FMRI Reveals Abnormal Central Processing of Sensory and Pain Stimuli in Ill Gulf War Veterans - Europe PMC Article. Abstract. Many veterans chronically ill from the 1. Gulf War exhibit symptoms of altered sensation, including chronic pain. In this study of 5. Construction Battalion previously examined in 1. MRI protocol in control veterans and groups representing three syndrome variants. Testing outside the scanner revealed no significant differences in warm detection or heat pain threshold among the four groups. In the f. MRI study, Syndrome 1 and Syndrome 2, but not Syndrome 3, exhibited hypo- activation to innocuous heat and hyper- activation to noxious heat stimuli compared to controls. The results indicate abnormal central processing of sensory and painful stimuli in 2 of 3 variants of Gulf War illness and call for a more comprehensive study with a larger, representative sample of veterans. Keywords: functional MRI, neuroimaging, innocuous heat, noxious heat, sensory, pain, Brain Diseases, Gulf War Illness. Insect Molecular Biology, and Vector Biology & Control. Log In; Sign Up; About; Papers 24;. Clinician-Administered PTSD Scale (CAPS). Troops’ Exposure Cannot Be Adequately Supported. Wind Field Vector Model. CAPS Clinician Administered Posttraumatic Stress. Introduction. An estimated 2. Gulf War veterans experience multisymptom conditions not explained by stress or psychiatric illness (Binns et al., 2. Although factor analysis has yielded symptom clusters and syndrome classifications of Gulf War Illness (Haley and Kurt, 1. Participants also were administered the Clinician-Administered PTSD Scale (CAPS.Iannacchione et al., 2. Abnormalities of sensation, including paresthesias, numbness, heat or cold intolerance and chronic pain, are common components of the illness (Binns et al., 2. Haley, 1. 99. 9). A study of British Gulf War veterans (Jamal et al., 1. QST) of right foot. Title: When combat prevents PTSD symptoms. Clinician-Administered PTSD Scale (CAPS) or any other scale? 2002), the Clinician-Administered PTSD Scale (CAPS. Thermal hyposensitivity in the form of higher cooling detection thresholds (in all extremities) and higher warm detection thresholds (in the hands) were also found in a previous study of American Gulf War veterans (Haley et al., unpublished data by personal communication). A recent study (Cook et al., 2. GW veterans, but increased pain intensity and affect ratings in ill GW veterans, during QST of the thenar eminence of the no- dominant hand. Blood oxygenation level dependent (BOLD) f. MRI has become a highly useful modality to investigate the normal central nervous system (CNS) processing of pain (Apkarian et al., 2. Event- related f. MRI using thermal stimuli has also successfully demonstrated abnormalities in the central processing of pain in a variety of chronic pain conditions of unknown pathophysiology (Chen, 2. In the current study, differences in brain activation to innocuous and noxious heat among four groups of Gulf War veterans- -Syndrome 1 (Syn. Syndrome 2 (Syn. 2), Syndrome 3 (Syn. Haley and Kurt, 1. Iannacchione et al., 2. MRI studies. The aims were to examine differences in cerebral processing of innocuous heat and noxious heat between the three syndrome groups and controls, to elucidate the nature of CNS dysfunction in Gulf War illness and to compare the CNS abnormalities in GWI with those of fibromyalgia (Clauw, 2. Cook et al., 2. 00. Nebel and Gracely, 2. Staud et al., 2. 00. Williams and Gracely, 2. Defrin et al., 2. Kraus et al., 2. 00. Methods. 2. 1 Subjects. Fifty- four right – handed male Gulf War veterans from the 2. Reserve Naval Mobile Construction Battalion participated in a week- long battery of neuroimaging, clinical, neuropsychology, and psychiatry tests, including the innocuous and noxious heat f. MRI. Selected as a nested case- control study from a larger survey that defined three primary variants of Gulf War syndrome (Haley and Kurt, 1. Iannacchione et al., 2. Sharma, 2. 01. 1), the subjects (Table 1) included 1. Syndrome 1 group (mild cognitive impairment), 1. Syndrome 2 (more severe confusion- ataxia), 1. Syndrome 3 (central neuropathic pain, and 1. The subjects were classified based on the syndromes defined by factor analysis of symptoms they endorsed in an earlier study reported in 1. Haley and Kurt, 1. One Syn. 2 patient was subsequently removed from the study due to excessive motion during the MRI scan (see Results section 3. Diagnoses of psychiatric comorbidities including major depressive disorder, alcohol abuse or dependence, and drug abuse or dependences were made by the Structured Clinical Interview for DSM- IV Axis I Disorders (SCID) (First et al., 1. PTSD by a score of 4. Clinician- Administered PTSD Scale (CAPS), conducted by a neuropsychologist trained in their administration. Veterans were diagnosed to have PTSD if they had a CAPS score of 4. Weathers et al., 2. Fibromyalgia (FM) diagnosis was made by the survey definition comprised of the pain distribution criteria of the. American College of Rheumatology without the tender point examination (Wolfe et al., 1. CFS) was diagnosed by Centers for Disease Control and Prevention (CDC) criteria (Fukuda et al., 1. Differences in age and years of education were assessed with 4- group analysis of variance, and