Publications by authors named "Jonathan C W Brooks"

28 Publications

  • Page 1 of 1

An Age-Specific Atlas for Delineation of White Matter Pathways in Children Aged 6-8 Years.

Brain Connect 2021 Jul 1. Epub 2021 Jul 1.

University of Bristol, 1980, Clinical Research and Imaging Centre, Bristol, United Kingdom of Great Britain and Northern Ireland.

Introduction: Diffusion MRI allows non-invasive assessment of white matter connectivity in typical development and of changes due to brain injury or pathology. Probabilistic white matter atlases allow diffusion metrics to be measured in specific white matter pathways, and are a critical component in spatial normalisation for group analysis. However, given the known developmental changes in white matter it may be sub-optimal to use an adult template when assessing data acquired from children.

Methods: By averaging subject-specific fibre bundles from 28 children aged from 6 to 8 years, we created an age-specific probabilistic white matter atlas for 12 major white matter tracts. Using both the newly developed and Johns Hopkins adult atlases, we compared the atlas to subject-specific fibre bundles in two independent validation cohorts, assessing accuracy in terms of volumetric overlap and measured diffusion metrics.

Results: Our age-specific atlas gave better overall performance than the adult atlas, achieving higher volumetric overlap with subject-specific fibre tracking and higher correlation of FA measurements with those measured from subject-specific fibre bundles. Specifically, estimates of FA values for cortico-spinal tract, uncinate fasciculus, forceps minor, cingulate gyrus part of the cingulum and anterior thalamic radiation were all significantly more accurate when estimated with an age-specific atlas.

Discussion: The age-specific atlas allows delineation of white matter tracts in children aged 6-8 years, without the need for tractography, more accurately than when normalising to an adult atlas. To our knowledge, this is the first publicly available probabilistic atlas of white matter tracts for this age group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/brain.2021.0058DOI Listing
July 2021

Central pain modulatory mechanisms of attentional analgesia are preserved in fibromyalgia.

Pain 2021 May 1. Epub 2021 May 1.

School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, United Kingdom Anaesthesia, Pain & Critical Care Sciences, Bristol Medical School, University Hospitals Bristol, Bristol, United Kingdom School of Psychological Science, University of Bristol, Bristol, United Kingdom University of East Anglia Brain Imaging Centre, School of Psychology, Norwich, United Kingdom.

Abstract: Fibromyalgia is a prevalent pain condition that is associated with cognitive impairments including in attention, memory, and executive processing. It has been proposed that fibromyalgia may be caused by altered central pain processing characterised by a loss of endogenous pain modulation. We tested whether attentional analgesia, where cognitive engagement diminishes pain percept, was attenuated in patients with fibromyalgia (n = 20) compared with matched healthy controls (n = 20). An individually calibrated, attentional analgesia paradigm with a 2 × 2 factorial design was used with brain and brainstem-focussed functional magnetic resonance imaging. Patients with fibromyalgia had both lower heat pain thresholds and speeds in a visual attention task. When this was taken into account for both attentional task and thermal stimulation, both groups exhibited an equivalent degree of attentional analgesia. Functional magnetic resonance imaging analysis showed similar patterns of activation in the main effects of pain and attention in the brain and brainstem (with the sole exceptions of increased activation in the control group in the frontopolar cortex and the ipsilateral locus coeruleus). The attentional analgesic effect correlated with activity in the periaqueductal gray and rostral ventromedial medulla. These findings indicate that patients with fibromyalgia can engage the descending pain modulatory system if the attentional task and noxious stimulus intensity are appropriately titrated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/j.pain.0000000000002319DOI Listing
May 2021

Disrupted brain connectivity in children treated with therapeutic hypothermia for neonatal encephalopathy.

Neuroimage Clin 2021 10;30:102582. Epub 2021 Feb 10.

Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; Neonatal Intensive Care Unit, St Michael's Hospital, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United Kingdom. Electronic address:

Therapeutic hypothermia following neonatal encephalopathy due to birth asphyxia reduces death and cerebral palsy. However, school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy still have reduced performance on cognitive and motor tests, attention difficulties, slower reaction times and reduced visuo-spatial processing abilities compared to typically developing controls. We acquired diffusion-weighted imaging data from school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy at birth, and a matched control group. Voxelwise analysis (33 cases, 36 controls) confirmed reduced fractional anisotropy in widespread areas of white matter in cases, particularly in the fornix, corpus callosum, anterior and posterior limbs of the internal capsule bilaterally and cingulum bilaterally. In structural brain networks constructed using probabilistic tractography (22 cases, 32 controls), graph-theoretic measures of strength, local and global efficiency, clustering coefficient and characteristic path length were found to correlate with IQ in cases but not controls. Network-based statistic analysis implicated brain regions involved in visuo-spatial processing and attention, aligning with previous behavioural findings. These included the precuneus, thalamus, left superior parietal gyrus and left inferior temporal gyrus. Our findings demonstrate that, despite the manifest successes of therapeutic hypothermia, brain development is impaired in these children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2021.102582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906894PMC
July 2021

Parallel cortical-brainstem pathways to attentional analgesia.

Neuroimage 2021 02 11;226:117548. Epub 2020 Nov 11.

