Biology subjects

Morrison, I.

Publications and source records attributed to Morrison, I..

8 recordsLinked to original sources

bioRxiv2025

White matter reorganization of motor and affective-motivational networks in pain-indifferent carriers of the R221W mutation

Congenital insensitivity to pain (CIP) due to the R221W mutation on the nerve growth factor gene results in reduced peripheral C-nociceptor density and behavioural indifference to painful stimuli. While functional neuroimaging has revealed altered cortical and sub-cortical pain processing in R221W carriers, structural white matter changes remain unexplored and may suggest an anatomical basis of symptoms. Heterozygous R221W carriers (n = 11) and age-, sex-, education-matched controls (n = 11) diffusion tensor imaging data were compared using fixel-based analysis, and complimentary edge and node analyses using graph theory, and network-based statistics. Whole-brain and region of interest (ROI) fixel-based analyses revealed significantly reduced fibre density and fibre-bundle cross-section in brainstem motor tracts of R221W carriers, encompassing the corticospinal pathways, corona radiata, external capsule, cerebellar peduncles, and pontine crossing (p < 0.05). Graph theory analysis of pain-processing ROIs demonstrated reduced local efficiency in right anterior cingulate cortex (ACC) and altered betweenness centrality in bilateral insula and left ACC of R221W carriers. Despite R221W carriers showing higher node degrees in the somatosensory cortex and ACC, these connections had reduced efficiency and integration with cortical network regions. Network-based statistics identified a possible compensatory subnetwork with stronger connectivity from right thalamus to left ACC and left insula in R221W carriers (p < 0.019). These findings suggest that congenitally reduced peripheral nociception could lead to abnormalities in the thalamocortical and motor efferent pathway, but not sensory afferent pathways. The combination of reduced brainstem motor tract integrity and altered cortical network efficiency, alongside potentially compensatory thalamo-cortical connectivity, could support a model of R221W CIP as motor under-reactivity rather than sensory insensitivity.

neuroscience↗

bioRxiv2021

Prediction and action in cortical pain processing

Predicting that a stimulus is painful facilitates action to avoid harm. But how distinct are the neural processes underlying the prediction of upcoming painful events, and those taking action to avoid or prevent them? In this fMRI experiment, we addressed this by investigating brain activity as a function of current and predicted painful or nonpainful thermal stimulation, and the ability of voluntary action to affect the duration of the upcoming stimulation. Participants (n = 30) performed a task which involved the administration of a painful or nonpainful stimulus (S1), which predicted an immediately subsequent very painful or nonpainful stimulus (S2). On action-effective trials, pressing a response button within a specified time window during S1 reduced the duration of the upcoming stimulation in S2. On action-ineffective trials, pressing the button had no effect on upcoming stimulation. Predicted pain increased activation in regions including anterior cingulate cortex (ACC), midcingulate cortex (MCC), and insula; however, activation in ACC and MCC depended on whether a meaningful action was performed, with MCC activation showing a direct relationship with motor output. Region-of-interest analyses revealed that insulas responses for predicted pain were also modulated by potential action consequences, especially in the left hemisphere, albeit without a direct relationship with motor output. Taken together, these findings suggest that cortical pain processing is not specifically tied to the sensory stimulus, but instead depends on the consequences of that stimulus for sensorimotor control of behavior. Significance statementDuring acute pain, the processing of an acute sensory event likely occurs in parallel with predictive processing about its relevance for current and upcoming voluntary behavior. Here, we temporally separated the functional processes underlying current and predicted pain and found that activation in regions typically implicated in acute pain is modulated both by the noxious nature of upcoming events and by the possibility to affect those events via voluntary action (a button press). Our findings suggest that cortical pain processing is not specifically tied to the sensory stimulus, but instead is processed in "consequence-level" terms based on what the stimulus implies for sensorimotor control of behavior.

neuroscience↗

bioRxiv2021

Human endogenous oxytocin and its neural correlates show adaptive responses to social touch based on recent social context

