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A meta-analysis of structural and functional brain imaging in dementia of the Alzheimer's type: a neuroimaging profile.

We conducted a quantitative review of the imaging literature using meta-analytic methodology to characterize further the magnitude of hippocampal deficit in probable Alzheimer's disease (AD) and to determine whether other neuroanatomic structures in AD can better discriminate the disease from normal aging. Additionally, we parceled the discriminability of neuroanatomic structures by duration of disease to determine those structures most sensitive to AD in its early and late stages. One hundred twenty-one studies published between 1984 and 2000 met criteria for inclusion in the present analysis. In total, structural (i.e., CT and MRI) and functional (i.e., SPECT and PET) neuroimaging results from 3511 patients with AD, and 1632 normal healthy controls were recorded across meta-analyses. Our results include neuroimaging profiles for both early onset and longer duration patients with AD. In sum, these profiles yield a signature of diagnostic markers in both cortical and subcortical neuroanatomic areas. This signature is consistent with the clinical phenomenology of Alzheimer's dementia and should aid in the positive identification of AD.

Aged↗

A psychodynamic (NonOedipal) and brain function hypothesis regarding a type of male sexual masochism.

A clinical observation suggests a hypothesis that differs from classical analytic oedipal theory as to the origin and psychodynamics of a type of male sexual masochism. This type of masochism may occur when a painful childhood life experience regarding severely forbidden sexual pleasure is associated and amalgamated with shame, humiliation, and feared physical and psychological punishment resulting in sexual pleasure. If this takes place with sufficient frequency during the critical phases of childhood sexual development, possibly including early adolescent sexual development, it becomes recorded as long-term memory in brain neural networks. The phenomenon of its recording includes, at least in part, the commonly accepted theory of Donald Hebb. In later years, the man feels compelled to reproduce in a masochistic ritual the former childhood psychological and physical conditions, to bring about the most intense sexual pleasure. Humiliation, shame, discomfort, helplessness, and even possible pain are simulated or actually instigated. By voluntarily placing himself in charge of the type of sadistic treatment he receives in acts of masochism, a patient may unconciously place himself in charge of his plight, in an attempt to master it, in contrast to his childhood helpless state. This formulation does not require an Oedipal explanation.

Adult↗

Automated detection of the intercommissural line for stereotactic localization of functional brain images.

A technique has been developed for automated detection of the intercommissural (AC-PC) line for positron emission tomography (PET). The AC-PC line is estimated from the location of four internal landmarks; the frontal and occipital poles, the inferior aspect of the anterior corpus callosum, and the subthalamic point. The landmarks are detected automatically in PET mid-sagittal slices by combining edge detection, interpolation and profile curve analysis techniques. The anatomical relationships between the true and estimated AC-PC lines from the landmarks was confirmed by analysis of magnetic resonance (MR) images. Accuracy of the automated estimation technique was assessed in co-registered PET and MR images, which showed minimal angular differences and displacements of the estimated from the true AC-PC lines. The automated detection of the AC-PC line in a PET study enables accurate stereotactic localization of functional signals without the need for additional anatomical imaging and provides a basis for objective and reproducible intersubject comparison.

Brain↗

Mitochondrial involvement in brain function and dysfunction: relevance to aging, neurodegenerative disorders and longevity.

It is becoming increasingly evident that the mitochondrial genome may play a key role in neurodegenerative diseases. Mitochondrial dysfunction is characteristic of several neurodegenerative disorders, and evidence for mitochondria being a site of damage in neurodegenerative disorders is partially based on decreases in respiratory chain complex activities in Parkinson's disease, Alzheimer's disease, and Huntington's disease. Such defects in respiratory complex activities, possibly associated with oxidant/antioxidant balance perturbation, are thought to underlie defects in energy metabolism and induce cellular degeneration. Efficient functioning of maintenance and repair process seems to be crucial for both survival and physical quality of life. This is accomplished by a complex network of the so-called longevity assurance processes, which are composed of genes termed vitagenes. A promising approach for the identification of critical gerontogenic processes is represented by the hormesis-like positive effect of stress. In the present review, we discuss the role of energy thresholds in brain mitochondria and their implications in neurodegeneration. We then review the evidence for the role of oxidative stress in modulating the effects of mitochondrial DNA mutations on brain age-related disorders and also discuss new approaches for investigating the mechanisms of lifetime survival and longevity.

Aging↗

The effects of clozapine and high-dose olanzapine on brain function in treatment-resistant schizophrenia: a case study.