School of Psychological Science, University of Bristol, 12a Priory Road, Bristol BS8 1TU, United Kingdom. Electronic address:

Pain demands attention, yet pain can be reduced by focusing attention elsewhere. The neural processes involved in this robust psychophysical phenomenon, attentional analgesia, are still being defined. Our previous fMRI study linked activity in the brainstem triad of locus coeruleus (LC), rostral ventromedial medulla (RVM) and periaqueductal grey (PAG) with attentional analgesia. Here we identify and model the functional interactions between these regions and the cortex in healthy human subjects (n = 57), who received painful thermal stimuli whilst simultaneously performing a visual attention task. RVM activity encoded pain intensity while contralateral LC activity correlated with attentional analgesia. Psycho-Physiological Interaction analysis and Dynamic Causal Modelling identified two parallel paths between forebrain and brainstem. These connections are modulated by attentional demand: a bidirectional anterior cingulate cortex (ACC) - right-LC loop, and a top-down influence of task on ACC-PAG-RVM. By recruiting discrete brainstem circuits, the ACC is able to modulate nociceptive input to reduce pain in situations of conflicting attentional demand.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2020.117548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836236PMC
February 2021

Cerebral Blood Flow Response to Simulated Hypovolemia in Essential Hypertension: A Magnetic Resonance Imaging Study.

Hypertension 2019 12 28;74(6):1391-1398. Epub 2019 Oct 28.

From the Faculty of Life Sciences, School of Physiology, Pharmacology and Neuroscience (S.N., Z.H.A., J.B., A.K.N., J.P., E.C.H.), University of Bristol, United Kingdom.

Hypertension is associated with raised cerebral vascular resistance and cerebrovascular remodeling. It is currently unclear whether the cerebral circulation can maintain cerebral blood flow (CBF) during reductions in cardiac output (CO) in hypertensive patients thereby avoiding hypoperfusion of the brain. We hypothesized that hypertension would impair the ability to effectively regulate CBF during simulated hypovolemia. In the present study, 39 participants (13 normotensive, 13 controlled, and 13 uncontrolled hypertensives; mean age±SD, 55±10 years) underwent lower body negative pressure (LBNP) at -20, -40, and -50 mmHg to decrease central blood volume. Phase-contrast MR angiography was used to measure flow in the basilar and internal carotid arteries, as well as the ascending aorta. CBF and CO decreased during LBNP (<0.0001). Heart rate increased during LBNP, reaching significance at -50 mmHg (<0.0001). There was no change in mean arterial pressure during LBNP (=0.3). All participants showed similar reductions in CBF (=0.3, between groups) and CO (=0.7, between groups) during LBNP. There was no difference in resting CBF between the groups (=0.36). In summary, during reductions in CO induced by hypovolemic stress, mean arterial pressure is maintained but CBF declines indicating that CBF is dependent on CO in middle-aged normotensive and hypertensive volunteers. Hypertension is not associated with impairments in the CBF response to reduced CO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069391PMC
December 2019

Sensorimotor, language, and working memory representation within the human cerebellum.

Hum Brain Mapp 2019 11 30;40(16):4732-4747. Epub 2019 Jul 30.

School of Psychological Science, University of Bristol, Bristol, UK.

The cerebellum is involved in a wide range of behaviours. A key organisational principle from animal studies is that somatotopically corresponding sensory input and motor output reside in the same cerebellar cortical areas. However, compelling evidence for a similar arrangement in humans and whether it extends to cognitive functions is lacking. To address this, we applied cerebellar optimised whole-brain functional MRI in 20 healthy subjects. To assess spatial overlap within the sensorimotor and cognitive domains, we recorded activity to a sensory stimulus (vibrotactile) and a motor task; the Sternberg verbal working memory (VWM) task; and a verb generation paradigm. Consistent with animal data, sensory and motor activity overlapped with a somatotopic arrangement in ipsilateral areas of the anterior and posterior cerebellum. During the maintenance phase of the Sternberg task, a positive linear relationship between VWM load and activity was observed in right Lobule VI, extending into Crus I bilaterally. Articulatory movement gave rise to bilateral activity in medial Lobule VI. A conjunction of two independent language tasks localised activity during verb generation in right Lobule VI-Crus I, which overlapped with activity during VWM. These results demonstrate spatial compartmentalisation of sensorimotor and cognitive function in the human cerebellum, with each area involved in more than one aspect of a given behaviour, consistent with an integrative function. Sensorimotor localisation was uniform across individuals, but the representation of cognitive tasks was more variable, highlighting the importance of individual scans for mapping higher order functions within the cerebellum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.24733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865458PMC
November 2019

Keeping track of 'alternative facts': The neural correlates of processing misinformation corrections.

Neuroimage 2019 06 11;193:46-56. Epub 2019 Mar 11.

School of Psychological Science, University of Bristol, Bristol, UK; School of Psychological Science, University of Western Australia, Perth, Australia.

Upon receiving a correction, initially presented misinformation often continues to influence people's judgment and reasoning. Whereas some researchers believe that this so-called continued influence effect of misinformation (CIEM) simply arises from the insufficient encoding and integration of corrective claims, others assume that it arises from a competition between the correct information and the initial misinformation in memory. To examine these possibilities, we conducted two functional magnetic resonance imaging (fMRI) studies. In each study, participants were asked to (a) read a series of brief news reports that contained confirmations or corrections of prior information and (b) evaluate whether subsequently presented memory probes matched the reports' correct facts rather than the initial misinformation. Both studies revealed that following correction-containing news reports, participants struggled to refute mismatching memory probes, especially when they referred to initial misinformation (as opposed to mismatching probes with novel information). We found little evidence, however, that the encoding of confirmations and corrections produced systematic neural processing differences indicative of distinct encoding strategies. Instead, we discovered that following corrections, participants exhibited increased activity in the left angular gyrus and the bilateral precuneus in response to mismatching memory probes that contained prior misinformation, compared to novel mismatch probes. These findings favour the notion that people's susceptibility to the CIEM arises from the concurrent retention of both correct and incorrect information in memory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2019.03.014DOI Listing
June 2019

Exploring the neural substrates of misinformation processing.

