The developing human pain connectome and brain dynamics of infant pain: sex differences, pain history and skin-to-skin care
Lead Research Organisation:
University College London
Abstract
Many infants need neonatal care at birth, either because they have been born prematurely or because they are unwell. Some of the most premature and unwell babies can spend months in hospital where they undergo numerous clinical procedures, many of which are tissue breaking and likely to be painful. Despite efforts to reduce the number of procedures and handling, the burden to these vulnerable individuals is considerable, particularly as they occur at a critical phase of brain development, when connections are forming between different brain regions. The developing brain requires sensory stimulation to develop normally, but if this stimulation is exaggerated or applied at inappropriate developmental stages, it can cause permanent harm. Indeed, repeated early exposure to painful procedures is associated with lasting adverse changes to the brain. The aim of this project is to understand how pain is processed in the human infant brain. We will map the structural and functional development of the brain circuits that are necessary to process pain and investigate how these are affected by the repeated tissue-damaging procedures of hospital stay. We will establish whether these circuits develop differently in males and females. Moreover, as the experience of pain is highly dependent upon what is already going on in the brain and what happens around us, we will explore how ongoing brain activity influences the response to a painful stimulus and how we can manipulate these processes with non-pharmacological interventions, such as caregiver skin-to-skin care, to reduce the pain experienced. This research project will provide the knowledge we need to alleviate infant pain and reduce any long-term adverse effects of neonatal intensive care procedures.
Technical Summary
This proposal aims to study the structural and functional development of pain networks in the human infant brain, focussing upon the dynamic interactions between brain oscillations and pain. We will record resting and noxious evoked activity in the brains of premature and term infants of 28-42 weeks corrected gestational age in the neonatal units at UCLH and St Thomas' Hospital, using electrophysiology and magnetic resonance imaging. We will: (i) map the developing human pain structural and functional networks using existing data and our own acquired diffusion weight (DWI), structural (MRI) and functional (fMRI) brain images and (ii) record brain oscillations and nociceptive event related potentials (nERPs) using non-invasive electroencephalography (EEG) to analyse the dynamics of these networks. Data will be entered into a unique open access database and will be used to test these hypotheses: 1. The pain connectome matures over the last trimester of gestation. 2. Functional pain dynamics (the interaction between brain dynamics and an incoming noxious stimulus) undergo distinct developmental changes over the perinatal period. 3. Sex differences in the developing pain connectome and functional pain dynamics are apparent from birth. 4.Pain history, that is the frequency, intensity and timing of painful events, alters the development of the pain connectome and functional pain dynamics in the newborn brain. 5. Care-giver skin-to-skin contact diminishes or alters the functional pain dynamics. The data will provide novel insights into the development of pain processing in the human brain, how these interact with ongoing brain oscillations and how they may be modified by intrinsic and contextual factors. The results will provide a brain-based rationale for designing effective methods of pain control in neonatal intensive care.
Planned Impact
The primary beneficiaries will be preterm and term infants that suffer from painful conditions or who require painful procedures as part of their clinical care.
Rates of preterm birth have globally increased accounting for approximately 11% of live births worldwide. In the UK alone about 60,000 infants are born before 37 weeks of gestation every year, and over 95,000 are cared for in neonatal units around the country because they have either been born prematurely, or full term, but sick. During intensive care, each neonate is subjected to an average of 14 noxious procedures per day, but clinical use of pain control measures remains sporadic and suboptimal. As these infants are unable to communicate their pain, we cannot easily measure or treat it. One problem is that we do not have a sufficient understanding of how pain is processed in the developing infant brain and how to distinguish the levels and time course of their pain experience. Pain is not only related to the incoming stimulus, but also depends on what is already going on in the brain and around us. By monitoring the status of the brain, we will potentially be able to time a painful intervention to a moment when the brain is less receptive and therefore reduce the impact. We will also be able to test the effect that holding a newborn in skin-to-skin contact has on the brain dynamics and consequently on the pain perception. This project will also provide new insight into pain processing in this group of individuals and provide a platform for studies of different pharmacological and non-pharmacological methods of pain relief and better patient care, therefore enhancing their quality of life.
Clinicians responsible for the care of these infants will also benefit from this research: neonatologists, paediatricians, paediatric anaesthetists and all health professionals involved in the management and treatment of pain in infants will have a better scientific basis upon which to treat infant pain. Neuroimaging protocols, especially combining multimodal imaging techniques, could ultimately identify biomarkers to be targeted therapeutically. Moreover, neuroimaging will have an invaluable screening scope in identifying those individuals at higher risk of abnormal neurodevelopment.
Families of affected infants will benefit from an increased understanding and interest in what their babies are experiencing and the drive towards better clinical management of their pain.
In the longer term, there will be benefits for society in general. Increasing evidence suggests that pain and stress in early life has long term consequences on brain development and on future pain experience in later life. Preterm infants who have experienced the most tissue breaking procedures in intensive care show the most severely decreased brain growth which has implications for their cognitive and behavioural outcomes. Furthermore, early life trauma is associated with chronic pain problems in later life. Infants who are born too young or too small and who have to spend time in intensive care undergoing numerous tissue damaging procedures will therefore benefit from this research, not only at the time but also in terms of better health and therefore quality of life over their whole lifespan. Rates of preterm birth are highest in low-income countries where access to care is most limited. In this context, skin-to-skin has already proved to reduce mortality and morbidity at discharge from the intensive care unit. Understanding the impact that skin-to-skin care has on the immediate and long-term processing of pain will add a new dimension to this no-cost intervention and help to roll it out worldwide. Considering that pain and disability are both a huge financial burden on society in terms of lost working days and the provision of care, better health outcomes for a growing subset of the population will also potentially have a large impact on society as a whole, helping to relieve this burden.
