(1/1403) N-Methyl-D-aspartate antagonists and apoptotic cell death triggered by head trauma in developing rat brain.
Morbidity and mortality from head trauma is highest among children. No animal model mimicking traumatic brain injury in children has yet been established, and the mechanisms of neuronal degeneration after traumatic injury to the developing brain are not understood. In infant rats subjected to percussion head trauma, two types of brain damage could be characterized. The first type or primary damage evolved within 4 hr and occurred by an excitotoxic mechanism. The second type or secondary damage evolved within 6-24 hr and occurred by an apoptotic mechanism. Primary damage remained localized to the parietal cortex at the site of impact. Secondary damage affected distant sites such as the cingulate/retrosplenial cortex, subiculum, frontal cortex, thalamus and striatum. Secondary apoptotic damage was more severe than primary excitotoxic damage. Morphometric analysis demonstrated that the N-methyl-D-aspartate receptor antagonists 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonate and dizocilpine protected against primary excitotoxic damage but increased severity of secondary apoptotic damage. 2-Sulfo-alpha-phenyl-N-tert-butyl-nitrone, a free radical scavenger, did not affect primary excitotoxic damage but mitigated apoptotic damage. These observations demonstrate that apoptosis and not excitotoxicity determine neuropathologic outcome after traumatic injury to the developing brain. Whereas free radical scavengers may prove useful in therapy of head trauma in children, N-methyl-D-aspartate antagonists should be avoided because of their propensity to increase severity of apoptotic damage. (+info)
(2/1403) Blind smell: brain activation induced by an undetected air-borne chemical.
EEG and behavioural evidence suggests that air-borne chemicals can affect the nervous system without being consciously detected. EEG and behaviour, however, do not specify which brain structures are involved in chemical sensing that occurs below a threshold of conscious detection. Here we used functional MRI to localize brain activation induced by high and low concentrations of the air-borne compound oestra-1,3,5(10),16-tetraen-3yl acetate. Following presentations of both concentrations, eight of eight subjects reported verbally that they could not detect any odour (P = 0.004). Forced choice detection performed during the presentations revealed above-chance detection of the high concentration, but no better than chance detection of the low concentration compound. Both concentrations induced significant brain activation, primarily in the anterior medial thalamus and inferior frontal gyrus. Activation in the inferior frontal gyrus during the high concentration condition was significantly greater in the right than in the left hemisphere (P = 0.03). A trend towards greater thalamic activation was observed for the high concentration than the low concentration compound (P = 0.08). These findings localize human brain activation that was induced by an undetectable air-borne chemical (the low concentration compound). (+info)
(3/1403) The role of ventral medial wall motor areas in bimanual co-ordination. A combined lesion and activation study.
Two patients with midline tumours and disturbances of bimanual co-ordination as the presenting symptoms were examined. Both reported difficulties whenever the two hands had to act together simultaneously, whereas they had no problems with unimanual dexterity or the use of both hands sequentially. In the first patient the lesion was confined to the cingulate gyrus; in the second it also invaded the corpus callosum and the supplementary motor area. Kinematic analysis of bimanual in-phase and anti-phase movements revealed an impairment of both the temporal adjustment between the hands and the independence of movements between the two hands. A functional imaging study in six volunteers, who performed the same bimanual in-phase and anti-phase tasks, showed strong activations of midline areas including the cingulate and ventral supplementary motor area. The prominent activation of the ventral medial wall motor areas in the volunteers in conjunction with the bimanual co-ordination disorder in the two patients with lesions compromising their function is evidence for their pivotal role in bimanual co-ordination. (+info)
(4/1403) A PET study of sequential finger movements of varying length in patients with Parkinson's disease.
To study the difficulty that patients with Parkinson's disease have in performing long sequential movements, we used H2(15)O PET to assess the regional cerebral blood flow (rCBF) associated with the performance of simple repetitive movements, well-learned sequential finger movements of varying length and self-selected movements. Sequential finger movements in the Parkinson's disease patients were associated with an activation pattern similar to that found in normal subjects, but Parkinson's disease patients showed relative overactivity in the precuneus, premotor and parietal cortices. Increasing the complexity of movements resulted in increased rCBF in the premotor and parietal cortices of normal subjects; the Parkinson's disease patients showed greater increases in these same regions and had additional significant increases in the anterior supplementary motor area (SMA)/cingulate. Performance of self-selected movements induced significant activation of the anterior SMA/cingulate in normal subjects but not in Parkinson's disease patients. We conclude that in Parkinson's disease patients more cortical areas are recruited to perform sequential finger movements; this may be the result of increasing corticocortical activity to compensate for striatal dysfunction. (+info)
(5/1403) Identification of the cerebral loci processing human swallowing with H2(15)O PET activation.