Neuropsychologia 2017 Nov 4;106:216-224. Epub 2017 Oct 4.

School of Experimental Psychology, University of Bristol, Bristol, UK; School of Psychological Science, University of Western Australia, Perth, Australia.

It is well known that information that is initially thought to be correct but then revealed to be false, often continues to influence human judgement and decision making despite people being aware of the retraction. Yet little research has examined the underlying neural substrates of this phenomenon, which is known as the 'continued influence effect of misinformation' (CIEM). It remains unclear how the human brain processes critical information that retracts prior claims. To address this question in further detail, 26 healthy adults underwent functional magnetic resonance imaging (fMRI) while listening to brief narratives which either involved a retraction of prior information or not. Following each narrative, subjects' comprehension of the narrative, including their inclination to rely on retracted information, was probed. As expected, it was found that retracted information continued to affect participants' narrative-related reasoning. In addition, the fMRI data indicated that the continued influence of retracted information may be due to a breakdown of narrative-level integration and coherence-building mechanisms implemented by the precuneus and posterior cingulate gyrus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuropsychologia.2017.10.003DOI Listing
November 2017

Resolving the Brainstem Contributions to Attentional Analgesia.

J Neurosci 2017 03 17;37(9):2279-2291. Epub 2017 Jan 17.

School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, United Kingdom, and

Previous human imaging studies manipulating attention or expectancy have identified the periaqueductal gray (PAG) as a key brainstem structure implicated in endogenous analgesia. However, animal studies indicate that PAG analgesia is mediated largely via caudal brainstem structures, such as the rostral ventromedial medulla (RVM) and locus coeruleus (LC). To identify their involvement in endogenous analgesia, we used brainstem optimized, whole-brain imaging to record responses to concurrent thermal stimulation (left forearm) and visual attention tasks of titrated difficulty in 20 healthy subjects. The PAG, LC, and RVM were anatomically discriminated using a probabilistic atlas. Pain ratings disclosed the anticipated analgesic interaction between task difficulty and pain intensity ( < 0.001). Main effects of noxious thermal stimulation were observed across several brain regions, including operculoinsular, primary somatosensory, and cingulate cortices, whereas hard task difficulty was represented in anterior insular, parietal, and prefrontal cortices. Permutation testing within the brainstem nuclei revealed the following: main effects of task in dorsal PAG and right LC; and main effect of temperature in RVM and a task × temperature interaction in right LC. Intrasubject regression revealed a distributed network of supratentorial brain regions and the RVM whose activity was linearly related to pain intensity. Intersubject analgesia scores correlated to activity within a distinct region of the RVM alone. These results identify distinct roles for a brainstem triumvirate in attentional analgesia: with the PAG activated by attentional load; specific RVM regions showing pronociceptive and antinociceptive processes (in line with previous animal studies); and the LC showing lateralized activity during conflicting attentional demands. Attention modulates pain intensity, and human studies have identified roles for a network of forebrain structures plus the periaqueductal gray (PAG). Animal data indicate that the PAG acts via caudal brainstem structures to control nociception. We investigated this issue within an attentional analgesia paradigm with brainstem-optimized fMRI and analysis using a probabilistic brainstem atlas. We find pain intensity encoding in several forebrain structures, including the insula and attentional activation of the PAG. Discrete regions of the rostral ventromedial medulla bidirectionally influence pain perception, and locus coeruleus activity mirrors the interaction between attention and nociception. This approach has enabled the resolution of contributions from a hub of key brainstem structures to endogenous analgesia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.2193-16.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354342PMC
March 2017

Investigating resting-state functional connectivity in the cervical spinal cord at 3T.

Neuroimage 2017 02 24;147:589-601. Epub 2016 Dec 24.

Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.

The study of spontaneous fluctuations in the blood-oxygen-level-dependent (BOLD) signal has recently been extended from the brain to the spinal cord. Two ultra-high field functional magnetic resonance imaging (fMRI) studies in humans have provided evidence for reproducible resting-state connectivity between the dorsal horns as well as between the ventral horns, and a study in non-human primates has shown that these resting-state signals are impacted by spinal cord injury. As these studies were carried out at ultra-high field strengths using region-of-interest (ROI) based analyses, we investigated whether such resting-state signals could also be observed at the clinically more prevalent field strength of 3T. In a reanalysis of a sample of 20 healthy human participants who underwent a resting-state fMRI acquisition of the cervical spinal cord, we were able to observe significant dorsal horn connectivity as well as ventral horn connectivity, but no consistent effects for connectivity between dorsal and ventral horns, thus replicating the human 7T results. These effects were not only observable when averaging along the acquired length of the spinal cord, but also when we examined each of the acquired spinal segments separately, which showed similar patterns of connectivity. Finally, we investigated the robustness of these resting-state signals against variations in the analysis pipeline by varying the type of ROI creation, temporal filtering, nuisance regression and connectivity metric. We observed that - apart from the effects of band-pass filtering - ventral horn connectivity showed excellent robustness, whereas dorsal horn connectivity showed moderate robustness. Together, our results provide evidence that spinal cord resting-state connectivity is a robust and spatially consistent phenomenon that could be a valuable tool for investigating the effects of pathology, disease progression, and treatment response in neurological conditions with a spinal component, such as spinal cord injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2016.12.072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5315056PMC
February 2017

Neural mechanisms underlying visual attention to health warnings on branded and plain cigarette packs.

