%0 Journal Article
%~ PubMed
%A James, Cheree
%A Macefield, Vaughan G
%A Henderson, Luke A
%T Real-time imaging of cortical and subcortical control of muscle sympathetic nerve activity in awake human subjects.
%B NeuroImage
%D 2013
%C United States
%I Academic Press
%V 70
%N 2013
%P 59-65
%@ 1053-8119
%X 
%Z FOR Codes: 110299 60699


%0 Journal Article
%~ PubMed
%A Brown, Rachael
%A James, Cheree
%A Henderson, Luke A
%A Macefield, Vaughan G
%T Autonomic markers of emotional processing: skin sympathetic nerve activity in humans during exposure to emotionally charged images.
%B Frontiers in Physiology
%D 2012
%C Switzerland
%I Frontiers Research Foundation
%V 3
%N 
%P 394
%@ 1664-042X
%X 
%Z FOR Codes: 110901 170101


%0 Journal Article
%~ PubMed
%A Bhatia, Kartik D
%A Henderson, Luke
%A Ramsey-Stewart, George
%A May, James
%T Diffusion Tensor Imaging to Aid Subgenual Cingulum Target Selection for Deep Brain Stimulation in Depression.
%B Stereotactic and Functional Neurosurgery
%D 2012
%C Switzerland
%I S. Karger AG
%V 90
%N 4
%P 225-232
%@ 1423-0372
%X Background: The most investigated target for deep brain stimulation in depression is the subgenual cingulate gyrus (Cg25) which has been shown to be a critical hub for signalling in the condition. Diffusion tensor imaging (DTI) is a form of MR sequence that can visualise white matter connections and potentially aid target selection. Objectives: To assess whether targets selected using DTI to find the area of maximal tract crossover (maximal isotropy) underlying the subgenual cingulum differ significantly in location from those selected using standard T(2) sequences. Methods: Fifty-nine non-depressed adult volunteers underwent MR imaging using T(1), T(2) and DTI sequences of the brain. Each patient had targets selected for both hemispheres using both T(2) and DTI sequences. The significance of the differences in coordinates in all three dimensions was tested using the paired t test. Results: There was a significant difference in the mediolateral (x) and dorsoventral (z) coordinates of DTI targets when compared with T(2) targets (p < 0.001). Conclusions: Targets within Cg25 selected using DTI are significantly different in location from those selected using T(2) sequences and have the potential to enhance treatment outcome by reducing the impact of interindividual variability.
%Z FOR Codes: 110323


%0 Journal Article
%~ PubMed
%A Henderson, Luke A
%A James, Cheree
%A Macefield, Vaughan G
%T Identification of Sites of Sympathetic Outflow During Concurrent Recordings of Sympathetic Nerve Activity and fMRI.
%B Anatomical Record
%D 2012
%C United States
%I John Wiley & Sons, Inc.
%V 295
%N 9
%P 1396-1403
%@ 1932-8494
%X The sympathetic division of the nervous system is critical for maintaining both resting arterial pressure and for producing changes in regional perfusion required by behavioral state changes. A primary determinant of arterial pressure is the level of vasoconstriction within skeletal muscle. It is well established that there is a tight relationship between dynamic changes in arterial pressure and muscle sympathetic nerve activity (MSNA) through the workings of the baroreflex. While the central circuitry underlying the baroreflex has been extensively investigated in anesthetized experimental animals, few studies have investigated the central circuitry responsible for the baroreflex in awake human subjects. Recently we were the first to record concurrently MSNA (using microneurography) and brain activity (using functional magnetic resonance imaging) in awake humans in a series of experiments designed to determine the central circuitry underlying the baroreflex in humans. We confirmed that the baroreflex involves activity changes within the nucleus tractus solitarius, caudal ventrolateral, and rostral ventrolateral medulla. Because conditions such as essential hypertension, obesity, and obstructive sleep apnea are all characterized by significant increases in resting MSNA, it is important to understand both brainstem and cortical sites involved in regulating resting levels of MSNA. Future investigations which define cortical sites involved in generating and modulating MSNA are important if we are to understand the underlying mechanisms of many conditions characterized by hypertension. Anat Rec, 2012. ?? 2012 Wiley Periodicals, Inc.
%Z FOR Codes: 110901


%0 Journal Article
%~ PubMed
%A Gustin, Sylvia M
%A Peck, Chris C
%A Cheney, Lukas B
%A Macey, Paul M
%A Murray, Greg M
%A Henderson, Luke A
%T Pain and plasticity: is chronic pain always associated with somatosensory cortex activity and reorganization?
%B The Journal of Neuroscience
%D 2012
%C United States
%I Society for Neuroscience
%V 32
%N 43
%P 14874-14884
%@ 1529-2401
%X 
%Z FOR Codes: 110903 110599


%0 Journal Article
%~ PubMed
%A Rubin, Troy K
%A Lake, Sally
%A van der Kooi, Saskia
%A Lucas, Nicholas P
%A Mahns, David A
%A Henderson, Luke A
%A Macefield, Vaughan G
%T Predicting the spatiotemporal expression of local and referred acute muscle pain in individual subjects.
%B Experimental Brain Research
%D 2012
%C Germany
%I Springer
%V 223
%N 1
%P 11-18
%@ 1432-1106
%X While current data suggest that all referred pain derives from common mechanisms of central sensitisation, there is a paucity of data directly comparing referral in different limbs. Does a common mechanism result in similar precepts of referral from similar stimuli in different limbs? We tested the hypothesis that, in a given subject, the incidence, intensity and spatiotemporal expression of referred pain are similar during the muscle pain induced by bolus intramuscular injection of hypertonic saline into flexor carpi radialis (FCR) and tibialis anterior (TA). We also tested the hypothesis that an increase in stimulus intensity causes a parallel increase in the incidence and intensity of local and referred pain, by comparing the responses to 5 and 10??% hypertonic saline in two groups of subjects. 29 subjects mapped areas of local and referred pain, rating intensities on a visual analogue scale every 30??s until the cessation of pain. Following an injection of 5??% hypertonic saline into TA, 86??% of subjects who had previously reported referred pain (or its absence) in the hand during FCR pain reported referred pain (or its absence) in the foot. Following an injection of the 10??% solution, 67??% of subjects reported a pattern in the lower limb that was the same as that seen in the upper limb. We conclude that the expression of referred pain is largely consistent in widely separated limb segments in individual subjects and is largely dependent on inter-subject differences. This may have implications for the development of chronic pain following an acute episode of pain.
%Z FOR Codes: 110906


