Neural abnormalities during cognitive generation of affect in treatment-resistant depression
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Updated: Aug 30, 2026

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Published on: March 14, 2025
Veena Kumari1, Martina T Mitterschiffthaler, John D Teasdale
1Section of Cognitive Psychopharmacology, Institute of Psychiatry, King's College, London, UK.
Background:
Dysfunctions in brain regions known to be involved in affect and mood states are thought to be implicated in depression and may have a role in determining the type and symptoms of this illness.
Methods:
Functional magnetic resonance imaging was used to elucidate neural correlates of cognitive generation of affect, using a previously published paradigm of evoking affect with picture-caption pairs, in patients with unipolar, treatment-resistant depression.
Results:
Compared with control participants, patients showed relatively decreased response in the anterior cingulate (rostral; right) with both negative and positive picture-caption pairs and in the medial frontal gyrus and hippocampus (all left) with positive picture-caption pairs. They demonstrated increased response in the inferior (right) and middle temporal gyri (left) with negative picture-caption pairs, and in the parahippocampal gyrus (right), inferior frontal gyrus (left), subgenual cingulate (right), striatum (right), and brain stem (left) with positive picture-caption pairs.
Conclusions:
Reduced medial/middle prefrontal and hippocampal activity may account for positive affect disturbances and temporal lobe hyperactivity for negative affect disturbances in treatment-resistant depression. The results also corroborate previous observations from resting positron emission tomography studies and further elucidate the association between hypoactive rostral cingulate and nonresponsiveness to treatment in depression.
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