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How abuse beats up the brain 

UAMS neuroscientists see the scars; perhaps repairs, too.

click to enlarge MIND READER: Dr. Josh Cisler and UAMS employee Jasmine Medley illustrate how the fMRI scanner at the Brain Imaging Research Center on the UAMS campus is used. - BRIAN CHILSON
  • Brian Chilson
  • MIND READER: Dr. Josh Cisler and UAMS employee Jasmine Medley illustrate how the fMRI scanner at the Brain Imaging Research Center on the UAMS campus is used.

The number of children in Arkansas and the nation who have been subjected to sexual abuse is appalling, if not surprising to the professionals who work with such children every day. Based on historical studies, the Centers for Disease Control and Prevention says one in four girls and one in six boys will experience some form of sexual abuse by the age of 18. In Arkansas, reported incidents indicate that 14 children per 1,000 suffer from some form of maltreatment, such as neglect or physical abuse, and of that number, 22 percent will have been sexually abused. This compares to a national rate of 9.1 children per 1,000; nearly one in 1,000 children nationally have suffered sexual abuse.

The typical victim of sexual abuse that Stacy Thompson, director of Children's Advocacy Centers of Arkansas, sees is a girl 9 years old or younger who's been molested by someone she knows or even loves: a family member, or a stepfather, or a coach, or a minister. The abuse may have taken the form of fondling, oral sex or rape. It could have happened even without touching, such as a "sexted" picture gone viral — something Thompson said is on the rise — or a pornographic image shown to a child.

Such trauma can have long-lasting ill effects on a child's life. Children who have been abused may turn to drugs, and the physical repercussions of abuse include heart disease, cancer, even autoimmune diseases.

But research and therapy at the University of Arkansas for Medical Sciences suggest that children who've suffered at the hands of abusers need not lead lives defined by their pain. Therapy can help them change the way they think, creating not just behavioral changes but changes in the way their brains are wired. Brains, it appears, are altered by trauma, but can possibly be healed.

UAMS' Helen L. Porter and James T. Dyke Brain Imaging Research Center, in the Psychiatric Research Institute, has since its creation in 2009 focused on addiction and the brain. Dr. Clinton Kilts came to UAMS from Emory University School of Medicine in Atlanta as founding director of the brain imaging program, which introduced advanced technology into the work done in UAMS' Center for Addiction Research, created in 2004. That technology is the functional magnetic resonance imaging (fMRI) scanner, which allows neuroscientists to look at activity in the brain.

The neuroscientists in the research center are now using imaging to study the impact of trauma on the structure and function of the brain. Dr. Joshua Cisler, a Ph.D. psychiatric researcher, has focused his studies on how the adolescent brain changes in response to trauma and whether one can predict how well a young patient will respond to therapy.

In the blood flow of a child's brain, Cisler can see the scars of abuse.

***

Consider this child, an amalgam of patients such as those seen by UAMS therapists, who we'll call Clara. Clara was both physically and sexually abused. Her stepfather, who moved in with her mother and brother when she was 7, beat her with a broom handle. Her mother began to beat her as well. When Clara turned 9, her stepfather began to abuse her sexually. Eventually the brother reported the father to authorities, and the children were removed to the home of an aunt and uncle, who sought help for Clara.

If Clara were cocooned in the research center's fMRI scanner, the blood flow in her brain — lit by radio waves and magnetism — might show Cisler this: The connection between her hippocampus and prefrontal cortex, parts of the brain believed to help control emotion and memory, and her left amygdala, which processes emotion and helps identify important things around us, is weak. What that means for patients like Clara, Cisler believes, is that the normal brain balance that would keep the amygdala in check is malfunctioning.

That disconnect is brought on by the stress of repeated abuse, stress that bombards the brain with the hormone cortisol. When we sense danger, Cisler explained, our bodies produce cortisol to allow us "to stay in a preparedness mode," so we can act quickly to protect ourselves. But if the stress is prolonged, the cortisol begins to do damage to neural pathways, so that the "preparedness" effect is lost. The overproduction of cortisol shrinks the neuronal branches in the parts of the brain that help us exercise control, like the hippocampus and prefrontal cortex, and expands them in areas where emotion is experienced, like the amygdala. Cisler likens the action to a river that is flowing so hard and fast that it overcomes a weakened dam. The hippocampus and prefrontal cortex can no longer ameliorate the emotions, making the child who has been subject to high levels of stress hyperemotional.

In Cisler's work — with both volunteers and patients at the Psychiatric Research Institute and girls from other therapeutic facilities (see sidebar for volunteer opportunities) — he's looked at decision-making in the brains of abused vs. nonabused girls.

