Trajectory of aberrant reward processing in patients with bipolar disorder - A longitudinal fMRI study

J Affect Disord. 2022 Sep 1:312:235-244. doi: 10.1016/j.jad.2022.06.053. Epub 2022 Jun 26.


Background: Bipolar disorder (BD), and especially the mania phenotype, is characterized by heightened reward responsivity and aberrant reward processing. In this longitudinal fMRI study, we investigated neuronal response during reward anticipation as the computed expected value (EV) and outcome evaluation as reward prediction error (RPE) in recently diagnosed patients with BD.

Methods: Eighty remitted patients with BD and 60 healthy controls (HC) underwent fMRI during which they performed a card guessing task. Of these, 41 patients and 36 HC were re-scanned after 16 months. We compared reward-related neural activity between groups at baseline and longitudinally and assessed the impact of mood relapse.

Results: Patients showed lower RPE signal in areas of the ventrolateral prefrontal cortex (vlPFC) than HC. In these regions, the HC showed decrease in RPE signal over time, which was absent in patients. Patients further exhibited decreased EV signal in the occipital cortex across baseline and follow-up. Patients who remained in remission showed normalization of the EV signal at follow-up. Baseline activity in the identified regions was not associated with subsequent relapse.

Limitations: Follow-up scans were only available in a relatively small sample. Medication status, follow-up time and BD illness duration prior to diagnosis varied.

Conclusions: Lower RPE signal in the vlPFC in patients with BD at baseline and its lack of normative reduction over time may represent a trait marker of dysfunctional reward-based learning or habituation. The increase in EV signal in the occipital cortex over time in patients who remained in remission may indicate normalization of reward anticipation activity.

Keywords: Bipolar disorder; Expected value; Longitudinal fMRI; Prediction error.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bipolar Disorder* / diagnostic imaging
  • Cerebral Cortex
  • Humans
  • Magnetic Resonance Imaging
  • Recurrence
  • Reward