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PubMed2004

Functional brain mapping of extraversion and neuroticism: learning from individual differences in emotion processing.

This review outlines how functional brain imaging, using an individual-differences approach in the processing of emotional stimuli, has begun to reveal the neural basis of extraversion (E) and neuroticism (N), two traits that are linked to both emotion and health. Studies using functional magnetic resonance imaging have shown that individual differences in participants' E and N scores are correlated with individual differences in brain activation in specific brain regions that are engaged during cognitive-affective tasks. Imaging studies using genotyped participants have begun to address the molecular mechanisms that may underlie these individual differences. The multidisciplinary integration of brain imaging and molecular genetic methods offers an exciting and novel approach for investigators who seek to uncover the biological mechanisms by which personality and health are interrelated.

Amygdala↗

PubMed2006

Brain function in obstructive sleep apnea: results from the Brain Resource International Database.

Obstructive sleep apnea (OSA) is expected to impair vigilance and executive functioning, owing to the sensitivity of the prefrontal cortex to the effects of sleep fragmentation and intermittent hypoxia. Studies examining the pattern of cognitive dysfunction show variable results, with the heterogeneity in part due to small sample sizes in current studies and little consistency of the tests used. We examined a group of fifty subjects from the Brain Resource International Database (BRID), predicted to have OSA on the basis of the Multivariable Apnea Prediction Index, and compared them with 200 matched controls. On electrophysiological tests, the OSA group showed reduced eyes closed alpha power, increased auditory oddball N100 and P200 amplitude, but reduced N200 and P300 amplitude. The latency to P300 was not significantly different between groups, but latencies to N200 and P200 were prolonged in the OSA group. Performance testing of the executive function found that verbal interference and the switching of attention were impaired in the OSA group. We have demonstrated that a diagnostic algorithm based on apnea symptoms and demographic factors can be used to select a group with likely OSA manifesting deficits in information processing and executive function.

Acoustic Stimulation↗

PubMed1998

Reduced prefrontal and increased subcortical brain functioning assessed using positron emission tomography in predatory and affective murderers.

There appear to be no brain imaging studies investigating which brain mechanisms subserve affective, impulsive violence versus planned, predatory violence. It was hypothesized that affectively violent offenders would have lower prefrontal activity, higher subcortical activity, and reduced prefrontal/subcortical ratios relative to controls, while predatory violent offenders would show relatively normal brain functioning. Glucose metabolism was assessed using positron emission tomography in 41 comparisons, 15 predatory murderers, and nine affective murderers in left and right hemisphere prefrontal (medial and lateral) and subcortical (amygdala, midbrain, hippocampus, and thalamus) regions. Affective murderers relative to comparisons had lower left and right prefrontal functioning, higher right hemisphere subcortical functioning, and lower right hemisphere prefrontal/subcortical ratios. In contrast, predatory murderers had prefrontal functioning that was more equivalent to comparisons, while also having excessively high right subcortical activity. Results support the hypothesis that emotional, unplanned impulsive murderers are less able to regulate and control aggressive impulses generated from subcortical structures due to deficient prefrontal regulation. It is hypothesized that excessive subcortical activity predisposes to aggressive behaviour, but that while predatory murderers have sufficiently good prefrontal functioning to regulate these aggressive impulses, the affective murderers lack such prefrontal control over emotion regulation.

Affect↗

PubMed2004

Repeated intracerebral microinjections: efficacy in studying brain functions.

Injection of chemicals into the brain has been considered as an important technique to study various functions of the brain. In these studies, as a rule, only one bilateral injection is given in one animal. This study was undertaken to evaluate the quality of the body temperature data obtained after first and second injections of methoxamine and artificial cerebrospinal fluid into the medial preoptic area. Though there was quantitative decrease in the effects produced after the second injection of the drug, there was no significant change in the effects produced by the second injections of artificial cerebrospinal fluid, which was used as a vehicle. Results of this study support the earlier recommendation to perform only one injection in any of the brain sites for evaluating the effect of any drug. But the vehicle can be administered as a second injection, without compromising on the quality of data.

Animals↗

PubMed2006

Optical monitoring of brain function in vivo: from neurons to networks.

The precise understanding of the cellular and molecular basis of brain function requires the direct assessment of the activity of defined cells in vivo. A promising approach for such analyses is two-photon microscopy in combination with appropriate cell labeling techniques. Here, we review the multi-cell bolus loading (MCBL) method that involves the use of membrane-permeant fluorescent indicator dyes. We show that this approach is useful for the functional analysis of clusters of neurons and glial cells in vivo. Work from our and other laboratories shows that the techniques that were previously feasible only in brain slices, like targeted patch clamp recordings from identified cells or pharmacological manipulations in confined brain regions, can now be used also in vivo. We also show that MCBL and two-photon imaging can be easily combined with other labeling techniques, particularly with those involving the use of genetically encoded, green-fluorescent-protein-based indicators. Finally, we examine recent applications of MCBL/two-photon imaging for the analysis of various brain regions, including the somatosensory and the visual cortex.