Both oxytocin (OT) and touch are key mediators of social attachment. In rodents, tactile stimulation elicits endogenous release of OT, potentially facilitating attachment and other forms of prosocial behavior, yet the relationship between endogenous OT and neural modulation remains unexplored in humans. Using serial sampling of plasma hormone levels during functional neuroimaging across two successive social interactions, we show that contextual circumstances of social touch facilitate or inhibit not only current hormonal and brain responses, but also calibrate later responses. Namely, touch from a male to his female romantic partner enhanced subsequent OT release for touch from an unfamiliar stranger, yet OT responses to partner touch were dampened following stranger touch. Hypothalamus and dorsal raphe activation reflected plasma OT changes during the initial interaction. In the subsequent social interaction, time- and context-dependent OT changes modulated precuneus and parietal-temporal cortex pathways, including a region of medial prefrontal cortex that also covaried with plasma cortisol. These findings demonstrate that hormonal neuromodulation during successive human social interactions is adaptive to social context, and point to mechanisms that flexibly calibrate receptivity in social encounters.

neuroscience↗

bioRxiv2020

Integral use of immunopeptidomics and immunoinformatics for the characterization of antigen presentation and rational identification of BoLA-DR-presented peptides and epitopes

Major histocompatibility complex (MHC) peptide binding and presentation is the most selective event defining the landscape of T cell epitopes. Consequently, understanding the diversity of MHC alleles in a given population and the parameters that define the set of ligands that can be bound and presented by each of these alleles (the immunopeptidome) has an enormous impact on our capacity to predict and manipulate the potential of protein antigens to elicit functional T cell responses. Liquid chromatography-mass spectrometry (LC-MS) analysis of MHC eluted ligands (EL data) has proven to be a powerful technique for identifying such peptidomes, and methods integrating such data for prediction of antigen presentation have reached a high level of accuracy for both MHC class I and class II. Here, we demonstrate how these techniques and prediction methods can be readily extended to the bovine leukocyte antigen class II DR locus (BoLA-DR). BoLA-DR binding motifs were characterized by EL data derived from cell lines expressing a range of DRB3 alleles prevalent in Holstein-Friesian populations. The model generated (NetBoLAIIpan - available as a web-server at www.cbs.dtu.dk/services/NetBoLAIIpan) was shown to have unprecedented predictive power to identify known BoLA-DR restricted CD4 epitopes. In summary, the results demonstrate the power of an integrated approach combining advanced MS peptidomics with immunoinformatics for characterization of the BoLA-DR antigen presentation system and provide a novel tool that can be utilised to assist in rational evaluation and selection of bovine CD4 T cell epitopes.

bioinformatics↗

bioRxiv2020

Contrasting population genetics of cattle- and buffalo- derived Theileria annulata causing tropical theileriosis

The present study was designed to improve understanding of Theileria annulata in sympatric water buffalo and cattle in the Punjab province of Pakistan. The prevalence of tropical theileriosis is high, buparvaquone resistance is widespread, and vaccine protection is poor in the field. Better understanding is, therefore, needed of the factors that influence the genetics of T. annulata populations both within its hosts and in its overall populations. Here we utilise a panel of six satellites and a mitochondrial cytochrome b marker to explore the multiplicity of T. annulata infection and patterns of emergence and spread of different parasite genotypes. Parasite materials were collected from infected animals in defined regions, where water buffalo and cattle are kept together. Our results show that T. annulata is genetically more diverse in cattle- than in water buffalo-derived populations (the mean numbers of unique satellite alleles were 13.3 and 1.8 and numbers of unique cytochrome b locus alleles were 65 and 27 in cattle- and water buffalo-derived populations, respectively). The data show a high level of genetic diversity among the individual host-derived populations (the overall heterozygosity (He) indices were 0.912 and 0.931 in cattle, and 0.874 and 0.861 in buffalo, based on satellite and cytochrome b loci, respectively). When considered in the context of high parasite transmission rates and frequent animal movements between different regions, the predominance of multiple T. annulata genotypes, with multiple introductions of infection in the hosts from which the parasite populations were derived, may have practical implications for the spread of parasite genetic adaptations; such as those conferring vaccine cross-protection against different strains affecting cattle and buffalo, or resistance to antiprotozoal drugs.

genetics↗

bioRxiv2019

Development of a deep amplicon sequencing method to determine the proportional species composition of piroplasm haemoprotozoa as an aid in their control

