Biology subjects

Meek, J.

Publications and source records attributed to Meek, J..

5 recordsLinked to original sources

bioRxiv2024

Differential maturation of the brain networks required for the sensory, emotional and cognitive aspects of pain in human newborns

Pain is multidimensional and complex, including sensory-discriminative, affective- motivational, and cognitive-evaluative components. While the concept of pain is learned through life experience, it is not known when and how the brain networks that are required to encode these different dimensions of pain develop. Using the two largest databases of human brain magnetic resonance (MR) images in the world - the developing Human Connectome Project and the Human Connectome Project - we have mapped the development of the neural pathways required for pain perception in the human brain in infants from <32 weeks to 42 weeks postmenstrual age (n = 372), compared to adults (n = 98). Partial correlation analysis of 15 mins resting BOLD signal between all possible pairwise combinations of 12 pain-related regions of interest showed that overall functional connectivity is significantly weaker in 32- week infants compared to adults. However, over the following weeks, significantly different developmental patterns of connectivity emerge in sensory-discriminative, affective- motivational, and cognitive-evaluative pain networks. The first subnetwork to reach adult levels in strength and proportion of connections is the sensory-discriminative subnetwork (34- 36 weeks PMA), followed by the affective-motivational subnetwork (36-38 weeks PMA), while the cognitive-evaluative subnetwork has still not reached adult levels at 42 weeks. This study reveals a previously unknown pattern of postnatal development of connectome subnetworks necessary for mature pain processing. The brain networks that form the infrastructure to encode different components of pain experience, change rapidly in the equivalent of the last gestational trimester but are still immature at the time of normal birth. Newborn neural pathways required for mature pain processing in the brain are incomplete in newborns compared to adults, particularly with respect to the emotional and evaluative aspects of pain. This data suggests that pain-related networks may have distinct periods of vulnerability to untimely noxious procedures during hospitalization, particularly in preterm infants.

neuroscience↗

bioRxiv2022

Spontaneous activation of cortical somatosensory networks depresses their excitability in preterm human neonates

In the developing cortex of preterm human infants, neuronal activity is discontinuous - characterized by sudden, high-amplitude bursts that interrupt periods of quiet background activity. While the functional significance of these bursts is well established, the underlying cause remains unclear. We propose that this burst-quiescence pattern arises from a temporary "refractoriness" in cortical networks following spontaneous activation. To investigate this, we examined whether spontaneous activity in sensory networks reduces their excitability by assessing how ongoing brain activity influences responses to external sensory stimuli. We recorded electroencephalographic (EEG) responses to tactile stimulation of the hands and feet in 35 preterm infants, with a median post-menstrual age of 32 weeks. This stimulation triggered increases in wideband cortical power, showing two distinct peaks: one in the delta range and another in the alpha-beta range. Delta-band activity is widespread across the scalp, while the faster alpha-beta responses were confined to somatotopically specific regions. Importantly, we found that when the baseline activity shared similar spectral and spatial characteristics with the evoked somatosensory response, the magnitude of the evoked response was reduced. This suggests that spontaneous events transiently engage and saturate both widespread (tangential) and localized (columnar) cortical circuits. As a result, the same cortical regions become temporarily less responsive--a form of refractoriness--preventing immediate reactivation. This mechanism may explain the cyclical pattern of bursting and quiescence observed in the preterm brain. Significance StatementIt is well known that the preterm human brain exhibits a characteristic alternation between high-amplitude activity and quiescence, yet the underlying mechanism remains unclear. Drawing inspiration from developmental neuroscience in animal models, the present study provides the first potential neurobiological explanation for this rhythmic pattern. Using EEG recordings and a somatosensory stimulation paradigm, it demonstrates that preterm cortical bursts induce a refractory period during which external stimuli fail to elicit a response - revealing an intrinsic, activity-dependent depression mechanism. By presenting fundamental novel insights into the neurobiology of preterm cortical activity, this work has broad implications, offering both basic neuroscientists and clinical specialists new understanding of the developmental origins of sensory processing and neonatal EEG patterns linked to later neurobehavioural outcomes.

neuroscience↗

bioRxiv2022

Developmental switch in prediction and adaptation to pain in human neonates

Habituation to recurrent non-threatening or unavoidable noxious stimuli is an important aspect of adaptation to pain and indicates the ability of the brain to encode expectation of imminent nociception. However, it is not known whether the newborn brain can predict and habituate to recurrent noxious inputs. We used electroencephalography to investigate changes in cortical microstates, which represent the complex sequential processing of noxious inputs, following repeated clinically-required heel lances in term and preterm infants. Noxious stimulus repetition decreased the engagement of early sensory-related microstates and associated behavioural and physiological responses in term infants, while preterm infants did not show signs of adaptation. Nevertheless, both groups displayed a switch between different microstates at longer latencies. These data suggests that the preterm brain is capable of encoding high-level contextual differences in pain, but cannot update its prediction, which allows for adaptation, emphasising the vulnerability of this population to recurrent pain. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/486988v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1f237bborg.highwire.dtl.DTLVardef@1290318org.highwire.dtl.DTLVardef@18a4d76org.highwire.dtl.DTLVardef@e3be5e_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Widespread nociceptive maps in the human neonatal somatosensory cortex

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.

neuroscience↗

bioRxiv2019

Smartphone screening for neonatal jaundice via ambient-subtracted sclera chromaticity: neoSCB app pilot study

Jaundice is a major cause of mortality and morbidity in the newborn. Globally, early identification and home monitoring are significant challenges in reducing the incidence of jaundice-related neurological damage. Smartphone cameras are promising as colour-based screening tools as they are low-cost, objective and ubiquitous. We propose a novel smartphone method and app called neoSCB to screen for neonatal jaundice by imaging the sclera. It does not rely on colour calibration cards or accessories, which may facilitate its adoption at scale and in less economically developed regions. Our approach is to explicitly address three confounding factors in relating colour to jaundice: (1) skin pigmentation, (2) ambient light, and (3) camera spectral response. (1) The variation in skin pigmentation is avoided by imaging the sclera. (2) With the smartphone screen acting as an illuminating flash, a flash/ no-flash image pair is captured using the front-facing camera. The contribution of ambient light is subtracted. (3) This permits a device-and ambient-independent measure of sclera chromaticity following a one-time calibration. We introduce the concept of Scleral-Conjunctival Bilirubin (SCB), in analogy with Transcutaneous Bilirubin (TcB). The scleral chromaticity is mapped to an SCB value. A pilot study was conducted in the UCL Hospital Neonatal Care Unit. 51 neonates were imaged using the neoSCB app and had a blood test for total serum bilirubin (TSB). The better of two models for SCB based on ambient-subtracted sclera chromaticity achieved r = 0.75 (p<0.01) correlation with TSB. Ambient subtraction improved chromaticity estimates in laboratory tests and screening performance within our study sample. Using an SCB decision threshold of 190mol/L, the sensitivity was 100% (specificity 61%) in identifying newborns with TSB>250mol/L (area under receiver operating characteristic curve, AUROC, 0.86), and 92% (specificity 67%) in identifying newborns with TSB>205mol/L (AUROC 0.85). These results are comparable to modern transcutaneous bilirubinometers.

bioengineering↗