Action Potentials↗

PubMedDate not supplied

[Evaluation of the higher brain functions in 1st and 7th grade schoolchildren belonging to two different socioeconomic groups].

INTRODUCTION: The higher brain functions, together with the devices that sustain them, are essential assets belonging to human beings which are used to situate themselves in the world. They can be studied by conducting neuropsychological tests, the results of which vary according to demographic factors, such as age, sex, hand dominance, culture and level of schooling. The socioeconomic level (SEL) is another factor to be taken into account and must also be evaluated. AIMS: Our objective was to evaluate and analyse the influence of SEL on the results obtained from neuropsychological tests carried out in normal school-age children. SUBJECTS AND METHODS: We studied 401 normal children, of both sexes, taken at random, at the beginning (1st grade, 6 years old) and at the end (7th grade, 12 years old) of elementary school and belonging to two different SEL: high and low. Schools belonging to different categories were selected: public, private, urban and suburban. A battery of tests that is commonly used in Neuropsychology was utilised to evaluate laterality, spatial orientation, integration (Bender's test and the Rey figure test), attention, memory and the areas of language, gnosis and praxis. RESULTS: Significant differences were found in relation to the SEL in the 1st and 7th grade tests: 20/27 (74%) and 17/27 (62%), respectively. These always meant lower results in the low SEL, except body scheme, ideomotor praxis and phonological coding, which in the 7th grade run in the opposite direction. Results were not related to the type of school (urban-suburban, public-private), sex, laterality or teachers' characteristics. Differences were more striking in the area of language, basic devices (attention, memory) and in the tests that integrate several different functions (Bender's test, Rey figure test). CONCLUSIONS: SEL is linked to the results obtained in neuropsychological evaluation tests. There is a direct relationship with low results in the low level. There is also a correlation between certain family characteristics associated to the SEL and the scores in the cognitive evaluation tests.

Adolescent↗

PubMed2003

How accurate is magnetic resonance imaging of brain function?

Since it was introduced a decade ago, functional magnetic resonance imaging (fMRI) has come to dominate research on the human brain. However, fMRI maps are based on secondary metabolic and hemodynamic events that follow neuronal activity, and not on the electrical activity itself. Therefore, the representation provided by fMRI cannot be assumed a priori to be exact. The accuracy of these maps depends on the spatial extent of the metabolic and hemodynamic changes induced by neuronal activity, and the role played by the vasculature in converting these changes to signals detected by magnetic resonance imaging. Significant progress has been made in both areas, suggesting that it is possible to obtain both spatially accurate and quantitative data on brain function from magnetic resonance methodologies.

Brain↗

PubMed2004

Brain function and structure in adults with attention-deficit/hyperactivity disorder.

Cross-sectional data suggest that brain dysfunctions are a central component of attention-deficit/hyperactivity disorder (ADHD) in children, and a growing literature is suggesting the same for adults. This article reviews the current state of the literature pertaining to the structural and functional brain abnormalities that are found in adults with ADHD. Because the literature on ADHD in children is more extensive than that reported heretofore in ADHD in adults,the authors include brief summaries of the child literature to help inform that found in adults.

Adolescent↗

PubMed1985

Biochemical and neuropsychological effects of elevated plasma phenylalanine in patients with treated phenylketonuria. A model for the study of phenylalanine and brain function in man.

Phenylketonuria provides a human model for the study of the effect of phenylalanine on brain function. Although irreversible mental retardation is preventable through newborn diagnosis and dietary phenylalanine restriction, controversy exists regarding the effects of increased concentrations of phenylalanine in older patients. We have studied ten older, treated, phenylketonuric patients using a triple-blind, multiple trials, crossover design. Each patient was tested at the end of each of three 1-wk periods of high or low phenylalanine intakes. Tests included a repeatable battery of neuropsychological tests, analysis of plasma amino acids, and measurement of urine amino acids, phenyl organic acids, dopamine, and serotonin. In all 10 patients plasma phenylalanine rose (900-4,000 microM). In 9 of 10 patients there was an inverse relationship between plasma phenylalanine and urine dopamine excretion. When blood phenylalanine was elevated, these patients had prolonged performance times on neuropsychological tests of higher but not lower integrative function. Urinary serotonin fell during phenylalanine loading in six patients. The concentration of phenylacids in the urine was not proportional to the plasma phenylalanine at concentrations below 1.5 mM. In one patient, neither performance time nor dopamine excretion varied as blood phenylalanine rose or fell. We interpret these data as follows: blood phenylalanine above 1.3 mM impairs performance on neuropsychological tests of higher integrative function, this effect is reversible, and one mechanism may involve impaired biogenic amine synthesis.