Rates of preterm birth have globally increased accounting for approximately 11% of live births worldwide. In the UK alone about 60,000 infants are born before 37 weeks of gestation every year, and over 95,000 are cared for in neonatal units around the country because they have either been born prematurely, or full term, but sick. During intensive care, each neonate is subjected to an average of 14 noxious procedures per day, but clinical use of pain control measures remains sporadic and suboptimal. As these infants are unable to communicate their pain, we cannot easily measure or treat it. One problem is that we do not have a sufficient understanding of how pain is processed in the developing infant brain and how to distinguish the levels and time course of their pain experience. Pain is not only related to the incoming stimulus, but also depends on what is already going on in the brain and around us. By monitoring the status of the brain, we will potentially be able to time a painful intervention to a moment when the brain is less receptive and therefore reduce the impact. We will also be able to test the effect that holding a newborn in skin-to-skin contact has on the brain dynamics and consequently on the pain perception. This project will also provide new insight into pain processing in this group of individuals and provide a platform for studies of different pharmacological and non-pharmacological methods of pain relief and better patient care, therefore enhancing their quality of life.
Clinicians responsible for the care of these infants will also benefit from this research: neonatologists, paediatricians, paediatric anaesthetists and all health professionals involved in the management and treatment of pain in infants will have a better scientific basis upon which to treat infant pain. Neuroimaging protocols, especially combining multimodal imaging techniques, could ultimately identify biomarkers to be targeted therapeutically. Moreover, neuroimaging will have an invaluable screening scope in identifying those individuals at higher risk of abnormal neurodevelopment.
Families of affected infants will benefit from an increased understanding and interest in what their babies are experiencing and the drive towards better clinical management of their pain.
In the longer term, there will be benefits for society in general. Increasing evidence suggests that pain and stress in early life has long term consequences on brain development and on future pain experience in later life. Preterm infants who have experienced the most tissue breaking procedures in intensive care show the most severely decreased brain growth which has implications for their cognitive and behavioural outcomes. Furthermore, early life trauma is associated with chronic pain problems in later life. Infants who are born too young or too small and who have to spend time in intensive care undergoing numerous tissue damaging procedures will therefore benefit from this research, not only at the time but also in terms of better health and therefore quality of life over their whole lifespan. Rates of preterm birth are highest in low-income countries where access to care is most limited. In this context, skin-to-skin has already proved to reduce mortality and morbidity at discharge from the intensive care unit. Understanding the impact that skin-to-skin care has on the immediate and long-term processing of pain will add a new dimension to this no-cost intervention and help to roll it out worldwide. Considering that pain and disability are both a huge financial burden on society in terms of lost working days and the provision of care, better health outcomes for a growing subset of the population will also potentially have a large impact on society as a whole, helping to relieve this burden.
Organisations
- University College London (Lead Research Organisation, Project Partner)
- Swiss Federal Institute of Technology in Lausanne (EPFL) (Collaboration)
- University College London (Collaboration)
- York University Toronto (Collaboration)
- King's College London (Collaboration, Project Partner)
- Great Ormond Street Hospital (Project Partner)
- York University (Project Partner)
Publications



Chang P
(2022)
Early Life Pain Experience Changes Adult Functional Pain Connectivity in the Rat Somatosensory and the Medial Prefrontal Cortex.
in The Journal of neuroscience : the official journal of the Society for Neuroscience

Fitzgerald M
(2020)
The Oxford Handbook of the Neurobiology of Pain

Fitzgerald M
(2021)
Encountering Pain Hearing, seeing, speaking

Georgoulas A
(2021)
Sleep-wake regulation in preterm and term infants.
in Sleep

Jones L
(2021)
The impact of parental contact upon cortical noxious-related activity in human neonates.
in European journal of pain (London, England)

Jones L
(2022)
Widespread nociceptive maps in the human neonatal somatosensory cortex.
in eLife

Laudiano-Dray MP
(2020)
Quantification of neonatal procedural pain severity: a platform for estimating total pain burden in individual infants.
