Safety learning, avoidance behaviour, and ventromedial prefrontal circuits

 

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This is one of two research projects studying the generation and regulation of fear responses. The University of Melbourne is the home institution for this project. View the KU Leuven-based partner project.

Applications for these projects are no longer being accepted

Despite growing interest in the role of ‘safety signals’ and their contribution to adaptive and maladaptive forms of fear regulation, safety learning remains poorly understood. Additionally, it remains unknown as to how safety signals correspond to the inhibition of avoidance behaviour, a behavioural pattern of immense clinical relevance. Human neuroimaging investigations emphasise an extended neural circuitry centred on the ventromedial prefrontal cortex (vmPFC) as a key mediator of the inhibitory properties of safety signals.

However, these studies rely on suboptimal models of inhibitory learning and could be better addressed via models of Pavlovian ‘conditioned inhibition’ – a learning process where the true inhibitory properties of safety signals can be formally tested. Little is yet known about how avoidance learning manifests in functional brain activity, especially in relation to safety learning via conditioned inhibition.

The goal of this project will be to develop novel experimental models of conditioned inhibition, with direct translatability to brain functional magnetic resonance imaging (fMRI). In the project’s first phase (KUL), a novel experimental paradigm will be validated in order to formally examine the fear inhibitory properties of learned safety signals across autonomic, behavioural and subjective domains.

This work will then be translated to ultra-high field neuroimaging investigations (UOM) in order to characterise its extended neural circuitry, with emphasis on the vmPFC, both in healthy and clinically anxious help-seeking participants.

Project goals

The objective of the project will be to translate the experimental design and insights of the project on Safety learning, reward-prediction error and midbrain-striatal circuits to a novel investigation of the underlying neural circuitry of safety learning via RPE using ultra-high field functional magnetic resonance imaging (UHF fMRI).

Threat omission RPEs, generated via the blocking experiment, will map onto the selective engagement of midbrain-striatal circuitry, with prominent involvement of the ventral tegmental area (VTA) and nucleus accumbens (NAcc). The magnitude of differential activation and connectivity of these regions will predict individual differences in physiological and cognitive responses to the RPE-driven safety signal vs blocked CS combination.

Supervision team

KU Leuven: Bram Vervliet

The University of Melbourne: Professor Ben Harrison

Who we are looking for

We are seeking a PhD candidate with the following skills:

  • Demonstrated experience in the field of health and or psychological sciences.
  • Demonstrated experience in behavioural sciences.
  • Demonstrated ability to work independently and as part of a team.
  • Demonstrated time and project management skills.
  • Demonstrated ability to write research reports or other publications to a publishable standard (even if not published to date).
  • Excellent written and oral communication skills.
  • Demonstrated organisational skills, time management and ability to work to priorities.
  • Demonstrated problem-solving abilities.

Further details

The PhD candidate will benefit from a world-class graduate research training experience, that will include exposure to the broader research environments of KU Leuven and The University of Melbourne. In addition, they will be provided access to the broader graduate research support mechanisms provided by each institution, including early career research networks, graduate research training opportunities and support services. The candidate will be supported to attend local and international research conferences, where appropriate, and will be actively connected to the supervisors’ broader research networks in  order to facilitate future career development.

Professor Ben Harrison is Professor of Cognitive and Clinical Neuroscience and holds dual appointments in the Department of Psychiatry (Deputy Head) and Melbourne Neuropsychiatry Centre (Deputy Scientific Director). Over the past decade, Ben has established the 'Depression and Anxiety Neuroscience' program at UoM: a research program devoted to the neuroscience of affective processes and their role in mood and anxiety disorders – the most common form of mental illness. His team conducts experimental functional neuroimaging research in healthy and clinical populations and has a central interest in the capacity for neuroimaging to inform treatment outcome prediction. This work has been continually supported by NHMRC fellowships and project grants.

Professor Bram Vervliet directs the laboratory of Brain Research of Affective Mechanisms and more than a decade ago, he founded the European network of human fear conditioning. Building on this unique combination of skills and theoretical expertise, his team now conducts translational research with behavioural, psychophysiological and neuroimaging measurements in healthy individuals, anxiety patients, and rodents, to elucidate pathological mechanisms and optimize psychotherapeutic treatments for clinical anxiety.

This PhD project will be based at the University of Melbourne with a minimum 12-month stay at the KU Leuven.

The candidate will be enrolled in the PhD program at the Department of Psychiatry at the University of Melbourne and in the PhD program at the Faculty of Psychology and Educational Sciences at KU Leuven.

Applications for these projects are no longer being accepted

First published on 1 February 2022.

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