Adolescent↗

PubMed2006

Continuous brain-function monitoring: state of the art in clinical practice.

Continuous electroencephalographic (EEG) monitoring gives direct information on brain function in newborn infants needing intensive care. To improve the possibilities of long-term monitoring, the EEG is time-compressed and recorded with a reduced number of electrodes. A trend measure of the EEG, the amplitude-integrated EEG (aEEG), has proved capable of giving relevant information in newborn infants of differing levels of maturity. The electrocortical background activity gives information on the level of brain activity, which is associated with outcome in both term asphyxiated infants and in preterm infants. However, the background activity is also affected by several medications, and this must be considered when interpreting the aEEG trace. The aEEG also reveals subclinical epileptic seizure activity, and can be used for evaluation of anti-epileptic treatment. The aEEG should be used as a complement to the standard EEG, and close collaboration between neonatologists and clinical neurophysiologists is necessary for optimal performance of EEG monitoring.

Brain↗

PubMed1986

Role of the supraoptic decussation in the development of asymmetry of brain function in the chicken.

The supraoptic decussation plays an important role in the development of asymmetry of brain function for visual discrimination learning in the chicken. Lesioning the decussation on day 2 has no effect on the asymmetry normally revealed by unilaterally treating either the left or right forebrain hemisphere with cycloheximide on day 4 of life. However, the lesion removes the asymmetry revealed by cycloheximide treatment on day 8 and reverses that revealed by treatment on day 10, albeit to a lesser extent. The asymmetry of learning performance between the left and right eyes present in untreated chickens tested monocularly in the second week of life is also removed by lesioning the supraoptic decussation. Thus, in the first week of life functional asymmetry is present but not dependent on left-to-right side coupling via the supraoptic decussation. The difference between lesioning during the first and second week of life may relate to the relative degree of maturation in the supraoptic decussation.

Age Factors↗

PubMed1990

Improvement of brain function in hemodialysis patients treated with erythropoietin.

To evaluate the effects of recombinant human erythropoietin (rHuEPO) on brain function, 15 chronic hemodialysis patients were studied by event-related P300, stimulus-related evoked potentials, and trailmaking before (hematocrit 22.7%) and after rHuEPO (hematocrit 30.6%). P300 peak latency elicited by a tone discrimination paradigm improved (391 before vs. 366 ms after; Cz = vertex; P less than 0.01) confirming beneficial effects on cerebral cognitive processing. P300 amplitude (13.6 vs. 15.8 microV; P = 0.06) and trailmaking tended to improve (55 vs. 43 s). P300 measures were influenced by low hemoglobin levels before rHuEPO (P less than 0.01), suggesting that severe anemia may contribute to uremic brain dysfunction. Furthermore, decrease of stimulus-related auditory brainstem I-V interpeak latency (4.28 before vs. 4.17 ms after; P less than 0.05) and increase of somatosensory N20/P25 amplitude (4.8 vs. 7.0 microV; P less than 0.05) pointed to improvement of sensory pathways by mechanisms unrelated to cognition. Brain dysfunction in chronic hemodialysis patients may, beside other factors, in part be caused by severe anemia and can be improved by rHuEPO treatment.

Anemia↗

PubMed2005

[Localisation of brain function, 125 years after the thesis of Aletta Jacobs, the first Dutch female physician].

Aletta H. Jacobs was the first female physician in the Netherlands. In 1879, she defended her thesis which addressed the subject of localising brain functions. In it she described three neurological patients using systematic conventions highly resembling those in use today. Moreover, she discussed whether or not functions were regionally represented. Her discussion concluded in favour of localisation. These days, the concept of distributed networks goes beyond simple topographical representation. This is illustrated in the cerebral organisation of vision. It is possible to discern visual centres that are specialised in processing specific qualities such as colour or visual motion. An additional feature of such segregated processing streams is the presence of underlying connections to specific brain areas at a distance. Functioning as a node in multiple networks, one single brain region may potentially be involved in multiple functions. This depends on the interactions with other regions and on the actual dominance of information processing within such networks.

Brain↗

PubMed1999

The role of neural activity in synaptic development and its implications for adult brain function.