in Pain
Title | Single-channel event-related potentials versus cortical microstate analysis of nociceptive responses in human neonates Item |
Description | This poster was presented at the 2022 UCL Neuroscience Symposium. This work compares the traditional event-related potential (ERP) analysis with Microstates analysis using real electroencephalographic (EEG) data from premature neonates receiving 2 identical clinically-required noxious blood tests. |
Type Of Art | Film/Video/Animation |
Year Produced | 2022 |
URL | https://figshare.com/articles/poster/Single-channel_event-related_potentials_versus_cortical_microst... |
Title | Single-channel event-related potentials versus cortical microstate analysis of nociceptive responses in human neonates Item |
Description | This poster was presented at the 2022 UCL Neuroscience Symposium. This work compares the traditional event-related potential (ERP) analysis with Microstates analysis using real electroencephalographic (EEG) data from premature neonates receiving 2 identical clinically-required noxious blood tests. |
Type Of Art | Film/Video/Animation |
Year Produced | 2022 |
URL | https://figshare.com/articles/poster/Single-channel_event-related_potentials_versus_cortical_microst... |
Description | Citation in "Cumulative procedural pain and brain development in very preterm infants: A systematic review of clinical and preclinical studies" |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in systematic reviews |
Impact | Publications used in a systematic review |
URL | https://doi.org/10.1016/j.neubiorev.2020.12.016 |
Description | Citation in "Effectiveness of technology-based interventions compared with other non-pharmacological interventions for relieving procedural pain in hospitalized neonates: A systematic review protocol" |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in systematic reviews |
Impact | Contribution to a systematic review |
URL | https://doi.org/10.11124/JBIES-21-00010 |
Description | Citation in systematic review about the use of Event Related Potentials to assess pain processing in neonates |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in systematic reviews |
URL | https://www.mdpi.com/2227-9067/8/2/58/htm |
Description | Co-chair of the EEG reliability taskforce of the EPSRC/MRC R4N Network |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | Main objective of the taskforce: to produce a white paper to provide guidelines on assessment of EEG, NIRS and fMRI reliability in the pediatric population. |
Description | Co-chair of the International Pediatric ICD-11 taskforce |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | Main objective of the taskforce: design new pediatric-specific classifications of chronic pain and recommend their inclusion to the ICD-11 definitions to the World Health Organization. Our initial perspective has been accepted for publication in Pain (IF: 7.9) |
Description | Fetal Awareness: Updated review of Research and Recommendations for Practice for Royal College of Obstetrics and Gynaecology |
Geographic Reach | National |
Policy Influence Type | Contribution to a national consultation/review |
Impact | The RCOG is currently considering how to create a version of the report for lay readers. Key findings and recommendations for obstetric practice:- Pain research to date indicates that the perception of pain requires a comprehensive network of neural connections in the brain rather than the presence or absence of a specific region or set of connections. Advances in neuroimaging have revealed the maturation of fetal brain resting state networks, which consist largely of local patterns of connectivity from approximately 28 weeks of gestation, with long range functional connectivity emerging and gradually increasing after 30 weeks of gestation. Advances in ultrasound imaging and dynamic MRI have increased the quality of recordings of fetal behaviour. While these early movements are spontaneously generated and do not require a sensory stimulus to trigger them, distinct reflex responses to innocuous sensory stimuli, such as auditory events, can be measured at 28 weeks of gestation, as spontaneous movements decline. A measurable difference between the facial responses to a noxious and an innocuous stimulation is first seen from approximately 33 weeks of gestation. At the same stage, brain activity distinguishes between the two types of stimulation. |
URL | https://www.rcog.org.uk/guidance/browse-all-guidance/other-guidelines-and-reports/fetal-awareness-up... |
Guideline Title | Guidelines for Pain Assessment and Management |
Description | Publication used to draw Sickkids (Toronto, Canada) Guidelines for Pain Assessment and Management |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Citation in clinical guidelines |
Impact | Pain management strategies recommended on the basis of the estimated severity of pain presented in the paper. |
Guideline Title | Management of Pain and Sedation in Neonates |
Description | Publication used to draw UCLH Management of Pain and Sedation in Neonates Guidelines |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Citation in clinical guidelines |
Impact | • More emphasis on non-pharmacological approach to managing pain and sedation in neonates • Introduction of tiered approach |
URL | https://www.uclh.nhs.uk/our-services/find-service/womens-health-1/neonatal-care |
Description | Collaborative Health Research Project, Co-Is Prof Fitzgerald and Dr Fabrizi |
Amount | $1,484,330 (CAD) |
Organisation | Canadian Institutes of Health Research |
Sector | Public |
Country | Canada |
Start | 07/2019 |
End | 08/2022 |
Description | Dr Jones - UCL Research Culture Award |
Amount | £1,952 (GBP) |
Organisation | University College London |
Sector | Academic/University |
Country | United Kingdom |
Start | 07/2022 |
End | 09/2022 |
Description | Dr L Jones IASP travel grant |
Amount | $1,000 (USD) |
Organisation | International Association for the Study of Pain (IASP) |
Sector | Academic/University |
Country | United States |
Start | 08/2018 |
End | 09/2018 |
Description | Dr L Jones travel grant |
Amount | £500 (GBP) |
Organisation | Physiological Society |
Sector | Charity/Non Profit |
