Fibromyalgia (FM) has been associated with alterations in brain morphometry and abnormal dopaminergic neurotransmission. Evidence from preclinical models has demonstrated that dopamine plays a role in promoting neuronal integrity. We therefore sought to confirm previous findings of reduced gray matter density in subjects with FM and to determine whether variations in dopamine metabolism might affect gray matter density. Voxel-based morphometry was used to evaluate anatomical magnetic resonance imaging data from 30 female FM subjects in comparison with 20 age- and gender-matched healthy control subjects. in addition, data from a subset of subjects from both groups who had previously participated in our positron emission tomography study using radiolabeled DOPA (n = 14; 6 FM subjects and 8 control subjects) was used to determine whether correlation might exist between gray matter density and dopamine metabolism. We found a significant reduction in gray matter density within the bilateral parahippocampal gyri, right posterior cingulate cortex, and left anterior cingulate cortex. in addition, a positive correlation was demonstrated between an index of dopamine metabolism from the ventral tegmental area wherein cell bodies of corticolimbic projection neurons originate and gray matter density, specifically in the bilateral parahippocampal gyri and left pregenual cortex. The current results confirm our previous findings that FM is associated with altered brain morphometry. Alterations in dopamine metabolism might contribute to the associated changes in gray matter density.Perspective: Fibromyalgia is associated with reductions in gray matter density within brain regions ostensibly involved in phenomena related to the disorder, including enhanced pain perception, cognitive dysfunction, and abnormal stress reactivity. Given mounting evidence of abnormal dopaminergic neurotransmission associated with the disorder the strong correlation between dopamine metabolism and gray matter density provides insight as to the pathophysiology that might contribute to these changes. (C) 2009 by the American Pain Society

Although the pathology of fibromyalgia is poorly understood, a growing body of evidence suggests involvement of the central nervous system. The hippocampus is a brain center that is sensitive to the effects of stress exposure and has been demonstrated to be affected in a variety of disorders whose onset, like fibromyalgia, are associated with stressful experience. We therefore interrogated the bilateral hippocampus of 16 female fibromyalgia patients in comparison to 8 age- and gender-matched healthy control subjects using single voxel proton magnetic resonance spectroscopy. Our results demonstrate a significant reduction in the ratio of N-acetylaspartate to creatine (NAA/Cr) in fibromyalgia patients versus matched control subjects specifically in the right temporal lobe from a voxel centered on the right hippocampus (patient vs control, mean standard deviation: 1.20 +/- 0.13 vs 1.34 +/- 0.10, P = .03). Moreover, correlation analysis demonstrated a significant negative correlation between patient scores on the Fibromyalgia Impact Questionnaire and NAA/Cr ratio within the right hippocampus (Spearman rank correlation, rho = -0,681, P = .018). Our results indicate that fibromyalgia is associated with brain metabolite abnormalities within the right hippocampus that correlate with patient symptoms.Perspective: We have demonstrated an abnormality in hippocampal brain metabolites in premenopausal female fibromyalgia patients with no psychiatric comorbidity. A significant negative correlation between patient subjective experience of symptoms and a reduced NAA/Cr ratio suggests a role for hippocampal pathology in fibromyalgia. (C) 2009 by the American Pain Society

Although the pathophysiology underlying the pain of fibromyalgia syndrome (FMS) remains unknown, a variety of clinical and investigational findings suggests a dysregulation of dopaminergic neurotransmission. We therefore investigated presynaptic dopaminergic function in 6 female FMS patients in comparison to 8 age- and gender-matched controls as assessed by positron emission tomography with 6-[F-18]fluoro-L-DOPA as a tracer. Semiquantitative analysis revealed reductions in 6-[F-18]fluoro-L-DOPA uptake in several brain regions, indicating a disruption of presynaptic dopamine activity wherein dopamine plays a putative role in natural analgesia. Although the small sample size makes these findings preliminary, it appears that FMS might be characterized by a disruption of dopaminergic neurotransmission.Perspective: An association between FMS and reduced dopamine metabolism within the pain neuromatrix provides important insights into the pathophysiology of this mysterious disorder. (C) 2007 by the American Pain Society.

This paper discusses the use of computational neural modeling with functional neuroimaging data, especially the data obtained from positron emission tomography and functional magnetic resonance imaging (fMRI) studies of human cognition. We point out that such data require network analysis to most thoroughly interpret them. Two types of modeling methods are discussed. The first is systems-level modeling, which attempts to determine the nodes of the neural networks mediating specific tasks and die strengths of the interactions between the nodes. The second is large-scale neural modeling, which uses large numbers of neurally realistic elements, arranged into different interacting populations and regions, to simulate the tasks of interest, the neural activities in the multiple populations, and the neuroimaging data (e.g., fMRI) in each region of the model for comparison with experimental data. We will lastly show that these two types of modeling can be combined and used to obtain insight into interregional neural interactions.