Piroplasmosis is caused by tick-borne haemoprotozoa of the genera Theileria and Babesia. These parasitic infections can cause serious impact on the health of livestock and production. Multiple piroplasm species can infect a single host, but reliable molecular diagnostic tools are needed with which to understand the composition of these complex parasite communities. Theileria and Babesia vary in their epidemiology, drug sensitivity, pathogenicity and interaction of co-infecting species, but are similar in the animals, become persistent carriers after recovery from primary infection, acting as reservoir hosts. Here, we describe for the first time the use of a deep amplicon sequencing platform to identify proportions of piroplasm species in co-infecting communities and develop the concept of a \"haemoprotobiome\". First, four phenotypically-verified species of Theileria and Babesia were used to prepare mock pools with random amounts of the parasites and amplified with four different numbers of PCR cycles to assess sequence representation of each species. Second, we evaluated the detection threshold of the deep amplicon sequencing assay for each of the four species and to assess the accuracy of proportional quantification of all four species. Finally, we applied the assay to the field samples to afford insight of the species composition of piroplasm communities in small and large ruminants in the Punjab province of Pakistan. The \"haemoprotobiome\" concept has several potential applications in veterinary and human research, including understanding of responses to drug treatment; parasite epidemiology and ecology; species interactions during mixed infections; and parasite control strategies.

microbiology↗

bioRxiv2018

Bodily sensations in social scenarios: Where in the body?

Bodily states are fundamental to emotions emergence and are believed to constitute the first step in the chain of events that culminate in emotional awareness. Recent works have given fresh support to this view by showing that distinct topographical maps can be derived to describe how basic and more complex emotions are represented in the body. However, it is still unclear whether these bodily maps can also extend to emotions experienced specifically within social interactions and how these representations relate to basic emotions. To address this issue, we used the emBODY tool to obtain high-resolution bodily maps that represent the body activation and deactivation experienced by healthy participants in social scenarios depicting establishment or loss of social bonds. We show that clear patterns of activation/deactivation across the body emerge depending on the valence and on the characteristics of the single social scenarios, but also a common activation of head, chest and limbs across scenarios. Furthermore, we showed that maps related to complex social scenarios are strongly correlated with bodily states experienced in basic emotions, suggesting that the patterns of body activation/deactivation found for social scenarios might represent a combination of different basic emotions these experiences elicit. Our data tackle conscious emotional experiences and show for the first time how painful social events are felt on the body, providing findings that complement verbal reports and neuroimaging data on social rejection. Furthermore, they show that bodily feelings related to complex social scenarios, despite referring to unified independent emotional states, are also related to bodily correlates of basic emotions.

neuroscience↗

bioRxiv2018

A congenital pain insensitivity mutation in the nerve growth factor gene uncouples nociception from affective pain in heterozygous humans and mice

Pain is an unpleasant but necessary sensory experience, which facilitates adaptive behaviours, such as fear. Despite recent advances, the question of how the pain experience influences learning of the fear response is still debated1,2. Genetic disorders rendering patients congenitally unable to feel pain have been described, and are usually explained by defects in peripheral nociceptors3-5. It is not known how growing up without pain affects central emotional and motivational responses to aversive stimuli. The rare autosomal recessive Hereditary Sensory and Autonomic Neuropathy type V (HSAN V) is caused by a mutation in the nerve growth factor (NGF) gene (R100W). HSAN V homozygous patients display a congenital indifference to painful events, with deficits in peripheral nociceptors but without overt cognitive impairment6. In contrast, heterozygous carriers do not present with pain-related deficits and have been identified only through pedigree and genetic screening7,8. We exploited this clinically silent population to dissociate nociceptive from affective features of pain. To address this we investigated both heterozygous knock-in mice bearing the R100W mutation (NGFR100W/m mice) and a cohort of HSAN V heterozygous human carriers. Surprisingly, we found that NGFR100W/m mice, despite normal responses to a noxious conditioning stimulus, show a deficit in learned fear while their social and innate fear responses are normal. The lack of pain-related fear response was linked to a reduced activation of anterior cingulate and motor cortices and of striatum, but not in primary somatosensory cortex. Likewise, human heterozygous R100W carriers, despite perceiving noxious stimuli and reporting subjective pain thresholds, show increased reaction latencies in response to painful stimulation, alongside a decreased subjective urgency to react. Functional magnetic resonance imaging (fMRI) revealed, comparably to the mouse data, an altered processing of painful stimuli in rostral anterior cingulate, medial premotor cortical regions and striatum. These findings from both human and mouse HSAN V carriers uncover behavioural and motivational consequences of a mild genetic pain insensitivity on the establishment of pain-dependent affective responses and memories.

neuroscience↗