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[Modeling different regimes of bioelectrical activity in the brain in normal subjects and in "increased readiness" in a network of neuron-like elements].

Desynchronous (low voltage fast activity), synchronous (high voltage slow waves) as well as convulsive brain activities were stimulated by a computer model of neuronal population. Network excitatory and inhibitory elements possessed fundamental dynamic properties of real neurones. Being independent both of the excitability of elements and of external influence efficacy, synchronous (desynchronous) network activity resulted from the increase (decrease) of the average power of "neuronal" interconnections which imitated mutual and recurrent excitation and inhibition. The inhibition efficacy being reduced as compared with excitation, synchronization of elements became intensified. As a consequence, the rhythmic activity amplitude increased and the appearance of self-sustained oscillations simulating convulsive activity was facilitated. The probable mechanism of EEG activation by virtue of the reduction of mutual and recurrent excitation and inhibition efficacy as well as the significance of inhibitory mechanism deficiency for epileptogenesis are discussed.

Brain↗

Source analysis of polyspike and wave complexes in juvenile myoclonic epilepsy.

We applied dipole modeling and brain distributed source analysis to find current sources comprising spikes and slow waves of polyspike and wave complexes (PSWC) in patients with juvenile myoclonic epilepsy (JME). The dipoles were localized in frontal, parietal and temporal lobes. The frontal dipoles were clustered in the frontal medial gyrus and fronto-orbital region. A midsagittal frontal current source was observed using brain distributed source analysis in all patients. When the slow wave was analyzed, multiple sources in different cortical regions were detected using dipole modeling and brain distributed analysis. These results show pre-frontal medial current sources corresponding to spikes and many diffuse sources in cortical regions corresponding to wave components of PSWC in patients with JME.

Adolescent↗

Nicotine and smoker status moderate brain electric and mood activation induced by ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist.

As the increased smoking prevalence in schizophrenics may be interpreted as an adaptive response to an underlying biological defect, investigations into nicotine's actions within N-methyl-d-aspartate (NMDA) antagonist drug models of schizophrenia may improve our understanding of the role of glutamatergic neurotransmission in initiating and maintaining nicotine dependence in this disorder. In this double-blind, placebo-controlled, randomized study, the electroencephalographic (EEG) and subjective response to a sub-psychotomimetic intravenous dose of the NMDA antagonist ketamine was examined in 20 regular smokers and 20 non-smokers pretreated with placebo or nicotine gum. Although nicotine increased EEG arousal, ketamine produced electrocerebral signs of brain activation (decreased slow wave power) and sedation (decreased fast wave power and frequency), which were not affected by nicotine pretreatment and were evident only in non-smokers. Ketamine increased a number of self-report indices of subjective arousal, some of which were attenuated and potentiated by nicotine in smokers and non-smokers, respectively. These findings suggest that long-term (evidenced by smoker vs. non-smoker comparisons) and short-term (acute) nicotine exposure may alter NMDA receptor-mediated arousal and mood systems in a way that promotes nicotine dependence in smokers, and addresses neurobiological deficiencies in smokers with schizophrenia.

Adult↗

Is migraine explained by Leao's spreading depression?

Spreading depression (SD) is a severe but transient disruption of neural activity in the brain, which spreads like waves in a pond in which a stone has been cast. It propagates to normal tissues and is accompanied by flux of Na+, Ca++, and Cl- ions into the cells, resulting in a brief burst of action potentials followed by electrical silence. Its rate of spread correlates almost exactly with the observed spread of the aura of classical migraine. It is accompanied in animal experiments by changes in regional cerebral blood flow which closely simulate changes observed in man during the migraine aura. There are serious difficulties in extrapolating from SD in animals to migraine in man, but the possibility of SD as the initiating event accords with the notion of migraine as a cerebral (neural) disorder and encourages further investigation in man.

Brain↗

Patterning of chick brain vesicles as revealed by peanut agglutinin and cholinesterases.

