fMRI offers a glimpse into how the brain processes loss. For one researcher, the method provides surprising insights.

Although the emotion of grief is universal, no two experiences are alike. For most people, the effects of grief begin to lessen after the first 6 months, but some cases are more severe. For an estimated 6% to 20% of people, the loss of a loved one can be so debilitating that they cannot resume their normal routine, even after several months have passed, according to research by the Mayo Clinic. The causes of this condition, called complicated grief, are largely unknown.

To shed light on this mystery, Mary-Frances O’Connor, PhD, assistant professor at the Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, turned to functional magnetic resonance imaging (fMRI) technology. “It has been used very successfully in emotion research,” O’Connor said. “We’re learning much more about the types of networks in the brain that lead to, or underlie, our emotional experiences.”

Since the 1980s, fMRI has been a tool of choice for researchers studying the brain. The idea is to track blood-oxygen-level dependent (BOLD) signals to determine brain activity. When a subject is introduced to certain stimuli, fMRI shows the fluctuations in BOLD signals throughout the regions of the brain: The greater the BOLD signal, the more activity in the region.

Knowing which regions of the brain react to certain stimuli can help researchers like O’Connor determine how a person processes emotion. “It’s wonderful to be able to look inside the brain in a living person while they are doing something and know what regions of the brain they’re using to do it,” O’Connor said.

Surprising Results

For O’Connor, a clinical psychologist by training, researching the effects of grief on the brain came naturally. “Bereavement just seemed like a really natural time to study emotion because, of course, you have people who are suddenly confronted with such a difficult emotional experience,” she said. “They have quite profound emotional fluctuations.”

By comparing the fMRI scans of participants who had complicated grief with those who had noncomplicated grief, O’Connor wanted to discover whether a difference in BOLD signal distribution could lead to a better understanding of the underlying causes. “How we experience something in the world and how that gets translated through our brain was sort of fascinating to me,” O’Connor said. “And why that might lead some people to adapt well and others not to adapt well led me to want to find out more about how the brain is processing in people who are bereaved.”

Over an 18-month period, O’Connor studied 23 women who had recently lost a mother or a sister to breast cancer. These women ranged in age from 19 to 60, but the average age was 42. Twelve of the participants had noncomplicated grief, while 11 of the women had complicated grief.

Each participant described her experience of loss, and researchers took note of grief-related words. Every woman also brought a photograph of her loved one to be used during the study. “We did this because the scanner environment is sort of a cold and unemotional place, and we really wanted to capture these women when they were having a grief experience,” O’Connor noted.

O’Connor’s team used fMRI to measure the brain’s response to specific stimuli. Via video goggles, each woman was shown photographs of their loved ones as well as images of someone unknown to them. “We matched the pictures of the deceased with pictures of a stranger so that we would be able to look at brain activity not specific to visual stimulation or even visual stimulation of a person, but of their reaction to this specific individual they had lost.”

The 6-minute presentation also included grief-related words, such as “cancer” and “funeral,” provided by the participants, and neutral words, such as “strawberry” and “ceiling.” “We were accessing the grief both by words and by pictures,” O’Connor said.

fMRI allowed O’Connor to track the rise of blood flow in particular areas of the brain when the subjects were introduced to a new image or word. “After a few seconds, there is a shift in blood flow as they use different areas to process the new stimuli,” she said. “So, we’re really modeling the rise of blood flow in these different areas.”

A clinical environment, such as the inside of an fMRI scanner, may seem like an unlikely venue to access emotion. However, better technology, such as video goggles, helps subjects to focus on a task without the distractions of the machine itself. O’Connor says that the goggles are a big improvement over the days when images were projected on the scanner wall with the help of mirrors.

“The goggles are better because of the resolution of the image, but also because the participant is less aware that they’re in a scanner, because they can’t see it while they’re actually doing the task,” O’Connor said. She also provided study participants with earphones so that they would not be distracted by the ambient sounds in the room, especially from the machine itself.

O’Connor interpreted the images from the study based on what is known about functional neuroanatomy, or which areas of the brain are believed to perform certain tasks. This body of knowledge has been gleaned from prior MRI studies and animal models, as well as prior human-lesion studies, which help determine functional deficits caused by partial injury to the brain.

The results of O’Connor’s study were published in NeuroImage. Predictably, areas related to emotional pain, such as the dorsal anterior cingulate cortex, were activated in all participants. But to O’Connor’s surprise, the nucleus accumbens, an area associated with reward processing, was activated in subjects with complicated grief.

“We thought this was a little strange, having a reward area light up in the group that was not doing well,” O’Connor said. “But in thinking more about the theory behind complicated grief, it is certainly rewarding for us to be around those who we love. And reminders of those that we love often predict that we’re going to see them again.”

fMRI offers a glimpse into how the brain processes loss. For one researcher, the method provides surprising insights.

In addition to symptoms such as depression, irritability, bitterness, and detachment, people with complicated grief often experience intense longing for their lost loved one. This can manifest as focusing intently on reminders of the deceased. “It is one of the tasks in adapting to this new reality to understand that this person will not be seen again, will not be coming back,” O’Connor said. “So, we think that perhaps they were still processing these visual images and words in a way that stimulated reward, and the level of activation in this area correlated with the amount of yearning that these women experienced.”

Future Exploration

O’Connor continues to research grief in her current study, which focuses on older adults (aged 65 to 80) who have lost a spouse. She will use fMRI technology again to look at three groups: 11 adults with complicated grief, 11 adults with noncomplicated grief, and 11 adults with living spouses.

“I’m using something called an emotional Stroop task, and it allows us to determine how distracted a person is by grief-related cues,” O’Connor said.

Participants will provide O’Connor with grief-related words. These words, along with neutral words, will be presented to the participants via video goggles during the fMRI scans. The words will change very rapidly—every 1,500 milliseconds—and O’Connor will measure participants’ reaction times based on when they press the response keypad. “Basically, it’s a reaction-time paradigm,” she said. “You’re getting reaction time in the scanner to these grief-related words, or to neutral words. And the degree to which the reaction time is longer to grief-related words, gives you some indication that the brain is taking longer to process it. It is more distracted by that word than by a neutral word.”

The study, which is already in progress, will take 2 to 3 years to complete. O’Connor hopes the research will help uncover a potential cause of cognitive decline in older adults. “I’m interested in this because sometimes the death of a spouse is the beginning of cognitive decline,” she said. “And so I’m interested to see if this is an age-related effect. Is this grief-specific, or is this just distraction in general?”

Once the study is complete, O’Connor plans to continue using fMRI to study the effects of grief on the brain. “Given that we know that this reward pathway was involved with folks with complicated grief, I’m interested in sort of teasing that apart a little bit,” O’Connor said.

A potential avenue of research would be having subjects perform a task in the scanner for which they are rewarded. Studying the different reward pathways may lead to more insight into how they are used in those with complicated grief. Another possibility is focusing on those with complicated grief who are going through psychotherapy. This research would aim to detect brain-related changes before and after treatment.

No matter which direction O’Connor chooses, fMRI will play a major role in her research. The technology allows her access to living humans in real time, rather than having to rely on animal models. “It’s just really exciting. The equipment gets better and better all the time, and new techniques are developed for doing the imaging and for analyzing the imaging,” she said. “I think it’s just a wonderful method.”

Ann H. Carlson is a contributing writer for Medical Imaging. For more information, contact .