PsychDigest

Anticipating the outcome: Brain activity predicts treatment success

A network of emotion-regulating brain regions implicated in the pathological worry that can grip patients with anxiety disorders may also be useful for predicting the benefits of treatment.

A new study reports that high levels of brain activity in the amygdala reflect patients' hypersensitivity to anticipation of adverse events. At the same time, high activity in a regulatory region known as the anterior cingulate cortex (ACC) is associated with a positive clinical response to a common antidepressant medication.

Psychologists know that for individuals with anxiety disorders, the anticipation of a bad outcome can be worse than the outcome itself. To study how the brain responds to anticipation, researchers used functional magnetic resonance imaging (fMRI) to examine patients with generalized anxiety disorder (GAD) as they viewed a set of negative and neutral images. Patients were shown pre-image cues several seconds before each picture so they would know what to expect: a circle before a neutral image and a minus sign before an aversive image.

While GAD patients showed no difference in brain activation— compared to healthy subjects—in response to the aversive or neutral pictures themselves, they displayed unusually high levels of amygdala activity in response to both anticipatory cues. The response suggests that the patients are hypersensitive to the anticipation of any stimuli, even those they are told will not be negative.

The researchers believe the high levels of amygdala activity seen in GAD patients reflects an indiscriminate and disproportionately large response to the idea that something negative might happen in the future, even in a laboratory setting where they know nothing bad will actually occur. It suggests that there are differences in anticipatory brain processing in these individuals.

The patterns of brain activity also appear to hold predictive power for how patients will respond to treatment for their anxiety. After their brain scans, the GAD patients in the study received an eight-week course of treatment with venlafaxine (Effexor), a common antidepressant. Clinical improvement on the medication was associated with higher levels of pre-treatment brain activity in the ACC in anticipation of both aversive and neutral stimuli. The ACC is a regulatory brain region important for modulating emotional responses. Activity in the same area has been shown to predict clinical outcome in patients with depression.

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Sources:

Nitschke, J.B., Sarinopoulos, I., Oathes, D.J., Johnstone, T., Whalen, P.J., Davidson, R.J., & Kalin, N.H. (2009, January 2). Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response. American Journal of Psychiatry [Article published online before print]. Retrieved February 5, 2009, from the journal website at http://ajp.psychiatryonline.org/cgi/content/abstract/appi.ajp.-2008.07101682v1g. The full article can be accessed online for $15.

University of Wisconsin–Madison (2009, January 2). Expectant brains help predict anxiety treatment success. Retrieved February 5, 2009, from http://www.news.wisc.edu/releases/14982

Changes in brain structure due to chronic and short-term stress: New evidence

Research presented at Neuroscience 2008 (November 2008, Washington, DC, USA) reports new evidence that a wide range of stressful experiences change the physical structure and function of the brain, potentially affecting child development, adult brain wiring, and cognitive performance.

The new findings show:

• Early-life stress physically alters brain structures associated with the regulation of stress and emotions, according to animal research. Monkeys that had experienced early-life stress showed enlargement of the medial prefrontal cortex, dorsal anterior cingulate cortex, and cerebellar vermis. These findings are consistent with human brain-imaging studies showing structural changes in the brains of children and adults exposed to early-life stress. However, in humans, it has been difficult to determine whether the structural abnormalities were present at birth, or occurred as a result of early-life stress. Researchers speculate that enlargement of the regions during childhood may indicate vulnerability to neuropsychiatric diseases caused by stress. (Spinelli, S., Chefer, S.I., Suomi,S.J., Higley, J.D., Barr, C.S., & Stein, E. “Stress during a critical developmental period induces long-term morphological changes in primate brain.”)
  
• Children who have experienced early-life stress are more likely to use brain circuits involved in emotion, according to new imaging research. Children who spent time in institutions as infants use different brain circuits than other children when performing an emotionally arousing task. The findings suggest that adverse conditions in early life can affect the development of brain circuits involved in emotion. These types of experiences may lead to increased anxiety and difficulty regulating emotions. (Tottenham, N.L., Hare, T.A., Millner, A.,Gilhooly, T., & Casey, B. “Early-life stress is associated with a neural bias towards emotionality.”)
  
• Short-term stress—even that lasting just a few hours—can reduce cellular connections in the hippocampus, a brain region involved in learning and memory. Previous research had shown the impact of long-term stress; this study shows the same effect for short-term stress, but suggests that chronic and short-term stress may use different hormones to shape brain cell connections. The stress hormone cortisol, which circulates throughout the body, is thought to be involved in reducing the number of dendritic spines following chronic stress. Following short-term stress, the researchers found that a different stress hormone, corticotrophin-releasing hormone (CRH)—which is produced solely in the brain—is involved. The study also identified a drug that may prevent stress’s harmful effect. (Chen, Y., Dubé, C., Rice, C., Korosi, A., Ivy, A., & Baram, T.Z.”Stress induces dendritic spine loss within hours in adult hippocampus: Novel mechanisms.”)
  
