Encoding and Decoding of Pain Relief in the Human Brain


Type
Thesis
Change log
Abstract

The studies in this thesis explored how pain and its relief are represented in the human brain. Pain and relief are important survival signals that motivate escape from danger and search for safety, however, they are often evaluated by subjective descriptions only. Studying how humans learn and adapt to pain and relief allows objective investigation of the information processing and neural circuitry underlying these internal experiences.

My research set out to use computational learning models to provide mechanistic explanations for the behavioural and functional neuroimaging data collected in pain/relief learning experiments with independent groups of healthy human participants.

With a Pavlovian acute pain conditioning task in Experiment 1, I found that 'associability' (a form of uncertainty signal) had a crucial role in controlling the learning rates of different conditioned responses, and can be used to anatomically dissociate underlying neural systems.

Experiment 2 focused on relief learning of terminating a tonic pain stimulus, in which the priority for relief-seeking is in conflict with the general suppression of cognition and attention. I showed that associability during active learning not only controls the relief learning rate, but also correlates with endogenously modulated (reduced) ongoing pain.

This finding was confirmed in Experiment 3 using an independent active relief learning paradigm in a complex dynamic environment. Critically, both experiments showed that associability was correlated with responses in the pregenual anterior cingulate cortex (pgACC), a brain region previously implicated in aspects of endogenous pain control related to attention and controllability. This provided a potential computational account of an information-sensitive endogenous analgesic mechanism.

In Experiment 4, I explored the implications of endogenous controllability for technology-based pain therapeutics. I designed an adaptive closed-loop system that learned to control pain stimulation using decoded real-time pain representations from the brain. Subjects were shown to actively enhance the discriminability of pain only in the pgACC, and uncertainty during learning again correlated with endogenously modulated pain and were associated with pgACC responses.

Together, these studies (i) show the importance of uncertainty in controlling learning during both acute and tonic pain, (ii) describe how uncertainty also flexibly modulates pain to maximise the impact of learning, (iii) illustrate a central role for the pgACC in this process, and (iv) reveal the implications for future technology-based therapeutic systems.

Description
Date
2018-03-23
Advisors
Seymour, Ben
Lee, Michael
Keywords
pain, computational neuroscience, learning, fMRI, brain-machine interface, uncertainty, associability, pregenual anterior cingulate cortex, pgACC, reinforcement learning
Qualification
Doctor of Philosophy (PhD)
Awarding Institution
University of Cambridge
Sponsorship
Financial support was generously provided by the WD Armstrong Fund and the Cambridge Trust.