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A single photon emission computerised tomography study of regional brain function in elderly patients with major depression and with Alzheimer-type dementia.

The uptake, at rest, of 99mTc-exametazime into different brain regions was compared using SPECT for 20 elderly subjects with major depressive disorder, 20 with Alzheimer-type dementia, and 30 age-matched normal volunteers. Uptake was referred to calcarine-occipital cortex as a reference sensory area. Cross-sectional differences between the three groups were highly statistically significant, but reflected primarily the reductions in cortical uptake in the Alzheimer group. A detailed comparison of depressed patients and controls identified decrements in anterior cingulate, temporal and frontal cortex and in caudate and thalamus in men only. These decrements were correlated with impairment of performance on a trail-making task, but were also associated with continuing treatment with antidepressants or benzodiazepines. However, most depressed patients had quantitatively normal scans for posterior parietal association cortex, and this suggests that SPECT may find a limited role in the differential diagnosis of depression and dementia. The reduced brain function in some depressed patients may parallel the findings from studies of brain structure in elderly depressives; there was between good outcome at 6-18 months and increased tracer uptake in subcortical areas.

Age of Onset↗

Blood glucose and brain function: interactions with CNS cholinergic systems.

We recently found that glucose injections attenuate amnesia and hyperactivity produced by scopolamine, a muscarinic antagonist. The present study examined whether glucose would augment behavioral effects produced by a muscarinic agonist, physostigmine. In experiment I, doses were first determined for which neither glucose (10 mg/kg) nor physostigmine (0.05 mg/kg) altered scopolamine-induced hyperactivity. However, combined glucose-physostigmine injections significantly reduced scopolamine hyperactivity. Experiment II evaluated the effects of glucose on physostigmine-induced tremors. Glucose (10, 100, and 250 mg/kg) or saline injections were given 20 min before physostigmine injections (0.4 or 0.05 mg/kg). Observations of glucose effects on the severity of physostigmine-induced tremors were then obtained at 5-min intervals for 25 min after physostigmine injections. Glucose (100 mg/kg) significantly facilitated the onset of tremors when injected before either dose of physostigmine, and augmented (at 100 and 250 mg/kg) tremor severity when injected before the lower dose of physostigmine. These findings indicate that glucose can facilitate the actions of a cholinergic agonist on two behaviors, locomotor activity and tremors, adding support to the view that circulating glucose levels can modulate central cholinergic function. More generally, the results provide additional evidence that circulating glucose levels can influence brain function.

Animals↗

Structural and functional brain asymmetries in human situs inversus totalis.

OBJECTIVE: To determine whether individuals with situs inversus totalis (SI), a condition in which there is a mirror-image reversal of asymmetric visceral organs, have alterations in brain asymmetries. BACKGROUND: The human brain is asymmetric in structure and function. Although correlations between anatomic asymmetries and functional lateralization in human brain have been demonstrated, it has been difficult to further analyze them. Characterization of asymmetries of brain structure and function in SI might advance the understanding of these relationships. METHODS: Using anatomic and functional MRI techniques, we analyzed asymmetries in the brains of three individuals with SI. RESULTS: Two major anatomic asymmetries of the cerebral hemispheres, the frontal and occipital petalia, were reversed in individuals with SI. In contrast, SI subjects had left cerebral hemisphere language dominance on functional MRI analysis as well as strong right-handedness. CONCLUSION: These observations suggest that the developmental factors determining anatomic asymmetry of the cerebral petalia and viscera are distinct from those producing the functional lateralization of language.

Adult↗

The central adaptation syndrome: psychosocial stress as a trigger for adaptive modifications of brain structure and brain function.

This review makes an attempt to combine data from biological and psychosocial stress literature and to suggest an alternative interpretation of the relationship between stress and disease. It rearranges the presently available knowledge on the short- and long-term effects of stress on many different aspects of brain structure and brain function in the form of a new conceptualization of the biological role of the stress response. The higher associative brain structures are not only the sites in which environmental and psychosocial demands are recognized and from which a less or more systemic, i.e. controllable or uncontrollable, stress response is initiated. They are also the sites which are primarily affected in the course of the stress response: the stress response acts as a trigger for the adaptive modification of the structure and the function of the brain of higher vertebrates and serves thus to adjust, in a self-optimizing manner, the behavior of an individual to the ever-changing requirements of its external world. This novel concept summarizes a large amount of information into a framework that lends itself to testable strategies for future research.

