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Level of ischemia and brain functions in the Mongolian gerbil in vivo.

The Mongolian gerbil (Meriones unguiculatus) provides a very useful animal model to study the effects of ischemia on brain functions. In this model it is possible to induce two levels of ischemia in the same animal. Thus, monitoring the brain in vivo in real-time will provide meaningful information regarding the development of ischemic injury as well as the follow-up during the recirculation period. The aims of the study were as follows: (1) To elucidate the mechanism behind the development of ischemic depolarization under unilateral and bilateral carotid artery occlusion. (2) To exclude the possibility that removal of the dura mater will affect the results. (3) To correlate the kinetics of the recovery processes to the level of ischemia. We tested the correlation between energy depletion level (evaluated by intramitochondrial NADH redox state) and the development of ischemic depolarization (ID) and vasospasm (evaluated by extracellular K+, DC potential and 366 nm reflectance changes, respectively) under partial and complete ischemia (induced by unilateral or bilateral carotid artery occlusion) using the multiparametric monitoring system (MPA). In 12 out of 32 gerbils monitored by the MPA, the dura mater remained intact, while in the other 20, it was removed very gently before connecting the MPA to the brain. Two types of responses to unilateral carotid artery occlusion were recorded and the gerbils were divided into groups according to the development of the ID. In a third group of 5 gerbils we tested the effect of 1-5 min of bilateral occlusion on the various parameters monitored.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Functional brain imaging in neuropsychiatric disorders of childhood.

This review article presents a summary of the current state-of-the-art of functional brain imaging, with a primary focus on childhood neuropsychiatric disorders. Coverage is emphasized for developments that appear to be of current or potential future importance for the child neurologist and related pediatric specialist, and also from the perspective of the developmental neuroscientist. Emphasis is placed on the modalities of single photon emission computed tomography (SPECT), positron emission tomography (PET), and both "conventional" and "functional" magnetic resonance imaging, (MRI) including reference to the major new radiopharmaceutical and magnetic resonance-based imaging agents and techniques. The fundamental physicochemical processes underlying such studies are outlined, with citation of sources of more detailed information for the interested reader. A variety of imaging studies are reviewed for selected groups of childhood neuropsychiatric disorders, designed to illustrate the achievements and future promise of these imaging modalities. Areas of concentration are suggested for future imaging research in the field of childhood behavioral disorders, where these methods seem critical to improved understanding of pathogenetic mechanisms, as well as development of more effective treatment strategies.

Adolescent↗

Neurostimulation and functional brain imaging.

Recent advancements in functional neuroimaging have furthered our understanding of the normal and pathological brain. These non-invasive imaging modalities have allowed us to study the human brain in vivo. Concurrently, the revival of neurostimulation in the treatment of pain, movement disorders, and epilepsy has allowed the synergistic combination of these two technologies. Several studies focusing on the use of functional imaging in patients with implanted neurostimulation devices are reviewed. The anticipated roles of these two disciplines are discussed.

Brain↗

Magnetic resonance imaging methods for study of human brain function and their application at high magnetic field.

Magnetic resonance imaging (MRI) sequences are finding a new application in the study of human brain function by monitoring localized changes in signal intensity which accompany neuronal activity. These sequences can be sensitized to changes in cerebral blood volume, cerebral blood flow, and blood oxygenation, all of which reflect aspects of neuronal activity in the brain. Many of these experiments benefit from being implemented at a higher magnetic field strength than conventional MRI. An overview of these techniques is presented, and examples of their use are given.

Blood Volume↗

The mechanism by which exercise modifies brain function.

The effect of exercise on central nervous system function was investigated in relation to the mechanism of calcium-calmodulin-dependent dopamine synthesis in the brain. It is shown here through animal experiments that exercise leads to an increase in the calcium level in the brain. This in turn enhances brain dopamine synthesis, and through this increased dopamine modifies and/or affects brain function, which might induce physiological, behavioral, and psychological changes.

Alcoholic Intoxication↗

Implementation of quantitative perfusion imaging techniques for functional brain mapping using pulsed arterial spin labeling.