Although demonstrating superior efficacy in people with treatment-resistant schizophrenia, clozapine may cause serious side effects, requires blood monitoring and is costly to administer. Olanzapine is similar to clozapine in molecular structure and pharmacologic action but has not demonstrated as robust results as clozapine at routine doses (10-25 mg). Here we present a case study measuring blood flow by positron emission tomography (PET) imaging for a patient treated sequentially with a high dose of olanzapine (50 mg/day) followed by clozapine each for 8 weeks in a double-blind design. During a task, clozapine produced more brain activation patterns than during treatment with olanzapine or during the drug free condition (2 week washout). Clozapine resulted in recruitment of frontal, parietal and cingulate regions that did not appear to be active during olanzapine in this 44 year old right handed male. Additionally, a more robust decrease in symptoms was noted on the Brief Psychiatric Rating Scale (BPRS) score than with olanzapine treatment. These findings suggest that high doses of olanzapine do not produce similar brain activation patterns as clozapine in people with treatment-resistant schizophrenia.

Adult↗

Histopathological alterations and functional brain deficits after transient hypoxia in the newborn rat pup: a long term follow-up.

To assess temporal brain deficits consecutive to severe birth hypoxia, newborn rats were exposed for 20 min to 100% N2. This treatment induced a long-term growth retardation and a delayed, but only transient, neuronal loss (approximately 25%) in the CA1 hippocampus and parietal cortex, starting from 3 days and peaking at 6 days post-hypoxia. The expression profiles of various apoptosis-regulating proteins (including Bcl-2, Bax, p53 and caspase-3) were well correlated to the alterations of nuclear morphology depicted by 4,6-diamidino-2-phenylindole (DAPI). Whereas they confirmed a gradual histological recovery, specific DNA fragmentation patterns suggested that birth hypoxia may transiently reactivate the developmental programme of neuronal elimination. Although they successfully achieved various behavioral tests such as the righting reflex, negative geotaxis, locomotor coordination, and the eight-arm maze tasks, both developing and adult hypoxic rats were repeatedly slower than controls, suggesting that birth hypoxia is associated to moderate but persistent impairments of functional capacities.

Animals↗

[An expert system based on the principle of brain functional asymmetry].

The generalized concept is proposed for automation of secondary data processing. Initial information is stored in the knowledge base. During processing the verbal description is generated for each object. All further operations are reduced to the transformation of the textual data. This approach makes it possible to accumulate information of diverse types and efficiently analyze it according to the universal scheme.

Brain↗

Regional brain function in hallucinations: a study of regional cerebral blood flow with 99m-Tc-HMPAO-SPECT in patients with auditory hallucinations, tactile hallucinations, and normal controls.

From the supposition that there exists a possible connection between certain psychopathological symptoms, and/or syndromes (e.g., hallucinations) and regional cerebral dysfunction, patients suffering from auditory and tactile hallucinations were investigated, in a symptom-oriented study, using the method of technetium-99m-Hexamethyl-propylenamine Oxime (99m-Tc-HMPAO)-Single Photon Emission Computed Tomography (SPECT) and compared with normal controls. The results support Jackson's hypothesis to the effect that hallucinatory phenomena will primarily occur when the normally inhibitive influence of the upper cortical centers over the lower brain structures diminishes, resulting in relative hyperactivity in the basal regions. In addition to the brain activity-changes generally observed in hallucinating patients, it was possible to identify regional cerebral blood flow (rCBF)-distribution patterns characteristic in certain forms of hallucinatory phenomena, i.e., a significant increase of activity in the hippocampal regions (including hippocampus, parahippocampus, and amygdala) only in patients with auditory hallucinations, and a significant reduction of rCBF in the inferior temporal regions in patients with tactile hallucinations.

Adult↗

Cognitive consonance: complex brain functions in the fruit fly and its relatives.

The fruit fly, Drosophila melanogaster, has become a model for the study of a growing number of human characteristics because of the power of its genetics. Higher cognitive functions, however, might be assumed to be out of reach for the little fly. But the cumulative history of cognitive studies in insects and some of their arachnid relatives, as well as specific probing of the capabilities of fruit flies, suggests that even in this ethereal realm these creatures have much to contribute. What are the degrees of sophistication in cognitive behavior displayed by these organisms, how have they been demonstrated, and what is their potential for understanding how our own brains work?

Animals↗

Noise-free magnetoencephalography recordings of brain function.

