Abstract

The dynamic modulation of instrumental behaviour by conditioned Pavlovian cues is an important process in decision-making. Patients with major depressive disorder (MDD) are known to exhibit mood-congruent biases in information processing, which may occur due to Pavlovian influences, but this hypothesis has never been tested directly in an unmedicated sample. To address this we tested unmedicated MDD patients and healthy volunteers on a computerized Pavlovian-Instrumental Transfer (PIT) task designed to separately examine instrumental approach and withdrawal actions in the context of Pavlovian appetitive and aversive cues. This design allowed us to directly measure the degree to which Pavlovian cues influence instrumental responding. Depressed patients were profoundly influenced by aversive Pavlovian stimuli, to a significantly greater degree than healthy volunteers. This was the case for instrumental behaviour both in the approach condition (in which aversive Pavlovian cues inhibited ‘go’ responses), and in the withdrawal condition (in which aversive Pavlovian cues facilitated ‘go’ responses). Exaggerated aversive PIT provides a potential cognitive mechanism for biased emotion processing in major depression. This finding also has wider significance for the understanding of disrupted motivational processing in neuropsychiatric disorders.

Highlights

  • Human behaviour automatically adapts to suit rapidly-changing situational demands[1]

  • Animal studies have contributed a rich understanding of the neurobiology of Pavlovian influences on instrumental behaviour[9,10,11]

  • There were no differences between patients and controls on demographic characteristics, but patients differed significantly from controls on depression and anhedonia scales (HAM-D, BDI, and SHAPS)

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Summary

Introduction

Human behaviour automatically adapts to suit rapidly-changing situational demands[1]. A rat might encode the association between a lever press and food access (instrumental) and separately learn passively that a flash of light predicts shock delivery, irrespective of any lever press (Pavlovian) These processes are dissociable[8]. Recent studies have employed comparable PIT paradigms in humans[6,14,15,16], suggesting that the circuits driving this process are similar in humans and animals These studies have begun to explore in more detail the effects of aversive Pavlovian stimuli on instrumental behaviour, implicating the ventromedial prefrontal cortex and caudate in behavioural suppression[14], as well as the serotonergic system, which may play a larger role in aversive than appetitive PIT15

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