We describe here experimental considerations in the implementation of quantitative perfusion imaging techniques for functional MRI using pulsed arterial spin labeling. Three tagging techniques: EPISTAR, PICORE, and FAIR are found to give very similar perfusion results despite large differences in static tissue contrast. Two major sources of systematic error in the perfusion measurement are identified: the transit delay from the tagging region to the imaging slice; and the inclusion of intravascular tagged signal. A modified technique called QUIPSS II is described that decreases sensitivity to these effects by explicitly controlling the time width of the tag bolus and imaging after the bolus is entirely deposited into the slice. With appropriate saturation pulses the pulse sequence can be arranged so as to allow for simultaneous collection of perfusion and BOLD data that can be cleanly separated. Such perfusion and BOLD signals reveal differences in spatial location and dynamics that may be useful both for functional brain mapping and for study of the BOLD contrast mechanism. The implementation of multislice perfusion imaging introduces additional complications, primarily in the elimination of signal from static tissue. In pulsed ASL, this appears to be related to the slice profile of the inversion tag pulse in the presence of relaxation, rather than magnetization transfer effects as in continuous arterial spin labeling, and can be alleviated with careful adjustment of inversion pulse parameters.

Arteries↗

Functional brain imaging and neuropsychological testing in Lyme disease.

Differentiating neuropsychiatric Lyme disease from a primary psychiatric disorder can be a daunting task. This article describes how functional brain imaging and neuropsychological testing can be particularly valuable in helping to make diagnostic distinctions. In addition to a review of the relevance of functional imaging to neuropsychiatry in general, recent findings are presented regarding the use of single photon emission computed tomographic (SPECT) imaging in Lyme disease.

Brain↗

Sensitivity to chlorpromazine effects on brain function of schizophrenics and normals. A preliminary report.

For the purpose of quantitative demonstration of the sensitivity to chlorpromazine (CPZ) effects on brain functions of schizophrenics and normal subjects, polygraphic recordings of electroencephalogram (EEG) and electrodermal response (EDR) were performed before and 3 h after oral administration of 25 mg of CPZ: percent time waking EEG (per cent W-EEG) and number per minute of EDR were measured during the resting period and the period of calculation. In 10 normal adult subject, both per cent W-EEG and number of EDR showed remarkable decrease after CPZ administration. In 22 schizophrenics, however, per cent W-EEG showed no significant decrease after CPZ administration. Number of EDR in schizophrenics during the period of calculation did not show any significant decrease. The neural mechanism underlying the lower sensitivity to CPZ effects in schizophrenics was discussed.

Adolescent↗

Behind the scenes of functional brain imaging: a historical and physiological perspective.

At the forefront of cognitive neuroscience research in normal humans are the new techniques of functional brain imaging: positron emission tomography and magnetic resonance imaging. The signal used by positron emission tomography is based on the fact that changes in the cellular activity of the brain of normal, awake humans and laboratory animals are accompanied almost invariably by changes in local blood flow. This robust, empirical relationship has fascinated scientists for well over a hundred years. Because the changes in blood flow are accompanied by lesser changes in oxygen consumption, local changes in brain oxygen content occur at the sites of activation and provide the basis for the signal used by magnetic resonance imaging. The biological basis for these signals is now an area of intense research stimulated by the interest in these tools for cognitive neuroscience research.

Animals↗

Brain function as revealed by current density analysis of magnetoencephalography signals.

Magnetoencephalography signals are used to extract two-dimensional estimates of the cortical current density associated with spontaneous and steady state brain activity as well as auditory and visual evoked responses. The results provide clues about the organization of the electrical activity across wide cortical regions. Similarities and differences in spontaneous and evoked responses are highlighted and related to findings from other techniques, raising the possibility that volume conduction currents may play some role in coordinating brain function across widely separated cortical regions.

Brain↗

Preliminary evaluation of dual wavelength phased array imaging on neonatal brain function.

Imaging of human tissue using noninvasive techniques has been of great interest in biomedical fields. Optical imaging has attracted a lot of attention because of its portability and economy. The possibility that a highly portable, fast, safe, and affordable imaging system which could obtain interpretable images of brain function for pre- and full-term neonates in a few seconds, has been explored in this article. We have used a sensitive optical topography system, termed phased array, in which a pair of equal-amplitude and antiphase light sources are applied to generate a sharp amplitude null and phase transition plane. This two-wavelength (750 and 830 nm), frequency encoded (50 and 52 MHz) phased array imaging system can indicate the blood concentration and oxygenation changes in blood model studies and during parietal brain activation in neonates. Significant functional responses, particularly to parietal stimulation in normal and pathological states of neonatal brain, have been revealed in our study. The preliminary clinical results are presented in this article.