%0 Journal Article
%~ PubMed
%A Henderson, Luke A
%A Stathis, Alexandra
%A James, Cheree
%A Brown, Rachael
%A McDonald, Skye
%A Macefield, Vaughan G
%T Real-time imaging of cortical areas involved in the generation of increases in skin sympathetic nerve activity when viewing emotionally charged images.
%B NeuroImage
%D 2012
%C United States
%I Academic Press
%V 62
%N 1
%P 30-40
%@ 1053-8119
%X The sympathetic innervation of the skin not only primarily subserves thermoregulation, but has also been commandeered as a means of emotional expression. While the majority of brain imaging studies of emotion have utilised the galvanic skin response as a means of inferring changes in skin sympathetic nerve activity (SSNA), spontaneous fluctuations in the galvanic skin response bear little relation to spontaneous fluctuations in SSNA. To improve our understanding of the central neural processes involved in the generation of autonomic emotional markers, we recorded SSNA concurrently with brain functional magnetic resonance imaging in 13 subjects. Emotional changes were evoked by presentation of positively-charged (erotica) or negatively-charged (mutilation) images from the International Affective Picture System. Positive and negative emotionally-charged images evoked significant increases in total SSNA and signal intensity in the orbital, dorsolateral and ventromedial prefrontal cortices, amygdala, nucleus accumbens and anterior insula. Increases in signal intensity during increases in SSNA occurred in a number of brain regions, including the central and lateral amygdala, dorsolateral pons, thalamus, nucleus accumbens, and cerebellar cortex. Signal intensity decreases during SSNA increases occurred in the left orbitofrontal, frontal and right precuneus cortices. These data reveal for the first time, cortical and subcortical sites involved in generating SSNA changes during emotions.
%Z FOR Codes: 1109 606


%0 Journal Article
%~ PubMed
%A Gustin, Sylvia M
%A Peck, Chris C
%A Wilcox, Sophie L
%A Nash, Paul G
%A Murray, Greg M
%A Henderson, Luke A
%T Different pain, different brain: thalamic anatomy in neuropathic and non-neuropathic chronic pain syndromes.
%B Journal of Neuroscience
%D 2011
%C United States
%I Society for Neuroscience
%V 31
%N 16
%P 5956-5964
%@ 1529-2401
%X Trigeminal neuropathic pain (TNP) and temporomandibular disorders (TMD) are thought to have fundamentally different etiologies. It has been proposed that TNP arises through damage to, or pressure on, somatosensory afferents in the trigeminal nerve, whereas TMD results primarily from peripheral nociceptor activation. Because some reports suggest that neuropathic pain is associated with changes in brain anatomy, it is possible that TNP is maintained by changes in higher brain structures, whereas TMD is not. The aim of this investigation is to determine whether changes in regional brain anatomy and biochemistry occur in both conditions. Twenty-one TNP subjects, 20 TMD subjects, and 36 healthy controls were recruited. Voxel-based morphometry of T1-weighted anatomical images revealed no significant regional gray matter volume change in TMD patients. In contrast, gray matter volume of TNP patients was reduced in the primary somatosensory cortex, anterior insula, putamen, nucleus accumbens, and the thalamus, whereas gray matter volume was increased in the posterior insula. The thalamic volume decrease was only seen in the TNP patients classified as having trigeminal neuropathy but not those with trigeminal neuralgia. Furthermore, in trigeminal neuropathy patients, magnetic resonance spectroscopy revealed a significant reduction in the N-acetylaspartate/creatine ratio, a biochemical marker of neural viability, in the region of thalamic volume loss. The data suggest that the pathogenesis underlying neuropathic and non-neuropathic pain conditions are fundamentally different and that neuropathic pain conditions that result from peripheral injuries may be generated and/or maintained by structural changes in regions such as the thalamus.
%Z FOR Codes: 110903


%0 Journal Article
%~ PubMed
%A Henderson, Luke A
%A Gustin, Sylvia M
%A Macey, Paul M
%A Wrigley, Paul J
%A Siddall, Philip J
%T Functional reorganization of the brain in humans following spinal cord injury: evidence for underlying changes in cortical anatomy.
%B Journal of Neuroscience
%D 2011
%C United States
%I Society for Neuroscience
%V 31
%N 7
%P 2630-2637
%@ 1529-2401
%X Loss of somatosensory drive results in functional reorganization of the primary somatosensory cortex (SI). While the phenomenon of functional cortical reorganization is well established, it remains unknown whether in humans, functional reorganization results from changes in brain anatomy, or simply reflects an unmasking of already existing dormant synapses. In 20 subjects with complete thoracic spinal cord injuries (SCIs) and 23 controls, we used functional and structural magnetic resonance imaging to determine whether SI reorganization was associated with changes in SI anatomy. SCI resulted in a significant SI reorganization, with the little finger representation moving medially toward the lower body representation (i.e., area of sensory loss). Furthermore, although SCI was associated with gray matter volume loss in the lower body representation, this loss was minimized as reorganization increased. That is, the greater the medial shift in little finger representation, the greater the gray matter preservation in the lower body representation. In addition, in the region of greatest SI reorganization (little finger), fractional anisotropy was correlated with SI reorganization. That is, as SI reorganization increased, the extent of aligned structures decreased. Finally, although thalamocortical fibers remained unchanged, the ease and direction of water movement within the little finger representation was altered, being directed more toward the midline in SCI subjects. These data show that SI reorganization following SCI is associated with changes in SI anatomy and provide compelling evidence that SI reorganization in humans results from the growth of new lateral connections, and not simply from the unmasking of already existing lateral connections.
%Z FOR Codes: 110903


%0 Journal Article
%~ PubMed
%A Gustin, Sylvia Maria
%A Wilcox, Sophie L
%A Peck, Chris C
%A Murray, Greg M
%A Henderson, Luke A
%T Similarity of suffering: Equivalence of psychological and psychosocial factors in neuropathic and non-neuropathic orofacial pain patients.
%B Pain
%D 2011
%C Netherlands, United States
%I Elsevier BV
%V 152
%N 4
%P 825-832
%@ 0304-3959
%X The degree to which neuropathic and non-neuropathic pain conditions differ in psychological and psychosocial status remains largely unexplored. A better understanding of these aspects would be of considerable benefit in helping to define whether similar psychological treatment strategies (eg, cognitive-behavioural therapy) can be adopted in the management of neuropathic pain as in non-neuropathic pain conditions. Chronic orofacial pain disorders present a unique opportunity to compare nociceptive and neuropathic pain in the same body region. Twenty-four patients with trigeminal neuropathic pain, 21 patients with temporomandibular disorder, and 38 healthy controls were assessed with a psychological/psychosocial battery encompassing the 4 dimensions of the pain experience; sensory-discriminative, affective-motivational, cognitive-evaluative, and psychosocial. Although patients with trigeminal neuropathic pain (neuropathic pain) and temporomandibular disorder (non-neuropathic pain) described the sensory aspects of their pain differently, they exhibited comparable negative affective-motivational, cognitive-evaluative, and psychosocial states, although these were significantly different compared to healthy controls. These findings support growing evidence that the negative affective, cognitive, and psychosocial state of chronic pain is universal, regardless of a neuropathic or nociceptive nature. Further characterisation of these 4 dimensions of the pain experience in different chronic pain subtypes may improve the efficacy of cognitive-behavioural therapy. Nociceptive/inflammatory and neuropathic chronic orofacial pain populations report similar affective-motivational, cognitive-evaluative, and psychosocial dimensions of their pain experience but exhibit different sensory-discriminative components.
%Z FOR Codes: 110903


