, because in 99% of circumstances we can't separate the mind and brain, they work at the exactly the same time. But then there are certain extreme examples, like when the brain shuts down, that we see that that this assumption may no longer seem to hold true. So a new science is needed in the same way that we had to have a new quantum physics. The CERN particle accelerator may take us back to our roots. It may take us back to the first moments after the big bang, the very beginning. With our study, for the first time, we have the technology and the means to be able to investigate this. To see what happens at the end for us. Does something continue?