Blood Flow Velocity↗

Assessment of brain function in clinical pediatric research: behavioral and biological strategies.

Psychobiological research in child psychiatry requires rigorous assessment of behavior and multiple perspectives on brain function through neurochemical, neuroendocrine, psychophysiological, and other advanced methods. The serious neuropsychiatric disorders of childhood, such as autism, attention deficit disorder, and language disorders, can be studied in complementary clinical protocols aimed at explicating patterns of behavioral and metabolic dysfunction which characterize various clinical syndromes. Clinical research with children raises sensitive ethical issues; the ethical problems can be addressed when children and families are active collaborators with the investigators and a long-term relationship is established. In this setting, participation in research can facilitate better treatment for a child. The use of novel biological strategies, such as pharmacological challenge tests, permits evaluation of the relation of specific neuronal systems to behavioral dimensions in clinical disorders. The development of a new treatment for Tourette's syndrome illustrates the integration of basic and clinical research methods.

Catecholamines↗

History of zinc as related to brain function.

Zinc (Zn) is essential for synthesis of coenzymes that mediate biogenic-amine synthesis and metabolism. Zn from vesicles in presynaptic terminals of certain glutaminergic neurons modulates postsynaptic N-methyl-D-aspartate (NMDA) receptors for glutamate. Large amounts of Zn released from vesicles by seizures or ischemia can kill postsynaptic neurons. Acute Zn deficiency impairs brain function of experimental animals and humans. Zn deficiency in experimental animals during early brain development causes malformations, whereas deficiency later in brain development causes microscopic abnormalities and impairs subsequent function. A limited number of studies suggest that similar phenomena can occur in humans.

Animals↗

[Brain function and blood flow velocity in the middle cerebral artery in subarachnoid hemorrhage: evaluation with multimodality evoked potentials (MEPs) and transcranial Doppler (TCD) ultrasound].

Brain dysfunction and blood flow velocity changes in the middle cerebral artery (MCAFV) were studied in 59 patients with ruptured cerebral aneurysms presenting subarachnoid hemorrhage. Brain function and blood flow velocity were evaluated by multimodality evoked potentials (MEPs) consisting of ABR, SEP and VEP as reported, and transcranial Doppler (TCD) ultrasound. The abnormality on MEPs were graded into 4 grades. Nearly normal, mildly abnormal, moderately abnormal and severely abnormal. The results on MEP study were compared with clinical Hunt and Hess (H. H) grade or Fisher's CT group of subarachnoid hemorrhage in 44 patients. MCAFV was measured in 15 patients and mean velocity as well as CO2 reactivity and effect of head elevation were studied. Control value of MCAFV was 64 +/- 13 cm/sec in 50 healthy adults. CO2 reactivity was determined by K values obtained from the modified formula of cerebral blood flow by Olesen et al. MEP grade in H. H grade III and IV patients showed, on admission, variations in their grades in comparison with those in H. H grade I II and V patients. There was no definite correlation between the abnormality in MEPs and the degree of subarachnoid hemorrhage in Fisher's group 3 and 4 patients. When the surgical results in early and late operation in H. H grade III and IV patients were compared, it was shown that the outcome was favourable in early operated patients of H. H grade III if initial MEP grades were between I-III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Disturbed functional brain interactions underlying deficient tactile object discrimination in Parkinson's disease.

Somatosensory discrimination of cuboid objects was studied in a group of healthy volunteers and patients with Parkinson's disease using regional cerebral blood flow (rCBF) measurements obtained with positron emission tomography (PET) and 15O labeled water [H2 15O]. A 6-[18F]-fluoro-L-dopa (FDOPA) PET scan demonstrated that the patients may be grouped into those with normal and those with abnormally lowA FDOPA uptake in the caudate nucleus. The categorical group comparisons revealed that task-induced rCBF increases were deficient in bilateral motor and sensory cortical areas in the Parkinson patients. Moreover, deficient rCBF increases were evident in the mesial and right dorsolateral prefrontal cortex for patients in a more advanced disease state, who showed low FDOPA uptake in the caudate nucleus. A principal component analysis (PCA), performed on the rCBF data, identified three patterns (principal components, PCs) that differentiated patients from normals. The first PC represented a right-hemisphere dominant, bilateral group of brain areas known to be involved in tactile exploration. A second PC reflected a cortical-subcortical pattern of functional interactions, comprising cortical areas important for working memory processes. The third group-differentiating PC revealed a pattern of functional interactions involving bilateral temporo-parieto-occipital association cortices, which was consistent with a hypothesized supramodal network necessary for object discrimination. In an additional subgroup analysis, greater expression of the third PC pattern predicted greater caudate FDOPA uptake in patients. Our neuroimaging data revealed a disturbance of distinct patterns of brain functional interactions related to the sensorimotor deficit in Parkinson's disease and to deficits of cognitive information processing deficits in the more advanced stage of Parkinson's disease.