%0 Journal Article
%~ PubMed
%A Nash, P G
%A Macefield, V G
%A Klineberg, I J
%A Gustin, S M
%A Murray, G M
%A Henderson, L A
%T Bilateral activation of the trigeminothalamic tract by acute orofacial cutaneous and muscle pain in humans.
%B Pain
%D 2010
%C Netherlands, United States
%I Elsevier BV
%V 151
%N 2
%P 384-93
%@ 0304-3959
%X The conscious perception of somatosensory stimuli is thought to be located in the contralateral cerebral cortex. However, recent human brain imaging investigations in the spinal system report bilateral primary somatosensory cortex (SI) activations during unilateral noxious stimuli and that this ipsilateral spinal representation may be independent of transcallosal connections. In the trigeminal system, there is primate evidence for an ipsilateral somatosensory pathway through the thalamus to the face SI. However, the organization of the trigeminal nociceptive pathway in the human is not clear. The aim of this study was to determine whether noxious stimuli applied to the face are transmitted to the cerebral cortex by bilateral pathways. We used functional magnetic resonance imaging (fMRI) to compare ipsilateral and contralateral activation of the thalamus, SI and secondary somatosensory cortex (SII) during muscle and cutaneous orofacial pain and innocuous facial stimulation in healthy human subjects. We found that both muscle and cutaneous noxious stimuli, from injections of hypertonic saline into the right masseter or overlying skin, evoked bilateral increases in signal intensity in the region encompassing the ventral posterior thalamus as well as the face region of SI and SII. In contrast, innocuous unilateral brushing of the lower lip evoked a strict contralateral ventroposterior thalamic activation, but bilateral activation of SI and SII. These data indicate that, in contrast to innocuous inputs from the face, noxious information ascends bilaterally to the face SI through the ventroposterior thalamus in humans.
%Z FOR Codes: 110903


%0 Journal Article
%~ PubMed
%A Gustin, S M
%A Wrigley, P J
%A Siddall, P J
%A Henderson, L A
%T Brain Anatomy Changes Associated with Persistent Neuropathic Pain Following Spinal Cord Injury.
%B Cerebral cortex (New York, N.Y. : 1991)
%D 2010
%C United Kingdom
%I Oxford University Press
%V 20
%N 6
%P 1409-19
%@ 1460-2199
%X Persistent neuropathic pain commonly occurs following spinal cord injury (SCI). It remains one of the most challenging management problems in this condition. In order to develop more effective treatments, a better understanding of the neural changes associated with neuropathic SCI pain is required. The aim of this investigation was to use diffusion tensor imaging (DTI) to determine if persistent neuropathic pain following SCI is associated with changes in regional brain anatomy and connectivity. In 23 subjects with complete thoracic SCI, 12 with below-level neuropathic pain and 11 without pain, and 45 healthy control subjects, a series of whole-brain DTI scans were performed. The mean diffusivity (MD) of each voxel was calculated and values compared between groups. This analysis revealed that neuropathic pain following SCI is associated with significant differences in regional brain anatomy. These anatomical changes were located in pain-related regions as well as regions of the classic reward circuitry, that is, the nucleus accumbens and orbitofrontal, dorsolateral prefrontal, and posterior parietal cortices. The right posterior parietal cortex projected to most regions that displayed an anatomical change. Analysis of the fiber tracts connecting areas of MD differences revealed no significance differences in MD values between the SCI pain, SCI no pain, and control groups.
%Z FOR Codes: 110399 110903


%0 Journal Article
%~ PubMed
%A Gustin, Sylvia M
%A Wrigley, Paul J
%A Henderson, Luke A
%A Siddall, Philip J
%T Brain circuitry underlying pain in response to imagined movement in people with spinal cord injury.
%B Pain
%D 2010
%C Netherlands, United States
%I Elsevier BV
%V 148
%N 3
%P 438-445
%@ 0304-3959
%X Pain following injury to the nervous system is characterized by changes in sensory processing including pain. Although there are many studies describing pain evoked by peripheral stimulation, we have recently reported that pain can be evoked in subjects with complete spinal cord injury (SCI) during a motor imagery task. In this study, we have used functional magnetic resonance imaging to explore brain sites underlying the expression of this phenomenon. In 9 out of 11 subjects with complete thoracic SCI and below-level neuropathic pain, imagined foot movements either evoked pain in a previously non-painful region or evoked a significant increase in pain within the region of on-going pain (3.2+/-0.7-5.2+/-0.8). In both controls (n=19) and SCI subjects, movement imagery evoked signal increases in the supplementary motor area and cerebellar cortex. In SCI subjects, movement imagery also evoked increases in the left primary motor cortex (MI) and the right superior cerebellar cortex. In addition, in the SCI subjects, the magnitude of activation in the perigenual anterior cingulate cortex and right dorsolateral prefrontal cortex was significantly correlated with absolute increases in pain intensity. These regions expanded to include right and left anterior insula, supplementary motor area and right premotor cortex when percentage change in pain intensity was examined. This study demonstrates that in SCI subjects with neuropathic pain, a cognitive task is able to activate brain circuits involved in pain processing independently of peripheral inputs.
%Z FOR Codes: 1109


%0 Journal Article
%~ PubMed
%A Nash, Paul G
%A Macefield, Vaughan G
%A Klineberg, Iven J
%A Gustin, Sylvia M
%A Murray, Greg M
%A Henderson, Luke A
%T Changes in human primary motor cortex activity during acute cutaneous and muscle orofacial pain.
%B Journal of Orofacial Pain
%D 2010
%C United States
%I Quintessence Publishing Co., Inc
%V 24
%N 4
%P 379-390
%@ 1064-6655
%X To use functional magnetic resonance imaging (fMRI) to determine whether orofacial cutaneous or muscle pain is associated with changes in primary motor cortex (M1) activity that outlast the duration of perceived pain, and whether these M1 changes are different during cutaneous pain compared with muscle pain.
%Z FOR Codes: 110599