Differentiation of individual rhombomeres of the chicken hindbrain directly follows the emergence of primary brain vesicles. Immediately after the constriction of the prosencephalon at HH9, a series of vesicles of decreasing size is established almost simultaneously between HH9 and HH10, including mesencephalon, four preotic (R2-R5) and one postotic (R6/R7) rhombomeres. Thereby, the cranial neural tube is ventrally embedded in a mesodermal PNA-binding matrix that particularly accumulates underneath vesicular constriction sites, as demonstrated for the segregation of the prosencephalon at HH9 and the cerebellar rhombomere R1 from R2 at HH13. The subsequent period of hindbrain differentiation is analyzed by cholinesterase (AChE, BChE) and peanut lectin histochemistry, by the BrdU and the neurite-specific G4 antibodies. Preotically, differentiation of two pairs of rhombomeres (R4 + R5, R2 + R3) starts in R4, immediately followed by R2. The caudal rhombomeres of both pairs are delayed (R5, R3). Then the postotic rhombomere is subdivided, whereby R7 differentiates before R6. Thus, the development in the direct vicinity of the otic vesicle is delayed (R5, R6). R7 is the last rhombomere that is demarcated caudally. Based on these findings, we postulate two processes that may regulate rhombomere formation in the chicken embryo: (a) an early rostrocaudal wave establishing the major brain vesicles, (b) a superimposed pairwise segmentation emanating rostrally and caudally from the otic vesicle. The segregation of the cerebellar rhombomere is a late step.

Animals↗

Brain stem response audiometry at speech frequencies.

Auditory-evoked brain stem response (BSR; wave V) was studied, using tone pips at three speech frequencies (500, 1 000 and 2 000 Hz) as stimuli. The tone pips consisted of 5-ms rise-decay times without a plateau. BSR recordings were made in 10 normal subjects and in 16 subjects with impaired hearing. In the normal subjects, BSR thresholds ranged from 10 to 20 dB SL at these three frequencies. In the subjects with impaired hearing, BSR thresholds corresponded well to conventional pure-tone thresholds at each frequency in cases of low- as well as high-frequency hearing loss. In all subjects with impaired hearing, the BSR thresholds were higher by as much as 25 dB than the pure-tone thresholds. The mean differences between these two thresholds at 500, 1 000 and 2 000 Hz were 11.3 +/- 8.0, 10.9 +/- 6.2 and 10.9 +/- 7.3 dB, respectively. Thus, we conclude that the BSR is useful for objective assessment of hearing thresholds at each of these speech frequencies.

Acoustic Stimulation↗

Detection of impaired cerebral autoregulation using spectral analysis of intracranial pressure waves.

Successful resuscitation following severe traumatic brain injury (TBI) requires rapid evaluation of intracranial pressure (ICP), cerebrovascular reactivity (autoregulation), and cerebral metabolism. During impaired autoregulation, inadequate cerebral blood flow (CBF) can lead to ischemia while excessive CBF can result in elevated ICP. Without information regarding the state of autoregulation, treatment of either situation may ameliorate one problem but exacerbate the other. It has been hypothesized that fast Fourier transform (FFT) analysis of arterial blood pressure (BP) and ICP waves can differentiate states of intact and impaired autoregulation. BP and ICP waves were recorded in canines before and after ischemic injury during arterial normotension, hypertension, and hypotension induced with dopamine or nitroprusside infusion. Transfer functions (TFn) were calculated from FFT spectra as ratios of ICP and BP harmonic peak amplitudes to distinguish states of vasoreactivity. During normotension and hypertension, autoregulation was intact and TF1 averaged 0.05. During hypotension, TF1 averaged 0.22 (8 x baseline, p < 0.010). During impaired autoregulation following ischemic injury, TF1 averaged 0.50 (18 x baseline, p < 0.010; 2 x nitroprusside levels, p < 0.01). This large difference in TF relative to baseline extended over a large range of BP (60 < BP < 180 mm Hg). Based on these data and previous results, it was estimated that TF can differentiate impaired autoregulation from effects solely related to elevated ICP or active vasodilation for ICP < 30-40 mm Hg. This suggests that for specific, but widely applicable physiologic conditions, spectral analysis can identify states of impaired autoregulation and, as an adjunct to traditional monitoring techniques, aid in acute resuscitation and prevention of secondary injury in TBI.

Animals↗

Regional metabolic activity in the rat brain during sleep-wake activity.

