Biology subjects

Fabrizi, L.

Publications and source records attributed to Fabrizi, L..

4 recordsLinked to original sources

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↗