This paper examines the effect on interfacial shear strength (IFSS) when grafting polyethyleneoxide (PEO) polymers of various molecular weights to a carbon fiber surface. Using copper-azide-alkyne ...cycloaddition click chemistry, PEO polymers of 1 kDa, 2 kDa, 5 kDa, and 10 kDa were tethered to the fiber surface without causing degradation of the fiber surface. The resulting IFSS increases were maximised (130% and 160%) for the 1 kDa and 10 kDa surface modified fibers, respectively. These data suggest that increases in IFSS are the result of an interplay between the density of surface modification versus the penetration of the grafted polymer into the matrix interphase. The trade-off between interphase penetration and surface grafting density is highlighted for the 2 and 5 kDa PEO chains on the fiber surface which display smaller IFSS increases (85% and 117%, respectively). Measuring the mobility of the PEO polymers by 1H NMR found an order of magnitude decrease in diffusion coefficient for each successive increase in molecular weight, supporting the hypothesis that grafting density decreases with molecular weight. Molecular dynamics simulations of the carbon fiber-matrix interface further supports these observations. These results will inform the design of complementary interfaces for various materials in a range of supporting media.
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...a concept goes beyond that of a function for light stimulating specialized retinal ganglion cells to entrain circadian rhythms but extends this to include light having a direct influence on all ...neurons to potentially influence a range of core higher-order brain activities. ...the chlorophyll ingested by animals can be converted into metabolites that become incorporated within mitochondria across a number of body tissues. ...other wavelengths across the light spectrum have been reported to be absorbed by yet other chromophores. From a transcranial approach, light can penetrate down to the level of the cerebral cortex (Hamblin, 2016; Mitrofanis, 2019). ...light, being an electromagnetic wave, can potentially influence the activity and frequency of neurons in the large-scale neural networks, for example to influence the functional connectivity within the default mode network, as well as within and with the other networks, such as the central executive and salience ones Figure 1B. The significance of why light would have such an effect on these networks perhaps subserves a key survival strategy for the organism.
Background
Migraine is a neurological disorder characterized by intense, debilitating headaches, often coupled with nausea, vomiting and sensitivity to light and sound. Whilst changes in sensory ...processes during a migraine attack have been well-described, there is growing evidence that even between migraine attacks, sensory abilities are disrupted in migraine. Brain imaging studies have investigated altered coupling between areas of the descending pain modulatory pathway but coupling between somatosensory processing regions between migraine attacks has not been properly studied. The aim of this study was to determine if ongoing functional connectivity between visual, auditory, olfactory, gustatory and somatosensory cortices are altered during the interictal phase of migraine.
Methods
To explore the neural mechanisms underpinning interictal changes in sensory processing, we used functional magnetic resonance imaging to compare resting brain activity patterns and connectivity in migraineurs between migraine attacks (
n
= 32) and in healthy controls (
n
= 71). Significant differences between groups were determined using two-sample random effects procedures (
p
< 0.05, corrected for multiple comparisons, minimum cluster size 10 contiguous voxels, age and gender included as nuisance variables).
Results
In the migraine group, increases in infra-slow oscillatory activity were detected in the right primary visual cortex (V1), secondary visual cortex (V2) and third visual complex (V3), and left V3. In addition, resting connectivity analysis revealed that migraineurs displayed significantly enhanced connectivity between V1 and V2 with other sensory cortices including the auditory, gustatory, motor and somatosensory cortices.
Conclusions
These data provide evidence for a dysfunctional sensory network in pain-free migraine patients which may be underlying altered sensory processing between migraine attacks.
We review our recent data obtained on the cortical and subcortical components of the human sympathetic connectome - the network of regions involved in the sympathetic control of blood pressure. ...Specifically, we functionally identified the human homologue of the rostral ventrolateral medulla (RVLM), the primary premotor sympathetic nucleus in the medulla responsible for generating sympathetic vasoconstrictor drive. By performing functional magnetic resonance imaging (fMRI) of the brain at the same time as recording muscle sympathetic nerve activity (MSNA), via a microlectrode inserted into the common peroneal nerve, we are able to identify areas of the brain involved in the generation of sympathetic outflow to the muscle vascular bed, a major contributor to blood pressure regulation. Together with functional connectivity analysis of areas identified through MSNA-coupled fMRI, we have established key components of the human sympathetic connectome and their roles in the control of blood pressure. Whilst our studies confirm the role of lower brainstem regions such as the NTS, CVLM and RVLM in baroreflex control of MSNA, our findings indicate that the insula – hypothalamus – PAG – RVLM circuitry is tightly coupled to MSNA at rest. This fits with data obtained from experimental animals, but also emphasizes the role of areas above the brainstem in the regulation of blood pressure.
