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Brooks, J.

Publications and source records attributed to Brooks, J..

At least 19 recordsLinked to original sources

The building blocks of social structure: simulating constraints of social network analysis for inference about group-level properties

The interdisciplinary usage of Social Network Analysis (SNA) means that, when researchers calculate global network metrics, the research interest can range from the ultimate ecological and evolutionary pressures that select for specific group-level structures or the proximate mechanisms by which those structures emerge. Despite major methodological advances, social structures measured via SNA metrics are rarely connected to the underlying forces shaped by latent individual dispositions, ecological constraints, and their interplay with group-level affordances. We build a model to simulate fission-fusion spatial association data from a specified set of parameters in order to address the "black box" of animal SNA. We broke down animal social systems into three building blocks: individual dispositions, external factors, and the social structure that emerges. Each of these building blocks was represented by one or more model parameters, which together describe a set of underlying processes that lead to different measurable features of animal social structure, which we quantified with commonly used global network metrics within an SNA framework (e.g., clustering coefficient, density, modularity). In doing so, our model directly links global network metrics to the underlying behavioural processes that generate them and demonstrates how global network metrics can be influenced by changes to their underlying behavioural processes. Holding all other parameters constant, we find that subtle changes to 1) demography (i.e., group size) and ecology (i.e., size and variability of foraging parties), 2) variation of individual behaviour and related observation bias, 3) imposed group sub-structures, and 4) observation effort, affect all network metrics calculated non-linearly and in some cases non-monotonically. Our findings indicate that failure to account for the underlying behavioural processes can bias inference drawn from SNA. This model and conceptual framework provide a novel tool with which to begin opening the black box of SNA and to systematically address the evolution of diverse group-level social structures.

animal behavior and cognition↗

SALRR: Scalable Analysis of Long-Read RNA-Seq Enables Comprehensive Transcriptome Profiling in Human Brain

Isoform-resolved transcriptomics is fundamental to decoding the molecular complexity of the human brain, yet population-scale long-read RNA sequencing has remained inaccessible due to labor-intensive library preparation, sensitivity to RNA degradation in postmortem tissue, and the absence of integrated, reproducible analysis pipelines. Here we present SALRR (Scalable Analysis of Long-Read RNA-seq), an integrated wet-lab and computational platform designed to overcome these barriers. Automated ONT long-read cDNA library preparation on the Hamilton Microlab NGS STAR platform reduces hands-on time by 67% and enables 24 libraries per operator per day while maintaining performance across RNA integrity values. A modular, Snakemake-based pipeline performs end-to-end processing from ONT signal data to isoform-level quantification, incorporating SIRV spike-in calibration, multi-stage quality control, and stringent isoform validation. Applied to 10 postmortem frontal cortex samples from the North American Brain Expression Consortium, SALRR identified 31,607 high-confidence isoforms from 10,075 genes, including 8,532 novel splice variants absent from GENCODE v49, and complex splicing events systematically missed by short-read sequencing at neurodegeneration-relevant loci, including GBA1, CCNF, CHCHD10, and TREM2. All protocols and code are openly available, providing a scalable, community-ready framework for isoform-resolved transcriptomics in neurodegeneration, aging, and complex brain disease.

genomics↗

The role of the Angular Gyrus in the Elaboration of Specific and Categoric Memories

This study investigated the role of the angular gyrus (AG) and its subregions in the elaboration of specific and categoric autobiographical memories (AMs). Using a cue-word fMRI paradigm, thirty-nine participants retrieved and elaborated on episodic (specific) and semantic (categoric) memories, rating the amount of detail of each recollection. Parametric analyses revealed that AG activity, particularly in posterior AG, was positively associated with the amount of detail retrieved, regardless of memory type. Specific memories elicited greater activation in right AG subregions compared to categoric memories. These findings support the AGs involvement in both episodic and semantic memory retrieval and suggest functional differentiation between its subregions.

neuroscience↗

Wild chimpanzee groups increase social connectivity prior to risky collective action