Country | Global |
Start | 08/2018 |
End | 09/2018 |
Description | Dr Rupawala - Devices & Diagnostics TIN Pilot Data Funding Scheme |
Amount | £5,000 (GBP) |
Organisation | University College London |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2023 |
End | 03/2023 |
Description | Medical Research Foundation Emerging Leaders Prize 2020 Pain Research |
Amount | £100,000 (GBP) |
Funding ID | MRF-160-0012-ELP-FABR-C0841 |
Organisation | Medical Research Council (MRC) |
Department | Medical Research Foundation |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 04/2021 |
End | 11/2022 |
Description | travel grant |
Amount | £740 (GBP) |
Organisation | Guarantors of Brain |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2018 |
End | 09/2018 |
Title | EEG from infants with Intraventricular hemorrhage (IVH) |
Description | In collaboration with Dr Whitehead, we have built a dataset of 48 EEGs from infants with pre-term brain injury (GM-IVH) and 60 matched controls, all with permission to collect a full pain history. This is important because how infants with brain injuries process pain provides insight into the pain connectome and its plasticity, plus infants with brain injury are over-represented on intensive care and therefore disproportionately affected by extensive neonatal pain experience. |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | No |
Impact | No impact yet |
Title | EEG, behavioural and physiological recordings following a painful procedure in human neonates - open access datasets |
Description | A dataset of cortical, behavioural, and physiological responses following a single, clinically required noxious stimulus in 112 infants |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | This dataset can be used to investigate the cortical, physiological, and behavioural pain-related processing in human infants and to evaluate the impact of medical conditions and experiences upon the infant response to noxious stimuli. Furthermore, it provides information on the formation of individual pain phenotypes. The description of this dataset has been published on Scientific Data (Jones et al., 2018) and access has been requested by 23 labs across the world (Germany (2 universities), Italy (2), USA, (2) Iran (2), Romania (1), Argentina (1), UK (2), China (3), Australia (1), and Canada (1)). This dataset led to a publication from a research group at Oxford University: van der Vaart, M., Hartley, C., Baxter, L., Mellado, G.S., Andritsou, F., Cobo, M.M., Fry, R.E., Adams, E., Fitzgibbon, S. and Slater, R., 2022. Premature infants display discriminable behavioral, physiological, and brain responses to noxious and nonnoxious stimuli. Cerebral Cortex, 32(17), pp.3799-3815. |
URL | https://www.nature.com/articles/sdata2018248 |
Title | Simultaneous EEG data with passive motor stimulus from preterm infants |
Description | Preprocessed EEG data - infants were fitted with neonatal 25-electrode EEG caps (29 - 32 cm head circumference) and connected to an MR-compatible system (EASYCAP and Brain Products GmbH). EEG data preprocessing was performed using Analyzer 2 software (Brain Products GmbH), with an initial 0.2 Hz high-pass filter used to remove slow frequency drift in the EEG data. After exclusion of TRs with visible motion on the raw EEG, MR gradient artifact was cleaned using a 25 TR sliding window template subtraction. A 40 Hz lowpass and 50 Hz notch filter were applied. Electrodes with poor signal or bridged to the reference (FCz) were removed. MRI data were acquired with a 3 Tesla Philips Achieva scanner (Best, Netherlands) and a 32 channel adult head coil. Infants were scanned following feeding, during natural sleep and were fitted with ear protection (molded dental putty and adhesive earmuffs: Minimuffs, Natus Medical Inc, San Carlos CA, USA) and immobilized in a vacuum cushion (Med-Vac, CFI Medical Solutions, Fenton, MI, USA). fMRI data were acquired using T2*-weighted single-shot gradient echo echo-planar imaging (GRE-EPI) sequence (resolution: 2.5*2.5*3.25mm; 21 slices; TE: 30ms; TR: 1500ms, flip angle: 90°, lasting up to 13.5 minutes). A custom-built MR compatible robotic device (Dall'Orso et al., 2018) was fitted to the right wrist to deliver blocks of 1Hz passive right wrist flexion-extension for 7.5 to 10.5 seconds (5 to 7 TRs, up to 24 epochs of stimulation), with a variable inter-stimulus interval (21 to 24 seconds) to minimize anticipatory responses. |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | This dataset demonstrates the existence of neurovascular coupling in the neonatal brain. This dataset is publicly available so other researchers will be able to compare their results with ours or use our data to integrate their own research program. This dataset has been viewed 64 times and downloaded 2 times to 09/03/2023 and led to a pre-print currently under review in eLIFE. |
URL | https://figshare.com/articles/dataset/Simultaneous_EEG_data_with_passive_motor_stimulus_from_preterm... |
Title | Widespread nociceptive maps in the human neonatal somatosensory cortex - RAW DATA |
Description | Brain activity (fNIRS) was recorded following a clinically-required heel lance procedure or innocuous mechanical stimulation of the limbs (heel and hand) at the bedside in the neonatal unit at University College London Hospitals. Files are in .nirs format for use with Homer2 open access software. Note: Accidental triggers during recording have been removed. To revert file to original state in Homer2 would reintroduce these triggers as well as remove trigger labels. Triggers currently 'excluded' (dashed lines) during heel or hand touches, denote those during which movement of the baby was observed. |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | This dataset demonstrates that the cortical activation following a noxious stimulus is less refined than that following a tactile stimulus, suggesting that the brain still needs to develop precise cortical maps of pain in the neonatal period. This dataset is publicly available so other researchers will be able to compare their results with ours or use our data to integrate their own research program. This dataset has been viewed 242 times and downloaded 41 times to 09/03/2023 and led to a publication in eLIFE by our group (Jones, L. et al 2022). |
