The functional anatomy of the normal human auditory system: responses to 0.5 and 4.0 kHz tones at varied intensities.
Most functional imaging studies of the auditory system have employed complex stimuli. We used positron emission tomography to map neural responses to 0.5 and 4.0 kHz sine-wave tones presented to the right ear at 30, 50, 70 and 90 dB HL and found activation in a complex neural network of elements traditionally associated with the auditory system as well as non-traditional sites such as the posterior cingulate cortex. Cingulate activity was maximal at low stimulus intensities, suggesting that it may function as a gain control center. In the right temporal lobe, the location of the maximal response varied with the intensity, but not with the frequency of the stimuli. In the left temporal lobe, there was evidence for tonotopic organization: a site lateral to the left primary auditory cortex was activated equally by both tones while a second site in primary auditory cortex was more responsive to the higher frequency. Infratentorial activations were contralateral to the stimulated ear and included the lateral cerebellum, the lateral pontine tegmentum, the midbrain and the medial geniculate. Contrary to predictions based on cochlear membrane mechanics, at each intensity, 4.0 kHz stimuli were more potent activators of the brain than the 0.5 kHz stimuli. (+info
Loss of endothelium and receptor-mediated dilation in pial arterioles of rats fed a short-term high salt diet.
A high salt diet often is regarded as an accessory risk factor in hypertension, coincidental to the deleterious effect of high blood pressure on vasodilator function. The aim of this study was to determine whether short-term ingestion of a high salt diet per se impairs vasodilator function in the cerebral circulation independent of blood pressure changes. Adult Sprague-Dawley rats were fed a normal salt (0.8%) or high salt (4%) diet for 3 days. Mean arterial pressures were similar in the normal and high salt groups (123+/-2 and 125+/-2 mm Hg, respectively). Subsequently, the responses of the in situ pial arterioles to acetylcholine, iloprost, and sodium nitroprusside were determined in cranial windows using intravital videomicroscopy. Pial arterioles of rats fed normal and high salt diets showed similar resting diameters of 69+/-2 and 72+/-3 microm, respectively, but their reactivity patterns to vasodilator stimuli were markedly different. Arterioles of rats fed a normal salt diet dilated progressively up to 17+/-3% in response to the endothelium-dependent agent acetylcholine (10(-9) to 10(-6) mol/L) and dilated by 22+/-2% in response to the prostaglandin I2 receptor agonist iloprost (3x10(-11) mol/L). In contrast, pial arterioles of rats fed a high salt diet constricted by 4+/-3% and 8+/-2% in response to acetylcholine and iloprost, respectively. Sodium nitroprusside (10(-6) mol/L), a nitric oxide donor, dilated pial arterioles of rats fed low and high salt diets by a similar amount (19+/-3% and 16+/-2%, respectively), suggesting that signaling mechanisms for dilation distal to the vascular smooth muscle membrane were intact after high salt intake. These results provide the first evidence that the short-term ingestion of a high salt diet may severely impair the vasodilator function of the in situ cerebral microcirculation independent of blood pressure elevation. (+info
Parametric mapping of cerebral blood flow deficits in Alzheimer's disease: a SPECT study using HMPAO and image standardization technique.