•We review our recent data obtained on the cortical and subcortical components of the human sympathetic connectome.•We performed fMRI of the brain at the same time as recording muscle sympathetic nerve activity (MSNA) via a microlectrode inserted into a peripheral nerve.•This allows us to identify areas of the brain involved in the generation of sympathetic outflow to the muscle vascular bed.•Our studies emphasize the contributions of areas above the brainstem in the regulation of blood pressure.
Preclinical investigations have suggested that altered functioning of brainstem pain-modulation circuits may be crucial for the maintenance of some chronic pain conditions. While some human ...psychophysical studies show that patients with chronic pain display altered pain-modulation efficacy, it remains unknown whether brainstem pain-modulation circuits are altered in individuals with chronic pain. The aim of the present investigation was to determine whether, in humans, chronic pain following nerve injury is associated with altered ongoing functioning of the brainstem descending modulation systems. Using resting-state functional magnetic resonance imaging, we found that male and female patients with chronic neuropathic orofacial pain show increased functional connectivity between the rostral ventromedial medulla (RVM) and other brainstem pain-modulatory regions, including the ventrolateral periaqueductal gray (vlPAG) and locus ceruleus (LC). We also identified an increase in RVM functional connectivity with the region that receives orofacial nociceptor afferents, the spinal trigeminal nucleus. In addition, the vlPAG and LC displayed increased functional connectivity strengths with higher brain regions, including the hippocampus, nucleus accumbens, and anterior cingulate cortex, in individuals with chronic pain. These data reveal that chronic pain is associated with altered ongoing functioning within the endogenous pain-modulation network. These changes may underlie enhanced descending facilitation of processing at the primary synapse, resulting in increased nociceptive transmission to higher brain centers. Further, our findings show that higher brain regions interact with the brainstem modulation system differently in chronic pain, possibly reflecting top-down engagement of the circuitry alongside altered reward processing in pain conditions.
Experimental animal models and human psychophysical studies suggest that altered functioning of brainstem pain-modulation systems contributes to the maintenance of chronic pain. However, the function of this circuitry has not yet been explored in humans with chronic pain. In this study, we report that individuals with orofacial neuropathic pain show altered functional connectivity between regions within the brainstem pain-modulation network. We suggest that these changes reflect largely central mechanisms that feed back onto the primary nociceptive synapse and enhance the transfer of noxious information to higher brain regions, thus contributing to the constant perception of pain. Identifying the mechanisms responsible for the maintenance of neuropathic pain is imperative for the development of more efficacious therapies.
•The uncinate fasciculus shows reduced integrity in the subgenual and polar stems in depression, but not in the lateral stem.•The subgenual and amygdaloid fibers of the cingulum bundle, but not the ...main body of the cingulum, show reduced integrity in depression.•Reduced white matter integrity in the uncinate fasciculus and cingulum are present from the first-onset of the disease.
The subgenual cingulate gyrus (Brodmann's Area 25: BA25) is hypermetabolic in depression and has been targeted successfully with deep brain stimulation. Two of the white matter tracts that play a role in treatment response are the uncinate fasciculus (UF) and the cingulum bundle. The UF has three prefrontal stems, the most medial of which extends from BA25 (which deals with mood regulation) and the most lateral of which extends from the dorso-lateral prefrontal cortex (concerned with executive function). The cingulum bundle has numerous fibers connecting the lobes of the cerebrum, with the longest fibers extending from BA25 to the amygdala. We hypothesize that there is reduced integrity in the UF, specific to the medial prefrontal stems, as well as in the subgenual and amygdaloid fibers of the cingulum bundle. Our secondary hypothesis is that these changes are present from the early stages of depression.
Compare the white matter integrity of stems of the UF and components of the cingulum bundle in first-onset depressed, recurrent/chronic depressed, and non-depressed control subjects.