%0 Journal Article
%~ PubMed
%A Rubin, Troy K
%A Henderson, Luke A
%A Macefield, Vaughan G
%T Changes in the Spatiotemporal Expression of Local and Referred Pain Following Repeated Intramuscular Injections of Hypertonic Saline: A Longitudinal Study.
%B The journal of pain : official journal of the American Pain Society
%D 2010
%C United States
%I Churchill Livingstone
%V 11
%N 8
%P 737-45
%@ 1528-8447
%X Intramuscular injection of hypertonic saline produces a dull ache that is felt in the muscle belly but also often refers into distal structures. We have previously observed in 2 subjects that the pattern of pain referral alters during painful stimuli separated by a week. In this investigation, we tested the hypothesis that the intensity and area of pain in the local and referred regions exhibits plasticity when an identical noxious stimulus is delivered to the same site over sequential trials. Bolus 1 mL intramuscular injections of 5% hypertonic saline were made into the same site of the tibialis anterior (TA) muscle on the same day each week for 4 consecutive weeks. Twenty-one subjects mapped the areas of local and referred pain and rated the intensities on a visual analog scale every 30 seconds until the cessation of pain. Over 4 weeks there was a progressive reduction in the area and intensity of local pain and a reciprocal increase in the expression of referred pain. We conclude that the decrease in perceived local pain and increase in perceived referred pain reflects plastic processes occurring centrally. PERSPECTIVE: What happens to the intensity of pain induced by repeated noxious stimuli over time? Does it stay the same, increase or decrease? Here we show that weekly injections of hypertonic saline into the tibialis anterior cause decreases in local but increases in referred pain, suggesting central changes in processing noxious inputs.
%Z FOR Codes: 1109


%0 Journal Article
%~ PubMed
%A Sander, Mikael
%A Macefield, Vaughan G
%A Henderson, Luke A
%T Cortical and brain stem changes in neural activity during static handgrip and postexercise ischemia in humans.
%B Journal of Applied Physiology
%D 2010
%C United States
%I American Physiological Society
%V 108
%N 6
%P 1691-1700
%@ 1522-1601
%X Static isometric exercise increases muscle sympathetic nerve activity (MSNA) and mean arterial pressure, both of which can be maintained at the conclusion of the exercise by occlusion of the arterial supply [postexercise ischemia (PEI)]. To identify the cortical and subcortical sites involved, and to differentiate between central command and reflex inputs, we used blood oxygen level-dependent (BOLD) functional MRI (fMRI) of the whole brain (3 T). Subjects performed submaximal static handgrip exercise for 2 min followed by 6 min of PEI; MSNA was recorded on a separate day. During the contraction phase, parallel increases in BOLD signal intensity occurred in the contralateral primary motor cortex and cerebellar nuclei and cortex; these matched the effort profile and ceased at the conclusion of the contraction. Progressive increases in the contralateral insula and primary and secondary somatosensory cortices, with progressive decreases in the perigenual anterior cingulate and midcingulate cortices, were sustained during the period of PEI and thus did not depend on central command. Discrete bilateral activation of the medial and lateral dorsal medulla was also observed during the contraction and PEI; we believe that these represent the nucleus tracts solitarius (NTS) and rostral ventrolateral medulla (RVLM), respectively. Given that metaboreceptor afferents are known to project to the NTS and that the RVLM is the primary output nucleus for MSNA, our data support that the metaboreflex is mediated by the medulla, whereas the somatosensory, insular, and anterior cingulate cortices are involved in the sensory and affective components of the maneuver.
%Z FOR Codes: 110603


%0 Book Section
%A Keay, Kevin
%A Henderson, Luke
%T Physical and Emotional Pain
%B Encyclopedia of Behavioral Neuroscience
%D 2010
%C United States
%I Elsevier Inc.
%V 
%N 
%P 54-63
%@ 9780080453965
%E Koob, George F.
%E Le Moal, Michel
%E Thompson, Richard F.
%X 
%Z FOR Codes: 110906


%0 Journal Article
%~ PubMed
%A Macefield, Vaughan G
%A Henderson, Luke A
%T Real-time imaging of the medullary circuitry involved in the generation of spontaneous muscle sympathetic nerve activity in awake subjects.
%B Human brain mapping
%D 2010
%C United States
%I John Wiley & Sons, Inc.
%V 31
%N 4
%P 539-49
%@ 1097-0193
%X To understand the central neural processes involved in blood pressure regulation we recorded muscle sympathetic nerve activity (MSNA) via a tungsten microelectrode in the common peroneal nerve while performing functional magnetic resonance imaging (fMRI) of the brainstem at 3T. Blood oxygen level dependent (BOLD) changes in signal intensity were measured over 4 s every 8 s (200) volumes; MSNA was recorded during the previous 4 s epoch, which takes into account peripheral conduction delays along unmyelinated axons and neurovascular coupling delays. Analysis of temporal coupling between BOLD signal intensity and nerve signal intensity revealed sites in which the two signals covaried, but only in the medulla. Because scans were conducted in a caudorostral direction, we could constrain the analysis to the medulla by only examining the first 1 s of the fMRI and nerve signals. Increases in MSNA were associated with robust bilateral increases in signal intensity in the dorsolateral region of the medulla that corresponds to the human equivalent of the rostal ventrolateral medulla (RVLM). Reciprocal decreases in signal intensity occurred in the regions of the nucleus tractus solitarius (NTS) and caudal ventrolateral medulla (CVLM). Group analysis also revealed increases in signal intensity in the caudal pressor area (CPA), medullary raph?? (MR), and dorsal motor nucleus of the vagus (DMX). We have shown for the first time that this combined approach of recording sympathetic neural activity and fMRI provides real-time imaging of the neural processes responsible for the generation of sympathetic nerve activity in awake human subjects.
%Z FOR Codes: 110901


%0 Journal Article
%~ PubMed
%A Henderson, Luke A
%A Rubin, Troy K
%A Macefield, Vaughan G
%T Within-limb somatotopic representation of acute muscle pain in the human contralateral dorsal posterior insula.
%B Human brain mapping
%D 2010
%C United States
%I John Wiley & Sons, Inc.
%V 32
%N 
%P 1592-601
%@ 1097-0193
%X It is well established that the insular cortex processes noxious information. We have previously shown that noxious inputs from the arm and leg are coarsely organized somatotopically within the dorsal posterior insula. The same has been shown for inputs from C tactile afferents, which mediate affective touch, and it has been suggested that the insula may be responsible for the localization of some somatosensory stimuli. Knowing the degree of spatial detail may have significant implications for the potential role of the dorsal posterior insula in the processing of noxious stimuli. Using high-resolution functional magnetic resonance imaging (fMRI), we compared insula activation patterns in 13 subjects during muscle pain induced by injection of hypertonic saline (5%) into three muscles within the same limb: shoulder (deltoid), forearm (flexor carpi radialis), and hand (first dorsal interosseous). Mapping the maximally activated voxels within the contralateral dorsal posterior insula in each individual subject during each pain stimulus revealed a clear somatotopy of activation within the contralateral dorsal posterior insula. Shoulder pain was represented anterior to forearm pain and medial to hand pain. This fine somatotopic organization may be crucial for pain localization or other aspects of the pain experience that differ depending on stimulation site.
%Z FOR Codes: 110906