This study assessed the accuracy and reliability of Automated Image Registration (AIR) for standardization of brain SPECT images of patients with Alzheimer's disease (AD). Standardized cerebral blood flow (CBF) images of patients with AD and control subjects were then used for group comparison and covariance analyses. METHODS: Thirteen patients with AD at an early stage (age 69.8+/-7.1 y, Clinical Dementia Rating Score 0.5-1.0, Mini-Mental State Examination score 19-23) and 20 age-matched normal subjects (age 69.5+/-8.3 y) participated in this study. 99mTc-hexamethyl propylenamine oxime (HMPAO) brain SPECT and CT scans were acquired for each subject. SPECT images were transformed to a standard size and shape with the help of AIR. Accuracy of AIR for spatial normalization was evaluated by an index calculated on SPECT images. Anatomical variability of standardized target images was evaluated by measurements on corresponding CT scans, spatially normalized using transformations established by the SPECT images. Realigned brain SPECT images of patients and controls were used for group comparison with the help of statistical parameter mapping. Significant differences were displayed on the respective voxel to generate three-dimensional Z maps. CT scans of individual subjects were evaluated by a computer program for brain atrophy. Voxel-based covariance analysis was performed on standardized images with ages and atrophy indices as independent variables. RESULTS: Inaccuracy assessed by functional data was 2.3%. The maximum anatomical variability was 4.9 mm after standardization. Z maps showed significantly decreased regional CBF (rCBF) in the frontal, parietal and temporal regions in the patient group (P < 0.001). Covariance analysis revealed that the effects of aging on rCBF were more pronounced compared with atrophy, especially in intact cortical areas at an early stage of AD. Decrease in rCBF was partly due to senility and atrophy, however these two factors cannot explain all the deficits. CONCLUSION: AIR can transform SPECT images of AD patients with acceptable accuracy without any need for corresponding structural images. The frontal regions of the brain, in addition to parietal and temporal lobes, may show reduced CBF in patients with AD even at an early stage of dementia. The reduced rCBF in the cortical regions cannot be explained entirely by advanced atrophy and fast aging process. (+info
Nitric oxide modulates endothelin 1-induced Ca2+ mobilization and cytoskeletal F-actin filaments in human cerebromicrovascular endothelial cells.
A functional interrelation between nitric oxide (NO), the endothelial-derived vasodilating factor, and endothelin 1 (ET-1), the potent vasoconstrictive peptide, was investigated in microvascular endothelium of human brain. Nor-1 dose-dependently decreased the ET-1-stimulated mobilization of Ca2+. This response was mimicked with cGMP and abrogated by inhibitors of guanylyl cyclase or cGMP-dependent protein kinase G. These findings indicate that NO and ET-1 interactions involved in modulation of intracellular Ca2+ are mediated by cGMP/protein kinase G. In addition, Nor-1-mediated effects were associated with rearrangements of cytoskeleton F-actin filaments. The results suggest mechanisms by which NO-ET-1 interactions may contribute to regulation of microvascular function. (+info
Expression of neuropeptide Y receptors mRNA and protein in human brain vessels and cerebromicrovascular cells in culture.
Neuropeptide Y (NPY) has been suggested as an important regulator of CBF. However, except for the presence of Y1 receptors in large cerebral arteries, little is known about its possible sites of action on brain vessels. In this study, we sought to identify the NPY receptors present in the human cerebrovascular bed. Specific Y1 receptor binding sites, localized on the smooth muscle of human pial vessels and potently competed by NPY, polypeptide YY (PYY), and the selective Y1 receptor antagonist BIBP 3226, were identified by quantitative radioautography of the Y1 radioligand [125I]-[Leu31, Pro34]-PYY. In contrast, no specific binding of the Y2-([125I]-PYY3-36) and Y4/Y5-(125I-human pancreatic polypeptide [hPP]) radioligands could be detected. By in situ hybridization, expression of Y1 receptor mRNA was restricted to the smooth muscle layer of pial vessels, whereas no specific signals were detected for either Y2, Y4, or Y5 receptors. Similarly, using reverse transcriptase-polymerase chain reaction (RT-PCR), mRNA for Y1 but not Y2, Y4, or Y5 receptors was consistently detected in isolated human pial vessels, intracortical microvessels, and capillaries. In human brain microvascular cells in culture, PCR products for the Y1 receptors were exclusively found in the smooth muscle cells. In cultures of human brain astrocytes, a cell type that associates intimately with brain microvessels, PCR products for Y1, Y2, and Y4 but not Y5 receptors were identified. Finally, NPY significantly inhibited the forskolin-induced cAMP production in smooth muscle but not in endothelial cell cultures. We conclude that smooth muscle Y1 receptors are the primary if not exclusive NPY receptors associated with human brain extraparenchymal and intraparenchymal blood vessels, where they most likely mediate cerebral vasoconstriction. (+info
Disrupted temporal lobe connections in semantic dementia.
