Masdeu, J. (José)

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    Topography of Cortical Activation Differs for Fundamental and Harmonic Frequencies of the Steady-State Visual-Evoked Responses. An EEG and PET H15 2 O Study
    (Oxford University Press, 2007) Artieda, J. (Julio); Valencia, M. (Miguel); Pastor, M.A. (María A.); Masdeu, J. (José); Alegre-Esteban, M. (Manuel)
    In humans, visual flicker stimuli of graded frequency (2--90 Hz) elicit an electroencephalographic (EEG) steady-state visual-evoked response (SSVER) with the same fundamental frequency as the stimulus and, in addition, a series of harmonic responses. The fundamental component of the SSVER is generated by increased synaptic activity in primary visual cortex (V1). We set out to determine the cortical origin of the harmonic responses in humans. For this purpose, we recorded the SSVERs at 5 different frequencies (5, 10, 15, 25, and 40 Hz) and measured regional cerebral blood flow (rCBF) with positron emission tomography-H15 2 O at rest and during visual stimulation at the same frequencies. The rCBF contrast weighted by the amplitude of the SSVERs first harmonics showed activation of a swath of cortex perpendicular to V1, including mostly the inferior half of the parietooccipital sulcus. This area overlapped minimally with the primary visual cortex activated by the fundamental frequency. A different method, estimating EEG cortical source current density with lowresolution brain electromagnetic tomography, gave the same results. Our finding suggests that the inferior portion of the banks of the parieto-occipital sulci contains association visual cortex involved in the procparieto-occipital sulcus,
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    Human Cerebral Activation during Steady-State Visual-Evoked Responses
    (Society for Neuroscience, 2003) Artieda, J. (Julio); Valencia, M. (Miguel); Pastor, M.A. (María A.); Masdeu, J. (José); Arbizu, J. (Javier)
    Flicker stimuli of variable frequency (2-90 Hz) elicit a steady-state visual-evoked response (SSVER) in the electroencephalogram (EEG) with the same frequency as the stimulus. In humans, the amplitude of this response peaks at approximately 15 Hz, decreasing at higher stimulation frequencies. It was not known whether this peak response corresponds to increased synaptic activity in the visual cortex or to other mechanisms [for instance, the temporal coherence (phase summation) of evoked responses]. We studied the SSVER in 16 normal volunteers by means of visual stimulation at 14 different frequencies (from 5 to 60 Hz) while recording the EEG. In nine subjects of the group, we measured regional cerebral blood flow (rCBF) with positron emission tomography (PET)-H2(15)O at rest and during visual stimulation at five different frequencies: 5, 10, 15, 25, and 40 Hz. We confirmed that the amplitude of the SSVER in occipital regions peaks at 15 Hz stimulation. Applying to the PET rCBF data a contrast weighted by the amplitude of the SSVER, we determined that the primary visual cortex rCBF follows an activation pattern similar to the SSVER. This finding suggests that the amplitude of the SSVER corresponds to increased synaptic activity, specifically in Brodmann's area 17. Additionally, this study showed that visual stimulation at 40 Hz causes selective activation of the macular region of the visual cortex, and that a region in the dorsal aspect of the Crus I lobule of the left cerebellar hemisphere is activated during repetitive visual stimulation.
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    La neuroimagen en la enfermedad de Alzheimer: perspectiva actual
    (Viguera, 2004) Masdeu, J. (José)
    Clinically, computerized tomography scanning and magnetic resonance imaging (MRI) are the neuroimaging techniques most frequently used in the work up of progressive cognitive impairment, in order to rule out tumors or other treatable etiologies. However, as we move closer to having more effective treatments for Alzheimer's disease (AD), we experience a greater need to use markers of early brain injury. Among them is neuroimaging. In this review we give some examples of the role of MRI and of functional MRI (fMRI) as markers of early brain changes. DEVELOPMENT: Regional metabolism, studied with positron emission tomography (PET) can also be used advantageously to depict early cortical changes in mild cognitive impairment (MCI) and even presymptomatic AD. SPECT, less expensive than PET, has a lower sensitivity, but has been extensively studied and using quantification methods can help even in MCI. Newer PET markers allow for the evaluation of activated microglia in vivo, as well as for the study of amyloid deposition in the brain and the activity of enzymes such as acetyl-cholinesterase. CONCLUSION: Future refinements in the neuroimaging techniques seem likely to help in the early diagnosis, evaluation of potential treatments and clarification of pathogenetic mechanisms in AD.
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    HLA-DR2 and white matter lesion distribution in MS
    (Wiley, 2008) Sepulcre, J. (Jorge); Masdeu, J. (José); Palacios, R. (Ricardo); Goñi, J. (Joaquín); Moreno, B. (Beatriz); Taínta, M. (M.); Bejarano-Herruzo, B. (Bartolomé); Villoslada, P. (Pablo)
    Human leukocyte antigen DR2 (HLA-DR2) is a well-established genetic risk factor for multiple sclerosis (MS). However, it is still unknown whether this factor is associated with a specific disease phenotype, and in particular, to a regional distribution of white matter (WM) lesion phenotype on magnetic resonance imaging (MRI). On a voxel-by-voxel basis, we analyzed the T1 and T2 MRI-derived lesion maps of 50 patients with MS in order to determine the possible influence of HLA-DR2 genotype on the lesional MRI pattern at early stages of the disease. HLA-DR2 was present in 15 (30%) patients of our cohort. They displayed similar WM lesion distribution as the subjects without this factor. Thus, lesion distribution in MS seems to be independent of the DR2 genotype.