%0 Journal Article
%~ PubMed
%A Wrigley, P J
%A Gustin, S M
%A Macey, P M
%A Nash, P G
%A Gandevia, S C
%A Macefield, V G
%A Siddall, P J
%A Henderson, L A
%T Anatomical changes in human motor cortex and motor pathways following complete thoracic spinal cord injury.
%B Cerebral Cortex
%D 2009
%C United Kingdom
%I Oxford University Press
%V 19
%N 1
%P 224-232
%@ 1460-2199
%X A debilitating consequence of complete spinal cord injury (SCI) is the loss of motor control. Although the goal of most SCI treatments is to re-establish neural connections, a potential complication in restoring motor function is that SCI may result in anatomical and functional changes in brain areas controlling motor output. Some animal investigations show cell death in the primary motor cortex following SCI, but similar anatomical changes in humans are not yet established. The aim of this investigation was to use voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) to determine if SCI in humans results in anatomical changes within motor cortices and descending motor pathways. Using VBM, we found significantly lower gray matter volume in complete SCI subjects compared with controls in the primary motor cortex, the medial prefrontal, and adjacent anterior cingulate cortices. DTI analysis revealed structural abnormalities in the same areas with reduced gray matter volume and in the superior cerebellar cortex. In addition, tractography revealed structural abnormalities in the corticospinal and corticopontine tracts of the SCI subjects. In conclusion, human subjects with complete SCI show structural changes in cortical motor regions and descending motor tracts, and these brain anatomical changes may limit motor recovery following SCI.
%Z FOR Codes: 110903


%0 Journal Article
%~ PubMed
%A Nash, Paul G
%A Macefield, Vaughan G
%A Klineberg, Iven J
%A Murray, Greg M
%A Henderson, Luke A
%T Differential activation of the human trigeminal nuclear complex by noxious and non-noxious orofacial stimulation.
%B Human brain mapping
%D 2009
%C United States
%I John Wiley & Sons, Inc.
%V 30
%N 11
%P 3772-82
%@ 1097-0193
%X There is good evidence from animal studies for segregation in the processing of non-nociceptive and nociceptive information within the trigeminal brainstem sensory nuclear complex. However, it remains unknown whether a similar segregation occurs in humans, and a recent tract tracing study suggests that this segregation may not exist. We used functional magnetic resonance imaging (fMRI) to define and compare activity patterns of the trigeminal brainstem nuclear complex during non-noxious and noxious cutaneous and non-noxious and noxious muscle orofacial stimulation in humans. We found that during cutaneous pain, signal intensity increased within the entire rostrocaudal extent of the spinal trigeminal nucleus (SpV), encompassing the ipsilateral oralis (SpVo), interpolaris (SpVi) and caudalis (SpVc) subdivisions. In contrast, muscle pain did not activate SpVi, but instead activated a discrete region of the ipsilateral SpVo and SpVc. Further, muscle noxious stimulation activated a region of the ipsilateral lateral pons in the region of the trigeminal principal sensory nucleus (Vp). Innocuous orofacial stimulation (lip brushing) also evoked a significant increase in signal intensity in the ipsilateral Vp; however, non-noxious muscle stimulation showed no increase in signal in this area. The data reveal that orofacial cutaneous and muscle nociceptive information and innocuous cutaneous stimulation are differentially represented within the trigeminal nuclear complex. It is well established that cutaneous and muscle noxious stimuli evoke different perceptual, behavioural and cardiovascular changes. We speculate that the differential activation evoked by cutaneous and muscle noxious stimuli within the trigeminal sensory complex may contribute to the neural basis for these differences.
%Z FOR Codes: 110903


%0 Journal Article
%~ PubMed
%A Rubin, Troy K
%A Gandevia, Simon C
%A Henderson, Luke A
%A Macefield, Vaughan G
%T Effects of Intramuscular Anesthesia on the Expression of Primary and Referred Pain Induced by Intramuscular Injection of Hypertonic Saline.
%B The journal of pain : official journal of the American Pain Society
%D 2009
%C United States
%I Churchill Livingstone
%V 10
%N 8
%P 829-35
%@ 1528-8447
%X Intramuscular injection of hypertonic saline produces pain in the belly of the injected muscle (primary pain) and, often, pain that projects distally (referred pain). While it is known that referred pain can be induced during complete sensory block of the distal site, there is little evidence as to whether the perception of referred pain depends on ongoing input from the primary stimulus. We assessed whether blocking the noxious input following the induction of pain blocks the primary but not the referred pain. A cannula was inserted into the tibialis anterior muscle in 15 subjects (8 male, 7 female). In a quasi-random crossover design conducted over 2 experimental sessions, each subject received a bolus intramuscular injection of .5 mL of 5% hypertonic saline, followed 90 seconds later by either: A) A second bolus injection or; B) An injection of 2 mL lignocaine through the same cannula. Protocol A was followed 60 seconds later by either a sham injection or an injection of lignocaine, while protocol B was followed 60 seconds later by either a sham injection or an injection of hypertonic saline. Subjects mapped the areas of primary and referred pain, and rated the intensities at these sites every 30 seconds until the cessation of pain. In all subjects, the area and intensity of primary pain rapidly disappeared within 7.5 minutes of intramuscular lignocaine injection (P < .02 relative to the nonanesthesia condition). With the exception of 2 subjects, in whom the referred pain continued in the absence of primary pain, the referred pain declined in parallel with local pain: the mean total pain intensity declined by 74% in both regions. We conclude that the maintenance of referred muscle pain usually depends on ongoing noxious inputs from the site of primary muscle pain. PERSPECTIVE: Referred pain is a significant clinical problem, and commonly occurs with pain originating in muscle but not from skin. It is important to know the primary source of the pain so that treatment can be directed to this site rather to the site of referral.
%Z FOR Codes: 110999