URL | https://figshare.com/articles/dataset/Widespread_nociceptive_maps_in_the_human_neonatal_somatosensor... |
Description | EPFL - Prof Olhede |
Organisation | Swiss Federal Institute of Technology in Lausanne (EPFL) |
Country | Switzerland |
Sector | Public |
PI Contribution | Description: This is a long-standing collaboration with Professor Sofia Olhede which is still active thanks to the support received by the Medical Research Council. Main purpose of this collaboration: application of advanced statistical and signal processing techniques to neonatal electroencephalographic recordings. My contributions to this partnership are: - Intellectual input: formulation of clinical and neuroscientific questions - access to EEG data - Expertise in neonatal EEG - Study design - Preparation of manuscripts and conference abstracts - Management fo the overall projects |
Collaborator Contribution | The contributions made by Sofia Olhede are: - Financial (part fuding a postdoc) - Expertise in statistical analysis - Expertise in advanced signal processing - Design of ad-hoc statistical and signal processing techniques - Training of postdoc in signal processing |
Impact | This collaboration is multi-disciplinary and involves: statistical sciences, electrophysiology (EEG), neonatology, neuroscience, signal processing. Current output: Open Access Publications: 1. Rupawala, M., Bucsea, O., Laudiano-Dray, M.P., Whitehead, K., Meek, J., Fitzgerald, M., Olhede, S., Jones, L. and Fabrizi, L., 2022. Developmental switch in prediction and adaptation to pain in human neonates. bioRxiv, pp.2022-04. 2. Whitehead, K., Rupawala, M., Laudiano-Dray, M.P., Meek, J., Olhede, S. and Fabrizi, L., 2022. Spontaneous activation of cortical somatosensory networks depresses their excitability in preterm human neonates. bioRxiv, pp.2022-12. |
Start Year | 2019 |
Description | KCL - developing pain connectome with MRI |
Organisation | King's College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have established a close collaboration with Dr Tomoki Arichi and Prof David Edwards from the Centre for the Developing Brain at King's College London. We are using MRI data aquired at KCL to characterise the development of the connections between pain related areas in premature neonates. Our contributions are: - Intellectual input: this project is based on our design - Experties in pain neurobiology - Data collection: the research nurse employed on this award is collecting the clinical data of the subjects in this study across different hospitals - Data analysis: a postdoc employed on this award is conducting the data analysis - Publications and conference abstracts preparation - Management of the overall project |
Collaborator Contribution | The Centre for the Developing Brain lead by Prof Edwards is the only centre in the UK to have an MR scanner on the neonatal intensive care unit. Here we have access to data and subjects. Contributions made our partners are: - Intellectual input - Data - Expertise in MRI/fMRI data processing and MRI images interpretation - Training in MRI/fMRI skills of our postdoc and myself |
Impact | This collaboration is multi-disciplinary and involves: brain imaging (MRI/fMRI), neonatology, neuroscience and signal processing. |
Start Year | 2019 |
Description | UCL Institute for Women's Health - Dr Whitehead - Perinatal Brain Injury |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Dr Whitehead was the research assistant on my MRC CDA and part-time PhD student during that time. She then obtained independent funding, moved to the UCL Institute for Women's Health and we now collaborate. We are conducting collaborative experiments investigating sleep and sensory perception in infants with perinatal brain injury. My and my research team contribution are: - Intellectual input: data discussion and interpretation - Expertise in EEG signal processing - Historical Data |
Collaborator Contribution | Dr Whitehead is carving herself a niche of expertise in perinatal brain injury and neonatal sleep so her contribution are: - Intellectual: the experiment/analysis are her ideas - Data collection and analysis - Management of the overall project |
Impact | This collaboration is multi-disciplinary and involves: electrophysiology (EEG), neuroscience of brain development, neonatology and signal processing. Current Output: Publications: 1. Rupawala, M., Bucsea, O., Laudiano-Dray, M.P., Whitehead, K., Meek, J., Fitzgerald, M., Olhede, S., Jones, L. and Fabrizi, L., 2022. Developmental switch in prediction and adaptation to pain in human neonates. bioRxiv, pp.2022-04. 2. Mistry, N., Meek, J., Fabrizi, L. and Whitehead, K., 2022. OC06: Naturally occurring tactile stimulation augments cortical activity in pre-term human infants with acquired brain injury. Clinical Neurophysiology, 135, p.e16. 3. Whitehead, K., Rupawala, M., Laudiano-Dray, M.P., Meek, J., Olhede, S. and Fabrizi, L., 2022. Spontaneous activation of cortical somatosensory networks depresses their excitability in preterm human neonates. bioRxiv, pp.2022-12. 4. Jones, L., Laudiano-Dray, M.P., Whitehead, K., Meek, J., Fitzgerald, M., Fabrizi, L. and Pillai Riddell, R., 2021. The impact of parental contact upon cortical noxious-related activity in human neonates. European Journal of Pain, 25(1), pp.149-159. 5. Georgoulas, A., Jones, L., Laudiano-Dray, M.P., Meek, J., Fabrizi, L. and Whitehead, K., 2021. Sleep-wake regulation in preterm and term infants. Sleep, 44(1), p.zsaa148. 6. Laudiano-Dray, M.P., Riddell, R.P., Jones, L., Iyer, R., Whitehead, K., Fitzgerald, M., Fabrizi, L. and Meek, J., 2020. Quantification of neonatal procedural pain severity: a platform for estimating total pain burden in individual infants. Pain, 161(6), pp.1270-1277. 7. Whitehead, K., Meek, J., Fabrizi, L. and Smith, B.A., 2020. Long-range temporal organisation of limb movement kinematics in human neonates. Clinical Neurophysiology Practice, 5, pp.194-198. |
Start Year | 2020 |
Description | UCL Medical Physics - Dr Cooper - NIRS of neonatal pain |
Organisation | University College London |
