Madeleine Verriotis | University College London (original) (raw)

Papers by Madeleine Verriotis

eLife, Apr 22, 2022

Topographic cortical maps are essential for spatial localisation of sensory stimulation and gener... more Topographic cortical maps are essential for spatial localisation of sensory stimulation and generation of appropriate task-related motor responses. Somatosensation and nociception are finely mapped and aligned in the adult somatosensory (S1) cortex, but in infancy, when pain behaviour is disorganised and poorly directed, nociceptive maps may be less refined. We compared the topographic pattern of S1 activation following noxious (clinically required heel lance) and innocuous (touch) mechanical stimulation of the same skin region in newborn infants (n = 32) using multioptode functional near-infrared spectroscopy (fNIRS). Within S1 cortex, touch and lance of the heel elicit localised, partially overlapping increases in oxygenated haemoglobin concentration (Δ[HbO]), but while touch activation was restricted to the heel area, lance activation extended into cortical hand regions. The data reveals a widespread cortical nociceptive map in infant S1, consistent with their poorly directed pain behaviour. Editor's evaluation This paper is of interest to developmental neuroscientists who study the early stages of cortical maturation and specialization, particularly in the context of somatosensory and pain system development. The authors suggest that, relative to the infant touch somatotopic map, the infant nociceptive map is more widespread and poorly localised, consistent with infants' poorly directed pain behaviour.

Oxford University Press eBooks, Jun 1, 2021

Pain reports, 2020

Introduction: Multimodal characterisation with questionnaires, Quantitative Sensory Testing (QST)... more Introduction: Multimodal characterisation with questionnaires, Quantitative Sensory Testing (QST), and neuroimaging will improve understanding of neuropathic pain (NeuP) in adolescents. Magnetic resonance imaging (MRI) data in adolescents with NeuP are limited, and the perceived practical or ethical burden of scanning may represent a barrier to research. Objective: To determine the feasibility of MRI scanning in adolescents with moderate-severe NeuP, with respect to consent rate, postscan acceptability, and data quality. Methods: This prospective cohort study evaluating questionnaires and QST recruited adolescents aged 10 to 18 years with clinically diagnosed NeuP from a tertiary clinic. Eligible adolescents aged 11 years and older could additionally agree/decline an MRI scan. After the scan, families rated discomfort, perceived risk, and acceptability of current and future MRI scans (0-10 numerical rating scales). Head motion during scanning was compared with healthy controls to assess data quality. Results: Thirty-four families agreed to MRI (72% recruitment), and 21 adolescents with moderate-severe pain (average last week 6.7 6 1.7; mean 6 SD) and with neuropathic QST profiles were scanned. Three adolescents reported positional or noise-related discomfort during scanning. Perceived risk was low, and acceptability of the current scan was high for parents (range [median]: 7 to 10/10 [10]) and adolescents (8-10/10 [10]). Willingness to undergo a future research scan was high for parents (7-10/10 [10]) and adolescents (5-10/10 [10]) and did not differ from future scans for clinical purposes. Mean head motion during resting state functional MRI did not differ from control adolescents. Conclusion: Research MRI is feasible and acceptable for many adolescents with moderate-severe NeuP.

ENeuro, Mar 1, 2016

Near-infrared spectroscopy (NIRS) and electroencephalography (EEG) have recently provided fundame... more Near-infrared spectroscopy (NIRS) and electroencephalography (EEG) have recently provided fundamental new information about how the newborn brain processes innocuous and noxious somatosensory information. However, results derived independently from these two techniques are not entirely consistent, raising questions about the relationship between hemodynamic and electrophysiological responses in the study of touch and pain processing in the newborn. To address this, we have recorded NIRS and EEG responses simultaneously for the first time in the human infant following noxious (time-locked clinically required heel lances) and innocuous tactile cutaneous stimulation in 30 newborn infants. The results show that both techniques can be used to record quantifiable and distinct innocuous and noxious evoked activity at a group level in the newborn cortex. Noxious stimulation elicits a peak hemodynamic response that is 10-fold larger than that elicited by an innocuous stimulus (HbO 2 : 2.0 vs 0.3 M) and a distinct nociceptive-specific N3P3 waveform in electrophysiological recordings. However, a novel single-trial analysis revealed that hemodynamic and electrophysiological responses do not always co-occur at an individual level, although when they do (64% of noxious test occasions), they are significantly correlated in magnitude. These data show that, while hemodynamic and electrophysiological touch and pain brain activity in newborn infants are comparable in group analyses, important individual differences remain. These data indicate that integrated and multimodal brain monitoring is required to understand central touch and pain processing in the newborn.

