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Preserved pontine glucose metabolism in Alzheimer disease: a reference region for functional brain image (PET) analysis.

OBJECTIVE: Our goal was to examine regional preservation of energy metabolism in Alzheimer disease (AD) and to evaluate effects of PET data normalization to reference regions. MATERIALS AND METHODS: Regional metabolic rates in the pons, thalamus, putamen, sensorimotor cortex, visual cortex, and cerebellum (reference regions) were determined stereotaxically and examined in 37 patients with probable AD and 22 normal controls based on quantitative 18FDG-PET measurements. Following normalization of metabolic rates of the parietotemporal association cortex and whole brain to each reference region, distinctions of the two groups were assessed. RESULTS: The pons showed the best preservation of glucose metabolism in AD. Other reference regions showed relatively preserved metabolism compared with the parietotemporal association cortex and whole brain, but had significant metabolic reduction. Data normalization to the pons not only enhanced statistical significance of metabolic reduction in the parietotemporal association cortex, but also preserved the presence of global cerebral metabolic reduction indicated in analysis of the quantitative data. CONCLUSION: Energy metabolism in the pons in probable AD is well preserved. The pons is a reliable reference for data normalization and will enhance diagnostic accuracy and efficiency of quantitative and nonquantitative functional brain imaging.

Aged

Towards measurement of brain function in operational environments.

In operational environments that demand sustained vigilance or that involve multiple tasks competing for limited attentional resources, continuous monitoring of the mental state of the operator could decrease the potential for serious errors and provide valuable information concerning the ergonomics of the tasks being performed. There is widespread discussion and appreciation of the basic feasibility of utilizing neurophysiological measurements to derive accurate, reliable, rapid and unobtrusive assessments of mental state. However, progress in transitioning this idea into practical applications has been impeded by the fact that at present no convenient, inexpensive and effective means exists to derive a meaningful index of brain activity outside of laboratory settings. In this paper, we review some recent advances in recording technology and signal processing methods that will help overcome this limitation. For example, rapid progress is being made in the engineering of recording systems that are small, rugged, portable and easy-to-use, and thus suitable for deployment in operational environments. Progress is also being made in the development of signal processing algorithms for detecting and correcting recording artifacts and for increasing the amount of useful information that can be derived from brain signals. Finally, results from basic research studies suggest that accurate and reliable inferences about the mental load and alertness of an individual can be derived from neurophysiological measures in a practical fashion. These research and engineering successes suggest that it is reasonable to expect that in the near term a basic enabling technology will be deployed that will permit routine measurement of brain function in operational environments.

Arousal

Deterministic nonlinear chaos in brain function and borderline psychopathological phenomena.

There exists a fundamental overall property of the brain which monitors, modulates, and ensures a smoothness of function and which further determines elegance and grace in functioning. This property also imparts a quality of, or a sense of proportion among all other faculties of the brain. It is postulated in this paper that such a property/function, up to now almost taken for granted, is maintained/exercised by a nonlinear deterministic chaotic mode of brain function. If this is the case, borderline psychopathological phenomena, when they flare up, can be explained as resulting from sudden reduction of such a deterministic chaotic mode and the emergence of a pathological order, as the system becomes an oscillating one.

Borderline Personality Disorder

Hypothermia protects brain function in acute carbon monoxide poisoning.

The role of body temperature in the morbidity and mortality resulting from acute severe carbon monoxide (CO) poisoning (2400 ppm CO, 90 min) was investigated using an unanesthetized animal model. Modified Levine prepared female rats (left common carotid artery and jugular cannulated) displayed a lower rate of recovery period (4 hr) re-warming, and an increased mortality rate and behaviorally-assessed neurologic index (NI) compared to normal rats. This indicated their greater susceptibility to CO hypoxia, although the degree of CO-induced hypothermia was the same in both groups. The whole-body cooling of Levine rats to a similar extent prior to CO exposure increased somewhat the post-CO re-warming rate, and marginally decreased NI and mortality during CO exposure (in-CO). In contrast, maintenance of constant body temperature by external heating during CO exposure resulted in a negative post-CO re-warming rate and sharply increased NI and in-CO mortality. Normal euthermic rats were much less severely affected by CO. The results suggest that hypothermia, whether CO-induced or produced by prior cooling, provides measurable protection of brain function during acute severe CO poisoning, and that maintenance of body temperature increases in-CO mortality and interferes with ability to thermoregulate and increases NI in survivors.

Animals

Noninvasive functional brain mapping by change-distribution analysis of averaged PET images of H215O tissue activity.