In much of the developing nervous system, electrical activity guides the formation of neural connections, with lasting effects on adult brain function. Epilepsy, a defect in neuronal excitability, might result from abnormal patterns of activity in the young brain. Many connections are organized by selective stabilization of synapses when they are activated simultaneously on the same postsynaptic cell during a sensitive period in early life. This process often involves calcium entry through the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. The magnitude of the current passed by this receptor depends on its subunit composition, which varies with age and brain region. Although receptor configurations that admit large calcium currents are permissive of synaptic plasticity, they also increase neural vulnerability to excitotoxic cell death. In most regions of developing brain, activity that can drive NMDA receptors initially is low and increases with maturation. Thus, the replacement of NMDA receptors that flux large calcium currents during early periods of synaptic organization with NMDA receptor subtypes that flux less calcium as synapses become more active, more effective, and less plastic allows maturing neurons to maintain optimal levels of intracellular calcium in the face of drastic developmental changes in their inputs. We have proposed that this transition in NMDA receptors from high to low calcium permeabilities is itself activity dependent. This idea is supported by data showing that many synaptic proteins, including receptor subunits, can be regulated by activity. Cultured cerebellar granule neurons require NMDA receptor stimulation for survival and differentiation, which may replicate the activation provided by the arrival of mossy fiber innervation in vivo. In these cultures, chronic depolarization and glutamate or NMDA treatment induces more mature NMDA receptor subunit expression patterns and function and also increases the expression of several gamma-aminobutyric acid type A (GABAA) receptor subunits, changing that receptor's function. In addition, evidence from in vivo studies indicates that synaptic maturation itself may depend on NMDA receptor activity. During the formation of topographic connections between the retina and superior colliculus (SC) of young rats, chronic local application of the competitive NMDA receptor antagonist +2-amino-5-phosphonovalerate (D-APV) blocks the normal developmental up-regulation of NMDA receptor subunit 1 (NR1) mRNA and nitric oxide synthase activity, as well as maturation of calcium and calmodulin-dependent kinase distribution, activity, and substrate phosphorylation. Together, these recent molecular findings suggest that chronic seizure disorders could result from any of a variety of early developmental events. Any disturbance that locally perturbs regulation of NMDA receptors or the temporal correlations in synaptic activity that drive these receptors has the potential to alter the normal development of local circuitry and the critical balance of inhibition and excitation required to contain seizure activity.

Aging↗

PubMed1999

Neural modeling, functional brain imaging, and cognition.

The richness and complexity of data sets acquired from PET or fMRI studies of human cognition have not been exploited until recently by computational neural-modeling methods. In this article, two neural-modeling approaches for use with functional brain imaging data are described. One, which uses structural equation modeling, estimates the functional strengths of the anatomical connections between various brain regions during specific cognitive tasks. The second employs large-scale neural modeling to relate functional neuroimaging signals in multiple, interconnected brain regions to the underlying neurobiological time-varying activities in each region. Delayed match-to-sample (visual working memory for form) tasks are used to illustrate these models.

Journal Article↗

PubMed2006

Impact of complex genetic variation in COMT on human brain function.

Catechol-O-methyltransferase (COMT) has been shown to be critical for prefrontal dopamine flux, prefrontal cortex-dependent cognition and activation. Several potentially functional variants in the gene have been identified, but considerable controversy exists regarding the contribution of individual alleles and haplotypes to risk for schizophrenia, partly because clinical phenotypes are ill-defined and preclinical studies are limited by lack of adequate models. Here, we propose a neuroimaging approach to overcome these limitations by characterizing the functional impact of ambiguous haplotypes on a neural system-level intermediate phenotype in humans. Studying 126 healthy control subjects during a working-memory paradigm, we find that a previously described risk variant in a functional Val158Met (rs4680) polymorphism interacts with a P2 promoter region SNP (rs2097603) and an SNP in the 3' region (rs165599) in predicting inefficient prefrontal working memory response. We report evidence that the nonlinear response of prefrontal neurons to dopaminergic stimulation is a neural mechanism underlying these nonadditive genetic effects. This work provides an in vivo approach to functional validation in brain of the biological impact of complex genetic variations within a gene that may be critical for its clinical association.

Adult↗

PubMed2001

[Long-term correction of brain function. Prospects of immunologic approaches].

Among various approaches to long-term correction of the highest functions of the brain there are two methods that are particularly promising. These included: 1) induction of autoantibodies against the enzymes involved in the metabolism of neuroregulators by means of immunization of respective heterologous enzymes; 2) immunization by covalent conjugates of monomolecular neurotropic compounds and neuropeptides with antigen carriers. The investigations of both methods are reviewed and illustrated in experiments on albino rats during alcoholization and some other processes of pathological behavior formation. Evidence is provided for that behavior can be corrected for several months or longer.

Alcoholism↗

PubMedDate not supplied

[New approaches in correcting disorders of higher integrative brain functions in the pharmacotherapy of arterial hypertension with propranolol].

In experiments on rats it is found that propranolol in a dose of 2 mg/kg has a negative effect on higher integrative functions of the brain. Nootropics--pyracetam (200 mg/kg), AKF-94 (20 mg/kg), PIR-87-6-O (50 mg/kg) and actoprotector bemityl (40 mg/kg)--normalized orientative-trying behavior, memory, and emotionality of the animals. A possible mechanism of the drug action and prospects of their clinical application are discussed.

Animals↗