NeuroImage, Sep 1, 2018

In adults, there are differences between male and female structural and functional brain connecti... more In adults, there are differences between male and female structural and functional brain connectivity, specifically for those regions involved in pain processing. This may partly explain the observed sex differences in pain sensitivity, tolerance, and inhibitory control, and in the development of chronic pain. However, it is not known if these differences exist from birth. Cortical activity in response to a painful stimulus can be observed in the human neonatal brain, but this nociceptive activity continues to develop in the postnatal period and is qualitatively different from that of adults, partly due to the considerable cortical maturation during this time. This research aimed to investigate the effects of sex and prematurity on the magnitude and spatial distribution pattern of the long-latency nociceptive event-related potential (nERP) using electroencephalography (EEG). We measured the cortical response time-locked to a clinically required heel lance in 81 neonates born between 29 and 42 weeks gestational age (median postnatal age 4 days). The results show that heel lance results in a spatially widespread nERP response in the majority of newborns. Importantly, a widespread pattern is significantly more likely to occur in females, irrespective of gestational age at birth. This effect is not observed for the short latency somatosensory waveform in the same infants, indicating that it is selective for the nociceptive component of the response. These results suggest the early onset of a greater anatomical and functional connectivity reported in the adult female brain, and indicate the presence of pain-related sex differences from birth.

Current Biology, Dec 1, 2017

Highlights d Infant pain behavior and nociceptive brain activity are generally correlated d Stres... more Highlights d Infant pain behavior and nociceptive brain activity are generally correlated d Stress disrupts the relationship between infant pain brain activity and behavior d Stress is associated with increased nociceptive brain activity, but not behavior d Stress is an important factor when assessing infant pain experience

bioRxiv (Cold Spring Harbor Laboratory), Jul 30, 2021

Topographic cortical maps are essential for spatial localisation of sensory stimulation and gener... more Topographic cortical maps are essential for spatial localisation of sensory stimulation and generation of appropriate task-related motor responses. Somatosensation and nociception are finely mapped and aligned in the adult somatosensory (S1) cortex, but in infancy, when pain behaviour is disorganised and poorly directed, nociceptive maps may be less refined. We compared the topographic pattern of S1 activation following noxious (clinically required heel lance) and innocuous (touch) mechanical stimulation of the same skin region in newborn infants (n=32) using multi-optode functional near-infrared spectroscopy (fNIRS). Signal to noise ratio and overall activation area did not differ with stimulus modality. Within S1 cortex, touch and lance of the heel elicit localised, partially overlapping increases in oxygenated haemoglobin (HbO), but while touch activation was restricted to the heel area, lance activation extended into cortical hand regions. The data reveals a widespread cortical nociceptive map in infant S1, consistent with their poorly directed pain behaviour. Introduction .