%0 Journal Article
%~ PubMed
%A Burton, A R
%A Birznieks, I
%A Spaak, J
%A Henderson, L A
%A Macefield, V G
%T Effects of deep and superficial experimentally induced acute pain on skin sympathetic nerve activity in human subjects.
%B Experimental Brain Research
%D 2009
%C Germany
%I Springer
%V 195
%N 2
%P 317-324
%@ 1432-1106
%X There is evidence in experimental animals that deep and superficial pain exert differential effects on cutaneous sympathetic activity. Skin sympathetic nerve activity (SSNA) was recorded from the common peroneal nerve of awake human subjects and injections of 0.5 ml hypertonic saline was made into the tibialis anterior muscle (causing a deep, dull ache) or 0.2 ml into the overlying skin (causing a sharp burning pain) at unexpected times. Both deep and superficial pain caused increases in SSNA immediately on injection and preceding the onset of pain for both muscle and skin pain (10.1 +/- 2.4 vs. 15.3 +/- 5.3 s; muscle versus skin, respectively). SSNA increases were short lasting (104.2 +/- 13.4 vs. 81.8 +/- 11.7 s; muscle versus skin pain) and did not follow muscle and skin pain profiles. Sweat release occurred following both intramuscular and subcutaneous injections of hypertonic saline. While muscle or skin pain invariably caused changes in skin blood flow as well as increases in sweat release, skin blood flow increased in females and decreased in males. We conclude that both acute muscle and skin pain cause an increase in SSNA, sweat release and gender-dependent changes in skin blood flow.
%Z FOR Codes: 60699


%0 Journal Article
%~ PubMed
%A Burton, Alexander R
%A Birznieks, Ingvars
%A Bolton, Philip S
%A Henderson, Luke A
%A Macefield, Vaughan G
%T Effects of deep and superficial experimentally-induced acute pain on muscle sympathetic nerve activity in human subjects.
%B The Journal of physiology
%D 2009
%C United Kingdom
%I Blackwell Publishing Ltd.
%V 587
%N 1
%P 183-93
%@ 0022-3751
%X Human studies conducted more than half a century ago have suggested that superficial pain induces excitatory effects on the sympathetic nervous system, resulting in increases in blood pressure (BP) and heart rate (HR), whereas deep pain is believed to cause vasodepression. To date, no studies have addressed whether deep or superficial pain produces such differential effects on muscle sympathetic nerve activity (MSNA). Using microneurography we recorded spontaneous MSNA from the common peroneal nerve in 13 awake subjects. Continuous blood pressure was recorded by radial arterial tonometry. Deep pain was induced by intramuscular injection of 0.5 ml hypertonic saline (5%) into the tibialis anterior muscle, superficial pain by subcutaneous injection of 0.2 ml hypertonic saline into the overlying skin. Muscle pain, with a mean rating of 4.9 +/- 0.8 (S.E.M.) on a 0-10 visual analog scale (VAS) and lasting on average 358 +/- 32 s, caused significant increases in MSNA (43.9 +/- 10.0%), BP (5.4 +/- 1.1%) and HR (7.0 +/- 2.0%) - not the expected decreases. Skin pain, rated at 4.9 +/- 0.6 and lasting 464 +/- 54 s, also caused significant increases in MSNA (38.2 +/- 12.8%), BP (5.1 +/- 2.1%) and HR (5.6 +/- 2.0%). The high-frequency (HF) to low-frequency (LF) ratio of heart rate variability (HRV) increased from 1.54 +/- 0.25 to 2.90 +/- 0.45 for muscle pain and 2.80 +/- 0.52 for skin pain. Despite the different qualities of deep (dull and diffuse) and superficial (burning and well-localized) pain, we conclude that pain originating in muscle and skin does not exert a differential effect on muscle sympathetic nerve activity, both causing an increase in MSNA and an increase in the LF:HF ratio of HRV. Whether this holds true for longer lasting experimental pain remains to be seen.
%Z FOR Codes: 1109 1102


%0 Journal Article
%~ PubMed
%A Wrigley, P J
%A Press, S R
%A Gustin, S M
%A Macefield, V G
%A Gandevia, S C
%A Cousins, M J
%A Middleton, J W
%A Henderson, L A
%A Siddall, P J
%T Neuropathic pain and primary somatosensory cortex reorganization following spinal cord injury.
%B Pain
%D 2009
%C Netherlands
%I Elsevier BV
%V 141
%N 1-2
%P 52-9
%@ 0304-3959
%X The most obvious impairments associated with spinal cord injury (SCI) are loss of sensation and motor control. However, many subjects with SCI also develop persistent neuropathic pain below the injury which is often severe, debilitating and refractory to treatment. The underlying mechanisms of persistent neuropathic SCI pain remain poorly understood. Reports in amputees describing phantom limb pain demonstrate a positive correlation between pain intensity and the amount of primary somatosensory cortex (S1) reorganization. Of note, this S1 reorganization has also been shown to reverse with pain reduction. It is unknown whether a similar association between S1 reorganization and pain intensity exists in subjects with SCI. The aim of this investigation was to determine whether the degree of S1 reorganization following SCI correlated with on-going neuropathic pain intensity. In 20 complete SCI subjects (10 with neuropathic pain, 10 without neuropathic pain) and 21 control subjects without SCI, the somatosensory cortex was mapped using functional magnetic resonance imaging during light brushing of the right little finger, thumb and lip. S1 reorganization was demonstrated in SCI subjects with the little finger activation point moving medially towards the S1 region that would normally innervate the legs. The amount of S1 reorganization in subjects with SCI significantly correlated with on-going pain intensity levels. This study provides evidence of a link between the degree of cortical reorganization and the intensity of persistent neuropathic pain following SCI. Strategies aimed at reversing somatosensory cortical reorganization may have therapeutic potential in central neuropathic pain.
%Z FOR Codes: 1109


%0 Journal Article
%~ PubMed
%A Buchbinder, R
%A March, L
%A Lassere, M
%A Briggs, A M
%A Portek, I
%A Reid, C
%A Meehan, A
%A Henderson, L
%A Wengier, L
%A van den Haak, R
%T Effect of treatment with biological agents for arthritis in Australia: the Australian Rheumatology Association Database.
%B Internal medicine journal
%D 2007
%C Australia
%I Blackwell Publishing Asia
%V 37
%N 9
%P 591-600
%@ 1444-0903
%X BACKGROUND: The Australian Rheumatology Association Database (ARAD), a voluntary national registry, has been established to collect health information from Australian patients with inflammatory arthritis for the purpose of monitoring the benefits and safety of new treatments, in particular the biological disease-modifying anti-rheumatic drugs (bDMARDs). These drugs are proving to be very effective, yet little is known of their long-term effectiveness or safety. Patient registries that systematically gather data on large cohorts of unselected patients are increasingly believed to be an essential means of answering questions of the long-term effectiveness and safety of new drugs. The aim of this report is to describe the role, development and structure of ARAD and provide some preliminary data. METHODS: As of 1 August 2006, 563 patients with rheumatoid arthritis prescribed a bDMARD have been enrolled in ARAD, involving 105 rheumatologists from across Australia. RESULTS: The data collected will enable examination of multiple domains of patient responses to bDMARDs, including quality of life, health-care utilization, incidence of adverse events and the effects of therapy switching. CONCLUSION: Evidence-based information about the long-term outcome of bDMARD therapy is essential for clinicians, consumers, policy-makers, drug development companies and approval agencies, to enable better care and improved outcomes for patients with inflammatory arthritis.
%Z FOR Codes: 110322


