Neural mechanisms of phantom limb pain

Thesis

After limb amputation, the majority of amputees report the presence of phantom limb pain (PLP), whereby chronic painful sensations are localised in the missing limb. In this thesis I assessed the potential neural mechanisms underlying PLP, with a set of experiments which evaluated a popular theory of PLP – the maladaptive plasticity model, and then explored alternative hypotheses of PLP.

First, I assessed one of the long-held, implicit assumptions of the maladaptive plasticity model – that the cortical neighbour to the hand in the primary somatosensory cortex (S1) is the lips/lower face. Controls participated in active somatotopic mapping of the upper and lower face using functional magnetic resonance imaging. Univariate and multivariate analyses indicated that the likely cortical neighbour to the hand was the upper, not lower, face. Subsequent recruitment of amputees and congenital one-handers (positive control group) found little evidence for somatotopic shifts of the upper and lower face towards the deprived hand region in amputees, with no significant associations to PLP. Conversely, congenital one-handers, who do not experience PLP, displayed gross somatotopic shifts of all facial parts tested.

Next, the role of associative learning mechanisms in PLP was explored. Specifically, a novel behavioural task was designed to assess how amputees learn about nociceptive information in relation to phantom movement. Controls indicated significant learning of probabilistic cues with movements, validating the use of the behavioural paradigm for future studies with amputees. Anecdotal results from computational modelling and quantification of expectation biases indicated idiosyncratic learning styles and preserved placebo responses in amputees. Finally, a well-replicated task used in computational psychiatry demonstrated that ‘jumping-to-conclusions’, where individuals require little sensory information before belief formation, was tentatively related to pain catastrophising.

Taken together, these results not only assessed one of the most common explanations of PLP, but also offered novel behavioural paradigms that encourage the exploration of PLP outside of S1, with the aim to improve future treatment.

Authors: Root, V

• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: phantom limb pain; primary somatosensory cortex; chronic pain; maladaptive plasticity