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•Impregnation of carbon fibers using aryl diazonium salts led to surface functionalisation.•Interfacial shear strength improvements of up to 150% observed.•Molecular dynamics suggests ...interfacial shear strength gains are via protrusion of molecules into the interphase.
It is widely acknowledged that the integrity of the fiber-to-matrix interface inherent to carbon fiber reinforced composites has scope for improvement. One promising and highly-researched strategy is the use of surface manipulation of carbon fibers to enhance their mechanical performance under shear. The complexity of commonly used surface treatments, such as plasma and oxidative etching, Requires modification of existing manufacturing infrastructure and thus their broad adoption in a manufacturing context has been limited. Herein we show that simply impregnating the carbon fibers with aryl diazonium salts and subjecting them to external stimuli, such as mild heating (100 °C), can induce surface modification which can deliver improvements of up to 150% in interfacial shear strength (IFSS) in epoxy resins. Interrogation of the fiber-to-matrix interface using molecular dynamics simulations suggests that the surface grafted molecules imparts a ‘dragging effect’ though the polymer phase and that the surface concentration of these compounds is critical to enhancing IFSS. This process obviates the practical limitations of current functionalization procedures for carbon fibers and requires infrastructure that is already routinely available on fiber manufacturing lines.
The neural mechanism responsible for migraine remains unclear. While the role of an external trigger in migraine initiation remains vigorously debated, it is generally assumed that migraineurs ...display altered brain function between attacks. This idea stems from relatively few brain imaging studies with even fewer studies exploring changes in the 24 h period immediately prior to a migraine attack. Using functional magnetic resonance imaging, we measured infra‐slow oscillatory activity, regional homogeneity, and connectivity strengths of resting activity in migraineurs directly before (n = 8), after (n = 11), and between migraine attacks (n = 26) and in healthy control subjects (n = 78). Comparisons between controls and each migraine group and between migraine groups were made for each of these measures. Directly prior to a migraine, increased infra‐slow oscillatory activity occurred in brainstem and hypothalamic regions that also display altered activity during a migraine itself, that is, the spinal trigeminal nucleus, dorsal pons, and hypothalamus. Furthermore, these midbrain and hypothalamic sites displayed increased connectivity strengths and regional homogeneity directly prior to a migraine. Remarkably, these resting oscillatory and connectivity changes did not occur directly after or between migraine attacks and were significantly different to control subjects. These data provide evidence of altered brainstem and hypothalamic function in the period immediately before a migraine and raise the prospect that such changes contribute to the expression of a migraine attack.
Pain perception can be powerfully influenced by an individual's expectations and beliefs. Although the cortical circuitry responsible for pain modulation has been thoroughly investigated, the ...brainstem pathways involved in the modulatory phenomena of placebo analgesia and nocebo hyperalgesia remain to be directly addressed. This study used ultra-high-field 7 tesla functional MRI (fMRI) to accurately resolve differences in brainstem circuitry present during the generation of placebo analgesia and nocebo hyperalgesia in healthy human participants (
= 25, 12 male). Over 2 successive days, through blinded application of altered thermal stimuli, participants were deceptively conditioned to believe that two inert creams labeled lidocaine (placebo) and capsaicin (nocebo) were acting to modulate their pain relative to a third Vaseline (control) cream. In a subsequent test phase, fMRI image sets were collected while participants were given identical noxious stimuli to all three cream sites. Pain intensity ratings were collected and placebo and nocebo responses determined. Brainstem-specific fMRI analysis revealed altered activity in key pain modulatory nuclei, including a disparate recruitment of the periaqueductal gray (PAG)-rostral ventromedial medulla (RVM) pathway when both greater placebo and nocebo effects were observed. Additionally, we found that placebo and nocebo responses differentially activated the parabrachial nucleus but overlapped in engagement of the substantia nigra and locus coeruleus. These data reveal that placebo and nocebo effects are generated through differential engagement of the PAG-RVM pathway, which in concert with other brainstem sites likely influences the experience of pain by modulating activity at the level of the dorsal horn.
Understanding endogenous pain modulatory mechanisms would support development of effective clinical treatment strategies for both acute and chronic pain. Specific brainstem nuclei have long been known to play a central role in nociceptive modulation; however, because of the small size and complex organization of the nuclei, previous neuroimaging efforts have been limited in directly identifying how these subcortical networks interact during the development of antinociceptive and pro-nociceptive effects. We used ultra-high-field fMRI to resolve brainstem structures and measure signal change during placebo analgesia and nocebo hyperalgesia. We define overlapping and disparate brainstem circuitry responsible for altering pain perception. These findings extend our understanding of the detailed organization and function of discrete brainstem nuclei involved in pain processing and modulation.