Doctoral thesis, UCL (University College London)., Jan 28, 2012

Previous research has shown that in two‐dimensional environments, ‘place cells’ and ‘grid cells’ ... more Previous research has shown that in two‐dimensional environments, ‘place cells’ and ‘grid cells’ in the hippocampal formation comprise two units of O’Keefe and Nadel’s (1978) ‘cognitive map’, coding for the rat’s present location and for metric distance information, respectively. Since the world is three‐dimensional, an important question is whether the cognitive map is also volumetric. To explore this issue, place and grid cells were recorded from rats as they shuttled up and down between two ends of a spiral staircase (the ‘helical track’), allowing the same horizontal locations to be sampled at different vertical levels. Using this novel paradigm, it was possible to investigate whether place and grid cell receptive fields are globular or planar. The first experiment demonstrated that place fields extended in the vertical, as well as horizontal, dimension, suggesting that they were globular. However, the vertical extent was larger than the horizontal extent, suggesting either a coarser representation of height, or contextual modulation of fields in the vertical dimension, in the absence of metric vertical distance. Both possibilities imply that the cognitive map is anisotropic (not uniform in all dimensions). The second set of experiments involved probe trials that showed that both distal and local cues influence place fields in the vertical dimension. The third experiment demonstrated that grid cells produced several subfields on the helical track that, similar to the place fields, were vertically elongated. However, they were more elongated than place fields, and showed no vertical periodicity, suggesting the lack of metric vertical information. Overall, these observations suggest that three‐dimensional space is anisotropically represented in the rat brain as a contextually modulated flat map, in which only the current navigation plane is metrically represented. Due to the complexity of a truly three‐dimensional representation, an anisotropic representation is likely in all surface‐navigating animals including humans.

Behavioral and Brain Sciences, Oct 1, 2013

The study of spatial cognition has provided considerable insight into how animals (including huma... more The study of spatial cognition has provided considerable insight into how animals (including humans) navigate on the horizontal plane. However, the real world is three-dimensional, having a complex topography including both horizontal and vertical features, which presents additional challenges for representation and navigation. The present article reviews the emerging behavioral and neurobiological literature on spatial cognition in non-horizontal environments. We suggest that three-dimensional spaces are represented in a quasiplanar fashion, with space in the plane of locomotion being computed separately and represented differently from space in the orthogonal axisa representational structure we have termed "bicoded." We argue that the mammalian spatial representation in surface-travelling animals comprises a mosaic of these locally planar fragments, rather than a fully integrated volumetric map. More generally, this may be true even for species that can move freely in all three dimensions, such as birds and fish. We outline the evidence supporting this view, together with the adaptive advantages of such a scheme.

Scientific Data, Jul 27, 2023

Scientific Data, Nov 13, 2018

We present a dataset of cortical, behavioural, and physiological responses following a single, cl... more We present a dataset of cortical, behavioural, and physiological responses following a single, clinically required noxious stimulus in a neonatal sample. Cortical activity was recorded from 112 neonates (29-47 weeks gestational age at study) using a 20-channel electroencephalogram (EEG), which was time-locked to a heel lance. This data is linked to pain-related behaviour (facial expression), physiology (heart rate, oxygenation) and a composite clinical score (Premature Infant Pain Profile, PIPP). The dataset includes responses to non-noxious sham and auditory controls. The infants' relevant medical and pain history was collected up to the day of the study and recorded in an extensive database of variables including clinical condition at birth, diagnoses, medications, previous painful procedures, injuries, and selected maternal information. 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. Design Type(s) observational design Measurement Type(s) brain activity measurement • behavioral response to pain Technology Type(s) electroencephalography • observational method Factor Type(s) biological sex • gestational age • age • experimental condition Sample Characteristic(s) Homo sapiens

Scientific Reports, Jun 1, 2016

Newborn human infants display robust pain behaviour and specific cortical activity following noxi... more Newborn human infants display robust pain behaviour and specific cortical activity following noxious skin stimulation, but it is not known whether brain processing of nociceptive information differs in infants and adults. Imaging studies have emphasised the overlap between infant and adult brain connectome architecture, but electrophysiological analysis of infant brain nociceptive networks can provide further understanding of the functional postnatal development of pain perception. Here we hypothesise that the human infant brain encodes noxious information with different neuronal patterns compared to adults. To test this we compared EEG responses to the same time-locked noxious skin lance in infants aged 0-19 days (n = 18, clinically required) and adults aged 23-48 years (n = 21). Timefrequency analysis revealed that while some features of adult nociceptive network activity are present in infants at longer latencies, including beta-gamma oscillations, infants display a distinct, long latency, noxious evoked 18-fold energy increase in the fast delta band (2-4 Hz) that is absent in adults. The differences in activity between infants and adults have a widespread topographic distribution across the brain. These data support our hypothesis and indicate important postnatal changes in the encoding of mechanical pain in the human brain.