Depressed patients (n = 103, first-onset = 57, chronic = 46) and non-depressed control subjects (n = 74) underwent MRI with 32-directional DTI sequences. The uncinate fasciculi and cingulum bundles were seeded, and the fractional anisotropy (FA) measured in each of the three prefrontal stems and the body of the UF, as well as the subgenual, body, and amygdaloid fiber components of the cingulum bundle. FA measurements were compared between groups using ANOVA testing with post-hoc Tukey analysis.
There were significant reductions in FA in the subgenual and polar stems of the UF bilaterally, as well as the subgenual and amygdaloid fibers of the cingulum bundle, in depressed patients compared with controls (p < 0.001). There was no significant difference seen in the lateral UF stem or the main body of the cingulum. No significant difference was demonstrated in any of the tracts between first-onset and chronic depression patients.
Depressed patients have reduced white matter integrity in the subgenual and polar stems of the uncinate fasciculi but not the lateral stems, as well as in the subgenual and amygdaloid cingulum fibers. These changes are present from the first-onset of the disease.
The neural mechanism responsible for migraine remains unclear. While an external trigger has been proposed to initiate a migraine, it has also been proposed that changes in brainstem function are ...critical for migraine headache initiation and maintenance. Although the idea of altered brainstem function has some indirect support, no study has directly measured brainstem pain modulation circuitry function in migraineurs particularly immediately before a migraine. In male and female humans, we performed fMRI in 31 controls and 31 migraineurs at various times in their migraine cycle. We measured brainstem function during noxious orofacial stimulation and assessed resting-state functional connectivity. First, we found that, in individual migraineurs, pain sensitivity increased over the interictal period but then dramatically decreased immediately before a migraine. Second, despite overall similar pain intensity ratings between groups, in the period immediately before a migraine, compared with controls and other migraine phases, migraineurs displayed greater activation in the spinal trigeminal nucleus during noxious orofacial stimulation and reduced functional connectivity of this region with the rostral ventromedial medulla. Additionally, during the interictal phase, migraineurs displayed reduced activation of the midbrain periaqueductal gray matter and enhanced periaqueductal gray connectivity with the rostral ventromedial medulla. These data support the hypothesis that brainstem sensitivity fluctuates throughout the migraine cycle. However, in contrast to the prevailing hypothesis, our data suggest that, immediately before a migraine attack, endogenous analgesic mechanisms are enhanced and incoming noxious inputs are less likely to reach higher brain centers.
It has been hypothesized that alterations in brainstem function are critical for the generation of migraine. In particular, modulation of orofacial pain pathways by brainstem circuits alters the propensity of external triggers or ongoing spontaneous activity to evoke a migraine attack. We sought to obtain empirical evidence to support this theory. Contrary to our hypothesis, we found that pain sensitivity decreased immediately before a migraine, and this was coupled with increased sensitivity of the spinal trigeminal nucleus to noxious stimuli. We also found that resting connectivity within endogenous pain modulation circuitry alters across the migraine cycle. These changes may reflect enhanced and diminished neural tone states proposed to be critical for the generation of a migraine and underlie cyclic fluctuations in migraine brainstem sensitivity.
•We examine the effect of photobiomodulation on brain activity using fMRI.•Photobiomodulation had no effect on cerebral blood flow or resting state activity.•After finger-tapping, photobiomodulation ...resulted in reduction in brain activity.•Affected regions were putamen, primary somatosensory and parietal association cortex.•These light-induced changes served to deactivate the so-called default mode network.
We explore whether near infrared light can change patterns of resting (task-negative) and/or evoked (task-positive; eg finger-tapping) brain activity in normal, young human subjects using fMRI (functional magnetic resonance imaging). To this end, we used a vielight transcranial device (810 nm) and compared the scans in subjects after active- and sham-light sessions. Our fMRI results showed that, while light had no effect on cerebral blood flow and global resting state brain activity (task-negative), there were clear differences between the active- and sham-light sessions in the patterns of evoked brain activity after finger-tapping (task-positive). The evoked brain regions included the putamen, primary somatosensory and parietal association cortex, and the overall effect of the light was to suppress or reduce their activity. We also found that while light had no effect on the resting functional connectivity of the putamen and primary somatosensory cortex and the rest of the brain, it did have an effect on the functional connectivity of parietal association cortex. In summary, our fMRI findings indicated that transcranially applied light did have a major impact on brain activity in normal subjects, but only when the brain region was itself functionally active, when undertaking a particular task. We suggest that these light-induced changes, particularly those in parietal association cortex, were associated with attention and novelty, and served to deactivate the so-called default mode network. Our results lay the template for our planned fMRI explorations into the effects of light in both Alzheimer's and Parkinson's disease patients.
Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder that typically occurs in the limbs, usually the upper limb. CRPS usually develops from a peripheral event but its ...maintenance relies on changes within the central nervous system. While functional abnormalities in the thalamus and primary somatosensory cortex (S1) of the brain are some of the most consistently reported brain findings in CRPS, the mechanisms are yet to be explored in full, not least of all how these two regions interact and how they might relate to clinical deficits, such as the commonly reported poor tactile acuity in this condition. This study recruited 15 upper‐limb CRPS subjects and 30 healthy controls and used functional magnetic resonance imaging (fMRI) to investigate infra‐slow oscillations (ISOs) in critical pain regions of the brain in CRPS. As hypothesised, we found CRPS was associated with increases in resting signal intensity ISOs (0.03–0.06 Hz) in the thalamus contralateral to the painful limb in CRPS subjects. Interestingly, there was no such difference between groups in S1, however CRPS subjects displayed stronger thalamo‐S1 functional connectivity than controls, and this was related to pain. As predicted, CRPS subjects displayed poor tactile acuity on the painful limb which, interestingly, was also related to thalamo‐S1 functional connectivity strength. Our findings provide novel evidence of altered patterns of resting activity and connectivity in CRPS which may underlie altered thalamocortical loop dynamics and the constant perception of pain.
Individuals with complex regional pain syndrome (CRPS) displayed increased infra‐slow oscillations (0.03–0.06 Hz) in the thalamus contralateral to the painful limb as well as stronger thalamo‐S1 functional connectivity than controls. CRPS subjects displayed poor tactile acuity on the painful limb which was also related to thalamo‐S1 functional connectivity strength. Our findings provide novel evidence of altered patterns of resting activity and connectivity in CRPS which may underlie altered thalamocortical loops dynamics and the constant perception of pain.
Chronic Neuropathic Pain: It's about the Rhythm Alshelh, Zeynab; Di Pietro, Flavia; Youssef, Andrew M ...
The Journal of neuroscience,
2016-Jan-20, 2016-01-20, 20160120, Letnik:
36, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The neural mechanisms underlying the development and maintenance of chronic neuropathic pain remain unclear. Evidence from human investigations suggests that neuropathic pain is associated with ...altered thalamic burst firing and thalamocortical dysrhythmia. Additionally, experimental animal investigations show that neuropathic pain is associated with altered infra-slow (<0.1 Hz) frequency oscillations within the dorsal horn and somatosensory thalamus. The aim of this investigation was to determine whether, in humans, neuropathic pain was also associated with altered infra-slow oscillations within the ascending "pain" pathway. Using resting-state functional magnetic resonance imaging, we found that individuals with orofacial neuropathic pain have increased infra-slow oscillatory activity throughout the ascending pain pathway, including within the spinal trigeminal nucleus, somatosensory thalamus, thalamic reticular nucleus, and primary somatosensory cortex. Furthermore, these infra-slow oscillations were temporally coupled across these multiple sites and occurred at frequencies similar to calcium waves in activated astrocytes. The region encompassing the spinal trigeminal nucleus also displayed increased regional homogeneity, consistent with a local spread of neural activity by astrocyte activation. In contrast, no increase in oscillatory behavior within the ascending pain pathway occurred during acute noxious stimuli in healthy individuals. These data reveal increased oscillatory activity within the ascending pain pathway that likely underpins increased thalamocortical oscillatory activity, a self-sustaining thalamocortical dysrhythmia, and the constant perception of pain. Significance statement: Chronic neuropathic pain is associated with altered thalamic firing and thalamocortical dysrhythmia. The mechanisms responsible for these changes remain unknown. In this study, we report in individuals with neuropathic pain increased oscillatory neural activity within the ascending pain pathway with evidence that these changes result from altered neural-astrocyte coupling. We propose a series of neural and glial events after nerve injury that result in the generation of altered thalamocortical activity and a persistent neuropathic pain state. Defining the underlying mechanisms responsible for neuropathic pain is critical if we are to develop more effective treatment regimens.
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