the incidence of clinical conditions (e. PTSD, FM, alcohol and drug abuse, etc.), and use of medications of different classes (e. The protocol was approved by the local Institutional Review Board (IRB), and informed consent was acquired from all the subjects prior to their participation. Tasks. Warm detection and heat pain thresholds were first determined outside the scanner with a Medoc Advanced Thermal Stimulator (Cary, NC). This stimulator has a 3 cm . Subjects were familiarized with the methods before the start of assessments using a standard set of instructions and procedures. Warm detection threshold was always obtained before the heat pain threshold. The thermode was placed against the ventral inner forearm of the right arm and the warm detection and heat pain thresholds were determined by the method of limits (Heldestad et al., 2. Yarnitsky, 1. 99. From a baseline of 3. The subjects subsequently underwent f. MRI in the scanner with first 3 runs with the innocuous heat stimuli and then 3 runs with the noxious heat stimuli. The subject- specific thermode test temperature for innocuous heat f. MRI runs was the average of the warm detection and heat pain thresholds determined outside the scanner. Each stimulus epoch consisted of 8 . There were 1. 0 such identical stimulus epochs in each run and the inter- stimulus interval (ISI) durations between stimuli were comprised of thermal stimulation at baseline temperature, with durations adjusted so that the time between onset of consecutive epochs was varied between 2. There were 3 innocuous heat f. MRI runs, each with duration of: 4 min and 2. The subject- specific thermode test temperature for the noxious heat f. MRI runs was the heat pain threshold temperature determined outside the scanner. Each stimulus epoch consisted of 8 . There were 1. 0 such identical stimulus epochs in each run and the inter- stimulus interval (ISI) durations between stimuli were comprised of thermal stimulation at baseline temperature, with durations adjusted so that the time between onset of consecutive epochs was varied between 2. The subjects were administered 3 such noxious heat stimulus epochs outside the MRI scanner to ensure they could tolerate the task inside the scanner. The noxious heat f. MRI runs were administered after completion of the innocuous heat f. MRI runs. There were 3 noxious heat f. MRI runs, each with duration of 5 min and 6 s. To minimize sensitization, there were 5–7 minute gaps between consecutive noxious heat f. MRI runs, during which other MRI scans were acquired. Image Acquisition. MR images were acquired on a 3. T Siemens Magnetom Trio TIM scanner with a 1. BOLD f. MRI scans were acquired using a conventional EPI sequence with FOV = 2. TR/TE/FA = 2. 00. There were 1. 50 (1. MRI scans. Prospective real- time motion correction (Thesen et al., 2. EPI f. MRI scans to minimize motion artifacts. A time- of- flight MR angiogram (TR/TE/FA = 2. A whole- brain 3. D T1- weighted MPRAGE sequence (FOV = 2. TR/TI/TE/FA = 2. 25. All scans were acquired with parallel imaging (GRAPPA; acceleration factor = 2; 2. Cardiac and respiration physiological responses were monitored and recorded with a BIOPAC (Goleta, CA) finger pulse- oximeter and respiration belt during all f. MRI scans. 2. 4 Data Analysis. Image analysis was conducted with AFNI, FSL and Matlab. BOLD EPI images from the scanner were volume registered to account for global rigid motion with an intensity- based, iterative, linearized, weighted least squares algorithm (Cox and Jesmanowicz, 1. For each voxel, the signal was modeled as the convolution of a stimulus vector, comprised of the onset- times of heat stimulus epochs, with their corresponding voxel impulse response functions (IRFs), plus 3rd order polynomial drifts and constant baseline. IRFs were deconvolved for each voxel from the knowledge of the observed voxel f. MRI intensity time- series and the stimulus vectors, under a multiple linear regression framework. The voxel time- series were also orthogonalized to the estimated motion parameters from the volume registration algorithm within the same regression model, and image volumes exhibiting more than 3 mm (~1 voxel) maximal displacement were excluded from analysis. The linear regression F- statistic was used to quantify activation at the individual subject level. The fractional (normalized to the regression- estimate baseline) amplitude of the hemodynamic response (HDR) was also calculated at each voxel. Each subject’s high resolution anatomic image was spatially normalized to the AFNI Talairach template. The resultant transformation matrix was used to warp the maps of voxel- wise fractional HDR amplitude for each run and each condition (noxious and innocuous heat) to Talairach space. Two- way mixed effects analyses of variance (ANOVA: Group x Runs; random subject factor nested within the levels of the Group factor) were employed to obtain individual group activation maps and between- group differences in activation for the innocuous and noxious heat conditions. The amplitude data were co- varied for age, since heat perception varies with age (Lariviere et al., 2. Lautenbacher et al., 2. Lin et al., 2. 00. Thus age- effects, if any, have been removed from the f.
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