Neuroscience, Dec 1, 2016

Pain, Dec 15, 2020

Pain descriptors did not differ between male (n=23) and female (n=43) adolescents with neuropathi... more Pain descriptors did not differ between male (n=23) and female (n=43) adolescents with neuropathic pain or CRPS. (A) Total scores on the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS, 0-24) (B) Average pain intensity during the last week reported on a numerical rating scale in the S-LANSS were consistent with measures on a 0-10cm VAS (Fig. 1) and indicated moderate-severe pain in both males and females (C) Total scores for sensory (0-33) and affective (0-12) pain descriptors reported on the McGill Pain Questionnaire were variable but did not differ between males and females. Data points = individual values; bars = median [IQR]. (D) Total S-LANSS scores correlated more strongly with McGill sensory (R 2 =0.22) than affective scores (R 2 =0.11). Data points = individual values. Solid lines=linear regression; dotted lines = 95%CI.

Paediatrics and International Child Health, Jan 22, 2020

Background: In the wake of the Ebola virus disease (EVD) epidemic in Sierra Leone, secondary care... more Background: In the wake of the Ebola virus disease (EVD) epidemic in Sierra Leone, secondary care facilities faced an increase in admissions with few members of medical staff available to assess and treat patients. This led to long waiting times in hospital outpatient departments. The study was undertaken in the outpatient department of Ola During Children's Hospital (the tertiary paediatric hospital for Sierra Leone) in the period immediately following the EVD epidemic of 2014-2015. Aims: This retrospective analysis of operational programme data aimed to assess whether a quality-improvement approach and task-sharing between medical and nursing staff improved the quality of triage and the timeliness of care. Methods: All staff working in the outpatient department were offered a 4-week training course, followed by on-the-job supervision and support for 6 months. Nurses who successfully completed the course were given responsibility for the initial assessment of sick patients and for prescribing and giving initial treatment. Data were collected at three points: before intervention and at 3 and 6 months after initiation of the intervention. All children presenting to the hospital for medical attention between 0800 and 1400 Monday to Friday were included. Triage assessment by the outpatient nurse was compared to that made by a clinically experienced observer, and the time taken for each child to be triaged, assessed and given initial treatment was recorded. Results: Between months 0 and 6 of the intervention, detection of emergency signs by the triage nurse improved from 30% to 100%, and detection of priority signs improved from 34% to 100%. For children presenting with emergency signs, the median time between triage and full assessment improved from 57 minutes before intervention to 17 minutes at 3 months and 5 minutes at 6 months (p < 0.0005). For the same group, median time between triage and first antibiotic or antimalarial treatment improved from 220 minutes before intervention to 40 minutes at 3 months and 18 minutes at 6 months (p = 0.006). Conclusion: The results indicate that, with appropriate training and support, extending the emergency assessment and treatment of sick children to nursing staff in West African hospitals may improve the accuracy of triage and the time to assessment and treatment of children presenting with signs of serious illness.

Archives of Disease in Childhood, 2013

Previous research has shown that in two‐dimensional environments, ‘place cells’ and ‘grid cells’ ... more Previous research has shown that in two‐dimensional environments, ‘place cells’ and ‘grid cells’ in the hippocampal formation comprise two units of O’Keefe and Nadel’s (1978) ‘cognitive map’, coding for the rat’s present location and for metric distance information, respectively. Since the world is three‐dimensional, an important question is whether the cognitive map is also volumetric. To explore this issue, place and grid cells were recorded from rats as they shuttled up and down between two ends of a spiral staircase (the ‘helical track’), allowing the same horizontal locations to be sampled at different vertical levels. Using this novel paradigm, it was possible to investigate whether place and grid cell receptive fields are globular or planar. The first experiment demonstrated that place fields extended in the vertical, as well as horizontal, dimension, suggesting that they were globular. However, the vertical extent was larger than the horizontal extent, suggesting either a co...

