Image: Basal ganglia activation in the gambling task. Left to right: Axial, coronal, and transverse sections of the brain. The top row displays the activation for the Win-Lose contrast, for the pooled sample of chronic fatigue syndrome (CFS)+control subjects, as a statistical parametric map thresholded at a p < 0.05 corrected threshold and masked with the atlas-based anatomic regions of interest portrayed in the bottom row (putamen: purple; caudate: orange; globus pallidus: turquoise) (Photo courtesy of Plos one).
A neuroimaging study has demonstrated that patients with chronic fatigue syndrome may have reduced responses, compared with healthy control study participants, in a region of the brain connected with fatigue. These findings suggest that chronic fatigue syndrome is associated with alterations in the brain involving brain circuits that control motor activity and motivation.
Compared with healthy controls, patients with chronic fatigue syndrome had less activation of the basal ganglia, as measured by functional magnetic resonance imaging (fMRI). This decrease of basal ganglia activity was also associated with the severity of fatigue symptoms.
According to the US Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA), chronic fatigue syndrome is a debilitating and complex disorder characterized by intense fatigue that is not improved by bed rest and that may be exacerbated by mental stress or exercise.
The findings were published May 23, 2014, in the journal PLOS One
. “We chose the basal ganglia because they are primary targets of inflammation in the brain,” said lead author Andrew Miller, MD, a professor of psychiatry and behavioral sciences at Emory University School of Medicine (Atlanta, GA, USA). “Results from a number of previous studies suggest that increased inflammation may be a contributing factor to fatigue in CFS patients, and may even be the cause in some patients.”
The study was a collaboration among researchers at Emory University School of Medicine, the CDC’s Chronic Viral Diseases Branch, and the University of Modena and Reggio Emilia (Modena, Italy). The basal ganglia are structures deep within the brain, thought to be responsible for control of movements and responses to rewards as well as cognitive functions. Several neurologic disorders involve dysfunction of the basal ganglia, including, for example, Huntington’s and Parkinson’s disease.
In earlier published research by Emory researchers, people taking interferon alpha as a treatment for hepatitis C, which can trigger severe fatigue, also demonstrated reduced activity in the basal ganglia. Interferon alpha is a protein naturally produced by the body, as part of the inflammatory response to viral infection. Inflammation has also been linked to fatigue in other groups such as breast cancer survivors.
“A number of previous studies have suggested that responses to viruses may underlie some cases of CFS,” Dr. Miller said. “Our data support the idea that the body’s immune response to viruses could be associated with fatigue by affecting the brain through inflammation. We are continuing to study how inflammation affects the basal ganglia and what effects that has on other brain regions and brain function. These future studies could help inform new treatments.”
Treatment implications might include the potential utility of medications to alter the body’s immune response by suppressing inflammation, or providing agents that enhance basal ganglia function, according to Dr. Miller. The researchers compared 18 patients diagnosed with chronic fatigue syndrome with 41 healthy volunteers. The 18 patients were recruited based on an initial telephone survey followed by extensive clinical evaluations. The clinical evaluations, which came in two phases, were completed by hundreds of Georgia (USA) residents.
Individuals who have major depression or who were taking antidepressants were excluded from the imaging study, although those with anxiety disorders were not. For the brain imaging portion of the study, participants were told they would win one dollar if they accurately guessed whether a preselected card was red or black. After they made a guess, the color of the card was revealed, and at that point researchers measured blood flow to the basal ganglia.
The key measurement the researchers examined was just how big was the disparity in activity between a win or a loss. Participants’ scores on a survey gauging their degrees of fatigue were tied to the difference in basal ganglia activity between winning and losing. Those with the most fatigue had the smallest changes, particularly in the right caudate and the right globus pallidus, both parts of the basal ganglia.
Emory University School of Medicine
US Centers for Disease Control and Prevention
University of Modena and Reggio Emilia