%0 Journal Article
%~ PubMed
%A Henderson, Luke A
%A Gandevia, S C
%A Macefield, Vaughan G
%T Gender differences in brain activity evoked by muscle and cutaneous pain: A retrospective study of single-trial fMRI data.
%B NeuroImage
%D 2007
%C United States
%I Academic Press Inc
%V 39
%N 
%P 1867-76
%@ 1053-8119
%X Gender greatly influences pain processing. Not only do females display greater pain sensitivity, many chronic pain conditions affect females more than males. Although gender-based differences in pain sensitivity may be related to cultural and social factors, animal studies also reveal gender differences in pain sensitivity, suggesting that physiological factors may contribute to differences in the processing of pain in males and females. It has been recently reported that noxious cutaneous heat stimuli evoke gender-based differences in activity in some brain regions. Given that most chronic pain conditions, including those with gender bias are of "deep" origin (e.g. arising in muscle, joints or viscera), we investigated whether gender differences also exist in the central processing of muscle pain. In 24 healthy adults we used functional magnetic resonance imaging (fMRI) to measure signal intensity changes during muscle and cutaneous pain induced by intramuscular and subcutaneous injections of hypertonic saline, respectively. In addition to activating the "pain neuromatrix", i.e. cingulate, insular, somatosensory and cerebellar cortices, both muscle pain and cutaneous pain evoked gender-based differences in the mid-cingulate cortex, dorsolateral prefrontal cortex, hippocampus and cerebellar cortex. These differences may reflect differences in emotional processing of noxious information in men and women and may underlie the gender bias that exists in many chronic pain conditions.
%Z FOR Codes: 110906


%0 Journal Article
%~ PubMed
%A Gustin, Sylvia M
%A Wrigley, Paul J
%A Gandevia, Simon C
%A Middleton, James W
%A Henderson, Luke A
%A Siddall, Philip J
%T Movement imagery increases pain in people with neuropathic pain following complete thoracic spinal cord injury.
%B Pain
%D 2007
%C Netherlands, US.
%I Elsevier BV
%V 137
%N 0
%P 237-44
%@ 1872-6623
%X Spinal cord injury (SCI) results in deafferentation and the onset of neuropathic pain in a substantial proportion of people. Based on evidence suggesting motor cortex activation results in attenuation of neuropathic pain, we sought to determine whether neuropathic SCI pain could be modified by imagined movements of the foot. Fifteen subjects with a complete thoracic SCI (7 with below-level neuropathic pain and 8 without pain) were instructed in the use of movement imagery. Movement imagery was practiced three times daily for 7days. On the eighth day, subjects performed the movement imagery in the laboratory and recorded pain ratings during the period of imagined movement. Six out of 7 subjects with neuropathic pain reported an increase in pain during imagined movements from 2.9+/-0.7 during baseline to 5.0+/-1.0 during movement imagery (p<0.01). In SCI subjects without neuropathic pain, movement imagery evoked an increase in non-painful sensation intensity from a baseline of 1.9+/-0.7 to 4.8+/-1.3 during the movement imagery (p<0.01). Two subjects without a history of pain or non-painful phantom sensations had onset of dysesthesia while performing imagined movements. This study reports exacerbation of pain in response to imagined movements and it contrasts with reports of pain reduction in people with peripheral neuropathic pain. The potential mechanisms underlying this sensory enhancement with movement imagery are discussed.
%Z FOR Codes: 110299


%0 Journal Article
%~ PubMed
%A Macefield, Vaughan G
%A Gandevia, S C
%A Henderson, Luke A
%T Discrete Changes in Cortical Activation during Experimentally Induced Referred Muscle Pain: A Single-Trial fMRI Study.
%B Cerebral cortex (New York, N.Y. : 1991)
%D 2006
%C UK
%I Oxford University Press
%V 17
%N 0
%P 2050-9
%@ 1047-3211
%X Noxious stimulation of skeletal muscle evokes pain that is often referred into distal areas. Despite referred pain being of significant clinical importance, the brain regions responsible for the perception of referred pain remain unexplored. The aim of this investigation is to define these regions using functional magnetic resonance imaging. We induced muscle pain by hypertonic saline injections (0.5 ml) into the tibialis anterior (TA) or flexor carpi radialis (FCR) muscle. TA injections evoked pain that was referred to the ankle/foot in 10/17 subjects, whereas FCR injections evoked pain that was projected into the wrist/hand in 6/12 subjects. Regional brain responses were statistically tested by convolving the temporal profile of the subjective pain intensity rating with the hemodynamic response function. For all subjects, signal increased in the region of primary somatosensory cortex (SI), which represents the leg or arm, that is, the area corresponding to the injection site. However, for those subjects who reported referred pain, signal intensity increases also occurred in the SI region representing the foot or hand. Interestingly, differential signal changes also occurred in anterior cingulate, cerebellar, and insular cortices. This is the first study to provide evidence of cortical differentiation in the processing of primary and referred pain.
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Henderson, L A
%A Bandler, R
%A Gandevia, S C
%A Macefield, V G
%T Distinct forebrain activity patterns during deep versus superficial pain.
%B Pain
%D 2006
%C Netherlands
%I Elsevier Science Bv
%V 120
%N 3
%P 286-96
%@ 0304-3959
%X All pain is unpleasant, but different perceptual and emotional qualities are characteristic of pain originating in different structures. Pain of superficial (cutaneous) origin usually is sharp and restricted, whereas pain of deep origin (muscle/viscera) generally is dull and diffuse. Despite the differences it has been suggested previously that all pain is mediated by an invariant set ("neuromatrix") of brain structures. However, we report here, using functional magnetic resonance imaging (fMRI), that striking regional differences in brain activation patterns were the rule. Signal differences were found in regions implicated in emotion (perigenual cingulate cortex), stimulus localization and intensity (somatosensory cortex) and motor control (motor cortex, cingulate motor area). Further, most fMRI signal changes matched perceived changes in pain intensity. These findings clearly indicate that distinct neural activity patterns in distinct sets of brain structures are evoked by pain originating from different tissues of the body. Further, we suggest that these differences underlie the different perceptual and emotional reactions evoked by deep versus superficial pain.
%Z FOR Codes: 110903 110903


