Abnormal neural response to feedback on planning and guessing tasks in patients with unipolar depression

Abstract

Background. It has been suggested that patients with unipolar depression show abnormal responses to negative feedback in the performance of cognitive tasks. Positron emission tomography (PET) has previously identified blood flow abnormalities in depressed patients during cognitive performance. We have also used PET to identify regions where there is differential neural response to performance feedback in normal volunteers. In this study we aimed to test the hypothesis that blood flow in these regions, the medial caudate and ventromedial prefrontal cortex, would be abnormal in depressed patients. Methods. Six patients with unipolar depression and six matched controls were scanned using PET while performing cognitive tasks in the presence and absence of feedback. Results. Compared with controls, depressed patients failed to show significant activation in the medial caudate and ventromedial orbitofrontal cortex. Blood flow was lower and a differential response, observed in normals, under different task and feedback conditions was not seen in the patients. Discussion. The findings suggest that the behavioural response to feedback in depressed patients is associated with an abnormal neural response within the medial caudate and ventromedial orbitofrontal cortex, regions implicated in reward mechanisms. We argue that the observed abnormalities may depend on a combination of psychological factors, with both cognitive and emotive components.

The effect of trial-to-trial feedback on the error-related negativity and its relationship with anxiety

“…For example, studies that have assessed the ERN in other psychiatric disorders, such as depression and substance abuse, have utilized only speeded response tasks with trial-to-trial feedback (Chiu & Deldin, 2007;Compton et al, 2008;Franken, van Strien, Franzek, & van de Wetering, 2007;Holmes & Pizzagalli, 2008;Schrijvers et al, 2008;Schrijvers et al, 2009). Because behavioral studies indicate that individuals with these psychiatric disorders are especially sensitive to negative feedback (Beats, Sahakian, & Levy, 1996;Elliott, Sahakian, Herrod, Robbins, & Paykel, 1997;Elliott, Sahakian, Michael, Paykel, & Dolan, 1998;Garavan & Stout, 2005;Steffens, Wagner, Levy, Horn, & Krishnan, 2001), increased error-related brain activity in depression might be evident only in tasks that present trial-to-trial performance feedback. This would lead to an intriguing set of results: Although both anxiety and depressive disorders might be characterized by increased error-related brain activity, the context in which hyperactive response monitoring is observed may differentiate the disorders.…”

Event-related functional magnetic resonance imaging of reward-related brain circuitry in children and adolescents

“…Abnormalities in cerebral blood flow and metabolism have been found in the basal ganglia and OFC of patients with major depression (see Drevets 2000 for review; Elliott et al 1998;Lafer et al 1997). Bechara et al (2000; have performed a number of gambling studies which have found poorer performance for participants with medial OFC lesions; these patients tend to make choices that lead to sporadic large rewards but overall lead to heavy losses.…”

“…Identification of specific elements of the reward system has become well established through electrophysiological studies in non-human primates, which have observed single-cell firing rates modulated by reward within the basal ganglia, ventral tegmental area, nucleus accumbens, amygdala, orbital-frontal and prefrontal cortex ( Knutson et al 2000;Thut et al 1997); abstract rewards such as video-game performance (Koepp et al 1998); simple feedback signals (Elliott et al 1997;Elliott et al 1998); and even faces (Aharon et al 2001). Many of these regions have also been linked to clinical pathologies related to gambling, depression, and substance abuse (Bechara et al 1994;Drevets 2000;Lafer et al 1997;Leshner and Koob 1999).…”

Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex

“…Results of these studies revealed resting abnormalities in the dorsolateral, ventrolateral, and medial aspects of the prefrontal cortex and the anterior cingulate, blunted responses in the anterior cingulate and medial prefrontal cortex to behavioral and pharmacological challenges, and abnormalities localized to the orbitofrontal cortex (100,101). Lower activity in the striatum of depressed patients in the resting state and in response to a reaction-time task and feedback have also been reported (102,103).…”