eLife, Apr 22, 2022

Topographic cortical maps are essential for spatial localisation of sensory stimulation and gener... more Topographic cortical maps are essential for spatial localisation of sensory stimulation and generation of appropriate task-related motor responses. Somatosensation and nociception are finely mapped and aligned in the adult somatosensory (S1) cortex, but in infancy, when pain behaviour is disorganised and poorly directed, nociceptive maps may be less refined. We compared the topographic pattern of S1 activation following noxious (clinically required heel lance) and innocuous (touch) mechanical stimulation of the same skin region in newborn infants (n = 32) using multioptode functional near-infrared spectroscopy (fNIRS). Within S1 cortex, touch and lance of the heel elicit localised, partially overlapping increases in oxygenated haemoglobin concentration (Δ[HbO]), but while touch activation was restricted to the heel area, lance activation extended into cortical hand regions. The data reveals a widespread cortical nociceptive map in infant S1, consistent with their poorly directed pain behaviour. Editor's evaluation This paper is of interest to developmental neuroscientists who study the early stages of cortical maturation and specialization, particularly in the context of somatosensory and pain system development. The authors suggest that, relative to the infant touch somatotopic map, the infant nociceptive map is more widespread and poorly localised, consistent with infants' poorly directed pain behaviour.

Oxford University Press eBooks, Jun 1, 2021

Pain reports, 2020

Introduction: Multimodal characterisation with questionnaires, Quantitative Sensory Testing (QST)... more Introduction: Multimodal characterisation with questionnaires, Quantitative Sensory Testing (QST), and neuroimaging will improve understanding of neuropathic pain (NeuP) in adolescents. Magnetic resonance imaging (MRI) data in adolescents with NeuP are limited, and the perceived practical or ethical burden of scanning may represent a barrier to research. Objective: To determine the feasibility of MRI scanning in adolescents with moderate-severe NeuP, with respect to consent rate, postscan acceptability, and data quality. Methods: This prospective cohort study evaluating questionnaires and QST recruited adolescents aged 10 to 18 years with clinically diagnosed NeuP from a tertiary clinic. Eligible adolescents aged 11 years and older could additionally agree/decline an MRI scan. After the scan, families rated discomfort, perceived risk, and acceptability of current and future MRI scans (0-10 numerical rating scales). Head motion during scanning was compared with healthy controls to assess data quality. Results: Thirty-four families agreed to MRI (72% recruitment), and 21 adolescents with moderate-severe pain (average last week 6.7 6 1.7; mean 6 SD) and with neuropathic QST profiles were scanned. Three adolescents reported positional or noise-related discomfort during scanning. Perceived risk was low, and acceptability of the current scan was high for parents (range [median]: 7 to 10/10 [10]) and adolescents (8-10/10 [10]). Willingness to undergo a future research scan was high for parents (7-10/10 [10]) and adolescents (5-10/10 [10]) and did not differ from future scans for clinical purposes. Mean head motion during resting state functional MRI did not differ from control adolescents. Conclusion: Research MRI is feasible and acceptable for many adolescents with moderate-severe NeuP.

ENeuro, Mar 1, 2016

Near-infrared spectroscopy (NIRS) and electroencephalography (EEG) have recently provided fundame... more Near-infrared spectroscopy (NIRS) and electroencephalography (EEG) have recently provided fundamental new information about how the newborn brain processes innocuous and noxious somatosensory information. However, results derived independently from these two techniques are not entirely consistent, raising questions about the relationship between hemodynamic and electrophysiological responses in the study of touch and pain processing in the newborn. To address this, we have recorded NIRS and EEG responses simultaneously for the first time in the human infant following noxious (time-locked clinically required heel lances) and innocuous tactile cutaneous stimulation in 30 newborn infants. The results show that both techniques can be used to record quantifiable and distinct innocuous and noxious evoked activity at a group level in the newborn cortex. Noxious stimulation elicits a peak hemodynamic response that is 10-fold larger than that elicited by an innocuous stimulus (HbO 2 : 2.0 vs 0.3 M) and a distinct nociceptive-specific N3P3 waveform in electrophysiological recordings. However, a novel single-trial analysis revealed that hemodynamic and electrophysiological responses do not always co-occur at an individual level, although when they do (64% of noxious test occasions), they are significantly correlated in magnitude. These data show that, while hemodynamic and electrophysiological touch and pain brain activity in newborn infants are comparable in group analyses, important individual differences remain. These data indicate that integrated and multimodal brain monitoring is required to understand central touch and pain processing in the newborn.

