A new study led by CDC investigator Elizabeth Unger, MD, PhD, with collaborators at Emory University, Atlanta, and the University of Modena and Reggio Emilia, Italy, has identified unique responses in the brain’s basal ganglia that suggest an association between a biologic functional response and chronic fatigue syndrome (ME/CFS).
In a paper presented April 24 at the Experimental Biology conference in San Diego,(1) the team reports that:
• Patients with ME/CFS have decreased activation in response to reward of an area of the brain known as the basal ganglia. (Ganglia are bundles of neurons providing relay points and interconnections. The basal ganglia are a constellation of interconnected areas deep in the brain. They appear to be associated with many functions, from motor activity and motivation/perceived reward to learning and habit encoding, and apparently with addictive disorders, OCD, and ADHD.)
• Problems with the basal ganglia tend to involve fatigue.
• The extent of the lowered activation in the ME/CFS patients’ basal ganglia is associated with the individual patient’s measured levels of physical and mental fatigue. (Less activation, more severe fatigue.)
How the Study Came About
Dr. Unger (chief of the CDC’s Viral Diseases Branch) says that she and her colleagues became curious about the role of the basal ganglia after previous studies by collaborators at Emory University showed that patients treated with interferon alpha, a common treatment for chronic hepatitis C and several other conditions, often experienced extreme fatigue.
Interferons are proteins that cells make to trigger immune defenses in response to pathogens such as viruses, and tumor cells. They ‘interfere’ with viral replication within host cells and activate immune cells.
Further investigation into this phenomenon showed that basal ganglia activity decreased in patients who received this immune therapy.
Since the fatigue induced by interferon alpha shares many characteristics with chronic fatigue syndrome, Dr. Unger and her colleagues decided to investigate whether the basal ganglia were also affected in this disorder.
• The researchers recruited 18 patients with chronic fatigue syndrome (ME/CFS), as well as 41 healthy volunteers with no symptoms of ME/CFS.
• Each study participant underwent functional magnetic resonance imaging, a brain scan technique that measures activity in various parts of the brain by blood flow, while they played a simple card game meant to stimulate feelings of reward.
• The participants were each told that they’d win a small amount of money if they correctly guessed whether a preselected card was red or black. After making their choice, they were presented with the card while researchers measured blood flow to the basal ganglia during winning and losing hands. This is considered a good test, as perceptions of winning or losing normally evoke strong activations of the basal ganglia.
More Muted Reaction to Stimulus = More Fatigue
The researchers showed that patients with chronic fatigue syndrome experienced significantly less change in basal ganglia blood flow between winning and losing than the healthy volunteers. (Stimulating activities can normally produce ‘razzle-dazzle’ activity in the basal ganglia, says one leading researcher.)
When the researchers looked at scores for the Multidimensional Fatigue Inventory, a survey often used to document fatigue for chronic fatigue syndrome and various other conditions, they also found that the extent of a patient’s fatigue was tightly tied with the change in brain activity between winning and losing.
Those with the most fatigue had the smallest change in brain activity.
Dopamine Dysfunction Involved; Inflammation Possible Cause
These findings add to our understanding of biological factors that may play a role in chronic fatigue syndrome, Dr. Unger says.
“Many patients with chronic fatigue syndrome encounter a lot of skepticism about their illness,” she says. “They have difficulty getting their friends, colleagues, coworkers, and even some physicians to understand their illness. These results provide another clue into the biology of chronic fatigue syndrome.”
The study also suggests some areas of further research that could help scientists develop treatments for this condition in the future.
• Since the basal ganglia use the chemical dopamine as their major neurotransmitter, dopamine metabolism may play an important role in understanding and changing the course of this illness. (Parkinson’s disease, for example, is a movement disorder known to be tied to the death of dopamine-producing neurons in the basal ganglia.)
• And in turn, the researchers speculate the difference in basal ganglia activation between the patients and healthy volunteers may be caused by inflammation, a factor now recognized as pivotal in a variety of conditions, ranging from heart disease to cancer.
These results shed some important light on the riddle of ME/CFS – information that researchers hope may eventually lead to better treatments for chronic fatigue syndrome.
* The study was conducted by Elizabeth R. Unger, James F. Jones, and Hao Tian of the Centers for Disease Control and Prevention (CDC); Andrew H. Miller and Daniel F. Drake of Emory University School of Medicine, and Giuseppe Pagnoni of the University of Modena and Reggio Emilia.
They discussed an abstract of their study – entitled “Decreased Basal Ganglia Activation in Chronic Fatigue Syndrome Subjects is Associated with Increased Fatigue” – on April 24 at the Experimental Biology Conference 2012 in San Diego.
The abstract is sponsored by the American Society for Investigative Pathology (ASIP).
Source: Based on a Federation of American Societies for Experimental Biology (FASB) news release, Apr 24, 2012