Addiction 2017 04 4;112(4):662-672. Epub 2017 Jan 4.

School of Experimental Psychology, University of Bristol, Bristol, UK.

Aims: To (1) test if activation in brain regions related to reward (nucleus accumbens) and emotion (amygdala) differ when branded and plain packs of cigarettes are viewed, (2) test whether these activation patterns differ by smoking status and (3) examine whether activation patterns differ as a function of visual attention to health warning labels on cigarette packs.

Design: Cross-sectional observational study combining functional magnetic resonance imaging (fMRI) with eye-tracking. Non-smokers, weekly smokers and daily smokers performed a memory task on branded and plain cigarette packs with pictorial health warnings presented in an event-related design.

Setting: Clinical Research and Imaging Centre, University of Bristol, UK.

Participants: Non-smokers, weekly smokers and daily smokers (n = 72) were tested. After exclusions, data from 19 non-smokers, 19 weekly smokers and 20 daily smokers were analysed.

Measurements: Brain activity was assessed in whole brain analyses and in pre-specified masked analyses in the amygdala and nucleus accumbens. On-line eye-tracking during scanning recorded visual attention to health warnings.

Findings: There was no evidence for a main effect of pack type or smoking status in either the nucleus accumbens or amygdala, and this was unchanged when taking account of visual attention to health warnings. However, there was evidence for an interaction, such that we observed increased activation in the right amygdala when viewing branded as compared with plain packs among weekly smokers (P = 0.003). When taking into account visual attention to health warnings, we observed higher levels of activation in the visual cortex in response to plain packaging compared with branded packaging of cigarettes (P = 0.020).

Conclusions: Based on functional magnetic resonance imaging and eye-tracking data, health warnings appear to be more salient on 'plain' cigarette packs than branded packs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/add.13699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347953PMC
April 2017

Denoising spinal cord fMRI data: Approaches to acquisition and analysis.

Neuroimage 2017 07 28;154:255-266. Epub 2016 Sep 28.

Clinical Research and Imaging Centre, University of Bristol, Bristol, UK. Electronic address:

Functional magnetic resonance imaging (fMRI) of the human spinal cord is a difficult endeavour due to the cord's small cross-sectional diameter, signal drop-out as well as image distortion due to magnetic field inhomogeneity, and the confounding influence of physiological noise from cardiac and respiratory sources. Nevertheless, there is great interest in spinal fMRI due to the spinal cord's role as the principal sensorimotor interface between the brain and the body and its involvement in a variety of sensory and motor pathologies. In this review, we give an overview of the various methods that have been used to address the technical challenges in spinal fMRI, with a focus on reducing the impact of physiological noise. We start out by describing acquisition methods that have been tailored to the special needs of spinal fMRI and aim to increase the signal-to-noise ratio and reduce distortion in obtained images. Following this, we concentrate on image processing and analysis approaches that address the detrimental effects of noise. While these include variations of standard pre-processing methods such as motion correction and spatial filtering, the main focus lies on denoising techniques that can be applied to task-based as well as resting-state data sets. We review both model-based approaches that rely on externally acquired respiratory and cardiac signals as well as data-driven approaches that estimate and correct for noise using the data themselves. We conclude with an outlook on techniques that have been successfully applied for noise reduction in brain imaging and whose use might be beneficial for fMRI of the human spinal cord.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2016.09.065DOI Listing
July 2017

Effects of the pattern of glucocorticoid replacement on neural processing, emotional reactivity and well-being in healthy male individuals: study protocol for a randomised controlled trial.

Trials 2016 Jan 22;17:44. Epub 2016 Jan 22.

Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK.

Background: Deviation from the physiological glucocorticoid dynamics (circadian and underlying ultradian rhythmicity) is a common characteristic of various neuropsychiatric and endocrine disorders as well as glucocorticoid-based therapeutics. These states may be accompanied by neuropsychiatric symptomatology, suggesting continuous dynamic glucocorticoid equilibrium is essential for brain homeostasis.

Methods/design: The study consists of two parts. The preliminary stage of the study aims to validate (technically and pharmacologically) and optimise three different patterns of systemic cortisol administration in man. These patterns are based on the combinatory administration of metyrapone, to suppress endogenous cortisol production, and concurrent hydrocortisone replacement. The second, subsequent, core part of the study is a randomised, double-blinded, placebo-controlled, crossover study, where participants (healthy male individuals aged 18-60 years) will undergo all three hydrocortisone replacement schemes. During these infusion regimes, we plan a number of neurobehavioural tests and imaging of the brain to assess neural processing, emotional reactivity and perception, mood and self-perceived well-being. The psychological tests include: ecological momentary assessment, P1vital Oxford Emotional Test Battery and Emotional Potentiated Startle Test, Leeds Sleep Evaluation Questionnaire and the visual working memory task (n-back). The neuroimaging protocol combines magnetic resonance sequences that capture data related to the functional and perfusion status of the brain.

Discussion: Results of this clinical trial are designed to evaluate the impact (with possible mechanistic insights) of different patterns of daily glucocorticoid dynamics on neural processing and reactivity related to emotional perception and mood. This evidence should contribute to the optimisation of the clinical application of glucocorticoid-based therapeutics.