NeuroImage, Sep 1, 2018

In adults, there are differences between male and female structural and functional brain connecti... more In adults, there are differences between male and female structural and functional brain connectivity, specifically for those regions involved in pain processing. This may partly explain the observed sex differences in pain sensitivity, tolerance, and inhibitory control, and in the development of chronic pain. However, it is not known if these differences exist from birth. Cortical activity in response to a painful stimulus can be observed in the human neonatal brain, but this nociceptive activity continues to develop in the postnatal period and is qualitatively different from that of adults, partly due to the considerable cortical maturation during this time. This research aimed to investigate the effects of sex and prematurity on the magnitude and spatial distribution pattern of the long-latency nociceptive event-related potential (nERP) using electroencephalography (EEG). We measured the cortical response time-locked to a clinically required heel lance in 81 neonates born between 29 and 42 weeks gestational age (median postnatal age 4 days). The results show that heel lance results in a spatially widespread nERP response in the majority of newborns. Importantly, a widespread pattern is significantly more likely to occur in females, irrespective of gestational age at birth. This effect is not observed for the short latency somatosensory waveform in the same infants, indicating that it is selective for the nociceptive component of the response. These results suggest the early onset of a greater anatomical and functional connectivity reported in the adult female brain, and indicate the presence of pain-related sex differences from birth.

Current Biology, Dec 1, 2017

Highlights d Infant pain behavior and nociceptive brain activity are generally correlated d Stres... more Highlights d Infant pain behavior and nociceptive brain activity are generally correlated d Stress disrupts the relationship between infant pain brain activity and behavior d Stress is associated with increased nociceptive brain activity, but not behavior d Stress is an important factor when assessing infant pain experience

bioRxiv (Cold Spring Harbor Laboratory), Jul 30, 2021

Topographic cortical maps are essential for spatial localisation of sensory stimulation and gener... more Topographic cortical maps are essential for spatial localisation of sensory stimulation and generation of appropriate task-related motor responses. Somatosensation and nociception are finely mapped and aligned in the adult somatosensory (S1) cortex, but in infancy, when pain behaviour is disorganised and poorly directed, nociceptive maps may be less refined. We compared the topographic pattern of S1 activation following noxious (clinically required heel lance) and innocuous (touch) mechanical stimulation of the same skin region in newborn infants (n=32) using multi-optode functional near-infrared spectroscopy (fNIRS). Signal to noise ratio and overall activation area did not differ with stimulus modality. Within S1 cortex, touch and lance of the heel elicit localised, partially overlapping increases in oxygenated haemoglobin (HbO), but while touch activation was restricted to the heel area, lance activation extended into cortical hand regions. The data reveals a widespread cortical nociceptive map in infant S1, consistent with their poorly directed pain behaviour. Introduction .