• Chronic stress shrinks the hippocampus. This study resolves controversial findings in people with post-traumatic stress disorder (PTSD); smaller hippocampi have been observed in imaging studies of people with PTSD, but these measurements were completed only after diagnosis. That made it impossible to determine whether the traumatic experience caused hippocampal size reduction, or if people with smaller hippocampi are more prone to develop PTSD. 3–D magnetic resonance imaging with rats showed that chronic stress reduced hippocampal size by more than 3%; however, chronic stress failed to alter the size of any other brain structure. These findings are consistent with studies in both animals and humans showing that stress impairs memory. (Helmstetter, F.J., Lee, T., Jaromei, T., Li, S–J., & Kim, J.J. “Chronic stress selectively reduces hippocampal volume in rats.”)
  
• Short-term stress impairs decision-making in adult rats. Animals exposed to stress had greater difficulty choosing among options that maximized a reward payoff, suggesting that even short-term stress can affect cognition. Research on the effects of stress on cognitive processes such as learning, memory, and decision-making will help to characterize the potential problems stress people face in their hectic lives. (Jones, L.K., Yoon, T., & Kim, J.J. “Acute uncontrollable stress alters subsequent decision-making processes in rats.”)

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Sources:

Society for Neuroscience (SfN) (2008, November 18). Research finds new evidence that chronic and short-term stress causes wide-ranging changes in brain structure and performance. SfN News Releases. Retrieved January 26, 2009, from http://www.sfn.org/index.cfm?pagename=news_111808d

‘Tetris’ may help reduce flashbacks to traumatic events

Playing the computer game ‘Tetris’ after traumatic events could reduce the flashbacks experienced in post-traumatic stress disorder (PTSD), according to preliminary research by Oxford University psychologists.

If this early-stage work continues to show promise, it could inform new clinical interventions for use immediately after trauma to prevent or lessen the flashbacks that are the hallmark symptom of PTSD. Existing treatments can only be provided once PTSD has become established.

The researchers report that for healthy volun­teers, playing ‘Tetris’ soon after viewing traumatic mate­rial in the laboratory can reduce the number of flashbacks to those scenes in the following week. They believe that the computer game may disrupt the memories that are retained of the sights and sounds witnessed at the time, and which are later re-experienced through involun­tary, distressing flashbacks of that moment.

The approach relies on three elements. First, the mind is considered to have two separate

“We know there is up to six hours in which it is possible to affect certain types of memories that are laid down in the human mind. We have shown that in healthy volunteers, playing ‘Tetris’ in this period can reduce flashback-type memories without wiping out the ability to make sense of the event.”—Dr Catherine Deeprose, Department of Psychiatry at Oxford University

channels of thought: one is sensory and deals with our direct perceptual experience of the world, the other is conceptual and draws meaning and narrative from our experiences to give them context. For example, we would use one channel to see and hear someone talk and the other to comprehend the meaning of what they were saying. Second, there appear to be limits to our abilities in each stream: it is difficult to hold a conversation while doing maths problems, for example. And third, there is a short time after an event in which it is possible to interfere with the way our memories are retained in the brain.

The Oxford team reasoned that recognising the shapes and moving the coloured building blocks around in ‘Tetris’ soon after seeing traumatic events should compete with the visions of trauma to be retained in the sensory part of the brain. The narrative and meaning of the events should be unaffected.

The Oxford team showed a film to 40 healthy volunteers that included traumatic images of injury from a variety of sources, including adverts highlighting the dangers of drunk driving. This is a recognised way to study the effects of trauma in the laboratory. After waiting 30 minutes, 20 of the volunteers played ‘Tetris’ for 10 minutes while the other half did nothing. Those who had played the computer game experienced significantly fewer flashbacks to the film over the next week.

“We wanted to find a way to dampen down flashbacks—that is, the raw sensory images of trauma that are over-represented in the memories of those with PTSD,” says Dr Emily Holmes of the Department of Psychiatry at Oxford University, who led the work. ‘Tetris may work by competing for the brain’s resources for sensory information. We suggest it specifically interferes with the way sensory memories are laid down in the period after trauma and thus reduces the number of flashbacks that are experienced afterwards.”

The group is now hoping to develop this approach further as a potential intervention to reduce the flashbacks experienced in PTSD, but they are keen to emphasise that these are only preliminary results. Dr Holmes also stresses that no conclusions can be drawn more generally for computer gaming and its effects.

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Sources:

Holmes, E.A., James, E.L., Coode–Bate, T., & Deeprose, C. (2009, January 7). Can playing the computer game “Tetris” reduce the build-up of flashbacks for trauma? A proposal from cognitive science. PLoS ONE 4(1): e4153. doi:10.1371/journal.pone.0004153. Retrieved February 6, 2009, from the journal website at http://www.plosone.-org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004153. The full article is freely available online.

University of Oxford (2009, January 7). ‘Tetris’ may help reduce flashbacks to traumatic events. Retrieved February 6, 2009, from http://www.ox.ac.uk/media/news_stories/2009/090701.html

Breast cancer patients with marital problems fare worse

Breast cancer patients who have a poor relationship with their spouse may face a more difficult road to recovery than would other women. Researchers found that, over five years, patients in distressed marriages had higher levels of stress, less physical activity, slower recovery, and more symptoms and signs of illness than did similar patients who reported good marriages.

Sources:

Ohio State University (2008, December 9). Poorer outcomes for breast cancer patients with marital problems. Medical News Today. Retrieved January 18, 2009, from http://www.medicalnewstoday.com/articles/132334.php