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Neural basis of abnormal response to negative feedback in unmedicated mood disorders.

ABSTRACT: Depressed individuals show hypersensitivity to negative feedback during cognitive testing, which can precipitate subsequent errors and thereby impair a broad range of cognitive abilities. We studied the neural mechanisms underlying this feedback hypersensitivity using functional magnetic resonance imaging (fMRI) with a reversal learning task that required subjects to ignore misleading negative feedback on some trials. Thirteen depressed subjects with major depressive disorder (MDD), 12 depressed subjects with bipolar disorder (BD) and 15 healthy controls participated. The MDD group, but not the BD group, demonstrated enhanced sensitivity to negative feedback compared to controls, as indicated by the rates of rule reversal following misleading negative feedback. In the control and BD groups, hemodynamic activity was significantly higher in the dorsomedial and ventrolateral prefrontal cortices during reversal shifting, and significantly lower in the right amygdala in response to negative feedback. The extent to which the amygdala showed less activity during negative feedback correlated inversely with the behavioral tendency to reverse after misleading feedback. This effect was not present in the MDD group, who also failed to recruit the prefrontal cortex during behavioral reversal. Hypersensitivity to negative feedback is present in unmedicated depressed patients with MDD. Disrupted top-down control by the prefrontal cortex of the amygdala may underlie this abnormal response to negative feedback in unipolar depression.

SUBMITTER: Taylor Tavares JV

PROVIDER: S-EPMC2745889 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Neural basis of abnormal response to negative feedback in unmedicated mood disorders.

Taylor Tavares Joana V JV Clark Luke L Furey Maura L ML Williams Guy B GB Sahakian Barbara J BJ Drevets Wayne C WC

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Depressed individuals show hypersensitivity to negative feedback during cognitive testing, which can precipitate subsequent errors and thereby impair a broad range of cognitive abilities. We studied the neural mechanisms underlying this feedback hypersensitivity using functional magnetic resonance imaging (fMRI) with a reversal learning task that required subjects to ignore misleading negative feedback on some trials. Thirteen depressed subjects with major depressive disorder (MDD), 12 depressed ...[more]

PMID: 18586109

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Project description:BackgroundMood and anxiety disorders are ubiquitous but current treatment options are ineffective for many sufferers. Moreover, a number of promising pre-clinical interventions have failed to translate into clinical efficacy in humans. Improved treatments are unlikely without better animal-human translational pipelines. Here, we translate a rodent measure of negative affective bias into humans, exploring its relationship with (1) pathological mood and anxiety symptoms and (2) transient induced anxiety.MethodsAdult participants (age = 29 ± 11) who met criteria for mood or anxiety disorder symptomatology according to a face-to-face neuropsychiatric interview were included in the symptomatic group. Study 1 included N = 77 (47 = asymptomatic [female = 21]; 30 = symptomatic [female = 25]), study 2 included N = 47 asymptomatic participants (25 = female). Outcome measures were choice ratios, reaction times and parameters recovered from a computational model of reaction time - the drift diffusion model (DDM) - from a two-alternative-forced-choice task in which ambiguous and unambiguous auditory stimuli were paired with high and low rewards.ResultsBoth groups showed over 93% accuracy on unambiguous tones indicating intact discrimination, but symptomatic individuals demonstrated increased negative affective bias on ambiguous tones [proportion high reward = 0.42 (s.d. = 0.14)] relative to asymptomatic individuals [0.53 (s.d. = 0.17)] as well as a significantly reduced DDM drift rate. No significant effects were observed for the within-subjects anxiety-induction.ConclusionsHumans with pathological anxiety symptoms directly mimic rodents undergoing anxiogenic manipulation. The lack of sensitivity to transient anxiety suggests the paradigm might be more sensitive to clinically relevant symptoms. Our results establish a direct translational pipeline (and candidate therapeutics screen) from negative affective bias in rodents to pathological mood and anxiety symptoms in humans.

Project description:Background: The clinical and etiological heterogeneity of mood disorders impede identification of effective treatments for the individual patient. This highlights a need for early neuronal and behavioral biomarkers for treatment efficacy, which can provide a basis for more personalized treatments. The present systematic review aimed to identify the most consistent neuronal and behavioral predictors of treatment efficacy on mood symptoms and cognitive impairment in mood disorders. Methods: We identified and included 60 original peer-reviewed studies investigating neuroimaging and behavioral predictors of treatment efficacy within the domains of emotional and non-emotional cognition, structural neuroimaging, and resting state functional connectivity in patients with unipolar or bipolar disorder. Results: Lower baseline responsivity in limbic regions coupled with heightened medial and dorsal prefrontal responses to emotional stimuli were the most consistent predictors of response to pharmacotherapy for depression. In contrast, heightened limbic and ventral prefrontal reactivity to emotional stimuli seemed to predict efficacy of psychological interventions. Early modulation of fronto-limbic activity and reduction in negative bias were also associated with treatment response. Better performance on non-emotional tests at baseline was relatively consistently associated with efficacy on mood symptoms, whereas the association between neural activity during non-emotional tests and treatment response was less clear. Other baseline factors associated with treatment response were greater white matter integrity, resting state functional connectivity, more prefrontal gray matter volume as well as an early increase following short administered treatment. Finally, emerging evidence indicates that baseline cognitive deficits are associated with greater chances of achieving treatment efficacy on cognition. Conclusions: Patients' profile of emotional and non-emotional cognition and neural activity-and the early treatment-associated changes in neural and cognitive function-may be useful for guiding treatments for depression. While cognitive deficits at baseline seem to improve chances of treatment efficacy on cognition, more studies of this association are urgently needed.

Dataset Information

Neural basis of abnormal response to negative feedback in unmedicated mood disorders.

Publications

Neural basis of abnormal response to negative feedback in unmedicated mood disorders.

Similar Datasets

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