Doctoral thesis, UCL (University College London)., Jan 28, 2012

Previous research has shown that in two‐dimensional environments, ‘place cells’ and ‘grid cells’ ... more Previous research has shown that in two‐dimensional environments, ‘place cells’ and ‘grid cells’ in the hippocampal formation comprise two units of O’Keefe and Nadel’s (1978) ‘cognitive map’, coding for the rat’s present location and for metric distance information, respectively. Since the world is three‐dimensional, an important question is whether the cognitive map is also volumetric. To explore this issue, place and grid cells were recorded from rats as they shuttled up and down between two ends of a spiral staircase (the ‘helical track’), allowing the same horizontal locations to be sampled at different vertical levels. Using this novel paradigm, it was possible to investigate whether place and grid cell receptive fields are globular or planar. The first experiment demonstrated that place fields extended in the vertical, as well as horizontal, dimension, suggesting that they were globular. However, the vertical extent was larger than the horizontal extent, suggesting either a coarser representation of height, or contextual modulation of fields in the vertical dimension, in the absence of metric vertical distance. Both possibilities imply that the cognitive map is anisotropic (not uniform in all dimensions). The second set of experiments involved probe trials that showed that both distal and local cues influence place fields in the vertical dimension. The third experiment demonstrated that grid cells produced several subfields on the helical track that, similar to the place fields, were vertically elongated. However, they were more elongated than place fields, and showed no vertical periodicity, suggesting the lack of metric vertical information. Overall, these observations suggest that three‐dimensional space is anisotropically represented in the rat brain as a contextually modulated flat map, in which only the current navigation plane is metrically represented. Due to the complexity of a truly three‐dimensional representation, an anisotropic representation is likely in all surface‐navigating animals including humans.

Behavioral and Brain Sciences, Oct 1, 2013

The study of spatial cognition has provided considerable insight into how animals (including huma... more The study of spatial cognition has provided considerable insight into how animals (including humans) navigate on the horizontal plane. However, the real world is three-dimensional, having a complex topography including both horizontal and vertical features, which presents additional challenges for representation and navigation. The present article reviews the emerging behavioral and neurobiological literature on spatial cognition in non-horizontal environments. We suggest that three-dimensional spaces are represented in a quasiplanar fashion, with space in the plane of locomotion being computed separately and represented differently from space in the orthogonal axisa representational structure we have termed "bicoded." We argue that the mammalian spatial representation in surface-travelling animals comprises a mosaic of these locally planar fragments, rather than a fully integrated volumetric map. More generally, this may be true even for species that can move freely in all three dimensions, such as birds and fish. We outline the evidence supporting this view, together with the adaptive advantages of such a scheme.

Scientific Data, Jul 27, 2023

Scientific Data, Nov 13, 2018

We present a dataset of cortical, behavioural, and physiological responses following a single, cl... more We present a dataset of cortical, behavioural, and physiological responses following a single, clinically required noxious stimulus in a neonatal sample. Cortical activity was recorded from 112 neonates (29-47 weeks gestational age at study) using a 20-channel electroencephalogram (EEG), which was time-locked to a heel lance. This data is linked to pain-related behaviour (facial expression), physiology (heart rate, oxygenation) and a composite clinical score (Premature Infant Pain Profile, PIPP). The dataset includes responses to non-noxious sham and auditory controls. The infants' relevant medical and pain history was collected up to the day of the study and recorded in an extensive database of variables including clinical condition at birth, diagnoses, medications, previous painful procedures, injuries, and selected maternal information. 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. Design Type(s) observational design Measurement Type(s) brain activity measurement • behavioral response to pain Technology Type(s) electroencephalography • observational method Factor Type(s) biological sex • gestational age • age • experimental condition Sample Characteristic(s) Homo sapiens

Scientific Reports, Jun 1, 2016

Newborn human infants display robust pain behaviour and specific cortical activity following noxi... more Newborn human infants display robust pain behaviour and specific cortical activity following noxious skin stimulation, but it is not known whether brain processing of nociceptive information differs in infants and adults. Imaging studies have emphasised the overlap between infant and adult brain connectome architecture, but electrophysiological analysis of infant brain nociceptive networks can provide further understanding of the functional postnatal development of pain perception. Here we hypothesise that the human infant brain encodes noxious information with different neuronal patterns compared to adults. To test this we compared EEG responses to the same time-locked noxious skin lance in infants aged 0-19 days (n = 18, clinically required) and adults aged 23-48 years (n = 21). Timefrequency analysis revealed that while some features of adult nociceptive network activity are present in infants at longer latencies, including beta-gamma oscillations, infants display a distinct, long latency, noxious evoked 18-fold energy increase in the fast delta band (2-4 Hz) that is absent in adults. The differences in activity between infants and adults have a widespread topographic distribution across the brain. These data support our hypothesis and indicate important postnatal changes in the encoding of mechanical pain in the human brain.