Trial Registration: UK Clinical Research Network, IRAS Ref: 106181, UKCRN-ID-15236 (23 October 2013).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-016-1159-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724084PMC
January 2016

A frontal attention mechanism in the visual mismatch negativity.

Behav Brain Res 2015 Oct 13;293:173-81. Epub 2015 Jul 13.

School of Experimental Psychology, University of Bristol, UK; Clinical Research and Imaging Centre, University of Bristol, UK.

Automatic detection of environmental change is a core component of attention. The mismatch negativity (MMN), an electrophysiological marker of this mechanism, has been studied prominently in the auditory domain, with cortical generators identified in temporal and frontal regions. Here, we combined electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to assess whether the underlying frontal regions associated with auditory change detection also play a role in visual change detection. Twenty healthy young adults completed a visual MMN task in separate EEG and fMRI sessions. Region of interest analyses were conducted on left and right middle frontal (MFG) and inferior frontal (IFG) gyri, i.e., the frontal areas identified as potential auditory MMN generators. A significant increase in activation was observed in the left IFG and MFG in response to blocks containing deviant stimuli. These findings suggest that a frontal mechanism is involved in the detection of change in the visual MMN. Our results support the notion that frontal mechanisms underlie attention switching, as measured via MMN, across multiple modalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbr.2015.07.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566935PMC
October 2015

MRI monitoring of pathological changes in the spinal cord in patients with multiple sclerosis.

Lancet Neurol 2015 Apr 4;14(4):443-54. Epub 2015 Mar 4.

Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience and Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.

The spinal cord is a clinically important site that is affected by pathological changes in most patients with multiple sclerosis; however, imaging of the spinal cord with conventional MRI can be difficult. Improvements in MRI provide a major advantage for spinal cord imaging, with better signal-to-noise ratio and improved spatial resolution. Through the use of multiplanar MRI, identification of diffuse and focal changes in the whole spinal cord is now routinely possible. Corroborated by related histopathological analyses, several new techniques, such as magnetisation transfer, diffusion tension imaging, functional MRI, and proton magnetic resonance spectroscopy, can detect non-focal, spinal cord pathological changes in patients with multiple sclerosis. Additionally, functional MRI can reveal changes in the response pattern to sensory stimulation in patients with multiple sclerosis. Through use of these techniques, findings of cord atrophy, intrinsic cord damage, and adaptation are shown to occur largely independently of focal spinal cord lesion load, which emphasises their relevance in depiction of the true burden of disease. Combinations of magnetisation transfer ratio or diffusion tension imaging indices with cord atrophy markers seem to be the most robust and meaningful biomarkers to monitor disease evolution in early multiple sclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1474-4422(14)70294-7DOI Listing
April 2015

Intrinsically organized resting state networks in the human spinal cord.

Proc Natl Acad Sci U S A 2014 Dec 3;111(50):18067-72. Epub 2014 Dec 3.

Clinical Research and Imaging Centre, University of Bristol, Bristol BS2 8DX, United Kingdom.

Spontaneous fluctuations in functional magnetic resonance imaging (fMRI) signals of the brain have repeatedly been observed when no task or external stimulation is present. These fluctuations likely reflect baseline neuronal activity of the brain and correspond to functionally relevant resting-state networks (RSN). It is not known however, whether intrinsically organized and spatially circumscribed RSNs also exist in the spinal cord, the brain's principal sensorimotor interface with the body. Here, we use recent advances in spinal fMRI methodology and independent component analysis to answer this question in healthy human volunteers. We identified spatially distinct RSNs in the human spinal cord that were clearly separated into dorsal and ventral components, mirroring the functional neuroanatomy of the spinal cord and likely reflecting sensory and motor processing. Interestingly, dorsal (sensory) RSNs were separated into right and left components, presumably related to ongoing hemibody processing of somatosensory information, whereas ventral (motor) RSNs were bilateral, possibly related to commissural interneuronal networks involved in central pattern generation. Importantly, all of these RSNs showed a restricted spatial extent along the spinal cord and likely conform to the spinal cord's functionally relevant segmental organization. Although the spatial and temporal properties of the dorsal and ventral RSNs were found to be significantly different, these networks showed significant interactions with each other at the segmental level. Together, our data demonstrate that intrinsically highly organized resting-state fluctuations exist in the human spinal cord and are thus a hallmark of the entire central nervous system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1414293111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273395PMC
December 2014

Physiological noise in brainstem FMRI.

Front Hum Neurosci 2013 4;7:623. Epub 2013 Oct 4.

Clinical Research and Imaging Centre, University of Bristol , Bristol , UK.

The brainstem is directly involved in controlling blood pressure, respiration, sleep/wake cycles, pain modulation, motor, and cardiac output. As such it is of significant basic science and clinical interest. However, the brainstem's location close to major arteries and adjacent pulsatile cerebrospinal fluid filled spaces, means that it is difficult to reliably record functional magnetic resonance imaging (fMRI) data from. These physiological sources of noise generate time varying signals in fMRI data, which if left uncorrected can obscure signals of interest. In this Methods Article we will provide a practical introduction to the techniques used to correct for the presence of physiological noise in time series fMRI data. Techniques based on independent measurement of the cardiac and respiratory cycles, such as retrospective image correction (RETROICOR, Glover et al., 2000), will be described and their application and limitations discussed. The impact of a physiological noise model, implemented in the framework of the general linear model, on resting fMRI data acquired at 3 and 7 T is presented. Data driven approaches based such as independent component analysis (ICA) are described. MR acquisition strategies that attempt to either minimize the influence of physiological fluctuations on recorded fMRI data, or provide additional information to correct for their presence, will be mentioned. General advice on modeling noise sources, and its effect on statistical inference via loss of degrees of freedom, and non-orthogonality of regressors, is given. Lastly, different strategies for assessing the benefit of different approaches to physiological noise modeling are presented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnhum.2013.00623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790256PMC
October 2013

Optimizing RetroICor and RetroKCor corrections for multi-shot 3D FMRI acquisitions.

