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Connections between insomnia and chronic pain: neural mechanisms of accelerated cognitive decline and brain ageing

Primary Supervisor: Professor Andrew Bagshaw, School of Psychology & Centre for Human Brain Health

Secondary supervisors: Dr Magdalena Chechlacz, School of Psychology & Centre for Human Brain Health; Prof Nicole Tang, Department of Psychology, University of Warwick

PhD project title: Connections between insomnia and chronic pain: neural mechanisms of accelerated cognitive decline and brain ageing

University of Registration: University of Birmingham

Project outline:

Ageing is associated with changes in sleep patterns and sleep architecture. Up to half of the elderly population experiences poor sleep quality or sleep less than is recommended due to difficulties in maintaining or initiating sleep, fragmentation of sleep, increased daytime napping and changes in the wake-sleep cycle. These sleep problems in older adults have been associated with poor health, brain atrophy underlying cognitive decline, as well as overall poor quality of life.

While sleep problems experienced by older adults are symptomatic of ageing itself, these might be also secondary in nature i.e., a result of other medical conditions and/or prescribed medication. For example, insomnia characterised by difficulty falling or staying asleep is commonly reported in chronic pain patients and like insomnia, the prevalence of chronic pain increases with age. The relationship between insomnia and chronic pain is thought to be bi-directional: on the one hand chronic pain is known to be associated with increased risk of insomnia or increase severity of insomnia symptoms, but on the other hand insomnia has been linked to more severe and prolonged chronic pain. In addition, patients with both chronic pain and insomnia are prone to higher levels of anxiety, depression and worse cognitive and psychosocial functioning. Finally, both sleep disruptions and chronic pain have been linked to accelerated brain ageing. The underlying neural mechanisms of insomnia are still poorly understood but increasing evidence suggests functional changes within brain networks underlying arousal and emotional control. We hypothesise that chronic pain exacerbates dysfunctions within these networks and thus results in increased severity of insomnia symptoms.

While evidence linking insomnia to grey matter atrophy is inconsistent, our recent work based on multimodal brain imaging indicates that poor sleep quality and sleep fragmentation in older adults without diagnosis of any sleep disorders results in accelerated brain ageing. The PhD project will examine the effects of insomnia with and without chronic pain on accelerated brain and cognitive ageing. In addition, the project will explore potential mechanisms of accelerated brain and cognitive ageing associated with insomnia and/or chronic pain based on the evidence linking brain changes and cognitive decline to cerebrovascular dysfunctions. Specifically, the proposed project will comprehensively examine cerebrovascular function in older adults with insomnia and/or chronic pain using magnetic resonance imaging (MRI) to measure cerebral blood flow and cerebral blood volume. The MRI measures of cerebrovascular function will be linked to estimates of accelerated brain ageing. Subsequently, the project will examine the associations between cerebrovascular dysfunctions within frontal brain regions and cognitive as well as psychosocial functioning in patients with insomnia with and without chronic pain. Finally, using resting state functional MRI the project will examine connectivity within networks regulating arousal and emotional control in older adults with insomnia with and without chronic pain.

References:

  1. Fayaz A, Croft P, Langford RM, Donaldson LJ, Jones GT. (2016). Prevalence of chronic pain in the UK: a systematic review and meta-analysis of population studies. BMJ Open, 6:e010364.
  2. Hester J, Tang NKY. (2008). Insomnia Co-Occurring with Chronic Pain: Clinical Features, Interaction, Assessments and Possible Interventions. Reviews in Pain; 2:2-7.
  3. Khalsa S, Mayhew SD, Przezdzik I, Wilson R, Hale J, Goldstone A, Bagary M, Bagshaw AP. (2016) Variability in Cumulative Habitual Sleep Duration Predicts Waking Functional Connectivity. Sleep, 39: 87–95.
  4. Khalsa S, Hale J, Goldstone A, Wilson R, Mayhew SD, Bagary M, Bagshaw AP (2017). Habitual sleep durations and subjective sleep quality predict white matter differences in the human brain. Neurobiology of Sleep and Circadian Rhythms, 3: 17-25.
  5. Facer-Childs ER, Campos BM, Middleton B, Skene DJ, Bagshaw AP. (2021) Temporal organisation of the brain’s intrinsic motor network: the relationship with circadian phenotype and motor performance. Neuroimage232 117840
  6. Facer-Childs ER, Middleton B, Skene DJ, Bagshaw AP. (2019) Resetting the late timing of ‘night owls’ has a positive impact on mental health and performance. Sleep Medicine 60 236 – 247
  7. Facer-Childs ER, Campos BM, Middleton M, Skene DJ, Bagshaw AP. (2019) Circadian phenotype impacts the brain’s resting state functional connectivity, attentional performance and sleepiness. Sleep 42(5) 1 – 12
  8. Ramduny J, Bastiani M, Huedepohl R, Sotiropoulos SN, Chechlacz M (2021). The Association Between Poor Sleep and Accelerated Brain Ageing. bioRxiv,06.16.448332.
  9. Van Someren EJW (2021). Brain mechanisms of insomnia: new perspectives on causes and consequences. Physiological Reviews, 101: 995-1046.
  10. Yu GZ, Ly M, Karim HT, Muppidi N, Aizenstein HJ, Ibinson JW (2021). Accelerated brain aging in chronic low back pain. Brain Research, 1755: 147263,

BBSRC Strategic Research Priority: Understanding the Rules of Life: Neuroscience and behaviour & Integrated Understanding of Health:Ageing

Techniques that will be undertaken during the project:

  • Programming Skills (e.g., Bash, Python, Matlab, R)
  • Advances statistical and machine learning analyses
  • Structural and perfusion/arterial spin labelling MRI
  • Clinical and experimental assessment of insomnia and chronic pain

Contact: Professor Andrew Bagshaw, University of Birmingham