[14C]2-Deoxyglucose autoradiography was used to demonstrate regional metabolic activity in the rat brain during wake, slow-wave sleep (SWS), and REM sleep. Data are expressed as values of relative metabolic activity (RMA, regional optic density/mean brain optic density), which show the level of metabolic activity in a region, relative to the mean level of the brain. Regions exhibiting obviously decreased RMA during SWS include the cerebellum, cortical layer IV, and most of the thalamus, including the massa intermedia and lateral geniculate nuclei. Low levels of RMA in sensory relay regions during SWS reflect functional deafference of the brain. In contrast, some limbic regions, including the hypothalamic core and hippocampal dentate fascia, exhibit increased RMA during SWS. Regions exhibiting increased RMA may have functions which are carried on at high levels during sleep. The metabolic appearance of the brain in REM is very different from that in SWS. The reticular core, substantia nigra, hippocampal dentate fascia, and stratum moleculare, and many regions associated with the extrapyramidal motor system, exhibit increased RMA. The cerebellum and ventral thalamic nucleus show decreased RMA, while the lateral thalamic nuclei and cortical layer IV show no metabolic state dependency. In sum, SWS is associated with a general decrease in RMA of sensory and motor areas, and with increased RMA in some limbic regions. RMA is similar in cerebellar and hippocampal regions during REM and SWS. In contrast, RMA in many sensory relay regions does not decrease during REM, and there is REM-specific increase of RMA in some pontomesencephalic regions associated with motor function.

Animals↗

Mitral annular motion as a surrogate for left ventricular function: correlation with brain natriuretic peptide levels.

BACKGROUND: Pulsed-wave (PW) Doppler tissue velocities of the mitral annulus correlate well with Left Ventricular (LV) diastolic(D) and systolic(S) functions. Brain natriuretic peptide (BNP) levels have been shown to be elevated in patients with symptomatic LV dysfunction (Dys) and correlate to the severity of symptoms and prognosis. OBJECTIVES: To validate the accuracy of mitral annular motion (MAM) assessed by Doppler Tissue Imaging (DTI) & M-mode Echocardiography (MME) as a surrogate for determination of LV function in comparison with BNP. METHODS: A series of 133 patients with a variety of cardiac pathologies referred for echocardiography and 20 healthy age & sex matched volunteers as a control group were included the study. Ejection fraction (EF) of LV, Doppler recordings of the mitral inflow, MME and PWDTI data (from each of 4 mitral annular sites, inferior, anterior, septum and lateral) were obtained. Mean peak (S) MAM velocity (Sm), mean annular early (D) velocity (Em) by PWDTI and mean mitral annular plane (S) excursion (MAPSE) by MME were calculated by averaging of values measured at each annular site. BNP levels were measured by a rapid immunoassay and blinded to cardiologist making the assessment of LV function. RESULTS: MAPSE < 12 mm determined by MME has 90% sensitivity, 88% specificity & 89% accuracy for detection of LVEF <50%, while these values were 94%, 93% & 94% respectively for (Sm) < 8 cm/s determined by PWDTI. BNP level>75 pg/ml has 98% sensitivity, 90% specificity & 97% accuracy for detection of LV Dys either (S,D, or both). BNP levels were significantly higher in patients with combined (S & D) Dys. Than those with only (S) Dys, the later group had significantly higher BNP levels than those with only (D) Dys. (1054.5 +/- 202.3 pg/ml vs. 500 +/- 39.9 pg/ml & 500 +/- 39.9 pg/ml vs. 215.3 +/- 100.9 pg/ml respectively, P < 0.001) & each were significantly higher than control group (12.3 +/- 5.7 pg/ml, P < 0.001). Significant correlations (P < 0.001 for all) were found between BNP levels and Em (r =-0.82), Sm (r=-0.7), early transmitral (E) to Em ratio (r=0.61), MAPSE (r=-0.54), LVEF(r=-0.64) & LV end D dimension (r=0.63). CONCLUSION: MME and PWDTI used for assessment of MAM are useful methods for evaluation of LV function but parameters measured by PWDTI correlate more strongly with plasma BNP levels than those measured by MME and provide a simple, sensitive, accurate and reproducible tool for early diagnosis of LV dysfunction.

Analysis of Variance↗

Extent of intercellular calcium wave propagation is related to gap junction permeability and level of connexin-43 expression in astrocytes in primary cultures from four brain regions.