Neuroimage 2014 Jan 7;84:394-405. Epub 2013 Sep 7.

FMRIB Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address:

Physiological noise, if unaccounted for, can drastically reduce the statistical significance of detected activation in FMRI. In this paper, we systematically optimize physiological noise regressions for multi-shot 3D FMRI data. First, we investigate whether 3D FMRI data are best corrected in image space (RetroICor) or k-space (RetroKCor), in which each k-space segment can be assigned its unique physiological phase. In addition, the optimal regressor set is determined using the Bayesian Information Criterion (BIC) for a variety of 3D acquisitions corresponding to different image contrasts and k-space readouts. Our simulations and experiments indicate that: (a) k-space corrections are more robust when performed on real/imaginary than magnitude/phase data; (b) k-space corrections do not outperform image-space corrections, despite the ability to synchronize physiological phase to acquisition time more accurately; and (c) the optimal model varied considerably between the various acquisition techniques. These results suggest the use of a tailored set of volume-wide regressors, determined by BIC or other selection criteria, that achieves optimal balance between variance reduction and potential over-fitting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2013.08.062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672603PMC
January 2014

Resting functional connectivity reveals residual functional activity in Alzheimer's disease.

Biol Psychiatry 2013 Sep 28;74(5):375-83. Epub 2013 May 28.

Oxford Project to Investigate Memory and Ageing, University of Oxford, United Kingdom.

Background: Functional magnetic resonance imaging (fMRI) has great potential for measuring mechanisms of functional changes in Alzheimer's disease (AD) and mild cognitive impairment, but task fMRI studies have produced conflicting results, partly due to failure to account for underlying morphological changes and to variations in patients' ability to perform the tasks. Resting fMRI has potential for assessing brain function independently from a task, but greater understanding of how networks of resting functional connectivity relate to the functioning of the brain is needed. We combined resting fMRI and task fMRI to examine the correspondence between these methods in individuals with cognitive impairment.

Methods: Eighty elderly (25 control subjects, 25 mild cognitive impairment, 30 AD) underwent a combined multimodal magnetic resonance imaging protocol including task fMRI and resting fMRI. Task fMRI data were acquired during the execution of a memory paradigm designed to account for differences in task performance. Structural and physiological confounds were modeled for both fMRI modalities.

Results: Successful recognition was associated with increased task fMRI activation in lateral prefrontal regions in AD relative to control subjects; this overlapped with increased resting fMRI functional connectivity in the same regions.

Conclusions: Our results show that task fMRI and resting fMRI are sensitive markers of residual ability over the known changes in brain morphology and cognition occurring in AD and suggest that resting fMRI has a potential to measure the effect of new treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopsych.2013.04.015DOI Listing
September 2013

Stimulus site and modality dependence of functional activity within the human spinal cord.

J Neurosci 2012 May;32(18):6231-9

Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, Nuffield Division of Anaesthetics, University of Oxford, Oxford OX3 9DU, UK.

Chronic pain is thought to arise because of maladaptive changes occurring within the peripheral nervous system and CNS. The transition from acute to chronic pain is known to involve the spinal cord (Woolf and Salter, 2000). Therefore, to investigate altered human spinal cord function and translate results obtained from other species, a noninvasive neuroimaging technique is desirable. We have investigated the functional response in the cervical spinal cord of 18 healthy human subjects (aged 22-40 years) to noxious thermal and non-noxious tactile stimulation of the left and right forearms. Physiological noise, which is a significant source of signal variability in the spinal cord, was accounted for in the general linear model. Group analysis, performed using a mixed-effects model, revealed distinct regions of activity that were dependent on both the side and the type of stimulation. In particular, thermal stimulation on the medial aspect of the wrist produced activity within the C6/C5 segment ipsilateral to the side of stimulation. Similar to data recorded in animals (Fitzgerald, 1982), painful thermal stimuli produced increased ipsilateral and decreased contralateral blood flow, which may reflect, respectively, excitatory and inhibitory processes. Nonpainful punctate stimulation of the thenar eminence provoked more diffuse activity but was still ipsilateral to the side of stimulation. These results present the first noninvasive evidence for a lateralized response to noxious and non-noxious stimuli in the human spinal cord. The development of these techniques opens the path to understanding, at a subject-specific level, central sensitization processes that contribute to chronic pain states.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.2543-11.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6622146PMC
May 2012

Assessment of physiological noise modelling methods for functional imaging of the spinal cord.

Neuroimage 2012 Apr 8;60(2):1538-49. Epub 2011 Dec 8.

Centre for Functional Magnetic Resonance Imaging of the Brain-FMRIB, University of Oxford, Oxford, UK.