Cooperation is foundational to complex sociality, yet presents profound evolutionary dilemmas - costs and benefits are rarely distributed evenly and the decision to collaborate or defect can involve a complex contextual calculus. These challenges are compounded when cooperation scales from pairs to groups. Group-level cooperation is fundamental to many species success, but how is it sustained and regulated in nature? One promising route to addressing this question is to examine how individuals reorganise their affiliative interactions in anticipation of group-level cooperation. We examine such pre-cooperative reorganisation using long-term data (2013-2018) from three neighbouring groups of wild chimpanzees at the Tai National Park, Cote dIvoire, who routinely cooperate as a collective to defend their territory against other groups. We found that chimpanzees adjusted the distribution of their social contacts in anticipation of risky and proactive territorial defence by forming more broadly connected, yet more diffuse, affiliative networks. Specifically, adult chimpanzees groomed and played with more group members on days of proactive territorial defence, and this pattern was temporally-sensitive, with increased affiliation occurring before, rather than after, the cooperative act. Chimpanzees accessed a broader range of partners through increased interaction efficiency by switching between more partners with shorter interactions per partner. This pattern suggests a shared evolutionary basis of dynamic social readjustment in preparation for group-level social dilemmas in hominids, potentially providing the foundation for the formalized systems of affiliation found in human societies.

animal behavior and cognition↗

The demonstration of a single origin for nodule evolution, with nodule engineering in a non-nodulating species

The nitrogen-fixing root-nodule symbiosis provides a sustainable source of nitrogen for plants within the Nitrogen (N)-fixing clade (NFC). A debate has raged over whether nodulation evolved once, with many losses or multiple times following a predisposition event. Here we demonstrate that nodule-organogenesis is fully conserved between an actinorhizal nodulator Datisca glomerata and the legume Medicago truncatula, showing entirely conserved programmes for Nodule INception (NIN)-controlled development leading to nodule emergence. Convergent losses of N-fixation within the NFC is associated with loss of NIN and we show the engineering of nodule-like development into strawberry, a non-nodulating member of the NFC, through the repair of NIN-functionality. Similar NIN-engineering resulted in altered-root developmental responses in barley. Our work is consistent with the single-gain hypothesis, where repair of NIN can recapitulate nodules in species within the NFC, demonstrating that understanding the ancestral state of nodulation facilitates its engineering.

plant biology↗

The Drosophila melanogaster Genetic Reference Panel, Version 3 (DGRP3)

Drosophila melanogaster is a leading animal model for understanding basic genetic principles for biomedical research and for quantitative, population and evolutionary genetics and genomics. The D. melanogaster Genetic Reference Panel (DGRP) of [~]200 inbred strains with full genome sequences is a publicly available resource for genome wide association (GWA) studies of quantitative traits, systems genetics, and population genomic analyses. However, the small size of the DGRP limits the power to map rare variants or variants with small effect sizes. Here, we describe the DGRP Version 3 (DGRP3), consisting of full genome sequences from 1,233 inbred lines, of which 1,037 are currently extant. The DGRP3 harbors extensive genetic diversity, with 8,760,339 molecular polymorphisms including single nucleotide polymorphisms, insertions, deletions, inversions, tandem duplications and complex rearrangements. We identified 80,894 damaging variants and 4,550 genes with at least one loss-of-function haplotype. We inferred 16 mitochondrial haplotype groups, determined the microbial composition, and quantified the numbers of sensory bristles for the DGRP3 lines. We performed GWA analyses for inbreeding depression, host control of microbiome composition, and numbers of sensory bristles, identifying novel candidate variants and genes for each. The accompanying online tool (flydgrp.org) implements state-of-the-art association mapping methods and provides results for users DGRP3 data.

genomics↗

TRIM9 switches the morphological phenotype of melanoma cells

Melanoma is a highly plastic cancer characterized by distinct cellular phenotypes associated with broadly unique gene expression profiles. TRIM9 is a brain-enriched E3 ubiquitin ligase detected in melanoma, but how TRIM9 expression regulates melanoma phenotype is unknown. Using two metastatic human melanoma cell lines and a mouse melanoma model, we found that TRIM9 promoted melanoma proliferation and altered cell morphology. In cell lines, TRIM9 promoted cellular blebbing and negatively regulated adhesion, secretion, and mesenchymal motility. TRIM9 interacted with VASP in melanoma cells, altering VASP modification, localization, and dynamics. In the absence of TRIM9, cells had an altered actin organization and more focal adhesions, where VASP accumulated and exhibited rapid turnover. We find the alterations in actin architecture and adhesion associated with TRIM9 deletion were coincident with increased motile and contractile mesenchymal behavior in vitro. In vivo loss of TRIM9 in melanoma slowed tumor growth and altered metastasis frequency, size, and destination. Our findings indicate TRIM9 alters the proliferative and morphological phenotypes of metastatic melanoma cells to influence disease progression.