We recently showed that transcranial alternating current stimulation of the dorsolateral prefrontal cortex modulates spontaneous bursts of muscle sympathetic nerve activity, heart rate, and blood ...pressure (Sesa-Ashton G, Wong R, McCarthy B, Datta S, Henderson LA, Dawood T, Macefield VG. Stimulation of the dorsolateral prefrontal cortex modulates muscle sympathetic nerve activity and blood pressure in humans. Cereb Cortex Comm. 2022:3:2tgac017.). Stimulation was delivered between scalp electrodes placed over the nasion and electroencephalogram (EEG) electrode site F3 (left dorsolateral prefrontal cortex) or F4 (right dorsolateral prefrontal cortex), and therefore the current passed within the anatomical locations underlying the left and right ventromedial prefrontal cortices. Accordingly, we tested the hypothesis that stimulation of the left and right ventromedial prefrontal cortices would also modulate muscle sympathetic nerve activity, although we predicted that this would be weaker than that seen during dorsolateral prefrontal cortex stimulation. We further tested whether stimulation of the right ventromedial prefrontal cortices would cause greater modulation of muscle sympathetic nerve activity, than stimulation of the left ventromedial prefrontal cortices. In 11 individuals, muscle sympathetic nerve activity was recorded via microelectrodes inserted into the right common peroneal nerve, together with continuous blood pressure, electrocardiogram, and respiration. Stimulation was achieved using transcranial alternating current stimulation, +2 to -2 mA, 0.08 Hz, 100 cycles, applied between electrodes placed over the nasion, and EEG electrode site FP1, (left ventromedial prefrontal cortices) or FP2 (right ventromedial prefrontal cortices); for comparison, stimulation was also applied over F4 (right dorsolateral prefrontal cortex). Stimulation of all three cortical sites caused partial entrainment of muscle sympathetic nerve activity to the sinusoidal stimulation, together with modulation of blood pressure and heart rate. We found a significant fall in mean blood pressure of ~6 mmHg (P = 0.039) during stimulation of the left ventromedial prefrontal cortices, as compared with stimulation of the right. We have shown, for the first time, that transcranial alternating current stimulation of the ventromedial prefrontal cortices modulates muscle sympathetic nerve activity and blood pressure in awake humans at rest. However, it is unclear if this modulation occurred through the same brain pathways activated during transcranial alternating current stimulation of the dorsolateral prefrontal cortex.
Loss of somatosensory drive results in functional reorganization of the primary somatosensory cortex (SI). While the phenomenon of functional cortical reorganization is well established, it remains ...unknown whether in humans, functional reorganization results from changes in brain anatomy, or simply reflects an unmasking of already existing dormant synapses. In 20 subjects with complete thoracic spinal cord injuries (SCIs) and 23 controls, we used functional and structural magnetic resonance imaging to determine whether SI reorganization was associated with changes in SI anatomy. SCI resulted in a significant SI reorganization, with the little finger representation moving medially toward the lower body representation (i.e., area of sensory loss). Furthermore, although SCI was associated with gray matter volume loss in the lower body representation, this loss was minimized as reorganization increased. That is, the greater the medial shift in little finger representation, the greater the gray matter preservation in the lower body representation. In addition, in the region of greatest SI reorganization (little finger), fractional anisotropy was correlated with SI reorganization. That is, as SI reorganization increased, the extent of aligned structures decreased. Finally, although thalamocortical fibers remained unchanged, the ease and direction of water movement within the little finger representation was altered, being directed more toward the midline in SCI subjects. These data show that SI reorganization following SCI is associated with changes in SI anatomy and provide compelling evidence that SI reorganization in humans results from the growth of new lateral connections, and not simply from the unmasking of already existing lateral connections.