The spinal cord is the main pathway for information between the central and the peripheral nervous systems. Non-invasive functional MRI offers the possibility of studying spinal cord function and central sensitisation processes. However, imaging neural activity in the spinal cord is more difficult than in the brain. A significant challenge when dealing with such data is the influence of physiological noise (primarily cardiac and respiratory), and currently there is no standard approach to account for these effects. We have previously studied the various sources of physiological noise for spinal cord fMRI at 1.5T and proposed a physiological noise model (PNM) (Brooks et al., 2008). An alternative de-noising strategy, selective averaging filter (SAF), was proposed by Deckers et al. (2006). In this study we reviewed and implemented published physiological noise correction methods at higher field (3T) and aimed to find the optimal models for gradient-echo-based BOLD acquisitions. Two general techniques were compared: physiological noise model (PNM) and selective averaging filter (SAF), along with regressors designed to account for specific signal compartments and physiological processes: cerebrospinal fluid (CSF), motion correction (MC) parameters, heart rate (HR), respiration volume per time (RVT), and the associated cardiac and respiratory response functions. Functional responses were recorded from the cervical spinal cord of 18 healthy subjects in response to noxious thermal and non-noxious punctate stimulation. The various combinations of models and regressors were compared in three ways: the model fit residuals, regression model F-tests and the number of activated voxels. The PNM was found to outperform SAF in all three tests. Furthermore, inclusion of the CSF regressor was crucial as it explained a significant amount of signal variance in the cord and increased the number of active cord voxels. Whilst HR, RVT and MC explained additional signal (noise) variance, they were also found (in particular HR and RVT) to have a negative impact on the parameter estimates (of interest)--as they may be correlated with task conditions e.g. noxious thermal stimuli. Convolution with previously published cardiac and respiratory impulse response functions was not found to be beneficial. The other novel aspect of current study is the investigation of the influence of pre-whitening together with PNM regressors on spinal fMRI data. Pre-whitening was found to reduce non-white noise, which was not accounted for by physiological noise correction, and decrease false positive detection rates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2011.11.077DOI Listing
April 2012

Identification and characterisation of midbrain nuclei using optimised functional magnetic resonance imaging.

Neuroimage 2012 Jan 16;59(2):1230-8. Epub 2011 Aug 16.

Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.

Localising activity in the human midbrain with conventional functional MRI (fMRI) is challenging because the midbrain nuclei are small and located in an area that is prone to physiological artefacts. Here we present a replicable and automated method to improve the detection and localisation of midbrain fMRI signals. We designed a visual fMRI task that was predicted would activate the superior colliculi (SC) bilaterally. A limited number of coronal slices were scanned, orientated along the long axis of the brainstem, whilst simultaneously recording cardiac and respiratory traces. A novel anatomical registration pathway was used to optimise the localisation of the small midbrain nuclei in stereotactic space. Two additional structural scans were used to improve registration between functional and structural T1-weighted images: an echo-planar image (EPI) that matched the functional data but had whole-brain coverage, and a whole-brain T2-weighted image. This pathway was compared to conventional registration pathways, and was shown to significantly improve midbrain registration. To reduce the physiological artefacts in the functional data, we estimated and removed structured noise using a modified version of a previously described physiological noise model (PNM). Whereas a conventional analysis revealed only unilateral SC activity, the PNM analysis revealed the predicted bilateral activity. We demonstrate that these methods improve the measurement of a biologically plausible fMRI signal. Moreover they could be used to investigate the function of other midbrain nuclei.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2011.08.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236997PMC
January 2012

Brainstem functional magnetic resonance imaging: disentangling signal from physiological noise.

J Magn Reson Imaging 2008 Dec;28(6):1337-44

Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Department of Clinical Neurology, University of Oxford, John Radcliffe Hospital, Oxford, UK.

Purpose: To estimate the importance of respiratory and cardiac effects on signal variability found in functional magnetic resonance imaging data recorded from the brainstem.

Materials And Methods: A modified version of the retrospective image correction (RETROICOR) method (Glover et al, [2000] Magn Reson Med 44:162-167) was implemented on resting brainstem echo-planar imaging (EPI) data in 12 subjects. Fourier series were fitted to image data based on cardiac and respiratory recordings (pulseoximetry and respiratory turbine), including multiplicative terms that accounted for interactions between cardiac and respiratory signals. F-tests were performed on residuals produced by regression analysis. Additionally, we evaluated whether modified RETROICOR improved detection of brainstem activation (in 11 subjects) during a finger opposition task.

Results: The optimal model, containing three cardiac (C) and four respiratory (R) harmonics, and one multiplicative (X) term, "3C4R1X," significantly reduced signal variability without overfitting to noise. The application of modified RETROICOR to activation data increased group Z-statistics and reduced putative false-positive activation.

Conclusion: In addition to cardiac and respiratory effects, their interaction was also a significant source of physiological noise. The modified RETROICOR model improved detection of brainstem activation and would be usefully applied to any study examining this brain region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.21623DOI Listing
December 2008

Pain relief as an opponent process: a psychophysical investigation.

Eur J Neurosci 2008 Aug 30;28(4):794-801. Epub 2008 Jul 30.

Oxford Centre for Functional MRI of the Brain, Clinical Neurology and Nuffield Department of Anaesthetics, Oxford University, John Radcliffe Hospital, Oxford, UK.