During relapses in relapsing-remitting multiple sclerosis (RRMS), serum soluble HLA class I surface antigen (sHLA-I) levels are reported to either decrease or remain unchanged, whereas serum sHLA-II levels increase. Interferon-beta 1b therapy was recently reported to increase serum sHLA-I in RRMS. In the present prospective study, solid-phase enzyme-linked immunosorbent assay was used to measure sHLA-I and sHLA-II in the sera of 21 RRMS patients during a clinical exacerbation, and then six weeks after treatment with high-dose interferon-beta 1a (IFN-beta 1a). Pretreatment serum sHLA-I was significantly lower in patients than in normal controls (P < 0.0005). Pretreatment sHLA-II was also significantly lower than in normal controls (P =.003) unless enhancing MRI lesions (objectified relapse) were present; then sHLA-II levels were similar to normal controls (relative increase). Six weeks after initiation of IFN-beta 1a treatment, a significant increase in serum sHLA-I was observed in all 21 RRMS patients (P <.0005). Conversely, serum sHLA-II decreased significantly after treatment in the entire patient group (P <.0005). The acute effect of IFN-beta 1a on serum sHLA-I and sHLA-II was observed to be the opposite of that occurring during RRMS relapses. Monitoring of both sHLA-I and sHLA-II appears necessary if these molecules are to be developed as RRMS activity markers.

Cortical speech disorders rarely occur in multiple sclerosis (MS). We report a patient with relapsing-remitting MS, who presented with acute verbal dyspraxia. Magnetic resonance imaging (MRI) demonstrated an acute T2/Flair hyperintense, primarily white matter lesion underlying the middle third of the inferior frontal gyrus. The verbal dyspraxia cleared beginning 48 hours after the initiation of iv dexamethasone. Follow-up MRI demonstrated qualitative and quantitative diminution of the hyperintensity. This is the first report of a clinically definite MS patient with acute verbal dyspraxia. Moreover, there was a suggestive localization of verbal praxis to Brodmann areas 44/45.

To clarify the neural systems deployed by individual subjects during working memory (WM), we collected functional neuroimaging data from healthy subjects, and constructed a model of 2-back WM using structural equation modeling (SEM). A group model was constructed, and models for each subject were validated against it. The group model consisted principally of regions in the prefrontal and parietal cortex, with considerable interindividual variance in the single-subject models. To explore this variance, subjects were split into two groups based on performance. Performance level and self-reported strategy scores were used in a correlation analysis against path weights between nodes of individual models. High performers utilized a left hemisphere sub-network involving inferior parietal lobule and Broca's area, whereas lower performers utilized a right hemisphere sub-network with interactions between inferior parietal lobule and dorsolateral prefrontal cortex. Further, we observed an interaction between the parahippocampal formation and the inferior parietal lobule that was related to the different strategies used by the individuals to perform the task. Strategy and performance level appear to be intricately related in this task, with neural systems supporting verbal processing producing better performance than those associated with spatial processing. These results demonstrate that individual behavioral characteristics are reflected in specific neurofunctional patterns at the system level and that these can be captured by analytical techniques such as SEM.

