Anterior cingulate activation and error processing during interferon-alpha treatment.
BACKGROUND
There has been increasing interest in the role of immunologic processes, notably cytokines, in the development of behavioral alterations, especially in medically ill patients. Interferon (IFN)-alpha is notorious for causing behavioral symptoms, including depression, fatigue, and cognitive dysfunction, and has been used to investigate the effects of cytokines on the brain.


METHODS
In the present study we assessed the effects of low-dose IFN-alpha on brain activity, using functional magnetic resonance imaging during a task of visuospatial attention in patients infected with hepatitis C virus (HCV).


RESULTS
Despite endorsing symptoms of impaired concentration and fatigue, IFN-alpha-treated patients (n = 10) exhibited task performance and activation of parietal and occipital brain regions similar to that seen in HCV-infected control subjects (n = 11). Interestingly, however, in contrast to control subjects, IFN-alpha-treated patients exhibited significant activation in the dorsal part of the anterior cingulate cortex (ACC), which highly correlated with the number of task-related errors. No such correlation was found in control subjects.


CONCLUSIONS
Consistent with the role of the ACC in conflict monitoring, ACC activation during IFN-alpha administration suggests that cytokines might increase processing conflict or reduce the threshold for conflict detection, thereby signaling the need to exert greater mental effort to maintain performance. Such alterations in ACC activity might in turn contribute to cytokine-induced behavioral changes.
Capuron
Lucile
L
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1001 Woodruff Circle, Atlanta, GA 30322, USA.
Pagnoni
Giuseppe
G
Demetrashvili
Marina
M
Woolwine
Bobbi J
BJ
Nemeroff
Charles B
CB
Berns
Gregory S
GS
Miller
Andrew H
AH
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001288:Attention / Q000187:drug effects*; D001931:Brain Mapping; D005260:Female; D006179:Gyrus Cinguli / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D006526:Hepatitis C / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation / Q000379:methods; D011930:Reaction Time / Q000187:drug effects; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use; D013028:Space Perception / Q000187:drug effects*
D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin; D010100:Oxygen