Neuroscience, Dec 1, 2016

Pain, Dec 15, 2020

Pain descriptors did not differ between male (n=23) and female (n=43) adolescents with neuropathi... more Pain descriptors did not differ between male (n=23) and female (n=43) adolescents with neuropathic pain or CRPS. (A) Total scores on the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS, 0-24) (B) Average pain intensity during the last week reported on a numerical rating scale in the S-LANSS were consistent with measures on a 0-10cm VAS (Fig. 1) and indicated moderate-severe pain in both males and females (C) Total scores for sensory (0-33) and affective (0-12) pain descriptors reported on the McGill Pain Questionnaire were variable but did not differ between males and females. Data points = individual values; bars = median [IQR]. (D) Total S-LANSS scores correlated more strongly with McGill sensory (R 2 =0.22) than affective scores (R 2 =0.11). Data points = individual values. Solid lines=linear regression; dotted lines = 95%CI.

Paediatrics and International Child Health, Jan 22, 2020

Background: In the wake of the Ebola virus disease (EVD) epidemic in Sierra Leone, secondary care... more Background: In the wake of the Ebola virus disease (EVD) epidemic in Sierra Leone, secondary care facilities faced an increase in admissions with few members of medical staff available to assess and treat patients. This led to long waiting times in hospital outpatient departments. The study was undertaken in the outpatient department of Ola During Children's Hospital (the tertiary paediatric hospital for Sierra Leone) in the period immediately following the EVD epidemic of 2014-2015. Aims: This retrospective analysis of operational programme data aimed to assess whether a quality-improvement approach and task-sharing between medical and nursing staff improved the quality of triage and the timeliness of care. Methods: All staff working in the outpatient department were offered a 4-week training course, followed by on-the-job supervision and support for 6 months. Nurses who successfully completed the course were given responsibility for the initial assessment of sick patients and for prescribing and giving initial treatment. Data were collected at three points: before intervention and at 3 and 6 months after initiation of the intervention. All children presenting to the hospital for medical attention between 0800 and 1400 Monday to Friday were included. Triage assessment by the outpatient nurse was compared to that made by a clinically experienced observer, and the time taken for each child to be triaged, assessed and given initial treatment was recorded. Results: Between months 0 and 6 of the intervention, detection of emergency signs by the triage nurse improved from 30% to 100%, and detection of priority signs improved from 34% to 100%. For children presenting with emergency signs, the median time between triage and full assessment improved from 57 minutes before intervention to 17 minutes at 3 months and 5 minutes at 6 months (p < 0.0005). For the same group, median time between triage and first antibiotic or antimalarial treatment improved from 220 minutes before intervention to 40 minutes at 3 months and 18 minutes at 6 months (p = 0.006). Conclusion: The results indicate that, with appropriate training and support, extending the emergency assessment and treatment of sick children to nursing staff in West African hospitals may improve the accuracy of triage and the time to assessment and treatment of children presenting with signs of serious illness.

Archives of Disease in Childhood, 2013

Previous research has shown that in two‐dimensional environments, ‘place cells’ and ‘grid cells’ ... more Previous research has shown that in two‐dimensional environments, ‘place cells’ and ‘grid cells’ in the hippocampal formation comprise two units of O’Keefe and Nadel’s (1978) ‘cognitive map’, coding for the rat’s present location and for metric distance information, respectively. Since the world is three‐dimensional, an important question is whether the cognitive map is also volumetric. To explore this issue, place and grid cells were recorded from rats as they shuttled up and down between two ends of a spiral staircase (the ‘helical track’), allowing the same horizontal locations to be sampled at different vertical levels. Using this novel paradigm, it was possible to investigate whether place and grid cell receptive fields are globular or planar. The first experiment demonstrated that place fields extended in the vertical, as well as horizontal, dimension, suggesting that they were globular. However, the vertical extent was larger than the horizontal extent, suggesting either a co...