Change-distribution analysis and intersubject averaging of subtracted positron emission tomography (PET) images are new techniques for detecting, localizing, and quantifying state-dependent focal transients in neuronal activity. We previously described their application to cerebral blood flow images (intravenous bolus H215O, Kety autoradiographic model). We now describe their application to images of H215O regional tissue activity without conversion to units of blood flow. The sensitivity and specificity of response detection and the accuracy of response localization were virtually identical for the two types of images. Response magnitude expressed in percent change from rest was slightly, but consistently smaller in tissue-activity images. Response magnitude expressed in z-score was the same for the two-image types. Most research and clinical applications of functional brain mapping can employ images of H215O tissue activity (intravenous bolus, 40-sec nondynamic scan) without conversion to units of blood flow. This eliminates arterial blood sampling, thereby simplifying and minimizing the invasivity of the PET procedure.

Adult

Functional brain imaging with SPECT in normal aging and dementia. Methodological, pathophysiological, and diagnostic aspects.

New developments in instrumentation, radiochemistry, and data analysis, particularly the introduction of 99M TC-labeled brain-retained tracers for perfusion studies, have opened up a new era of single photon emission computed tomography (SPECT). In this review critical methodological issues relating to the SPECT instrument, the radioactive tracers, the scanning procedure, the data analysis and interpretation of data, and subject selection are discussed together with the changes in regional cerebral blood flow (rCBF) observed in normal aging. An overview is given of the topography and the pathophysiological and diagnostic significance of focal rCBF deficits in Alzheimer's disease and in other dementia disorders, in which SPECT is capable of early or preclinical disease detection. In Alzheimer's disease, the diagnostic sensitivity and specificity of focal rCBF deficits measured with SPECT and brain-retained tracers are very high, in particular when combined with medial temporal lobe atrophy on CT. Together with neuropsychological testing, SPECT serves to map the topography of brain dysfunction. Thus, in the clinical setting, SPECT provides information that is supplemental to that obtained in other studies. Future applications include neuroreceptor studies and treatment studies, in which SPECT may serve as a diagnostic aid in the selection of patients and as a potential mean for monitoring treatment effects. Although positron emission tomography is the best characterized tool for addressing some of these clinical and research issues in dementia, only the less expensive and technically simpler SPECT technique will have the potential of being available as a screening diagnostic instrument in the clinical setting. It is concluded that, properly approached, functional brain imaging with SPECT represents an important tool in the diagnosis, management, and research of dementia disorders.

Aging

Lithium carbonate and brain function. I. Cerebral-evoked potentials, EEG, and symptom changes during lithium carbonate treatment.

Eighteen patients were studied with behavioral ratings and the somatosensory (SER), auditory (AER), and visual (VER) cerebral-evoked response and quantified EEG before and during lithium carbonate treatment. The amplitude of early positive SER components and most AER components increased during treatment, but VER did not change. The intensity of EEG delta and theta frequencies increased, and the dominant alpha frequency slowed. Before treatment, there were few significant correlations to symptom intensity. Patients with an increase in symptoms on treatment had the greatest increase in EEG delta intensity and the dominant alpha frequency slowed in patients who became more depressed. The EEG slowing in patients with a normal sensorium and the change in cerebral cortical activity after transmission in the somatosensory pathway over just three synapses demonstrate a unique and specific effect of lithium carbonate on brain function.

Adult

The effects of diazoxide upon fetal and maternal hemodynamics and fetal brain function and metabolism.

The effects of maternal infusion of Diazoxide (D) were evaluated in two groups of experiments: Nine ewes and their five nonhypoxic fetuses; the remaining four fetuses were excluded because of the development of hypoxia prior to the study. D was directly administered intravenously (IV) to the six fetuses. In group 1 maternal and fetal observations were made at 0, 5, 15, 30, and 45 minutes. A 60-minute observation was also made for the maternal infusion studies. Maternal infusion of 5 mg/kg maternal weight significantly reduced maternal pH from the control value at 5 minutes. Maternal metabolic acidosis was indicated by concomitant significant reductions in base deficit (BD) and total bicarbonate (HCO3), both of which remained low for all subsequent time periods. Maternal lactic acid concentration also increased at 15 minutes, although not significantly. Maternal PO2 also fell significantly at 5 minutes, remaining significantly low for the remaining observations. A profound maternal hypotension was elicited at 5 minutes. All following observations for maternal blood pressure (MBP) were also significantly low. Fetal carotid arterial (FCA) pH declined significantly from the control period value at 15 minutes, remaining significantly low for the remaining observations. FCA O2% saturation (O2%) also witnessed a significant decline from baseline for all observations. FCA serum lactate level rose at 15 minutes; however, this was not deemed significant. No significant changes were seen in fetal brain metabolic rate of oxygen or glucose. Fetal electroencephalogram (EEG) revealed a definite hypoxic change in a majority of cases. In group 2, the effects of a direct fetal IV administration of 30 mg D (mean dose = 7.97 mg/kg fetal weight) were studied in six experiments. No significant changes in fetal acid base status or fetal blood pressure (FBP) were witnessed for the 45 minutes under scrutiny. Fetal heart rate (FHR) showed a short transient rise from baseline at 5 and 15 minutes, returning to normal thereafter. A slight significant decrease in O2% saturation and O2 content were seen only for the 5-minute observation. There were no significant changes of fetal brain function and metabolism observed following D administration to the fetus. The significant fetal hypoxia and acidosis witnessed through the maternal infusion but not in the direct fetal bolus administration were probably owing to profound maternal hypotension resulting in deterioration of uteroplacental perfusion and fetal "gas exchange."