Adult↗

Functional brain imaging during anesthesia in humans: effects of halothane on global and regional cerebral glucose metabolism.

BACKGROUND: Propofol and isoflurane anesthesia were studied previously with functional brain imaging in humans to begin identifying key brain areas involved with mediating anesthetic-induced unconsciousness. The authors describe an additional positron emission tomography study of halothane's in vivo cerebral metabolic effects. METHODS: Five male volunteers each underwent two positron emission tomography scans. One scan assessed awake-baseline metabolism, and the other scan assessed metabolism during halothane anesthesia titrated to the point of unresponsiveness (mean +/- SD, expired = 0.7+/-0.2%). Scans were obtained using a GE2048 scanner and the F-18 fluorodeoxyglucose technique. Regions of interest were analyzed for changes in both absolute and relative glucose metabolism. In addition, relative changes in metabolism were evaluated using statistical parametric mapping. RESULTS: Awake whole-brain metabolism averaged 6.3+/-1.2 mg x 100 g(-1) x min(-1) (mean +/- SD). Halothane reduced metabolism 40+/-9% to 3.7+/-0.6 mg x 100 g(-1) x min(-1) (P< or =0.005). Regional metabolism did not increase in any brain areas for any volunteer. The statistical parametric mapping analysis revealed significantly less relative metabolism in the basal forebrain, thalamus, limbic system, cerebellum, and occiput during halothane anesthesia. CONCLUSIONS: Halothane caused a global whole-brain metabolic reduction with significant shifts in regional metabolism. Comparisons with previous studies reveal similar absolute and relative metabolic effects for halothane and isoflurane. Propofol, however, was associated with larger absolute metabolic reductions, suppression of relative cortical metabolism more than either inhalational agent, and significantly less suppression of relative basal ganglia and midbrain metabolism.

Anesthesia, General↗

Molecular diversity of glutamate receptors and implications for brain function.

The glutamate receptors mediate excitatory neurotransmission in the brain and are important in memory acquisition, learning, and some neurodegenerative disorders. This receptor family is classified in three groups: the N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-kainate, and metabotropic receptors. Recent molecular studies have shown that many receptor subtypes exist in all three groups of the receptors and exhibit heterogeneity in function and expression patterns. This article reviews the molecular and functional diversity of the glutamate receptors and discusses their implications for integrative brain function.

Amino Acid Sequence↗

Nuclear magnetic resonance imaging and spectroscopy of human brain function.

The techniques of in vivo magnetic resonance (MR) imaging and spectroscopy have been established over the past two decades. Recent applications of these methods to study human brain function have become a rapidly growing area of research. The development of methods using standard MR contrast agents within the cerebral vasculature has allowed measurements of regional cerebral blood volume (rCBV), which are activity dependent. Subsequent investigations linked the MR relaxation properties of brain tissue to blood oxygenation levels which are also modulated by consumption and blood flow (rCBF). These methods have allowed mapping of brain activity in human visual and motor cortex as well as in areas of the frontal lobe involved in language. The methods have high enough spatial and temporal sensitivity to be used in individual subjects. MR spectroscopy of proton and carbon-13 nuclei has been used to measure rates of glucose transport and metabolism in the human brain. The steady-state measurements of brain glucose concentrations can be used to monitor the glycolytic flux, whereas subsequent glucose metabolism--i.e., the flux into the cerebral glutamate pool--can be used to measure tricarboxylic acid cycle flux. Under visual stimulation the concentration of lactate in the visual cortex has been shown to increase by MR spectroscopy. This increase is compatible with an increase of anaerobic glycolysis under these conditions as earlier proposed from positron emission tomography studies. It is shown how MR spectroscopy can extend this understanding of brain metabolism.

Brain↗