In one task, subjects are given hypothetical money to lend to three computer girls. (A mirror placed in the fMRI allows the subjects to see a computer on which the girls appear.) One of the computer girls can be expected to give the money back half the time, one will give the money back 80 percent of the time and the third will return the loan only 20 percent of the time. Subjects have 48 encounters with the girls, thus learning who is likely to return the money and who is not: The task is to figure out which of the three girls is the most trustworthy.

Here's a twist: Sometimes the computer girls do not act as expected. A girl who has been giving the money back does not; or one that has not been giving the money back does. Cisler looks at the brain's response to these unexpected results. (What he's seeing is the change in oxygenated blood flow in the brain, a proxy for the neuronal response.)

Say a child like Clara was in the fMRI scanner. The girl who has been returning Clara's money four out of five times does not. But Clara's brain does not react to this unexpected outcome. There's no flash of activation in what Cisler called the "salience network," the parts of the brain that coordinate when we identify something as important. In girls who have been sexually assaulted, the brain doesn't "snap to attention," as Cisler put it, when one of the computer girls acts out of character.

As a result, the abused adolescent is less likely to be able to identify the most trustworthy girl. The difference between the abused child and the nonabused child is significant, and girls who've suffered the most abuse have the hardest time telling which of the girls is trustworthy.

Cisler likened these signals that something is not right to hearing fire alarms that go off all the time: You learn to ignore them.

Girls who have been abused might learn to ignore social danger signals and are thus more likely to be victimized again.

***

click to enlarge HEALING PTSD: PRI psychologist Teresa Kramer. - BRIAN CHILSON
  • Brian Chilson
  • HEALING PTSD: PRI psychologist Teresa Kramer.

Teresa Kramer, a Ph.D. psychologist at the Psychiatric Research Institute at UAMS who leads the ARBEST program (Arkansas Building Effective Service for Trauma), says Cisler's research may explain why the method PRI therapists use in treatment offers a path to recovery. That therapy is Trauma-Focused Cognitive Behavioral Therapy, which has been described by researchers as the "gold standard" in the treatment of post-traumatic stress disorder in abused children and adolescents.

Children who've been abused may suffer symptoms of PTSD: flashbacks, intrusive thoughts, nightmares. Some, even young children, may exhibit inappropriate sexual behaviors. Some may self-medicate with drugs. The goal of TF-CBT, a 12- to 16-week treatment that involves both the child and the nonabusive parent or guardian, is to show the child "how to keep her whole identity from being wrapped around the trauma," Kramer said. It is similar to treatment for PTSD in war veterans, who are sometimes exposed to virtual simulations of their traumatic memories to help desensitize them.

Therapists first work with patients to develop trust and introduce relaxation techniques. Then the patient is asked to tell the story of her trauma.

The story is not a forensic one, as described by an observer, Kramer said, but a narrative that will show how the child perceived the trauma. The patient — who may take some coaxing to acknowledge what has happened — is asked to tell who she is, what her life was like before the trauma, what her home was like, and, then, what happened. The narrative can take any form, Kramer said — some patients will write, some will draw, some will use rap songs or drama.

The idea is to relive the trauma until the memory no longer causes high anxiety, and to erase the child's wrong-thinking, such as "It was my fault," "I shouldn't have done ...," "I'm a bad person," "I'm the reason my family is torn apart."

Therapists work with the nonabusive parent or guardian to deal with what has happened. The child will eventually present the trauma narrative to the parent; the therapists prepare the caregiver to hear the recital of the trauma without overreacting.

When therapeutic goals are reached, "we want children to feel like they've accomplished something," Kramer said. "So when their treatment is through, we graduate them. We line the halls and applaud, and the children get a certificate," Kramer said.

Clara found it hard at first to talk about what had been done to her. Eventually, however, she was able to create the narrative to describe how the abuse made her think and feel.

With the help of the therapist, Clara also began to see a connection between the abuse she suffered and her problematic behavior: For example, because her stepfather called her "ugly," she sought attention or compliments from anyone. That meant she got involved in what her doctor called "high-risk relationships."

The therapy also helped her feel closer to her aunt and accepting of the limits, like curfew, in her new home. Her doctor said she felt more positive about herself, which meant she made healthier decisions. By the end of treatment, she was thinking about the future, not the past, and making new friends who were not involved in risky behavior.

***

Unfortunately, the TF-CBT therapy has its limits: It has been shown to work in only two-thirds of the patients at the PRI, Cisler said. He wondered, is it possible to predict who will benefit from the therapy by looking at their brains?

To test the hypothesis that he could see a difference, Cisler worked with 34 abused adolescent girls who had come to the PRI for therapy. The girls' brains were scanned before and after they had had 12 sessions of TF-CBT therapy. Researchers looked at how the girls' amygdalae (both right and left) reacted when the girls were shown faces expressing no emotion and faces showing fear. The fearful faces are themselves frightening.