Perhaps the greatest impediment to acquiring high-quality magnetoencephalography (MEG) recordings is the ubiquitous ambient magnetic field noise. We have designed and built a whole-head MEG system using a helmet-like superconducting imaging surface (SIS) surrounding the array of superconducting quantum interference device (SQUID) magnetometers used to measure the MEG signal. We previously demonstrated that the SIS passively shields the SQUID array from ambient magnetic field noise, independent of frequency, by 25-60 dB depending on sensor location. SQUID 'reference sensors' located on the outside of the SIS helmet measure ambient magnetic fields in very close proximity to the MEG magnetometers while being nearly perfectly shielded from all sources in the brain. The fact that the reference sensors measure no brain signal yet are located in close proximity to the MEG sensors enables very accurate estimation and subtraction of the ambient field noise contribution to the MEG sensors using an adaptive algorithm. We have demonstrated total ambient noise reduction factors in excess of 10(6) (> 120 dB). The residual noise for most MEG SQUID channels is at or near the intrinsic SQUID noise floor, typically 2-3 fT Hz-1/2. We are recording MEG signals with greater signal-to-noise than equivalent EEG measurements.

Artifacts↗

[Interactions between the epileptic network and brain function: an approach by nonlinear analysis of intracranial EEG].

Recent advances in the non-linear dynamics analysis have made it possible to identify hidden recurrences in EEG signals that could be missed by more traditional linear techniques such as power spectrum or coherence analysis. This is particularly true for epileptic EEG recordings either in animals or in humans as epileptic phenomena are usually concomitant with the emergence a strong non-linear EEG behavior. Non-linear dynamical analysis techniques quantify the relations between EEG signals. The literature concerning the spatio-temporal characteristics of the epileptic processes during seizures and interictal periods is reviewed. Our attention has been mainly focused on the interdependences between brain structures or on the dynamical changes of one particular brain region during intracranial recordings. These data could explain in part the dysfunctioning of the cerebral cortex induced by epileptic activities and provide an insight into the spatio-temporal organization of the epileptic network. Futhermore, by tracking the time variation of non-linear indices, one can anticipate the occurrence of seizures in temporal lobe epilepsies. All this information could contribute to improve definitions of the epileptogenic zone in partial epilepsy and also open the way to preventive interventions.

Brain↗

Task-independent functional brain activity correlation with skin conductance changes: an fMRI study.

Lesions of the ventromedial prefrontal cortex cause a loss of skin conductance response (SCR) to stimuli with affective content and an inability to integrate information with social consequences into decisions. Previous behavioral studies using a gambling task were able to differentiate patients with lesions in this region from normal subjects. In the present imaging study, this region, among others, was shown to be "spontaneously" activated during three different cognitive states: a gambling task, a working memory task, and resting state. SCR data were simultaneously collected during the scanning process. Six subjects were scanned at 1.5 T during all three states, and one subject was scanned at 3 T during the resting state only. SCR data were used as a reference function for correlation analysis with the fMRI time series during each of the three tasks. SCR changes were evident during the gambling and two-back tasks as well as during rest. SCR activity was not observed to be specifically related to reward-based decisions in the gambling task. Correlation of the fMRI time series directly with the SCR data revealed a consistent set of activated regions. The activity of these regions showing correlation with the SCR appeared independent of the cognitive state. Further, the subject scanned only at rest (without the possible confound of task-related carryover activity) replicated the findings in the original six subjects. From these data, SCR appears to be a marker of a network that is active during, but independent of, the task being studied.

Adult↗

Functional brain organization, handedness, and immune vulnerability in musicians and non-musicians.

In the current investigation an approach has been made to explore possible relations between musical talent, left-handedness, anomalous dominance for verbal materials, and immune vulnerability. Fifty-one young adult musicians and non-musicians were tested with Wing's Standardized Tests of Musical Intelligence, with a handedness questionnaire, a dichotic listening task, and with a questionnaire assessing asthma/allergies, migraine and myopia. In addition, IgE, Ig total, beta-endorphin, testosterone, and estradiol were measured in blood serum. Musical talent was related to left-handedness and to anomalous dominance; immune vulnerability was found in female musicians, and in subjects with reversed dominance for language functions as well as in male left-handers, independently of musical talent.

Adolescent↗

Innovations in the imaging of brain functions using fluorescent proteins.

Fluorescence imaging has enabled us to decipher spatiotemporal information coded in complex tissues. Genetically encoded probes that enable fluorescence imaging of excitable cell activity have been constructed by fusing fluorescent proteins to functional proteins that are involved in physiological signaling. The probes are introduced into an intact organism and targeted to specific tissues, cell types, or subcellular compartments, thereby allowing specific signals to be extracted more efficiently than was previously possible. In this primer, I will describe how this approach has met neuroscientists' demands and desires.