cancer biology↗

Spatial multi-omics identify an immunosuppressive lipid-laden macrophage niche in primary CNS lymphoma

Primary central nervous system lymphoma (PCNSL) is histologically a subtype of diffuse large B-cell lymphoma (DLBCL), sharing genetic and transcriptomic similarity, but with distinct clinical features, particularly its confinement to the CNS and higher relapse risk. The microenvironmental basis for its divergence from systemic DLBCL remains unclear. Using spatial transcriptomic approaches (Xenium/GeoMx digital spatial profiling) in a comparative study of PCNSL (n=17) and DLBCL (n=76), we found that PCNSL, unlike systemic DLBCL, is dominated by an immunosuppressive macrophage compartment enriched for cholesterol-metabolism programs. In independent cohorts of PCNSL profiled by single-cell RNA sequencing, we validated the presence of a recurrent population of lipid-laden macrophages (LLMs): TREM2/GPNMB-expressing, lipid-remodeled cells transcriptionally distinct from resident microglia and consistent with an infiltrating monocyte origin, not previously characterized in CNS lymphoma. LLMs formed immunosuppressive niches with regulatory T cells, and using Cellscape hyperplex proteomic imaging we demonstrate that LLM-Treg spatial interactions are associated with chemotherapy response. To test whether LLMs are lymphoma-driven and functionally important, we developed an immunocompetent syngeneic PCNSL mouse model, driven by Myd88L252P and Cd79b mutations with Bcl2 overexpression. Monocyte-derived macrophages in lymphoma-bearing brain regions acquired an LLM-like state, not seen in lymphoma-free brain regions or in splenic tumors driven by the same oncogenic lesions. TREM2-SYK signaling sustained this state, and SYK inhibition reversed its tumor-supportive activity ex vivo. These findings identify the LLM program as a targetable immunosuppressive myeloid state in CNS lymphoma.

cancer biology↗

Inflammatory signaling differentially changes chromatin accessibility and gene expression of the PD- associated kinase LRRK2 between human and mice

The genomic locus that encodes the Leucine-rich repeat kinase 2 (LRRK2) gene is highly pleiotropic, being associated with both Parkinsons disease (PD) and Crohns disease (CD). Coding variants associated with risk of PD and CD act as gain of function kinase mutations increasing phosphorylation of RAB substrates, and non-coding variants in the promoter region of LRRK2 increase expression of the gene, notably in immune cells. If regulation of LRRK2 expression is a causal contributor to age-related diseases, it is important to understand the mechanism(s) by which LRRK2 is regulated, particularly in the context of inflammation. Here, we show that interferon-{gamma} exposure induces robust LRRK2 activation in human iPSC-derived microglia through signaling of the Janus-activated Kinase complex to phosphorylate STAT1, which then binds to the LRRK2 promoter and is associated with remodeling of chromatin structure in this genomic locus. Additional regulatory mechanisms include the stress-induced transcription factor and long non-coding RNA encoded at the same locus, resulting in increased LRRK2 mRNA levels. We also show evidence of the same effect in acutely cultured human brain slices. While we were unable to demonstrate any induction of Lrrk2 mRNA in the mouse brain, the introduction of a human bacterial artificial chromosome transgene into the mouse genome recapitulated sensitivity to interferon-{gamma} in microglia. A comparative genomic analysis across mammals suggests that these species differences are driven by regulatory regions upstream of LRRK2 that are specific to anthropoid primates. These results demonstrate that there are differences between species in how genes associated with human diseases are regulated and provide important information that should be incorporated in disease modeling.

neuroscience↗

In vitro multi-assay cytotoxicity assessment of iron oxide nanoparticles on neural cells and addressing spectrophotometric interference