Over the past two decades, magnetic resonance imaging (MRI) studies have explored brain activation patterns during acute noxious stimuli. Whilst these human investigations have detailed changes in ...primarily cortical regions, they have generally not explored discrete changes within small brain areas that are critical in driving behavioural, autonomic, and endocrine responses to pain, such as within subregions of the hypothalamus, amygdala, and midbrain periaqueductal gray matter (PAG). Ultra-high field (7-Tesla) MRI provides enough signal-to-noise at high spatial resolutions to investigate activation patterns within these small brain regions during acute noxious stimulation in awake humans. In this study we used 7T functional MRI to concentrate on hypothalamic, amygdala, and PAG signal changes during acute noxious orofacial stimuli. Noxious heat stimuli were applied in three separate fMRI scans to three adjacent sites on the face in 16 healthy control participants (7 females). Images were processed using SPM12 and custom software, and blood oxygen level dependent signal changes within the hypothalamus, amygdala, and PAG assessed. We identified altered activity within eight unique subregions of the hypothalamus, four unique subregions of the amygdala, and a single region in the lateral PAG. Specifically, within the hypothalamus and amygdala, signal intensity largely decreased during noxious stimulation, and increased in the lateral PAG. Furthermore, we found sex-related differences in discrete regions of the hypothalamus and amygdala. This study reveals that the activity of discrete nuclei during acute noxious thermal stimulation in awake humans.
The surface of both oxidized and unoxidized unsized carbon fiber was functionalized using an aziridine linking group derived from reactive nitrenes. The aziridine functionality arose from the ...cyclization of a reactive nitrene species onto the highly electron rich graphitic surface of the carbon fibers; the nitrene species evolved from thermal N2 elimination from the corresponding (room temperature stable) azide. Surface functionalization using the nitrene approach was supported by X-ray Photoelectron Spectroscopy, in both oxidized and unoxidized carbon fiber. Attempts were also made to functionalize using amide chemistry, the two-step acid chloride coupling being successful for oxidized fibers by utilizing the carboxylic acid rich defect sites on the carbon fiber. None of the chemical treatment pathways had a significant impact on the tensile strength of the individual fibers, and atomic force microscopy revealed that fibers undergoing these treatment methodologies remained intact, without creating additional surface defects.
The tethering of an amphiphilic molecule to the surface of carbon fiber resulted in significant (+283%) improvements in interfacial shear strength. Molecular dynamics simulations revealed that ...lateral association of hydrophobic sections lead to a ‘hooked’ conformation through which polymer chains become entangled. Further simulations indicated that a small molecule, forced into this conformation via two covalent attachment points to the fiber surface (similar to a ‘horseshoe’), would provide similar adhesion improvements and confirm this conformational effect on interfacial phenomena. This prediction was confirmed by the synthesis and grafting of such a molecule to a carbon fiber surface, giving an almost identical improvement in interfacial adhesion (+276%). This work validates the use of molecular dynamics to inform molecular architectural design and demonstrates the translation of molecular conformation and shape at a composite interface from nano-to macroscale.
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Abstract Skin sympathetic nerve activity (SSNA) is primarily involved in thermoregulation and emotional expression; however, the brain regions involved in the generation of SSNA are not completely ...understood. In recent years, our laboratory has shown that blood-oxygen-level-dependent signal intensity in the ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are positively correlated with bursts of SSNA during emotional arousal and increases in signal intensity in the vmPFC occurring with increases in spontaneous bursts of SSNA even in the resting state. We have recently shown that unilateral transcranial alternating current stimulation (tACS) of the dlPFC causes modulation of SSNA but given that the current was delivered between electrodes over the dlPFC and the nasion, it is possible that the effects were due to current acting on the vmPFC. To test this, we delivered tACS to target the right vmPFC or dlPFC and nasion and recorded SSNA in 11 healthy participants by inserting a tungsten microelectrode into the right common peroneal nerve. The similarity in SSNA modulation between ipsilateral vmPFC and dlPFC suggests that the ipsilateral vmPFC, rather than the dlPFC, may be causing the modulation of SSNA during ipsilateral dlPFC stimulation.
Blood pressure is tightly controlled by the central nervous system, particularly the brainstem. The aim of this study was to investigate the relationship between mean blood pressure (MBP), muscle ...sympathetic nerve activity (MSNA) and resting regional brain activity in healthy human subjects. Pseudocontinuous arterial spin labeling and functional magnetic resonance imaging of the brain were performed immediately following a laboratory microneurography recording of MSNA and BP measurement in 31 young, healthy normotensive subjects. Regional cerebral blood flow (CBF) correlated significantly with resting MBP levels in the region encompassing the rostroventrolateral medulla (RVLM), dorsolateral pons, and insular, prefrontal and cingulate cortices. Functional connectivity analysis revealed that the ventrolateral prefrontal cortex displayed greater resting connectivity strength within the RVLM in the lower compared with the higher MBP group. No significant differences in CBF were found when subjects were divided based on their MSNA levels. These results suggest that even subtle differences in resting MBP are associated with significant differences in resting activity in brain regions, which are well known to play a role in cardiovascular function. These data raise the question of the potential long-term consequences of differences in regional brain activity levels and their relationship with systemic blood pressure.
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