Astrocytes are coupled via gap junctions, predominantly formed by connexin-43 proteins, into cellular networks. This coupling is important for the propagation of intercellular calcium waves and for the spatial buffering of K+. Using the scrape-loading/dye transfer technique, we studied gap junction permeability in rat astrocytes cultured from four different brain regions. The cultures were shown to display regional heterogeneity with the following ranking of the gap junction coupling strengths: hippocampus = hypothalamus > cerebral cortex = brain stem. Similar relative patterns were found in connexin-43 messenger RNA and protein levels using solution hybridization/RNase protection assay and western blots, respectively. The percentages of the propagation area of mechanically induced intercellular calcium waves for cortical, brain stem and hypothalamic astrocytes compared with hippocampal astrocytes were approximately 77, 42, and 52, respectively. Thus, the extent of calcium wave propagation was due to more than just gap junctional permeability as highly coupled hypothalamic astrocytes displayed relatively small calcium wave propagation areas. Incubation with 5-hydroxytryptamine decreased and incubation with glutamate increased the calcium wave propagation area in hippocampal (67% and 170% of the control, respectively) and in cortical astrocytes (82% and 163% of the control, respectively). Contrary to hippocampal and cortical astrocytes, the calcium wave propagation in brain stem astrocytes was increased by 5-hydroxytryptamine incubation (158% of control), while in hypothalamic astrocytes, no significant effects were seen. Similar effects from 5-hydroxytryptamine or glutamate treatments were observed on dye transfer, indicating an effect on the junctional coupling strength. These results demonstrate a strong relationship between connexin-43 messenger RNA levels, protein expression, and gap junction permeability among astroglial cells. Furthermore, our results suggest heterogeneity among astroglial cells from different brain regions in intercellular calcium signaling and in its differential modulation by neurotransmitters, probably reflecting functional requirements in various brain regions.

Animals↗

Effects of weak amplitude-modulated microwave fields on calcium efflux from awake cat cerebral cortex.

Calcium (45Ca2+) efflux was studied from preloaded cortex in cats immobilized under local anesthesia, and exposed to a 3.0-mW/cm2 450-MHz field, sinusoidally amplitude modulated at 16 Hz modulation depth 85%). Tissue dosimetry showed a field of 33 V/m in the interhemispheric fissure (rate of energy deposition 0.29 W/kg). Field exposure lasted 60 min. By comparison with controls, efflux curves from field exposed brains were disrupted by waves of increased 45Ca2+ efflux. These waves were irregular in amplitude and duration, but many exhibited periods of 20-30 min. They continued into the postexposure period. Binomial probability analysis indicates that the field-exposed efflux curves constitute a different population from controls at a confidence level of 0.96. In about 70% of cases, initiation of field exposure was followed by increased end-tidal CO2 excretion for about 5 min. However, hypercapnea induced by hypoventilation did not elicit increased 45Ca2+ efflux. Thus this increase with exposure does not appear to arise as a secondary effect of raised cerebral CO2 levels. Radioactivity measurements in cortical samples after superfusion showed 45Ca2+ penetration at about 1.7 mm/hr, consistent with diffusion of the ion in free solution.

Animals↗

Stimulus novelty, task relevance and the visual evoked potential in man.

Visual evoked potentials (VEPs) were recorded from normal adult subjects performing in a visual discrimination task. Subjects counted the number of presentations of the numeral 4 which was interposed rarely and randomly within a sequence of tachistoscopically flashed background stimuli (numeral 2s). Intrusive, task-irrelevant (not counted) stimuli were also interspersed rarely and randomly in the sequence of 2s; these stimuli were of two types: simples, which were easily recognizable (e.g., geometric figures), and novels, which were completely unrecognizable (i.e., complex, colorful patterns). It was found that the simples and the counted 4s evoked posteriorly distributed P3 waves (latency 380-430 msec) while the irrelevant novels evoked large, frontally distributed P3 waves (latency 360-380 msec). These large, frontal P3 waves to novels were also found to be preceded by large N2 waves (latency 278 msec). These findings indicate that "the P3" wave is not a unitary phenomenon but should be considered in terms of a family of waves, differing in their brain generators and in their psychological correlates. These late positive components are discussed in terms of task-relevance, recognition and Pavlov's "what is it" response.

Attention↗

Early auditory evoked potentials (EAEPs) in the rabbit. Normative data and effects of lesions in the cerebello-pontine angle.

