Biology subjects

Fabrizi, L.

Publications and source records attributed to Fabrizi, L..

7 recordsLinked to original sources

bioRxiv2026

Postnatal development of somatosensory corticospinal projections in the mouse lumbar spinal cord

Corticospinal projections from the primary somatosensory cortex (S1) form a distinct descending pathway that engages spinal dorsal horn circuits and modulates sensory processing. Despite advances in our understanding of the role of this pathway in the adult, the postnatal maturation of somatosensory corticospinal projections remains poorly defined. Here, we provide a quantitative anatomical analysis of the postnatal development of corticospinal projections from the hindlimb representation of S1 (S1hl) to the lumbar dorsal horn in mice. Using retrograde tracing, we show that lumbar-projecting S1hl corticospinal neurons are first detected at postnatal day (P) 9 and reach adult-like numbers in S1hl by P12. Using anterograde tracing we then show that S1hl CST axonal projections are initially confined to the dorsolateral funiculus when they reach the lumbar cord at P9, but then rapidly invade the lumbar dorsal horn, reaching peak grey matter terminal density at P14. During this early innervation period, projections transiently extend beyond their mature termination zones in laminae III-V before retracting and becoming confined to superficial laminae I-II by P17. Together, these findings define three developmental phases of somatosensory corticospinal dorsal horn connections: an initial arrival phase, followed by grey matter ingrowth, and finally laminar refinement of the terminal projections. These results provide an anatomical framework for understanding how descending corticospinal somatosensory control becomes integrated into spinal circuits during the early postnatal period.

neuroscience↗

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

Neurophysiological basis of hemodynamic responses in the developing human brain before the time of normal birth

Neurovascular coupling that links neural activity to localized increases in blood flow is essential both for brain function and to prevent tissue injury. In the healthy human brain, this underlies an association between the duration of EEG microstates, which represent coordinated and metastable activation of neuronal ensembles, and increases in hemodynamic activity. However, in early human life it is not clear whether neurovascular coupling is functional as the underlying physiological mechanisms may be too immature to effectively support it. Here, we combined MRI compatible robotics with simultaneous EEG and fMRI data acquisition in 13 preterm infants to assess whether the relationship between neural activity and hemodynamic responses is present in this critical period of early life. Passive sensorimotor stimulation elicited both a distinct sequence of four EEG microstates and a significant rise in the blood oxygen level dependent (BOLD) fMRI signal in the left primary sensorimotor cortex. Furthermore, EEG microstate duration was significantly related to BOLD response amplitude. These results suggest that effective neurovascular coupling is present in the human brain even before the normal time of birth and reveal a complex relationship between EEG and fMRI signals underpinned by patterns of activity across distinct neural ensembles.

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↗

bioRxiv2022

Early life pain experience changes adult functional pain connectivity in the rat somatosensory and the medial prefrontal cortex

Early life pain experience (ELP) alters adult pain behaviour and increases injury induced pain hypersensitivity, but the effect of ELP upon adult functional brain connectivity is not known. We have performed continuous local field potential (LFP) recording in the awake adult male rats to test the effect of ELP upon functional cortical connectivity related to pain behaviour. Somatosensory cortex (S1) and medial prefrontal cortex (mPFC) LFPs evoked by mechanical hindpaw stimulation were recorded simultaneously with pain reflex behaviour for 10 days after adult skin injury. We show that, post adult injury, S1 LFP delta and gamma energy and S1 LFP delta/gamma frequency modulation are significantly increased in ELP rats compared to controls. Adult injury also induces increases in S1-mPFC functional connectivity which is significantly prolonged in ELP rats, lasting 4 days compared to 1 day in controls. Importantly, the increases in LFP energy and connectivity in ELP rats were directly correlated with increased behavioural pain hypersensitivity. Thus, early life pain (ELP) alters adult brain functional connectivity, both within and between cortical areas involved in sensory and affective dimensions of pain. The results reveal altered brain connectivity as a mechanism underlying the effects of early life pain upon adult pain perception. Significance StatementPain and stress in early life has a lasting impact upon pain behaviour and may increase vulnerability to chronic pain in adults. Here we record pain-related cortical activity and simultaneous pain behaviour in awake adult male rats previously exposed to pain in early life. We show that functional connectivity within and between the somatosensory cortex and the medial prefrontal cortex is increased in these rats and that these increases are correlated with their behavioural pain hypersensitivity. The results reveal that early life pain alters adult brain connectivity, which may explain the impact of childhood pain upon adult chronic pain vulnerability.

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↗