Decreased activation of lateral orbitofrontal cortex during risky choices under uncertainty is associated with disadvantageous decision-making and suicidal behavior.

Decision-making impairment has been linked to orbitofrontal cortex lesions and to different disorders including substance abuse, aggression and suicidal behavior. Understanding the neurocognitive mechanisms of these impairments could facilitate the development of effective treatments. In the current study, we aimed to explore the neural and cognitive basis of poor decision-making ability associated with the vulnerability to suicidal behavior, a public health issue in most western countries. Twenty-five not currently depressed male patients, 13 of whom had a history of suicidal acts (suicide attempters) and 12 of whom had none (affective controls), performed an adapted version of the Iowa Gambling Task during functional Magnetic Resonance Imaging. Task-related functional Regions-of-Interest were independently defined in 15 male healthy controls performing the same task (Lawrence et al., 2009). In comparison to affective controls, suicide attempters showed 1) poorer performance on the gambling task 2) decreased activation during risky relative to safe choices in left lateral orbitofrontal and occipital cortices 3) no difference for the contrast between wins and losses. Altered processing of risk under conditions of uncertainty, associated with left lateral orbitofrontal cortex dysfunction, could explain the decision-making deficits observed in suicide attempters. These impaired cognitive and neural processes may represent future predictive markers and therapeutic targets in a field where identification of those at risk is poor and specific treatments are lacking. These results also add to our growing understanding of the role of the orbitofrontal cortex in decision-making and psychopathology.