Animals↗

Effects of hyperammonaemia on brain function.

Neuropsychiatric symptoms of hyperammonaemia include alterations of mood and personality, cognitive impairment, ataxia, convulsions and coma. The nature and severity of CNS dysfunction depend upon the aetiology and degree of hyperammonaemia, its acuteness of onset and the age of the patient. Neuropathological studies reveal Alzheimer type II astrocytosis in the adult hyperammonaemic patient, whereas hyperammonaemia in the infant resulting from congenital urea cycle disorders or Reye syndrome is accompanied by cerebral atrophy, neuronal loss and cerebral oedema. Several electrophysiological and biochemical mechanisms have been proposed to explain the deleterious effects of ammonia on CNS function. Such mechanisms include direct effects of the ammonium ion on excitatory and inhibitory neurotransmission and a deficit in cerebral energy metabolism due to ammonia-induced inhibition of alpha-ketoglutarate dehydrogenase. In addition, ammonia has been shown to interfere with normal processes of uptake, storage and release of various neurotransmitters. Ammonia disrupts monoamine storage, inhibits the high-affinity uptake of glutamate by both astrocytic and neuronal elements and activates 'peripheral-type' benzodiazepine receptors leading to the potential synthesis of neuroactive steroids in brain. On the basis of these actions, it has been proposed that ammonia disrupts neuron-astrocyte trafficking of amino acids and monoamines in brain. The increased formation of brain glutamine in hyperammonaemic syndromes could be responsible for the phenomenon of brain oedema in these disorders. Therapies aimed at either decreasing ammonia production in the gastrointestinal tract or increasing ammonia removal by liver or skeletal muscle are the mainstay in the prevention and treatment of the CNS consequences of hyperammonaemia. New therapeutic approaches aimed at correction of the neurotransmitter and cerebral energy deficits in these syndromes could hold promise for the future.

Ammonia↗

Assessment of general movements: towards a better understanding of a sensitive method to evaluate brain function in young infants.

The consistent presence of an abnormal quality of general movements (GMs) during the first postnatal months points to a high risk for the development of a neurological disability. To elucidate the significance of abnormal GMs during a single assessment, a classification system for abnormal GMs was developed. To this end six term and ten preterm infants with abnormal GMs were studied longitudinally with video and electromyographic (EMG) recordings till 59 weeks postmenstrual age (PMA). Two basic categories of abnormal GMs were distinguished: (1) mildly abnormal GMs (two types), which lacked fluency while conserving pattern complexity, and (2) definitely abnormal GMs (four types), which lacked fluency and complexity altogether. GM type before 39 weeks PMA correlated with findings on neonatal ultrasound brain scans. GM quality after 47 weeks PMA was strongly related to neurodevelopmental outcome at 1 1/2 years of age, suggesting that the absence of the age-specific 'fidgety' character of GMs could be a herald of disability.

Brain↗

Effect of irradiation at the early fetal stage on adult brain function in the mouse: locomotor activity.

PURPOSE: To study long-term changes in the adult locomotor activity of mice after exposure to gamma radiation at the early fetal stage of development. MATERIALS AND METHODS: Pregnant Swiss albino mice were exposed locally on the abdominal area to a single dose of 0.25-1.5 Gy of 60Co gamma radiation at the dose rate of 1 Gy/min. When the F1 offspring were 6 months old, their locomotor and exploratory behaviour was assessed by the open-field and dark/bright arena tests. Animals were again subjected to the dark/bright arena test at 12 and 18 months of age in order to study the persistence of the effects. RESULTS: Irradiation produced a noticeable disturbance in the normal behaviour pattern of the mice. There was a significant dose-dependent decrease in the open-field activity of 6-month-old mice. In the dark/bright arena test, the time spent and lines crossed in the dark area showed a significant decrease, while their activities in the brightly lit area increased significantly, indicating a reduced aversion to bright light. These effects were evident even at a dose of 0.3 Gy and increased linearly with dose. The significant behavioural changes persisted at 12 months, but at 18 months the difference in the time spent and lines crossed in the dark and bright areas were not significantly different from sham-irradiated control values below 0.5 Gy. CONCLUSIONS: These results show that day 14 of gestation in Swiss albino mice is a time of high risk for inducing long-term changes in the adult locomotor function by gamma-radiation doses below 1 Gy. Using a range of radiation doses and different observation times we have demonstrated that the effect increases linearly with dose, but there appears to be a threshold of 0.3-0.5 Gy for producing significant persistent changes in the adult ambulatory activity.

Age Factors↗