Studies of brain-damaged patients have revealed the existence of a selective impairment of face processing, prosopagnosia, resulting from lesions at different loci in the occipital and temporal lobes. The results of such studies have led to the identification of several cortical areas underlying the processing of faces, but it remains unclear what functional aspects of face processing are served by these areas and whether they are uniquely devoted to the processing of faces. The present study addresses these questions in a positron emission tomography (PET) study of regional cerebral blood flow in normal adults, using the 15 oxygen water bolus technique. The subjects participated in six tasks (with gratings, faces and objects), and the resulting level of cerebral activation was mapped on images of the subjects' cerebral structures obtained through magnetic resonance and was compared between tasks using the subtraction method. Compared with a fixation condition, regional cerebral blood flow (rCBF) changes were found in the striate and extrastriate cortex when subjects had to decide on the orientation of sine-wave gratings. A face-gender categorization resulted in activation changes in the right extrastriate cortex, and a face-identity condition produced additional activation of the fusiform gyrus and anterior temporal cortex of both hemispheres, and of the right parahippocampal gyrus and adjacent areas. Cerebral activation during an object-recognition task occurred essentially in the left occipito-temporal cortex and did not involve the right hemisphere regions specifically activated during the face-identity task. The results provide the first empirical evidence from normal subjects regarding the crucial role of the ventro-medial region of the right hemisphere in face recognition, and they offer new information about the dissociation between face and object processing.

Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that form a subfamily of the nuclear receptor gene family. Since both flow and PPAR␥ have atheroprotective effects and extracellular signal-regulated kinase 5 (ERK5) kinase activity is significantly increased by flow, we investigated whether ERK5 kinase regulates PPAR␥ activity. We found that activation of ERK5 induced PPAR␥1 activation in endothelial cells (ECs). However, we could not detect PPAR␥ phosphorylation by incubation with activated ERK5 in vitro, in contrast to ERK1/2 and JNK, suggesting a role for ERK5 as a scaffold. Endogenous PPAR␥1 was coimmunoprecipitated with endogenous ERK5 in ECs. By mammalian two-hybrid analysis, we found that PPAR␥1 associated with ERK5a at the hinge-helix 1 region of PPAR␥1. Expressing a hinge-helix 1 region PPAR␥1 fragment disrupted the ERK5a-PPAR␥1 interaction, suggesting a critical role for hinge-helix 1 region of PPAR␥ in the ERK5-PPAR␥ interaction. Flow increased ERK5 and PPAR␥1 activation, and the hinge-helix 1 region of the PPAR␥1 fragment and dominant negative MEK5␤ significantly reduced flow-induced PPAR␥ activation. The dominant negative MEK5␤ also prevented flow-mediated inhibition of tumor necrosis factor alpha-mediated NF-B activation and adhesion molecule expression, including vascular cellular adhesion molecule 1 and E-selectin, indicating a physiological role for ERK5 and PPAR␥ activation in flow-mediated antiinflammatory effects. We also found that ERK5 kinase activation was required, likely by inducing a conformational change in the NH 2 -terminal region of ERK5 that prevented association of ERK5 and PPAR␥1. Furthermore, association of ERK5a and PPAR␥1 disrupted the interaction of SMRT and PPAR␥1, thereby inducing PPAR␥ activation. These data suggest that ERK5 mediates flow-and ligand-induced PPAR␥ activation via the interaction of ERK5 with the hinge-helix 1 region of PPAR␥.Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that form a subfamily of the nuclear receptor gene family. Among PPAR family members, the expression of PPAR␣ and PPAR␥ has been reported in endothelial cells (ECs). Recently, Pasceri et al. reported that PPAR␥ activators inhibit expression of vascular cellular adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) in activated ECs and significantly reduce monocyte/macrophage homing to atherosclerotic plaques (23). Mitogen-activated protein (MAP) kinase signaling pathways have been shown to phosphorylate PPAR␥ and to decrease PPAR␥ transcriptional activity (7, 13). The NH 2 -terminal domain of PPAR␥ contains a consensus MAP kinase site in a region conserved between PPAR␥1 and PPAR␥2 isoforms (7, 13). Phosphorylation of PPAR␥2 Ser112 (13) and PPAR␥1 Ser82 (7) significantly inhibits both ligand-independent and ligand-dependent transcriptional activation by PPAR␥. Phosphorylation-mediated transcriptional repression is due to a diminished ability of PPAR␥ to become transcriptionally a...

When used to measure blood flow in the brain, water leaves a residue in the vascular bed that influences the estimation of blood flow by current methods. To assess the magnitude of this influence, we developed a two-compartment model of blood flow with separate parameters for transport and vascular distribution of brain water. Maps of the water clearance, K1 into brain tissue, separated from the circulation by a measurably resistant blood-brain barrier (BBB), were generated by time-weighted integration. Depending on the validity of the assumptions underlying the two-compartment model presented here, the maps revealed a significant overestimation of the clearance of water when the vascular residue was ignored. Maps of Vo, the estimate of the apparent vascular distribution volume of tracer H2(15)O, clearly revealed major cerebral arteries. Thus, we claim that the accumulation of radioactive water in brain tissue also reflects the volume of the arterial vascular bed of the brain.

Summary:We measured the rate of washout of 150_ labeled water generated from labeled oxygen accumu lated in brain after bolus [150]02 inhalation, and com pared the washout with that of labeled water measured with H2150. Contrary to the original expectation, the ra dioactive water generated from labeled oxygen failed to leave the brain tissue at the rate predicted by exogenous water. Therefore, the use of a separately measured value for exogenous water clearance led to an error in the cal culation of oxygen consumption. A new method pre sented in this paper eliminated the error by yielding ox ygen consumption in a single oxygen study. We used Measurements of the oxygen consumption of in dividual brain regions have been possible only after the advent of positron emission tomography (PET). Two methods have been reported, both intended to yield the unidirectional clearance of the very short lived oxygen isotope, oxygen-15. The equilibrium method (Frackowiak et aI., 1980) yielded the oxy gen clearance from the steady-state balance be tween oxygen influx, radioactive oxygen decay, and radioactive water efflux. The autoradiographic method (Mintun et aI., 1984) yielded the clearance from a transient (non-steady-state) analysis of the uptake. Both methods required separately obtained information about blood flow and blood volume and assumed, therefore, that the physiological state of the subject, and its position in the scanner, re mained unchanged for 30-60 min, the time required Abbreviation used: CBV, cerebral blood volume; CMROz, ce rebral metabolic rate for oxygen; FWHM, full width at half max imum; OEF, oxygen extraction fraction; PET, positron emission tomography; RMS, root mean squared. 179time-weighted integration to estimate three parameters, including the unidirectional clearance from blood to brain (K? 2 ), the fractional clearance of the distribution volume in brain (k�2), and the vascular volume correction (yo) ' We showed that the clearance of oxygen from blood to brain can be estimated with acceptable precision by this new approach, and that the new method yields a reliable measure of oxygen consumption. Key Words: Positron emission tomography-Oxygen consumption-U nidirec tional clearance of oxygen-Single oxygen study-Time weighted integration method.to perform three separate studies by positron emis sion tomography. In addition, both methods de pended on several simplifying assumptions which may cast doubt on the results. However, the uncer tainty is not easy to resolve because of the absence of independently obtained regional values that might serve as the ultimate standard.To examine the consequences of the specific an alytic method for the calculated oxygen consump tion values, we modified the experimental approach to yield values of oxygen consumption from a single short (3 min) bolus e50]02 inhalation study, elimi nating some assumptions but introducing others.