Semantic dementia refers to the variant of frontotemporal dementia in which there is progressive semantic deterioration and anomia in the face of relative preservation of other language and cognitive functions. Structural imaging and SPECT studies of such patients have suggested that the site of damage, and by inference the region critical to semantic processing, is the anterolateral temporal lobe, especially on the left. Recent functional imaging studies of normal participants have revealed a network of areas involved in semantic tasks. The present study used PET to examine the consequences of focal damage to the anterolateral temporal cortex for the operation of this semantic network. We measured PET activation associated with a semantic decision task relative to a visual decision task in four patients with semantic dementia compared with six age-matched normal controls. Normals activated a network of regions consistent with previous studies. The patients activated some areas consistently with the normals, including some regions of significant atrophy, but showed substantially reduced activity particularly in the left posterior inferior temporal gyrus (iTG) (Brodmann area 37/19). Voxel-based morphometry, used to identify the regions of structural deficit, revealed significant anterolateral temporal atrophy (especially on the left), but no significant structural damage to the posterior inferior temporal lobe. Other evidence suggests that the left posterior iTG is critically involved in lexical-phonological retrieval: the lack of activation here is consistent with the observation that these patients are all anomic. We conclude that changes in activity in regions distant from the patients' structural damage support the argument that their prominent anomia is due to disrupted temporal lobe connections. (+info
The cerebral haemodynamics of music perception. A transcranial Doppler sonography study.
The perception of music has been investigated by several neurophysiological and neuroimaging methods. Results from these studies suggest a right hemisphere dominance for non-musicians and a possible left hemisphere dominance for musicians. However, inconsistent results have been obtained, and not all variables have been controlled by the different methods. We performed a study with functional transcranial Doppler sonography (fTCD) of the middle cerebral artery to evaluate changes in cerebral blood flow velocity (CBFV) during different periods of music perception. Twenty-four healthy right-handed subjects were enrolled and examined during rest and during listening to periods of music with predominant language, rhythm and harmony content. The gender, musical experience and mode of listening of the subjects were chosen as independent factors; the type of music was included as the variable in repeated measurements. We observed a significant increase of CBFV in the right hemisphere in non-musicians during harmony perception but not during rhythm perception; this effect was more pronounced in females. Language perception was lateralized to the left hemisphere in all subject groups. Musicians showed increased CBFV values in the left hemisphere which were independent of the type of stimulus, and background listeners showed increased CBFV values during harmony perception in the right hemisphere which were independent of their musical experience. The time taken to reach the peak of CBFV was significantly longer in non-musicians when compared with musicians during rhythm and harmony perception. Pulse rates were significantly decreased in non-musicians during harmony perception, probably due to a specific relaxation effect in this subgroup. The resistance index did not show any significant differences, suggesting only regional changes of small resistance vessels but not of large arteries. Our fTCD study confirms previous findings of right hemisphere lateralization for harmony perception in non-musicians. In addition, we showed that this effect is more pronounced in female subjects and in background listeners and that the lateralization is delayed in non-musicians compared with musicians for the perception of rhythm and harmony stimuli. Our data suggest that musicians and non-musicians have different strategies to lateralize musical stimuli, with a delayed but marked right hemisphere lateralization during harmony perception in non-musicians and an attentive mode of listening contributing to a left hemisphere lateralization in musicians. (+info
Correlation of regional cerebral blood flow and change of plasma sodium concentration during genesis and satiation of thirst.
Positron emission tomography studies were conducted during genesis of moderate thirst by rapid i.v. infusion of hypertonic saline (0.51 M) and after satiation of thirst by drinking water. The correlation of regional cerebral blood flow with the change in the plasma Na concentration showed a significant group of cerebral activations in the anterior cingulate region and also a site in the middle temporal gyrus and in the periaqueductal gray. Strongest deactivations occurred in the parahippocampal and frontal gyri. The data are consistent with an important role of the anterior cingulate in the genesis of thirst. (+info