Adaptation, Physiological↗

Effects of estrogen deficiency on brain function. Implications for the treatment of postmenopausal women.

A growing body of evidence suggests that postmenopausal estrogen deficiency accelerates brain aging and increases the risk of various neurodegenerative processes, including Alzheimer's disease. Recent preclinical and clinical studies have indicated that estrogen has positive effects on brain homeostasis by preserving neural plasticity and the neurotransmitter pathways involved in learning, memory, and balance. In this article, Dr Birge and his coauthors address the effects of estrogen on brain function and discuss their implications for the use of selective estrogen receptor modulators, particularly tamoxifen and raloxifene, in postmenopausal women.

Aging↗

Insights into the pathophysiology of neuropathic pain through functional brain imaging.

We present here an example case of neuropathic pain with heat allodynia as a major symptom to illustrate how the functional imaging of pain may provide new insights into the pathophysiology of painful sensory disorders. Tissue injury of almost any kind, but especially peripheral or central neural tissue injury, can lead to long-lasting spinal and supraspinal re-organization that includes the forebrain. These forebrain changes may be adaptive and facilitate functional recovery, or they may be maladaptive, preventing or prolonging the painful condition, and interfering with treatment. In an experimental model of heat allodynia, we used functional brain imaging to show that: (1) the forebrain activity during heat allodynia is different from that during normal heat pain, and (2) during heat allodynia, specific cortical areas, specifically the dorsolateral prefrontal cortex, can attenuate specific components of the pain experience, such as affect, by reducing the functional connectivity of subcortical pathways. The forebrain of patients with chronic neuropathic pain may undergo pathologically induced changes that can impair the clinical response to all forms of treatment. Functional imaging, including PET, fMRI, and neurophysiological techniques, should help identify brain mechanisms that are critical targets for more effective and more specific treatments for chronic, neuropathic pain.

Adult↗

Sperry's concept of mind as an emergent property of brain function and its implications for the future of humankind.

Sperry's proposal that subjective experience plays a major role in brain function and in the emergence of mind, consciousness and human values represent a challenge to behaviorism as the dominant force in psychology. Mind is viewed as an emergent property of the brain, generated from and dependent upon neural activity, but nonetheless separate from it. Macrodeterministic factors result in the evolution of human values, which represent a critical key to world change. Two major conferences resulted from Sperry's challenge to the scientific community. The Trieste Conference led to a 'Declaration of Human Responsibilities', presently under consideration by the United Nations as a corollary to the 'Declaration of Human Rights'. The Japan Conference inspired work toward a Network University of the Green World, in which computer networking will support international communication in areas of environmental concern.

Brain↗

Functional brain imaging in apraxia.

BACKGROUND: An extensive literature describes structural lesions in apraxia, but few studies have used functional neuroimaging. We used positron emission tomography (PET) to characterize relative cerebral glucose metabolism in a 65-year-old, right-handed woman with progressive decline in ability to manipulate objects, write, and articulate speech. OBJECTIVE: To characterize functional brain organization in apraxia. DESIGN AND METHODS: The patient underwent a neurological examination, neuropsychological testing, magnetic resonance imaging, and fludeoxyglucose F 18 PET. The patient's magnetic resonance image was coregistered to her PET image, which was compared with the PET images of 7 right-handed, healthy controls. Hemispheric regions of interest were normalized by calcrine cortex. RESULTS: Except for apraxia and mild grip weakness, results of the neurological examination were normal. There was ideomotor apraxia of both hands (command, imitation, and object) and buccofacial apraxia. The patient could recognize meaningful gestures performed by the examiner and discriminate between his accurate and awkward pantomime. The magnetic resonance image showed moderate generalized atrophy and mild ischemic changes. Positron emission tomographic scans showed abnormal fludeoxyglucose F 18 uptake in the posterior frontal, supplementary motor, and parietal regions, the left affected more than the right. Focal metabolic deficit was present in the angular gyrus, an area hypothesized to store conceptual knowledge of skilled movement. CONCLUSIONS: Greater parietal than frontal physiological dysfunction and preserved gesture recognition are not consistent with the theory that knowledge of limb praxis is stored in the dominant parietal cortex. Gesture comprehension may be more diffusely distributed.