Animals

Magnetoencephalography in studies of human cognitive brain function.

Magnetoencephalography provides a new dimension to the functional imaging of the brain. The cerebral magnetic fields recorded noninvasively enable the accurate determination of locations of cerebral activity with an uncompromized time resolution. The first whole-scalp sensor arrays have just recently come into operation, and significant advances are to be expected in both neurophysiological and cognitive studies, as well as in clinical practice. However, although the accuracy of locating isolated sources of brain activity has improved, identification of multiple simultaneous sources can still be a problem. Therefore, attempts are being made to combine magnetoencephalography with other brain-imaging methods to improve spatial localization of multiple sources and, simultaneously, to achieve a more complete characterization of different aspects of brain activity during cognitive processing. Owing to its good time resolution and considerably better spatial accuracy than that provided by EEG, magnetoencephalography holds great promise as a tool for revealing information-processing sequences of the human brain.

Brain

The EEG, brain function, and Thomson's sampling theory.

If the EEG is regarded as a measure of functional organisation in the brain, it may yet be possible to use it as an independent variable in psychological studies. The method of Maxwell et al. (1974) suggest how this relationship may be quantified. These authors develop the hypothesis that EEG power is proportional to p, the number of brain components involved in cognition. However, evidence is reviewed here to suggest an alternative hypothesis for the case of EEG alpha activity, namely that power is proportional to (1--p).

Alpha Rhythm

Hypotensive anesthesia for total hip arthroplasty: a study of blood loss and organ function (brain, heart, liver, and kidney).

The authors attempted to determine whether hypotensive anesthesia or the method of inducing hypotension has any effect on postoperative brain, liver, or kidney function and myocardial status following total hip arthroplasty. Thirty patients were anesthestized with halothane-nitrous oxide for total hip arthroplasty and randomly assigned to one of three groups. In two groups mean arterial blood pressure was decreased to 50 torr by high inspired concentrations of halothane (n = 90) or sodium nitroprusside (n = 12). In the third group (n = 9) mean blood pressure was maintained within 20% of control. Intraoperative blood losses decreased from 1,183 +/- 172 ml in the normotensive group to 406 +/- 102 ml and 326 +/- 41 ml in the halothane and nitroprusside hypotensive groups, respectively. Neither method of inducing hypotension nor hypertensive technique affected the results of postoperative tests of cerebral, hepatic, or renal function and myocardial status. These tests were performed before anesthesia and operation and at intervals in the postoperative course. In this small group of patients, deliberate hypotension for total hip arthroplasty added no morbidity and significantly shortened operating time, decreased blood loss, and decreased the number of blood transfusions needed.

Aged

Long term effects of high altitude on brain function.

Absence of oxygen to the brain for even a very few minutes results in loss of consciousness and can cause permanent injury. Can the wanderer to the limits of earth-bound hypoxia suffer similar harm from more prolonged exposure to milder hypoxia that does not cause loss of consciousness? I shall review the results from studies where neurobehavioral function has been compared in mountaineers before and after return from great heights and in individuals with chronic pulmonary disease before and after prolonged, continuous oxygen therapy. Many (although not all) of these studies report mild impairment of neurobehavioral function after fairly prolonged hypoxic exposure. Impairment was manifest by deficits in memory storage and recall, aphasia, concentration, and finger tapping speed; the last deficit was still detectable a year later in one group of mountaineers. Limited evidence suggests that climbers with a high ventilatory response to hypoxia (HVR) may be more susceptible to impairment than those with a lower HVR.

Altitude Sickness

The development and evaluation of a low-cost microdensitometer for use with the 2-deoxy-D-glucose method of functional brain mapping.

The conversion of a standard laboratory compound microscope into a microdensitometer for use in the 2-deoxy-D-glucose autoradiographic method of functional mapping in the brain is described. A solid-state detector was attached to the camera port of a Zeiss Universal Microscope and minor modifications to the microscope optics were made to produce a microdensitometer with a field of view 0.15 mm in diameter. Details are presented showing the modifications to the microscope which do not permanently destroy its functional ability to perform as a viewing microscope. A simple electronic circuit is presented to digitally display the output of the photo detector. Calibration of the instrument in terms of optical density or 2-deoxy-D-glucose activity is also described. The primary design goal was the construction of a simple, reliable, inexpensive microdensitometer that could be assembled by laboratory personnel. This densitometer should allow laboratories on modest budgets to have access to quantitative methods for the study of brain functional activity at a cost considerably less than the price of a commercial microdensitometer.

Animals