Department | Department of Medical Physics and Biomedical Engineering |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have established a close collaboration with Dr Cooper from Medical Physics here at UCL. We have used NIRS to map the response to a noxious stimulus in the neonatal brain. This complement our expertise in EEG. Our contributions are: - Intellectual input - Data collection - Expertise in neonatal NIRS recording - Expertise in NIRS data processing - Publications and conference abstracts preparation |
Collaborator Contribution | Contributions made by Dr Cooper's group are: - Intellectual input - NIRS image reconstruction and analysis. |
Impact | This collaboration is multi-disciplinary and involves: brain imaging, neonatology, neuroscience and computational modelling. Current Outcome: Open Access Publication: 1. Jones, L., Verriotis, M., Cooper, R.J., Laudiano-Dray, M.P., Rupawala, M., Meek, J., Fabrizi, L. and Fitzgerald, M., 2022. Widespread nociceptive maps in the human neonatal somatosensory cortex. Elife, 11, p.e71655. |
Start Year | 2020 |
Description | York University (Toronto, Canada) - Miss Oana Bucsea - NFCS coding |
Organisation | York University Toronto |
Country | Canada |
Sector | Academic/University |
PI Contribution | We have established a close collaboration with Prof Rebecca Pillai-Riddell and her team, including PhD student Oana Bucsea. Our contributions are: - Intellectual input - Data collection - Expertise in EEG recording - Expertise in EEG data processing - Training in EEG analysis - Publications and conference abstracts preparation |
Collaborator Contribution | Oana Bucsea is trained in the use of the Neonatal Facial Coding System (NFCS), and has started to retrospectively score the behavioural response to the clinically-required heel lance for all of our previously collected data. To date she has scored ~100 videos. Other inputs are: Intellectual input - Expertise in neonatal behavioural coding - Publications and conference abstracts preparation. |
Impact | This collaboration is multi-disciplinary and involves: electrophysiology (EEG), psychology, neonatology, neuroscience and signal processing. This collaboration led to: - two ongoing projects: 1) Investigating the impact of repeated noxious stimuli on the multidimensional pain response (lead by the team at UCL); 2) Investigating the relationship between brain and behaviour in response to a noxious procedure (lead by the Canadian team). Current Output: Open Access Publications: 1. Bucsea, O., Rupawala, M., Shiff, I., Wang, X., Meek, J., Fitzgerald, M., Fabrizi, L., Riddell, R.P. and Jones, L., 2022. Clinical thresholds in pain-related facial activity linked to differences in cortical network activation in neonates. Pain, pp.10-1097. 2. Rupawala, M., Bucsea, O., Laudiano-Dray, M.P., Whitehead, K., Meek, J., Fitzgerald, M., Olhede, S., Jones, L. and Fabrizi, L., 2022. Developmental switch in prediction and adaptation to pain in human neonates. bioRxiv, pp.2022-04. |
Start Year | 2020 |
Description | York University (Toronto, Canada) - Prof Pillai-Riddell |
Organisation | York University Toronto |
Country | Canada |
Sector | Academic/University |
PI Contribution | We have established a close collaboration with Prof Rebecca Pillai-Riddell from York University (Toronto, Canada). We are conducting collaborative experiments using electrophysiology (EEG), behaviour and physiological recordings to improve pain assessment in neonates using machine learning. Our contributions are: - Intellectual input - Data collection - Expertise in EEG recording - Expertise in EEG data processing - Training in EEG skills of the team in Canada - Publications and conference abstracts preparation |
Collaborator Contribution | This collaboration is funded by a Canadian Institutes of Health Research Collaborative Health Research Project of which Prof Pillai-Riddell is Principal Investigator. Prof Pillai-Riddell contributions are: - Financial (this collaboration pays for a full-time clinical physiology research assistant to join our group) - Intellectual input - Data collection - Expertise in neonatal behaviour - Publications and conference abstracts preparation - Overall project management |
Impact | This collaboration is multi-disciplinary and involves: electrophysiology (EEG), psychology, neonatology, neuroscience and signal processing. Current Outputs: - Award of a Canadian Institutes of Health Research Collaborative Health Research Project of 1,484,330 CAD. This project will fund a full-time clinical physiologist to join our team for 3 years. - Submission of other 2 grants (UKRI and CIHR) - Publications: 1. Laudiano-Dray, M.P., Riddell, R.P., Jones, L., Iyer, R., Whitehead, K., Fitzgerald, M., Fabrizi, L. and Meek, J., 2020. Quantification of neonatal procedural pain severity: a platform for estimating total pain burden in individual infants. Pain, 161(6), pp.1270-1277. 2. Bucsea, O., Rupawala, M., Shiff, I., Wang, X., Meek, J., Fitzgerald, M., Fabrizi, L., Riddell, R.P. and Jones, L., 2022. Clinical thresholds in pain-related facial activity linked to differences in cortical network activation in neonates. Pain, pp.10-1097. |
Start Year | 2019 |
Description | A lecture at the Third Annual Management of Chronic Pain in Children and Adolescents, Boston USA |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Lecture explaining recent research on children's pain |
Year(s) Of Engagement Activity | 2021 |
URL | https://hopkinscme.cloud-cme.com/course/courseoverview?P=0&EID=32666 |
Description | Dr Fabrizi - Chair of the Award Committe of the International Association for the Study of Pain SIG Pain in Childhood |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Dr Fabrizi is chairing the 2023 Award Committee of the IASP SIG Pain in Childhood to select the scholars for the SIG in Childhood Early Career Award and SIG in Childhood Distinguished Career Award. These are prestigious international prizes in recognition of outstanding achievement in pediatric pain research. The award recipients give a plenary lecture at the International Symposium on Pediatric Pain and receive a money prize of 1500 USD. |
Year(s) Of Engagement Activity | 2023 |
