Modelling subject variability in the spatial and temporal characteristics of functional modes.

Recent work has highlighted the scale and ubiquity of subject variability in observations from functional MRI data (fMRI). Furthermore, it is highly likely that errors in the estimation of either the spatial presentation of, or the coupling between, functional regions can confound cross-subject analyses, making accurate and unbiased representations of functional data essential for interpreting any downstream analyses. Here, we extend the framework of probabilistic functional modes (PFMs) (Harrison et al.

Calibration of arterial spin labeling data-potential pitfalls in post-processing.

Purpose: To assess the impact of the different post-processing options in the calibration of arterial spin labeling (ASL) data on perfusion quantification and its reproducibility.

Theory And Methods: Absolute quantification of perfusion measurements is one of the promises of ASL techniques. However, it is highly dependent on a calibration procedure that involves a complex processing pipeline for which no standardized procedure has been fully established.

Imaging Clinically Relevant Pain States Using Arterial Spin Labeling.

Arterial Spin Labeling (ASL) is a perfusion-based functional magnetic resonance imaging technique that uses water in arterial blood as a freely diffusible tracer to measure regional cerebral blood flow (rCBF) noninvasively. To date its application to the study of pain has been relatively limited. Yet, ASL possesses key features that make it uniquely positioned to study pain in certain paradigms.

Defining the Functional Role of Na1.7 in Human Nociception.

Loss-of-function mutations in Na1.7 cause congenital insensitivity to pain (CIP); this voltage-gated sodium channel is therefore a key target for analgesic drug development. Utilizing a multi-modal approach, we investigated how Na1.

A brain-based pain facilitation mechanism contributes to painful diabetic polyneuropathy.

The descending pain modulatory system represents one of the oldest and most fundamentally important neurophysiological mechanisms relevant to pain. Extensive work in animals and humans has shown how a functional imbalance between the facilitatory and inhibitory components is linked to exacerbation and maintenance of persistent pain states. Forward translation of these findings into clinical populations is needed to verify the relevance of this imbalance.

A systematic study of the sensitivity of partial volume correction methods for the quantification of perfusion from pseudo-continuous arterial spin labeling MRI.

Arterial spin labeling (ASL) MRI is a non-invasive technique for the quantification of cerebral perfusion, and pseudo-continuous arterial spin labeling (PCASL) has been recommended as the standard implementation by a recent consensus of the community. Due to the low spatial resolution of ASL images, perfusion quantification is biased by partial volume effects. Consequently, several partial volume correction (PVEc) methods have been developed to reduce the bias in gray matter (GM) perfusion quantification.

The dorsal posterior insula is not an island in pain but subserves a fundamental role - Response to: "Evidence against pain specificity in the dorsal posterior insula" by Davis et al.

An interesting and valuable discussion has arisen from our recent article (Segerdahl, Mezue et al., 2015) and we are pleased here to have the opportunity to expand on the various points we made. Equally important, we wish to correct several important misunderstandings that were made by Davis and colleagues that possibly contributed to their concerns about power when assessing our paper (e.

The dorsal posterior insula subserves a fundamental role in human pain.

Several brain regions have been implicated in human painful experiences, but none have been proven to be specific to pain. We exploited arterial spin-labeling quantitative perfusion imaging and a newly developed procedure to identify a specific role for the dorsal posterior insula (dpIns) in pain. Tract tracing studies in animals identify a similar region as fundamental to nociception, which suggests the dpIns is its human homolog and, as such, a potential therapeutic target.

Optimization and reliability of multiple postlabeling delay pseudo-continuous arterial spin labeling during rest and stimulus-induced functional task activation.

Arterial spin labeling (ASL) sequences that incorporate multiple postlabeling delay (PLD) times allow estimation of when arterial blood signal arrives within a region of interest. Sequences that account for such variability may improve the reliability of ASL and therefore make the technique well suited for future clinical and experimental investigations of cerebral perfusion. This study assessed the within- and between-session reproducibility of an optimized pseudo-continuous ASL (pCASL) functional magnetic resonance imaging (FMRI) sequence that incorporates multiple postlabeling delays (multi-PLD pCASL).

Imaging the neural correlates of neuropathic pain and pleasurable relief associated with inherited erythromelalgia in a single subject with quantitative arterial spin labelling.

We identified a patient with severe inherited erythromelalgia secondary to an L858F mutation in the voltage-gated sodium channel Na(v)1.7. The patient reported severe ongoing foot pain, which was exquisitely sensitive to limb cooling.

Anxiety-like behaviour is attenuated by gabapentin, morphine and diazepam in a rodent model of HIV anti-retroviral-associated neuropathic pain.

Neuropathic pain is commonly associated with affective disorders such as anxiety and depression. We have previously characterised a rodent model of HIV, anti-retroviral-associated neuropathy in which rats develop hypersensitivity to a punctate mechanical stimulus and display anxiety-like behaviour in the open field paradigm. To assess the potential of this behavioural paradigm for the assessment of pain related co-morbidities in rodent models of pain, here we test the sensitivity of this anxiety-like behaviour to the analgesic agents gabapentin and morphine in comparison to the known anxiolytic drug diazepam.

Characterization of rodent models of HIV-gp120 and anti-retroviral-associated neuropathic pain.

A distal symmetrical sensory peripheral neuropathy is frequently observed in people living with Human Immunodeficiency Virus Type 1 (HIV-1). This neuropathy can be associated with viral infection alone, probably involving a role for the envelope glycoprotein gp120; or a drug-induced toxic neuropathy associated with the use of nucleoside analogue reverse transcriptase inhibitors as a component of highly active anti-retroviral therapy. In order to elucidate the mechanisms underlying drug-induced neuropathy in the context of HIV infection, we have characterized pathological events in the peripheral and central nervous system following systemic treatment with the anti-retroviral agent, ddC (Zalcitabine) with or without the concomitant delivery of HIV-gp120 to the rat sciatic nerve (gp120+ddC).

Pharmacological, behavioural and mechanistic analysis of HIV-1 gp120 induced painful neuropathy.

A painful neuropathy is frequently observed in people living with human immunodeficiency virus type 1 (HIV-1). The HIV coat protein, glycoprotein 120 (gp120), implicated in the pathogenesis of neurological disorders associated with HIV, is capable of initiating neurotoxic cascades via an interaction with the CXCR4 and/or CCR5 chemokine receptors, which may underlie the pathogenesis of HIV-associated peripheral neuropathic pain. In order to elucidate the mechanisms underlying HIV-induced painful peripheral neuropathy, we have characterised pathological events in the peripheral and central nervous system following application of HIV-1 gp120 to the rat sciatic nerve.