%0 Journal Article
%~ PubMed
%A Brown, Heidi J
%A Henderson, Luke A
%A Keay, Kevin A
%T Hypotensive but not normotensive haemorrhage increases tryptophan hydroxylase-2 mRNA in caudal midline medulla.
%B Neuroscience letters
%D 2006
%C Ireland
%I Elsevier Science Ireland Ltd
%V 398
%N 3
%P 314-8
%@ 0304-3940
%X Severe blood loss triggers shock, a precipitous hypotension and bradycardia. The integrity of (i) neurons in the vasodepressor region of the caudal midline medulla and (ii) central 5-HT neurotransmission are critical for the expression of haemorrhagic shock. This study investigated whether progressive blood loss triggers altered synthesis of 5-HT in the vasodepressor region of the caudal midline medulla by measuring changes in relative expression levels of tryptophan hydroxylase 2 (TpH 2) mRNA, the rate-limiting enzyme in the synthesis of neuronal 5-HT. Hypotensive but not normotensive haemorrhage triggered a significant increase in TpH 2 mRNA in the vasodepressor region of the caudal midline medulla, identifying an important role for 5-HT-containing caudal midline medullary neurons in haemorrhagic shock.
%Z FOR Codes: 110906


%0 Journal Article
%~ PubMed
%A Macefield, V G
%A Gandevia, S C
%A Henderson, L A
%T Neural sites involved in the sustained increase in muscle sympathetic nerve activity induced by inspiratory capacity apnea: a fMRI study.
%B Journal of applied physiology (Bethesda, Md. : 1985)
%D 2006
%C USA
%I American Physiological Society
%V 100
%N 1
%P 266-73
%@ 8750-7587
%X A maximal inspiratory breath hold (inspiratory capacity apnea) against a closed glottis evokes a large and sustained increase in muscle sympathetic nerve activity (MSNA). Because of its dependence on a high intrathoracic pressure, it has been suggested that this maneuver causes unloading of the low-pressure baroreceptors, known to increase MSNA. To determine the central origins of this sympathoexcitation, we used functional magnetic resonance imaging to define the loci and time course of activation of different brain areas. We hypothesized that, as previously shown for the Valsalvsa maneuver, discrete but widespread regions of the brain would be involved. In 15 healthy human subjects, a series of 90 gradient echo echo-planar image sets was collected during three consecutive 40-s inspiratory capacity apneas using a 3-T scanner. Global signal intensity changes were calculated and subsequently removed by using a detrending technique, which eliminates the global signal component from each voxel''s signal intensity change. Whole brain correlations between changes in signal intensity and the known pattern of MSNA during the maneuver were performed on a voxel-by-voxel basis, and significant changes were determined by using a random-effects analysis procedure (P < 0.01, uncorrected). Significant signal increases emerged in multiple areas, including the rostral lateral medulla, cerebellar nuclei, anterior insula, dorsomedial hypothalamus, anterior cingulate, and lateral prefrontal cortexes. Decreases in signal intensity occurred in the dorsomedial and caudal lateral medulla, cerebellar cortex, hippocampus, and posterior cingulate cortex. Given that many of these sites have roles in cardiovascular control, the sustained increase in MSNA during an inspiratory capacity apnea is likely to originate from a distributed set of discrete areas.
%Z FOR Codes: 110901


%0 Journal Article
%~ PubMed
%A Henderson, Luke A
%A Macey, Katherine E
%A Macey, Paul M
%A Woo, Mary A
%A Yan-Go, Frisca L
%A Harper, Ronald M
%T Regional brain response patterns to Cheyne-Stokes breathing.
%B Respiratory physiology & neurobiology
%D 2006
%C Netherlands
%I Elsevier BV
%V 150
%N 1
%P 87-93
%@ 1569-9048
%X Cheyne-Stokes breathing (CSB) results from impaired integration of sensory information with respiratory motor output; however, regions mediating the disturbed control are unknown. We examined functional magnetic resonance imaging signals during CSB within sleep to determine affected areas. Two male patients with severe obstructive sleep apnea were scanned while asleep over multiple sessions during which they exhibited CSB. Significant signal increases coincident with apneic periods emerged bilaterally in the cerebellar cortex, hippocampus, mediodorsal thalamus, frontal cortex and precentral gyrus. Signals declined bilaterally in the anterior cingulate cortex and postcentral gyrus. The reduced activation in primary sensory cortex and increased signals prior to breathing onset in the motor cortex are consistent with loss of sensory stimulation by airflow, and with anticipatory action of the motor cortex prior to initiation of breathing. Hippocampal and anterior cingulate cortex participation likely reflect previously-demonstrated roles for initiating inspiratory efforts and resolving sensory information and motor action, respectively.
%Z FOR Codes: 110901


%0 Journal Article
%~ PubMed
%A Henderson, L A
%A Gandevia, S C
%A Macefield, V G
%T Somatotopic organization of the processing of muscle and cutaneous pain in the left and right insula cortex: A single-trial fMRI study.
%B Pain
%D 2006
%C Netherlands
%I Elsevier BV
%V 128
%N 0
%P 20-30
%@ 1872-6623
%X The insula is involved in processing noxious information. It is consistently activated by acute noxious stimuli, can elicit pain on stimulation, and lesions encompassing the insula can alter pain perception. Anatomical tracing, electrophysiological and functional brain imaging investigations have suggested that the insula is somatotopically organized with respect to noxious cutaneous inputs. It has also recently been revealed that the anterior insula displays differential activation during cutaneous compared with muscle pain. Given this difference, it is important to determine if an insula somatotopy also exists for muscle pain. Using high-resolution functional magnetic resonance imaging (fMRI) we compared insula activation patterns in 23 subjects during muscle and cutaneous pain induced in the right leg and forearm. Group and frequency analyses revealed somatotopically organized signal increases in the posterior contralateral (left) and ipsilateral (right) anterior insula. Within the posterior contralateral insula, signal increases during both cutaneous and muscle forearm pain were located lateral and anterior to those evoked by leg pain, whereas in the ipsilateral anterior insula the pattern was reversed. Furthermore, within the ipsilateral anterior insula, muscle pain activated a region anterior to that activated by cutaneous pain. This somatotopic organization may be crucial for pain localization or other aspects of the pain experience that differ depending on both stimulation site and type of tissue activated. This study reveals that the insula is organized somatopically with respect to muscle and cutaneous pain and that this organization is further separated according to the tissue in which the pain originates.
%Z FOR Codes: 110903