Lesional and electrophysiological data implicate a role for the cerebral cortex in the initiation and modulation of human swallowing, and yet its functional neuroanatomy remains undefined. We therefore conducted a functional study of the cerebral loci processing human volitional swallowing with 15O-labeled water positron emission tomography (PET) activation imaging. Regional cerebral activation was investigated in 8 healthy right handed male volunteers with a randomized 12-scan paradigm of rest and water swallows (5 ml/bolus, continuous infusion) at increasing frequencies of 0.1, 0.2, and 0.3 Hz, which were visually cued and monitored with submental electromyogram (EMG). Group and individual linear covariate analyses were performed with SPM96. In five of eight subjects, the cortical motor representation of pharynx was subsequently mapped with transcranial magnetic stimulation (TMS) in a posthoc manner to substantiate findings of hemispheric differences in sensorimotor cortex activation seen with PET. During swallowing, group PET analysis identified increased regional cerebral blood flow (rCBF) (P < 0.001) within bilateral caudolateral sensorimotor cortex [Brodmann's area (BA) 3, 4, and 6], right anterior insula (BA 16), right orbitofrontal and temporopolar cortex (BA 11 and 38), left mesial premotor cortex (BA 6 and 24), left temporopolar cortex and amygdala (BA 38 and 34), left superiomedial cerebellum, and dorsal brain stem. Decreased rCBF (P < 0.001) was also observed within bilateral posterior parietal cortex (BA 7), right anterior occipital cortex (BA 19), left superior frontal cortex (BA 8), right prefrontal cortex (BA 9), and bilateral superiomedial temporal cortex (BA 41 and 42). Individual PET analysis revealed asymmetric representation within sensorimotor cortex in six of eight subjects, four lateralizing to right hemisphere and two to left hemisphere. TMS mapping in the five subjects identified condordant interhemisphere asymmetries in the motor representation for pharynx, consistent with the PET findings. We conclude that volitional swallowing recruits multiple cerebral regions, in particular sensorimotor cortex, insula, temporopolar cortex, cerebellum, and brain stem, the sensorimotor cortex displaying strong degrees of interhemispheric asymmetry, further substantiated with TMS. Such findings may help explain the variable nature of swallowing disorders after stroke and other focal lesions to the cerebral cortex. (+info)
(6/1403) Relation of impaired energy metabolism to apoptosis and necrosis following transient cerebral hypoxia-ischaemia.
This study investigated whether both mild and severe hypoxia-ischaemia (HI) caused significant numbers of cells to die by apoptosis in the developing brain in vivo. Newborn piglets were subjected to transient global HI and the fraction of all cells in the cingulate gyrus that were apoptotic or necrotic counted 48 h after resuscitation. The mean (S.D.) proportion of apoptotic cells was 11.9% (6.7%) (sham operated controls 4.1% (2.7%)), while 11.4% (8.4%) were necrotic (controls 0.7% (1.3%)) (P<0.05). Apoptotic and necrotic cell counts were both linearly related to the severity of impaired cerebral energy metabolism measured by magnetic resonance spectroscopy (P<0.05), as shown by: (1) the decline in the ratio of nucleotide triphosphates to the exchangeable phosphate pool during HI; (2) the fall in the ratio of phosphocreatine to inorganic phosphate 8 - 48 h after HI; and (3) an increased ratio of lactate to total creatine at both these times. Thus both apoptosis and necrosis occurred in the cingulate gyrus after both severe and mild HI in vivo in proportion to the severity of the insult. (+info)
(7/1403) The effect of age on odor-stimulated functional MR imaging.
BACKGROUND AND PURPOSE: The effects of age, sex, and handedness on olfaction have not been adequately addressed with odor-stimulated functional MR imaging studies. We sought to determine the effect of age on functional MR imaging experiments performed with odor stimulation. METHODS: Five right-handed subjects with a mean age of 73 years and five right-handed subjects with a mean age of 24 years underwent gradient-echo echo-planar functional MR imaging using binasal olfactory stimulation. Imaging parameters included 3000/30 (TR/TE) and a 5-mm section thickness in a 6-minute sequence with 30 seconds of pulsed odorants alternating with 30 seconds of room air. The data were normalized to a standard atlas, and individual and group statistical parametric maps (SPMs) were generated for each task. The SPMs were thresholded for a P < .01, and the volumes of activation and distribution of cluster maxima were compared for the two groups. RESULTS: Analysis of the group SPMs revealed activated voxels in the frontal lobes, perisylvian regions, and cingulate gyri, with greater volume in the younger group than in the older group. The right inferior frontal, right perisylvian, and right and left cingulum had the largest number of voxels activated. The most common sites of activation on individual maps in both groups were the right inferior frontal regions and the right and left superior frontal and perisylvian zones. CONCLUSION: Given similar olfactory task paradigms, younger subjects showed a greater number of activated voxels than did older subjects. One must be cognizant of this effect when designing studies of odor-stimulated functional MR imaging. (+info)
(8/1403) A large-scale distributed network for covert spatial attention: further anatomical delineation based on stringent behavioural and cognitive controls.
Functional MRI was used to examine cerebral activations in 12 subjects while they performed a spatial attention task. This study applied more stringent behavioural and cognitive controls than previously used for similar experiments: (i) subjects were included only if they showed evidence of attentional shifts while performing the task in the magnet; (ii) the experimental task and baseline condition were designed to eliminate the contributions of motor output, visual fixation, inhibition of eye movements, working memory and the conditional (no-go) component of responding. Activations were seen in all three hypothesized cortical epicentres forming a network for spatial attention: the lateral premotor cortex (frontal eye fields), the posterior parietal cortex and the cingulate cortex. Subcortical activations were seen in the basal ganglia and the thalamus. Although the task required attention to be equally shifted to the left and to the right, eight of 10 subjects showed a greater area of activation in the right parietal cortex, consistent with the specialization of the right hemisphere for spatial attention. Other areas of significant activation included the posterior temporo-occipital cortex and the anterior insula. The temporo-occipital activation was within a region broadly defined as MT+ (where MT is the middle temporal area) which contains the human equivalent of area MT in the macaque monkey. This temporo-occipital area appears to constitute a major component of the functional network activated by this spatial attention task. Its activation may reflect the 'inferred' shift of the attentional focus across the visual scene. (+info)