Relief from pain in humans is frequently measured by computing the reduction on an 11-point pain intensity scale. However, this definition of relief may be insufficient to capture the utility of pain relief for the individual. Based on pain literature and evidence from studies examining relief and reward, it is clear that pain relief is a broad concept comprising several factors, only one of which is pain intensity reduction. According to opponent process theory, all sensations consist of a primary process and a slow 'opponent process' of opposite valence, the purpose of which is to reduce the deviation from homeostatic balance. Here, opponent process theory provided a framework to explore the interaction between pain, relief and reward. We devised three psychophysical studies examining the temporal (Experiment I) and magnitude (Experiments I and II) relationships between pain severity and its subsequent relief. In Experiment III, we further manipulated the magnitude and pleasantness of relief experienced by applying innocuous cooling following noxious heat stimulation of capsaicin-sensitized skin. Results confirmed predictions from opponent process theory and showed that pain intensity reduction was significantly stronger than relief intensity ratings. Furthermore, continuous relief ratings appeared to reflect the speed of pain intensity reduction. Varying pain intensity parametrically confirmed that relief increases with pain intensity. That innocuous cooling following primary hyperalgesia intervention significantly increased the intensity, pleasantness and duration of relief provides further evidence that pain relief encapsulates more than a reduction in pain intensity. Importantly, the high relief pleasantness ratings confirmed the hypothesized link between relief and reward.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1460-9568.2008.06380.xDOI Listing
August 2008

Physiological noise modelling for spinal functional magnetic resonance imaging studies.

Neuroimage 2008 Jan 20;39(2):680-92. Epub 2007 Sep 20.

PaIN Group, Department of Physiology Anatomy and Genetics, Le Gros Clark Building, South Parks Road, Oxford OX1 3QX, UK.

Spinal cord functional imaging allows assessment of activity in primary synaptic connections made by sensory neurons relaying information about the state of the body. However, reported human data based on gradient-echo techniques have been largely inconsistent, with no clear patterns of activation emerging. One reason for this variability is the influence of physiological noise, which is typically not corrected for. By acquiring single-slice resting data from the spinal cord with a conventional gradient-echo EPI pulse sequence at TR=200 ms (critically sampled) and TR=3 s (under-sampled), we have characterised various sources of physiological noise. In 8 healthy subjects, the presence of physiologically dependent signal was explored using probabilistic independent component analysis (PICA). Based on the insights provided by PICA, we defined a new physiological noise model (PNM) based on retrospective image correction (RETROICOR), which uses independent physiological measurements taken from the subject to model sources of noise. Statistical significance of individual components included in the PNM was assessed by F-tests, which demonstrated that the optimal PNM included cardiac, respiratory, interaction and low-frequency regressors. In a group of 10 healthy subjects, activation data were acquired from the cervical spinal region (T1 to C5) during painful thermal stimulation of the right and left hands. The improvement obtained when using a PNM in estimating spinal cord activation was reflected in a reduction of false-positive activation (active voxels in the CSF space surrounding the cord), when compared to conventional GLM modelling without a PNM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2007.09.018DOI Listing
January 2008

Quantitative assessment of the reproducibility of functional activation measured with BOLD and MR perfusion imaging: implications for clinical trial design.

Neuroimage 2005 Aug;27(2):393-401

Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Department of Clinical Neurology, University of Oxford, England, UK.

BOLD contrast is the most commonly used functional MRI method for studies of brain activity. However, the underlying physiological processes giving rise to measured BOLD signal changes (which include contribution from changes in cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral metabolic rate of oxygen consumption (CMRO2)) vary substantially between sessions and subjects. To determine whether direct CBF measurement is a more reliable technique, we compared the localisation of activation and reproducibility of relative signal change measured by optimised BOLD versus CBF measured using the arterial spin labelling (ASL) technique. Data were collected within the primary sensorimotor cortex in normal healthy controls performing a simple finger-tapping task over three imaging sessions (two on same day and one on a different day). The displacement between the foci of BOLD and CBF activation was less than the linear dimension of one voxel (2.4 mm), however, BOLD activation was significantly closer to the nearest draining vein compared to CBF activation (P=0.030). For the relative signal change measurement, we found that CBF has a lower inter-subject variation than BOLD (P<0.05), enabling a smaller sample size for any given effect size, although the intra-subject variation across sessions for CBF was not significantly different from BOLD. BOLD imaging provides the optimal contrast for exploratory brain activation mapping, however, for a single time-point group study, CBF has reduced variance. In addition, the reduction of variance over time using CBF measurements (non-significant) suggests it could potentially provide a more useful approach when assessing longitudinal activation changes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2005.04.021DOI Listing
August 2005

fMRI of thermal pain: effects of stimulus laterality and attention.

Neuroimage 2002 Feb;15(2):293-301

Pain Research Institute, Clinical Sciences Centre, Lower Lane, Liverpool, L9 7AL, United Kingdom.

Brain activity was studied by fMRI in 18 healthy subjects during stimulation of the thenar eminence of the hand with either warm (non-painful, 40 degrees C) or hot (painful, 46-49 degrees C) stimuli using a contact thermode. Experiments were performed on the right and left hand independently and with two attentional contexts: subjects either attended to pain or attended to a visual global motion discrimination task (to distract them from pain). Group analysis demonstrated that attended warm stimulation of the right hand did not produce any significantly activated clusters. Painful thermal stimulation of either hand elicited significant activity over a large network of brain regions, including insula, inferior frontal gyrus, cingulate gyrus, secondary somatosensory cortex, cerebellum, and medial frontal gyrus (corrected P < 0.05). Insula activity was distributed along its anterior-posterior axis and depended on the hand stimulated and attentional context. In particular, activity within the posterior insula was contralateral to the site of stimulation, tested using regions of interest (ROI) analysis: significant side x site interaction (P = 0.001). With attention diverted from the painful stimulus bilateral anterior insula activity moved posteriorly to midinsula and decreased in extent (ROI analysis: significant main effect of attention (P = 0.03)). The role of the insula in thermosensation and attention is discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1006/nimg.2001.0974DOI Listing
February 2002
-->