Iron-rich nanoparticulate matter air pollution exposure is implicated in the pathophysiology of Alzheimers disease. The use of colorimetric cell viability assays to ascertain the potential cytotoxicity of iron oxide nanoparticles have highlighted conflicting results in various in vitro models, because of spectrophotometric interference. Attempts to resolve this confounding factor to reveal accurate measurements have been insufficient. To address this interference issue, we tested three control methods (readout correction, plate transfer, and above-plate reading) on in vitro cytotoxicity measurements via Neutral Red Uptake (NRU), Resazurin, and MTT assays, of iron oxide and magnetite nanoparticulate exposure on SK-N-SH and IMR-32 human neural cell lines. We observed varying degrees of interference based on cell line, nanoparticle type, exposure time, assay type, and the readout method (colorimetric or fluorometric). The readout correction method did not remove interference completely, the plate transfer method tended to cause overestimation of cell viability beyond the original interference, and fluorescence readings from above the plate were less sensitive than the conventional bottom reading. The Resazurin assay with fluorometric readout presented no interference in most conditions investigated in this work, therefore presents advantages over both colorimetric assays and interference control methods. It is recommended to forego colorimetric assays in future studies of nanoparticle cytotoxicity as they are more susceptible to interference.

pharmacology and toxicology↗

Spontaneous rhythmic and tool-assisted drumming across variable tempo and technique in a captive chimpanzee

Rhythmic drumming on percussive instruments is a common element of music across human cultures. Chimpanzees also drum on the buttress roots of trees and other resonant objects, and often combine their drumming with long-distance pant-hoot vocalizations. Previous studies have suggested that chimpanzees select drumming substrates for their acoustic properties and that chimpanzee drumming shares core elements of human musicality (e.g., non-random timing, isochronous - metronome-like rhythm, and de-contextualised production in captivity). But to what extent can chimpanzees flexibly control their drumming rhythm across percussive media and techniques? Here, we report on a long-lasting drumming event by a captive chimpanzee named Toon, which was performed across multiple pant-hoot displays and employed diverse action forms, including the use of multiple drumstick-on-drum multi-tools. We find flexible rhythmic production and isochrony across drumming implements, techniques, and tempos. Further, we describe tool set transport and reuse, selectivity of percussive acoustic properties associated with different vocal elements, and variable use of the facial expression "play face" associated with faster and less variable rhythms, potentially indicating intrinsic enjoyment of such rhythms. Together, these findings provide evidence for key elements of human musicality in Toons drumming, supporting the hypothesis of shared evolutionary roots of human and chimpanzee drumming.

animal behavior and cognition↗

Integrative analysis reveals generalizable human neurodegenerative disease-associated glial states

Glial cells are known to respond transcriptionally in multiple neurodegenerative diseases (NDDs). In particular, microglial states have been characterized in Alzheimers disease and mouse models of amyloidosis as disease-associated microglia. Although single-cell transcriptomic technologies have increased the dimensionality of information available across cell states, few studies have systematically tested for changes in glial transcription across brain regions and disease states. Here, we report a statistical framework for glial annotation, disease association, and transcriptional profiling, which facilitate identification of generalizable glial states that are present across a spectrum of NDDs (Alzheimers disease, Parkinsons disease, amyotrophic lateral sclerosis, and frontotemporal dementia) by re-analyzing data available in four multi-region atlases. We identify seven astrocyte substates, 14 microglia/myeloid substates, and five oligodendrocyte substates where transcriptional variability is attributable to region, disease, or study-specific effects. Regional heterogeneity of astrocytes masked disease associations, even within cortical subregions. We found only limited oligodendrocyte transcriptional heterogeneity, resulting in few substates for further interrogation. Notably, microglia showed the strongest evidence for disease association. We show, for the first time, that this association exists across different NDDs. Using latent factor analysis, we created a consensus human neurodegenerative disease-associated microglia (hnDAM) signature, which we experimentally validated in 11 independent sample series. We demonstrate that the hnDAM signature is a statistically testable biomarker for conserved microglial activation in NDDs by: i) comparing to murine DAM-like signatures, ii) performing transcription factor analysis, and iii) modeling transcriptional reprogramming perturbations in iPSC-derived microglia. Importantly, we find for the first time a way to make direct comparisons between DAM-like activation profiles in separate studies and propose a novel modeling paradigm via PIKfyve inhibition. Taken together, this work broadens our understanding of glial activation across neuropathologies and reveals hnDAM as a putative therapeutic target that can be utilized in any transcriptomic study of patients suffering from NDDs. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/678630v2_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1863095org.highwire.dtl.DTLVardef@dfa6c8org.highwire.dtl.DTLVardef@13e95f1org.highwire.dtl.DTLVardef@1e6165e_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Targeted Irradiation and STAT3 Inhibition Reprogram the AML Microenvironment and Extend Survival: Toward Translational Immunoradiotherapy