Description | Dr Fabrizi - Elected member of the Council of the Special Interest Group (SIG) on Pain in Childhood of the International Association for the Study of Pain |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Dr Fabrizi has been elected member of the SIG on Pain in Childhood through an open international vote. The objectives of the Pain in Childhood SIG are to: 1. promote education about pain in children; 2. share relevant information about children's pain control; 3. advance our ability to alleviate children's pain from an international and interdisciplinary perspective; 4. encourage research, particularly multicenter studies, and studies which focus on unique problems of pediatrics, including newborns. The main event sponsored by the SIG is the biannual International Symposium on Pediatric Pain. The International Symposium on Pediatric Pain (ISPP) is the premier international, interdisciplinary conference on pain in infants, children, and adolescents. |
Year(s) Of Engagement Activity | 2020,2021 |
URL | http://childpain.org/ |
Description | Dr Fabrizi - Invited Talk at the Versus Arthritis 4th Annual Pain Research in the UK Conference (London, UK) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Dr Fabrizi spoke abouthis work at the Versus Arthritis 4th Annual Pain Research in the UK Conference (London, UK). The outcome of this activity was (i) introduce the work of Dr Fabrizi and his colleagues to a nationwide audience |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.nottingham.ac.uk/paincentre/conferences/conference-versus-arthritis-pain-meeting.aspx |
Description | Dr Fabrizi - Invited talk at the IASP Pediatric SIG Pain Symposium (Toronto, Canada) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Dr Fabrizi was invited to speak at the IASP Pediatric SIG Pain Symposium in Toronto (Canada). The main outcome of this activity were: (i) advocate importance of study pain in neonates; (ii) communicate recent results to international audience; (iii) create international links |
Year(s) Of Engagement Activity | 2022 |
URL | https://iaspworldcongress2022.org/sessions/advances-in-pediatric-pain-prevention-and-treatment-from-... |
Description | Dr Fabrizi - Member of the Award Committe of the International Association for the Study of Pain SIG Pain in Childhood |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | I was part of the 2022 Award Committee of the IASP SIG Pain in Childhood to select the scholars for the SIG in Childhood Early Career Award and SIG in Childhood Distinguished Career Award. These are prestigious prizes in recognition of outstanding achievement in pediatric pain research. The award recipients give a plenary lecture at the International Symposium on Pediatric Pain and receive a money prize of 1500 CAD. |
Year(s) Of Engagement Activity | 2022 |
URL | http://childpain.org/ |
Description | Dr Fabrizi - Member of the Early Career Committee for the IASP Int. Symposium on Pediatric Pain 2023 (Halifax, Canada) |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Dr Fabrizi is part of the early career committee for the IASP Int. Symposium on Pediatric Pain to be held in Halifax, Canada in 2023. This is the largest International Symposium about Pediatric Pain. As part of this role Dr Fabrizi organised activities for early career participants (workshops, lunches, networking events) |
Year(s) Of Engagement Activity | 2023 |
Description | Dr Fabrizi - Member of the Scientific Committee for ISPP 2023 (Halifax, Canada) |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Dr Fabrizi is part of the scientific committee for the IASP Int. Symposium on Pediatric Pain to be held in Halifax, Canada in 2023. This is the largest International Symposium about Pediatric Pain. As part of this role Dr Fabrizi (i) contributed to the selection of the keynote speakers; (ii) symposia proposals and (iii) poster selection |
Year(s) Of Engagement Activity | 2023 |
URL | https://ispp.joyn-us.app/ |
Description | Dr Fabrizi attended a Patient and Public Involvement meeting |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Dr Fabrizi partecipated to a Patient and Public Involvement meeting to discuss research priorities. Parents identified basic science as important as direct medical research. |
Year(s) Of Engagement Activity | 2020 |
Description | Dr Jones - Trainee poster prize presentation at the 12th International Symposium on Pediatric Pain (Basel, Switzerland) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Dr L Jones was invited to give a prize lecture at the 12th International Symposium on Pediatric Pain |
Year(s) Of Engagement Activity | 2019 |
Description | Dr Jones and Ms Laudiano-Dray - teaching seminars on the UCLH neonatal wards |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Dr Jones and Ms Laudiano-Dray presented our results at the UCLH teaching seminar series. The main outcome of this activity is to directly inform healthcarers of the results of our research to improve the understanding of neonatal pain. |
Year(s) Of Engagement Activity | 2022 |
Description | Dr Jones teaching seminar for the UCLH neonatal wards (2021) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Dr Jones was invited to give a seminar about our research as part of the UCLH neonatal wards teaching seminar series. The main outcomes of this activity was: (i) inform clinical practitioners about our research and how that can affect their clinical practice; (ii) give Dr Jones the possibility to present to clinicians, improving her presentation skills to a wider audience. |
Year(s) Of Engagement Activity | 2021 |
Description | Dr L Fabrizi - Chair and speaker of virtual workshop for the International Association for the Study of Pain Virtual Series on Pain & Expo |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Dr L Fabrizi organised, chaired and talked at a virtual workshop in a high profile virtual conference series leading up to the in-person World Congress in 2021. |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.eventscribe.com/2020/IASP-Virtual-Series-on-Pain/ |
Description | Dr L Fabrizi and Prof M Fitzgerald - Participants to the Wellcome's 'Centring in on Pain' Virtual Meeting |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Supporters |