Early auditory evoked potentials (EAEPs) were measured in rabbits. After establishing normative data an operative method was developed to expose the cerebello-pontine angle. Compression of the VIIIth nerve and a reduction of blood supply to the cochlea via the labyrinthine artery altered the EAEP systematically. In all cases of an VIIIth nerve lesion wave 1 continued to be elicited whereas waves 2-5 disappeared. Circulatory disturbances had an effect upon wave 1. The results indicate that the generator of wave 1 is the unit cochlea/acoustic nerve and of waves 2-5 the auditory pathway within the brain stem. The resultant data help to understand wave alterations in patients with acoustic neuromas.

Animals↗

PET and P300 relationships in early Alzheimer's disease.

The P300 (P3) wave of the auditory brain event-related potential was investigated in patients with probable Alzheimer's disease to determine whether P300 latency discriminated these patients from controls and whether prolonged P300 latency correlated with rates of brain glucose metabolism as measured by Positron Emission Tomography. P300 latency was prolonged by more than 1.5 standard deviations from age expectancy in 14 of 18 patients, but none of 17 controls. In these subjects P300 latency was shown to be inversely correlated with relative metabolic rates of parietal and, to a lesser extent, temporal and frontal association areas, but not with subcortical areas.

Aged↗

[Periventricular leukomalacia and brain protection. II. Diagnosis, sequelae and neuroprotection].

The term 'periventricular leukomalacia' (PVL) usually covers necrotic and/or gliotic lesions from perinatal origin occurring in the periventricular ring of telencephalic white matter. Carrying motor and neuropsychological consequences, PVLs could be the most severe danger for very premature brains. Positive rolandic sharp waves recorded on EEG and precocious abnormally echogenous periventricular images on ultrasound suggest prospective periventricular cysts. Cystic periventricular cavitations certify the diagnosis of PVL. More subtle lesions of PVL do not reach the cystic grade and their diagnosis is confirmed by MRI. Treatment of infections is already available and potentially a tool for prevention. When the overwhelming glutamatergic signal has been triggered, neuroprotective agents turning off the excitotoxic cascade, including calcium blockers, growth factors and others, are promising therapeutic tools.

Humans↗

Evaluation of conduction in central motor pathways: techniques, pathophysiology, and clinical interpretation.

This communication summarizes the highlights of this symposium and reviews our current understanding of the clinical neurophysiology of conduction in central motor pathways produced by transcranial or direct brain stimulation. Direct (D wave) and indirect (I wave) volleys of descending impulses in the pyramidal system result from motor cortex stimulation and determine the measured responses. The advantages and disadvantages of the electrical and the magnetic stimulating modalities are assessed. The increased latency produced by magnetic as opposed to electrical stimulation is considered. Present clinical applications are discussed. The safety record is encouraging, but has aspects that must be addressed. Potential problems of the interpretation of motor evoked potentials in patients with central nervous system disease are emphasized in light of the pathophysiological mechanism underlying these potentials.

Cerebellum↗

Day- and nighttime injection of a nitric oxide synthase inhibitor elicits opposite sleep responses in rats.

Previous studies suggest that nitric oxide (NO) may play a role in sleep regulation, particularly in the homeostatic process. The present studies were undertaken to compare the sleep effects of injecting a NO synthase (NOS) inhibitor when homeostatic sleep pressure is naturally highest (light onset) or when it is at its nadir (dark onset) in rats. Sleep, electroencephalogram delta-wave activity during nonrapid eye movement sleep (NREMS), also known as slow-wave activity (SWA), and brain temperature responses to three doses of the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME ; 5, 50, and 100 mg/kg) injected intraperitoneally at light or dark onset were examined in rats (n = 6 to 8). The effects of 5 mg/kg L-NAME were determined in both normal and vagotomized (VX) rats. Light onset administration of 50 mg/kg L-NAME decreased NREMS amounts and suppressed SWA and increased rapid eye movement sleep (REMS) amounts. At dark onset, L-NAME injection also dose dependently suppressed SWA; however, unlike light onset injections, both NREMS and REMS amounts were increased after all three doses. Sleep responses to 5 mg/kg L-NAME were not different in control and VX rats, suggesting that the sleep effects of L-NAME are not mediated through the activation of sensory vagal mechanisms. The present findings suggest that timing of the injection is a major determinant of the sleep responses observed after systemic L-NAME injection in rats.

Animals↗