PurposeDespite advances in acute myeloid leukemia (AML) therapy, relapses remain challenging. While AML is radiation-sensitive, total body irradiation (TBI) causes organ toxicities and activates tolerogenic/proangiogenic STAT3 signaling. CSI-2, a myeloid cell-targeted STAT3 inhibitor, promotes anti-leukemic immune responses but has limited efficacy against high disease burden. We investigated whether image-guided targeted marrow irradiation (TMI), which focuses radiation on leukemia sites while sparing critical organs, could synergize with CSI-2 to improve leukemia clearance and establish durable immunity. MethodsMice were intravenously engrafted with CMM-AML cells reaching 20-30% in bone marrow (BM) infiltration (moderate-to-high disease burden) before receiving IV-injections of CSI-2 (5mg/kg) with or without TMI. Fluorescently labeled CSI-2 biodistribution was assessed using flow cytometry and quantitative multiphoton microscopy. Survival was monitored for 3-4 months before evaluating BM composition using flow cytometry and immunohistochemistry. ResultsTMI significantly improved vascular permeability and scavenger receptor/TLR9-dependent uptake of CSI-2 by AML cells and leukemia-associated myeloid cells. Combined TMI/CSI-2 treatment more effectively reduced high leukemia burden than CSI-2 alone, achieving >80% survival at 120 days with increased CD8+ cytotoxic and CD4+ helper T cell infiltration. TMI/CSI-2-treated mice were protected from AML rechallenge suggesting that they developed protective immune memory. In an aggressive MLL-AF9 AML model, TMI/CSI-2 combination significantly extended survival compared to either monotherapy. ConclusionTMI/CSI-2 strategy represents a novel organ-sparing immunoradiotherapy that synergistically enhances leukemia clearance while promoting long-term protective immunity. These findings warrant further investigation of this strategy for high-burden or relapsed AML and provide the foundation for clinical translation.

immunology↗

An eye-tracking study of visual attention in chimpanzees and bonobos when viewing different tool-using techniques

Chimpanzees and bonobos are excellent tool users and can socially learn various skills. Previous studies on social learning mainly measure success/failure in acquiring new techniques, with less direct measurement of proximate mechanisms like visual attention during the process. This study investigates how apes observe tool-using demonstrations through eye-tracking. After checking initial techniques, six chimpanzees and six bonobos were shown video demonstrations of human demonstrators using a tube to dip (low-efficiency) or suck (high-efficiency) juice, and then tried the task themselves. Attention to each video was compared to participants knowledge. Although no individuals acquired the high-efficiency technique through video demonstrations, eye-tracking results revealed attentional differences between individuals familiar with different techniques. Compared with individuals already familiar with both techniques, individuals knowing only the dipping technique showed less attention to the unfamiliar sucking technique. This result indicates that apes may not attend much to what they do not know well, which aligns with reported interplay of action observation and understanding. Attentional patterns to specific areas was similar between species, though there was a tendency towards more attention to faces in bonobos and food in chimpanzees. This study emphasizes the importance of detailed investigation into social learning process using eye-tracking.

animal behavior and cognition↗

Combinatorial CRISPR screens and lectin microarrays identify novel glycosylation regulators

Glycans play critical roles in cellular signaling and function. Unlike proteins, glycan structures are not templated from genes but the concerted activity of many genes, making them historically challenging to study. Here, we present a strategy that utilizes pooled CRISPR screens and lectin microarrays to uncover and characterize regulators of cell surface glycosylation. We applied this approach to study the regulation of high mannose glycans - the starting structure of all asparagine(N)-linked-glycans. We used CRISPR screens to uncover the expanded network of genes controlling high mannose surface levels, followed by lectin microarrays to fully measure the complex effect of select regulators on glycosylation globally. Through this, we elucidated how two novel high mannose regulators - TM9SF3 and the CCC complex - control complex N-glycosylation via regulating Golgi morphology and function. Notably, this method allowed us to interrogate Golgi function in-depth and reveal that similar disruption to Golgi morphology can lead to drastically different glycosylation outcomes. Collectively, this work demonstrates a generalizable approach for systematically dissecting the regulatory network underlying glycosylation.