When the results of those scans were compared with the clinical results post-therapy, the researchers discovered that girls whose amygdalae activated only at the sight of fearful faces — apparently discerning threat from nonthreat — were those who also showed the greatest reduction in their PTSD symptoms from their therapy.

But girls whose amygdalae showed reaction to both neutral and frightened faces, who appeared to fear both expressions before therapy, did not seem to benefit as much from TF-CBT.

The post-therapy fMRI scans showed a change in the brains of girls who did well with TF-CBT, as if the therapy was actually causing a change in the neural pathways. Are the girls' PTSD symptoms reduced because the therapy is actually rewiring the brain?

"We are on the cusp of understanding the effects of trauma on brain development," Kramer said.

***

Some of the children who have volunteered for Cisler's research come from Youth Home Inc., which provides residential treatment for clients ages 11 to 17. Cisler's work is "much needed," Peggy Kelly, chief clinical officer at Youth Home, said, especially in that it shows the connection between trauma and substance abuse. "We are thrilled [researchers] are putting together the connections of trauma and addiction and how those two correlate," Kelly said.

Kelly, who came to Youth Home from Atlanta a year ago, says she sees a need in Arkansas "for education and awareness. ... People still have such a stigma attached to addiction and mental illness. They don't see it as a brain disorder, but a willpower issue. ... This imaging is critical to prove to people that it is a physiological problem we are trying to address." Kelly said Youth Home is seeking grants to present such information to schools and families.

***

Addiction causes multiple changes in the brain: from volume and shape to cognition, decreases in the release of neurotransmitters and their receptors, and alterations in the patterns of connectivity, the "salience network."

click to enlarge ADDICTION RESEARCHER: BIRC Director Clinton Kilts. - BRIAN CHILSON
  • Brian Chilson
  • ADDICTION RESEARCHER: BIRC Director Clinton Kilts.

In his work, Brain Imaging Research Center director Kilts is trying to answer the question, does addiction represent a pre-existing brain state? Do some people have a susceptibility to addiction? Or is it an acquired disorder? Kilts believes addiction is caused by both a pre-existing brain state and acquired changes by drug misuse. He also believes it's possible that the brain can be retrained to control the strong impulse to use drugs, and hopes that early intervention in younger, at-risk individuals can prevent the acquired brain state of addiction and thus its development.

Addicts have trouble with impulsivity. The drive to use drugs or alcohol is so strong that few "perceive a need for help or treatment," Kilts said; addiction "creates a motivational structure" all its own.

Much addiction research has centered on "delayed discounting" — the addict's inability to choose a greater reward over a lesser one if the greater one cannot be achieved instantly. Another of the tests PRI researchers use to study impulsivity and addiction is the "stop signal" task. Subjects are asked to tap whenever a letter comes up on a computer screen. However, if the letter has a circle around it (the signal to stop) they are asked to stop the tap response. While the task is going on, functional magnetic resonance imaging (fMRI) is mapping activity in the brain to detect what aspects of brain function are failing the addict and, in comparison, how the healthy brain works to control impulsive behavior.

Addicts have trouble stopping the tendency to respond when they see the letter with the circle around it, Kilts said. Their ability to stifle impulses — to not take the drink, to not use the drug, to not respond to the stop signal — is impaired. The difference between addicted individuals who perform these tasks and nonaddicted people is such that Kilts can identify which is which by looking at the way their brains are behaving during the tests.

Addiction, Kilts said, is "one of the few diseases that rob you of function in the organ necessary to getting help — the brain." But the brain, once thought "immutable," Kilts said, has the ability to reorganize throughout one's life, "to erase the footprint left by the trauma."

In adolescents, for every year that you can delay drug use, Kilts said, the risk of addiction drops 5 percent. But treating trauma-related disorders, like addiction, is difficult. Kilts hopes that brain-imaging research will show ways to train functions of the brain to allow one to inhibit the impulse to use drugs. "I'm interested in the behavior you don't express," Kilts said, the desire not to use drugs.

Like Cisler, Kilts hopes the research going on at the BIRC will show ways to retrain areas of the brain — to restore salience in the traumatized and perhaps fend off the desire to abuse drugs or repair the addicted brain.

Other ongoing studies in the BIRC look at how the brain responds while participants recall traumatic experiences; family decision-making and adolescent PTSD; suicidal thoughts; and how depression or drug use interferes with infant caregiving. Kilts noted particular interest in the work of colleague Dr. Lisa Brents, a molecular pharmacist who, with the Women's Mental Health Program, is conducting studies of depression and drug misuse in postpartum women, and how these problems impact the brain representation of maternal care.

"We are training the next generation of clinical neuroscientists to do much more" to advance the study of the brain, Kilts said. "We are creating a group that thinks differently," to study addiction and abuse in new ways that will translate to the treatment.

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