INTRODUÇÃO: Estudos que utilizam as técnicas de PET, SPECT e ressonância magnética funcional têm permitido o mapeamento dos circuitos cerebrais ativados durante diversas tarefas cognitivas. O campo da memória declarativa tem sido um dos mais intensamente estudados. No presente estudo, usa-se a técnica de mapeamento do fluxo sangüíneo cerebral regional (FSCr) por SPECT para investigar mudanças na atividade cerebral durante uma tarefa de memória episódica, em voluntários idosos sadios (n=15). MÉTODOS: Duas avaliações de SPECT foram realizadas na mesma sessão, usando a técnica de dose dividida do traçador 99 m-Tc-HMPAO. Medidas de FSCr foram registradas durante uma tarefa de reconhecimento de material verbal previamente aprendido e durante uma tarefa-controle mais simples. Comparações de FSCr foram realizadas automaticamente, utilizando o programa Statistical Parametric Mapping (SPM). RESULTADOS: Observou-se aumento de FSCr durante a tarefa de memória em várias regiões cerebrais, incluindo: córtex pré-frontal lateral bilateralmente (mais acentuadamente à esquerda); porções posteriores e mediais de córtex parieto-occipital à esquerda; hemisférios cerebelares bilateralmente; e córtex temporal lateral bilateralmente (p<0,001, não corrigido para comparações múltiplas). Foram observados também focos inesperados de diminuição de FSCr em cíngulo posterior direito, córtex orbitofrontal esquerdo, córtex temporal inferior direito e vérmis cerebelar esquerdo (p<0,05, corrigido para comparações múltiplas). CONCLUSÃO: Esses resultados sugerem que circuitos neuronais multifocais são engajados durante memória de reconhecimento e replicam localizações cerebrais descritas anteriormente na literatura. O uso desse protocolo em pacientes com transtornos neuropsiquiátricos poderá permitir a investigação de anormalidades cerebrais subjacentes aos déficits de memória presentes nesses transtornos.INTRODUCTION: PET, SPECT and functional magnetic resonance imaging studies have allowed the delineation of brain circuits activated during several types of cognitive tasks. The field of declarative memory has been one of the most extensively investigated. In the present study, the regional cerebral blood flow (rCBF) SPECT technique was used to investigate changes in brain activity during a verbal memory task in a group of elderly healthy volunteers (n=15). METHODS:Two SPECT acquisitions were performed in the same session, using the split-dose 99mTc-HMPAO technique. Measures of rCBF were taken during a recognition memory task and a simpler control task. Between-task comparisons were performed automatically using the Statistical Parametric Mapping (SPM) program. RESULTS: Increased rCBF during the memory task was seen in several brain regions, including: the lateral prefrontal cortex on both hemispheres (more intensely on the left side); posterior and medial portions of the left occipital and parietal cortices; the right and left cerebellar hemispheres; and the right and left lateral temporal cortex (p<0.001, uncorrected for multiple comparisons). Unexpected foci of decreased rCBF were seen in the right posterior cingulate cortex, left orbitofrontal cortex, right inferior temporal cortex and left cerebellar vermis (p<0.05, corrected for multiple comparisons). CONCLUSION:These results suggest that multifocal neural circuits are engaged during recognition memory, and replicate locations seen in previous studies in the literature. The use of the protocols described here in patients with neuropsychiatric disorders may allow investigation of brain abnormalities underlying the memory deficits seen in these disorders.

INTRODUÇÃO: Estudos que utilizam as técnicas de PET, SPECT e ressonância magnética funcional têm permitido o mapeamento dos circuitos cerebrais ativados durante diversas tarefas cognitivas. O campo da memória declarativa tem sido um dos mais intensamente estudados. No presente estudo, usa-se a técnica de mapeamento do fluxo sangüíneo cerebral regional (FSCr) por SPECT para investigar mudanças na atividade cerebral durante uma tarefa de memória episódica, em voluntários idosos sadios (n=15). MÉTODOS: Duas avaliações de SPECT foram realizadas na mesma sessão, usando a técnica de dose dividida do traçador 99 m-Tc-HMPAO. Medidas de FSCr foram registradas durante uma tarefa de reconhecimento de material verbal previamente aprendido e durante uma tarefa-controle mais simples. Comparações de FSCr foram realizadas automaticamente, utilizando o programa Statistical Parametric Mapping (SPM). RESULTADOS: Observou-se aumento de FSCr durante a tarefa de memória em várias regiões cerebrais, incluindo: córtex pré-frontal lateral bilateralmente (mais acentuadamente à esquerda); porções posteriores e mediais de córtex parieto-occipital à esquerda; hemisférios cerebelares bilateralmente; e córtex temporal lateral bilateralmente (p<0,001, não corrigido para comparações múltiplas). Foram observados também focos inesperados de diminuição de FSCr em cíngulo posterior direito, córtex orbitofrontal esquerdo, córtex temporal inferior direito e vérmis cerebelar esquerdo (p<0,05, corrigido para comparações múltiplas). CONCLUSÃO: Esses resultados sugerem que circuitos neuronais multifocais são engajados durante memória de reconhecimento e replicam localizações cerebrais descritas anteriormente na literatura. O uso desse protocolo em pacientes com transtornos neuropsiquiátricos poderá permitir a investigação de anormalidades cerebrais subjacentes aos déficits de memória presentes nesses transtornos.

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G. w. ASHCROFT, Aberdeen D. BROADBENT, Oxford w. F. BYNUM, London A. CARLSSON, Gothenburg T. J. CROW, Harrow s. G A R A T T I N I , Milan N. GAMERZY, Minneapolis D. GRAHAME-SMITH, Oxford j . A. GRAY, London H. HAFNER, Mannheim R. A. HINDE, Cambridge A. L. JOHNSON, Cambridge M. LADER, London p. L. LANTOS, London A. LAWSON, London w. A. LISHMAN, London M. MARMOT, London c. D. MARSDEN, London P. R. MCHUGH, Baltimore D. PLOOG, Munich L. N. ROBINS, St Louis G. F. RUSSELL, London M. L. RUTTER, London J. R. SMYTHIES, Birmingham, Alabama p. VENABLES, York P. WILLIAMS, London J. K. WING, London M . W Y K E , London