cell biology↗

Oxytocin promotes social grooming in bonobos: testing the biobehavioural feedback loop hypothesis

Oxytocin has attracted research attention due to its role in promoting social bonding. In bonobos and chimpanzees, the two Pan species closely related to humans, urinary oxytocin is known to correlate with key behaviours related to social bonding, such as social grooming in chimpanzees and female-female sexual behaviour in bonobos. However, no study has demonstrated that the administration of oxytocin promotes real-life social interactions in Pan, leaving it unclear whether oxytocin is merely correlated with social behaviors or does affect them in these species. To test this, we administered nebulized oxytocin or saline placebo to a group of female bonobos and subsequently observed the change in their gross behavior during free interaction. We found an overall effect of more frequent grooming in the oxytocin condition. However, on the individual level this effect remained significant for only one participant in our follow-up models, suggesting future work should explore inter-individual variation. Our results provide some experimental support for the biobehavioural feedback loop hypothesis, which posits that some functions of the oxytocin system support the formation and maintenance of social bonds through a positive feedback loop; however, further tests with a larger number of individuals are required. Our results, at a minimum, demonstrated that oxytocin affects spontaneous, naturalistic social interactions of at least some female bonobos, adding to accumulating evidence that oxytocin modulates complex social behaviors of Pan.

animal behavior and cognition↗

"Understanding Cortical Arousals during Sleep from Leg Movements: A Pilot Study."

Leg movements during sleep occur in patients with sleep pathology and healthy individuals. Some (but not all) leg movements during sleep are related to cortical arousals which occur without conscious awareness of the patient but have a significant effect of sleep fragmentation. Detecting leg movements during sleep that are associated with cortical arousals can provide unique insight into the nature and quality of sleep in both health and disease. In this study, a novel leg movement monitor is used in conjunction with polysomnography to better understand the relationship between leg movement and electroencephalogram (EEG) defined cortical arousals. In an approach that we call neuro-extremity analysis, graph theoretic, directed connectivity metrics are used to interrogate the causal links between neural activity measured by EEG and leg movements measured by the sensors within the leg movement monitor. The leg movement monitor in this study utilizes novel capacitive displacement sensors, and a 9-axis inertial measurement unit to characterize leg and foot movements. First, the capacitive displacement measures more closely related to EEG-defined cortical arousals than inertial measurements. Second, the neuro-extremity analysis reveals a temporally evolving connectivity pattern that is consistent with a model of cortical arousals in which brainstem dysfunction leads to near-instantaneous leg movements and a delayed, filtered signal to the cortex. Neuro-extremity analysis reveals causal relationships between EEG and leg movement sensor time-series data that may aid researchers to better understand the pathophysiology of cortical arousals associated with leg movements during sleep.

neuroscience↗

Simultaneous Brain, Brainstem and Spinal Cord pharmacological-fMRI reveals multilevel opioidergic roles in attentional analgesia in humans

Pain perception is decreased by shifting attentional focus away from a threatening event. This attentional analgesia engages parallel descending control pathways from anterior cingulate (ACC) to locus coeruleus, and ACC to periaqueductal grey (PAG) - rostral ventromedial medulla (RVM), indicating possible roles for noradrenergic or opioidergic neuromodulators. To determine which pathway modulates nociceptive activity in humans we used simultaneous whole brain-spinal cord pharmacological-fMRI (N=39) across three sessions. Noxious thermal forearm stimulation generated somatotopic-activation of dorsal horn (DH, C6 segment) whose activity mirrored attentional pain modulation. Activity in an adjacent cluster reported the interaction between task and noxious stimulus. Effective connectivity analysis revealed that ACC recruits PAG and RVM to modulate spinal cord activity. Blocking endogenous opioids with Naltrexone impairs attentional analgesia and disrupts RVM-DH and ACC-PAG connectivity. Noradrenergic augmentation with Reboxetine did not alter attentional analgesia. Cognitive pain modulation is mediated by opioidergic ACC-PAG-RVM descending control which supresses spinal nociceptive activity.

neuroscience↗