Pathological amygdala activation during working memory performance: Evidence for a pathophysiological trait marker in bipolar affective disorder.
Recent evidence suggests that deficits of working memory may be a promising neurocognitive endophenotype of bipolar affective disorder. However, little is known about the neurobiological correlates of these deficits. The aim of this study was to determine possible pathophysiological trait markers of bipolar disorder in neural circuits involved in working memory. Functional magnetic resonance imaging was performed in 18 euthymic bipolar patients and 18 matched healthy volunteers using two circuit-specific experimental tasks established by prior systematic neuroimaging studies of working memory. Both euthymic bipolar patients and healthy controls showed working memory-related brain activations that were highly consistent with findings from previous comparable neuroimaging studies in healthy subjects. While these patterns of brain activation were completely preserved in the bipolar patients, only the patients exhibited activation of the right amygdala during the articulatory rehearsal task. In the same task, functional activation in right frontal and intraparietal cortex and in the right cerebellum was significantly enhanced in the patients. These findings indicate that the right amygdala is pathologically activated in euthymic bipolar patients during performance of a circuit-specific working memory task (articulatory rehearsal). This pathophysiological abnormality appears to be a trait marker in bipolar disorders that can be observed even in the euthymic state and that seems to be largely independent of task performance and medication.
Gruber
Oliver
O
Centre for Translational Research in Systems Neuroscience and Clinical Psychiatry, Department of Psychiatry and Psychotherapy, Georg August University, Goettingen, Germany. ogruber@gwdg.de
Tost
Heike
H
Henseler
Ilona
I
Schmael
Christine
C
Scherk
Harald
H
Ende
Gabriele
G
Ruf
Matthias
M
Falkai
Peter
P
Rietschel
Marcella
M
D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D015415:Biomarkers; D001714:Bipolar Disorder / Q000150:complications / Q000503:physiopathology*; D001931:Brain Mapping; D004292:Dominance, Cerebral / Q000502:physiology; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology*; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
D015415:Biomarkers