Results and Impact | Working group organised by the Wellcome Trust to facilitate interaction between established pain researchers and experts in cognitive and computational neuroscience, neurology, psychiatry and psychology to determine the potential for new interdisciplinary collaborations and approaches that will advance understanding of pain. |
Year(s) Of Engagement Activity | 2020,2021 |
Description | Dr L Jones - BBC radio 4 Woman's Hour interview |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Dr L Jones was invited to give a short radio interview regarding our recent publication demonstrating the impact of skin-to-skin care on the neonatal brain response to a painful procedure. |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.bbc.co.uk/programmes/m000my6w |
Description | Dr L Jones - Chair and speaker of workshop at the 12th International Symposium on Pediatric Pain (Basel, Switzerland) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Dr L Jones organised, chaired and talked at a workshop at the 12th International Symposium on Pediatric Pain (Basel, Switzerland) |
Year(s) Of Engagement Activity | 2019 |
Description | Dr L Jones - UCL Biosciences Postgraduate seminar |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Dr L Jones gave a seminar as part of the UCL Biosciences Postgraduate seminar series |
Year(s) Of Engagement Activity | 2019 |
Description | Dr L Jones and Ms M Laudiano-Dray 5-days training to Mount Sinai Hospital Canada |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Dr L Jones and Ms M Laudiano-Dray organised and delivered a 5-days training course to research and clinical staff at Mount Sinai Hospital, Canada. The training was paid for by our CIHR collaborative grant. |
Year(s) Of Engagement Activity | 2019 |
Description | Dr Rupawala - Poster and flash talk at the Physiological Society Meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Dr Rupawala submitted a poster for the Physiological Society Meeting Processing and Modulation of Sensory Signals: From the Periphery to the Cortex and was selected to give a flash talk. The outcome of this activity were: (i) communicate our result to the scientific community; (ii) provide experience to Dr Rupawala to present his results. |
Year(s) Of Engagement Activity | 2022 |
Description | Dr Rupawala - Poster presentation at the UCL Neuroscience Symposium in Top 10 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Dr Rupawala submitted a poster presentation at the UCL Neuroscience Symposium and was ranked in the top 10. The outcomes of this activity were: (i) Dr Rupawala recognition within the UCL Neuroscience Domain; (ii) opportunity to present results; (iii) receive feedback on work. |
Year(s) Of Engagement Activity | 2022 |
Description | Dr Rupawala oral presentation at the UCL Neuroshort Seminar Series (2021) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Other audiences |
Results and Impact | Dr Rupawala gave an oral presentation at the Neuroshort Seminar Series to the Neuroscience Community at UCL. The outcome of this presentation were: (i) introduce Dr Rupawala to the UCL Neuroscience Community; (ii) allow Dr Rupawala to practice his presentation skills. |
Year(s) Of Engagement Activity | 2021 |
Description | Drs Rupawala and Jones and Ms Laudiano-Dray poster presentations at the International Association for the Study of Pain Meeting, Toronto, Canada (2022) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Drs Jones, Rupawala and Ms Laudiano-Dray presented their research results as posters. The outcome of this activity were: (i) communicate to the pain scientific community the results from our group; (ii) networking; (iii) receive feedback on our work. |
Year(s) Of Engagement Activity | 2022 |
URL | https://iaspworldcongress2022.org/ |
Description | Hilda Tracy Lecture - Institute Translational Medicine, Liverpool University |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Other audiences |
Results and Impact | University public lecture |
Year(s) Of Engagement Activity | 2019 |
URL | https://lng.org.uk/event/itm-hilda-tracy-lecture-pain-a-lifelong-journey/ |
Description | Invited lecture - Montreal international conference on recent advances of nociceptive neuronal circuit function |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Increased international interest in our research |
Year(s) Of Engagement Activity | 2019 |
URL | https://montrealpaincircuits.com/ |
Description | Lecture at The Challenge of Chronic Pain 04 - 06 March 2019 Wellcome Genome Campus, UK |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Study participants or study members |
Results and Impact | Focusing on the translation of basic research insights into new therapies for pain |
Year(s) Of Engagement Activity | 2019 |
URL | https://coursesandconferences.wellcomegenomecampus.org/our-events/chronic-pain-2019/ |
Description | Miss Laudiano-Dray attended a Patient and Public Involvement meeting |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Miss Laudiano-Dray attended a Patient and Public Involvement meeting to discuss the information sheet for our study recruitment. The information sheet was modified according to the feedback received. |
Year(s) Of Engagement Activity | 2019 |
Description | Mss. Willers-Moore and Laudiano-Dray poster presentations at the International Association for the Study of Pain Meeting (2021) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Mss. Willers-Moore, a Master student in our lab, and Laudiano-Dray, a research nurse in our lab, were given the opportunity to attend their first ever international scientific meeting with a poster presentation about their work. The main outcome of this activity were: (i) provide experience to an early postgraduate student and clinical practitioner/research assistant in participating to an international meeting; (ii) communicate to the pain scientific community the results of Ms Willers-Moore study about the development of nociceptive responses over the last trimester of gestation; (iii) communicate to the pain scientific community the results of Ms Laudiano-Dray study about pain burden in infants with patent ductus arteriosus. |
Year(s) Of Engagement Activity | 2021 |