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MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder
Published on: August 11, 2015
Blunted neural responses to reward in remitted major depression: A high-density event-related potential study
Alexis E Whitton1, Pragya Kakani1, Dan Foti2
1McLean Hospital & Harvard Medical School.
Background:
Major depressive disorder (MDD) is a highly recurrent condition, and improving our understanding of the abnormalities that persist in remitted MDD (rMDD) may provide insight into mechanisms that contribute to relapse. MDD has been characterized by reward learning deficits linked to dysfunction in frontostriatal regions. Although initial behavioral evidence of reward learning deficits in rMDD has recently emerged, it is unclear whether these reflect impairments in neural reward processing that persist into remission.
Methods:
We examined behavioral reward learning and 128-channel event-related potentials (ERP) during a well-validated probabilistic reward task in 26 rMDD individuals and 34 never-depressed controls. Temporo-spatial principal components analysis (PCA) was used to separate overlapping ERP components, and group differences in neural activity in a priori regions were examined using low-resolution electromagnetic tomography (LORETA).
Results:
Individuals with rMDD displayed reduced behavioral reward learning, as well as blunted ERP amplitude to reward feedback. Importantly, the reduction in ERP amplitude occurred at a PCA factor that peaked during the time at which phasic reward feedback-related signaling - hypothesized to originate in the striatum and project to the anterior cingulate cortex (ACC) - are thought to modulate scalp-recorded activity. Consistent with this, LORETA analyses revealed reduced activity in the ACC in the rMDD group, and this blunting correlated with poorer reward learning.
Conclusion:
These findings suggest that the reward learning impairment observed in acute MDD persists into full remission and that these impairments may be attributable to abnormalities in the neural processes that support reward feedback monitoring, particularly within the ACC.
Insights
Major depressive disorder (MDD) is a recurrent condition. Reward learning deficits and neural processing abnormalities in the anterior cingulate cortex (ACC) persist even in remitted MDD (rMDD), suggesting ongoing neural dysfunction.
Area of Science:
- Neuroscience
- Psychiatry
- Cognitive Science
Background:
- Major depressive disorder (MDD) is characterized by high recurrence rates.
- Reward learning deficits and frontostriatal dysfunction are hallmarks of MDD.
- It remains unclear if these deficits persist into remission (rMDD).
Purpose of the Study:
- To investigate persistent behavioral and neural reward processing deficits in individuals with remitted MDD (rMDD).
- To explore the neural underpinnings of reward learning impairments in rMDD.
Main Methods:
- Examined behavioral reward learning and event-related potentials (ERPs) using a probabilistic reward task.
- Analyzed 128-channel ERP data with temporo-spatial principal components analysis (PCA).
- Utilized low-resolution electromagnetic tomography (LORETA) to assess neural activity in specific brain regions.
Main Results:
- Individuals with rMDD showed reduced behavioral reward learning and blunted ERP amplitude to reward feedback.
- Reduced ERP amplitude correlated with impaired reward learning and was linked to anterior cingulate cortex (ACC) activity.
- LORETA revealed decreased neural activity in the ACC among individuals with rMDD.
Conclusions:
- Reward learning impairments persist in individuals with remitted MDD (rMDD).
- Neural abnormalities in reward feedback processing, particularly in the ACC, contribute to these persistent deficits.
- Findings suggest ongoing neural dysfunction in rMDD may increase relapse risk.