Aged↗

Effects of QiGong on brain function.

QiGong is an ancient and widely practiced Chinese meditation exercise. We studied the effects of QiGong on brain function with modern neuromonitoring tools in two subjects. In a male QiGong master (extremely trained practitioner), the technique induced reproducible changes in transcranial Doppler sonography, EEG, stimulus-induced 40 Hz oscillations, and near-infrared spectroscopy findings. Similar effects were seen after the application of multimodal stimuli and when the master concentrated on intense imagined stimuli (e.g. 22.2% increase in mean blood flow velocity (vm) in the posterior cerebral artery, and a simultaneous 23.1% decrease of vm in the middle cerebral artery). Similar effects were seen in the female subject. Neuromonitoring during QiGong appears able to objectify accompanied cerebral modulations surrounding this old Chinese meditation exercise.

Acoustic Stimulation↗

Normalizing hematocrit in dialysis patients improves brain function.

Recombinant human erythropoietin (rHuEPO) treatment has been shown to improve brain and cognitive function in anemic dialysis patients. Significant debate continues, however, regarding the appropriate target hematocrit (Hct) that will lead to the greatest benefits while considering possible side effects and costs of rHuEPO. Current practice results in an Hct averaging only 31% to 32% in dialysis patients, a level less than that achieved in the initial clinical trials and well less than normal. This study was designed to evaluate dialysis patients at the current practice Hct levels versus normal Hct levels (40% to 45%) to see if improvement in brain function resulted. Twenty patients with end-stage renal disease (ESRD) currently being treated with rHuEPO (mean Hct, 31.6%) were administered additional rHuEPO to reach normal Hct levels (mean, 42. 8%). Electroencephalogram (EEG) frequency analysis showed a significant decrease in EEG slowing at greater Hct values, and the auditory oddball and Continuous Performance Task tasks yielded significant electrode and time-by-electrode effects for P300 amplitude. Changes in P300 latency significantly correlated with increased Hct in the auditory oddball task. These findings suggest that further correction of anemia to normal Hct levels may result in continued improvement in neurocognitive function by improving the ability to sustain attention in easier tasks and by enhancing the ability to recognize, discriminate, and hold stimuli in memory for more difficult tasks.

Anemia↗

Iron in brain function and dysfunction with emphasis on Parkinson's disease.

Metals such as lead, zinc, copper, aluminum and manganese have been implicated in neuropsychiatric disorders. However, until fairly recently the role of iron in brain function was rather obscure, because little attention was paid to its metabolism in the brain. It is now apparent that maintenance of brain iron homoeostasis is important for the normal functioning of his organ. Most of the studies have been directed towards the cognitive and attentional deficit resulting from nutritional iron deficiency. Evidence so far suggests subsensitivity of striatal dopamine neurotransmission. By contrast the selective increase in free iron in the substantia nigra pars compacta of parkinsonian brains is thought to initiate oxidative stress, from iron-induced liberation of cytotoxic oxygen free radicals. Such radicals are known to promote membrane fluidity, alteration in cellular calcium homoeostasis, lipid peroxidation and finally cell death in systemic organs. Evidence supporting similar processes being responsible for nigrostriatal dopamine neuron degeneration in Parkinson's disease is now becoming available. Such possibilities afford the development of neuroprotective drugs as a means to retard the progression of this disorder. These include other selective monoamine oxidase B inhibitors, iron chelators with the ability to cross the blood-brain barrier, selective calcium channel antagonists and mitochondrial electron transport system protectors.

Anemia, Hypochromic↗

Functional brain imaging in pediatrics.

With the development of noninvasive tomographic imaging techniques, it is now possible to measure local chemical and physiologic functions in various body organs. Studies of local cerebral glucose metabolism in infants and children using positron emission tomography (PET) have provided important information on human brain functional development and plasticity. The clinical application of functional neuroimaging techniques in the management of pediatric neurologic disorders has yielded encouraging results. In children with intractable epilepsy being considered for surgical intervention, PET is highly sensitive in localizing focal areas of cortical dysplasia, heterotopias, and other migrational defects corresponding to surface electrographic localization of epileptogenic regions. Expanding PET technology provides a new approach that holds great promise in the diagnosis and management of brain disorders in children.

Brain↗

Effect of tunicamycin on the expression of functional brain neurotransmitter receptors and voltage-operated channels in Xenopus oocytes.

The role of N-glycosylation on the expression of functional brain neurotransmitter receptors and voltage-operated channels was studied by injecting Xenopus oocytes with mRNA from rat brain or chick optic lobe, and culturing them in the presence or absence of tunicamycin, an inhibitor of asparagine linked glycosylation. Electrophysiological recordings were then made to assess the amounts of functional receptors and channels present in the oocyte membrane. The appearance of gamma-aminobutyric acid (GABA) receptors and voltage-activated Na+ channels was profoundly reduced. In contrast, the functional expression of kainate receptors, and voltage-activated K+ and Ca2+ channels was much less affected. Thus, it seems that kainate receptors, and K+ and Ca2+ channels can be expressed and function normally without being glycosylated. On the other hand, GABA receptors and Na+ channels may need to be N-glycosylated in order to function properly, or to ensure their correct insertion into the membrane.

Amino Acids↗

[Effects of propentofylline (HWA285) on recovery of brain function following total cerebral ischemia (TCI) in dogs].

We examined the effects of a xanthine derivative, propentofylline, on recovery of brain function following TCI in 23 adult mongrel dogs. TCI was produced by clamping ascending aorta with aortoatrial bypass formation. The dogs were divided into 3 groups: preischemic administration (0.3 mg.kg-1.min-1, 30 min), post-ischemic administration (0.5 mg.kg-1.min-1, 6h) and control. The progress of recovery of EEG, respiration, reflexes, motor functions, arousal state and behavior were observed for 7 days after TCI and the latter 5 functions were analysed using neurologic deficit score (NDS). Propentofylline shortened the time necessary for reappearance of EEG after the starting of recirculation but could not improve the NDS.

Animals↗

[The progress of non-invasive examination of the brain function and child neurology].

During the last 2 decades of the 20th century, various non-invasive examinations of the brain function developed strikingly with the advance of electronics. The examination procedures were tentatively classified into the following generations: the 1st generation: EEG, the 2nd: evoked potentials using signal averaging system, the 3rd: CT and MRI using reconstruction of imaging, 4th: PET, SPECT, fMRI, MEG, MRS and DTI which are categorized in functional imaging, 5th: optic topography combining the functional imaging and time factor. In this article, the outlines of the principle and application of the 4th and 5th generation methods are described. Their application to children requires the development of less invasive and simpler methods. These examination tools still stand on the start line, and will be widely applied to the neurology field in future. Child neurologists should be concerned with the development of their application.

Brain↗

Functional brain changes in presymptomatic Huntington's disease.

Evidence suggests early structural brain changes in individuals with the Huntington's disease (HD) genetic mutation who are presymptomatic for the movement symptoms of the illness. The aim of this study was to investigate the presence of functional brain changes in this same population using functional magnetic resonance imaging. Subjects and matched controls underwent an functional magnetic resonance imaging "interference" protocol, a task known to be mediated in part by corticostriatal circuitry. In the setting of normal cognitive performance, presymptomatic HD subjects had significantly and specifically less activation in the left anterior cingulate cortex (BA 24, 32) compared with matched controls.

Adult↗

Is heading a soccer ball injurious to brain function?

With the growing popularity of soccer both in the United States and worldwide, reports of adverse effects of 'heading' on brain function are a source of concern. This article reviews the related research literature on neurologic and neuropsychological findings. Neurologic and neuropsychological abnormalities have been reported in a significant minority of older former professional players in Norway. Purportedly unrelated to age, the most prominent findings were cerebral atrophy and impairment on intelligence test abilities that are particularly vulnerable to brain damage. Also noteworthy in these retired players were persistent physical, cognitive, and emotional complaints consistent with a postconcussive syndrome. Younger amateur players appear to be free of major abnormalities, although some report persistent difficulties with memory and concentration. The severity of these complaints may be related to a history of soccer-related head injuries and not necessarily specific to heading. Research findings specific to heading are not more than suggestive at best, and clarification of the risks of heading a soccer ball awaits more definitive studies.

Biomechanical Phenomena↗