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PubMed2004

Microarray analysis of microRNA expression in the developing mammalian brain.

BACKGROUND: MicroRNAs are a large new class of tiny regulatory RNAs found in nematodes, plants, insects and mammals. MicroRNAs are thought to act as post-transcriptional modulators of gene expression. In invertebrates microRNAs have been implicated as regulators of developmental timing, neuronal differentiation, cell proliferation, programmed cell death and fat metabolism. Little is known about the roles of microRNAs in mammals. RESULTS: We isolated 18-26 nucleotide RNAs from developing rat and monkey brains. From the sequences of these RNAs and the sequences of the rat and human genomes we determined which of these small RNAs are likely to have derived from stem-loop precursors typical of microRNAs. Next, we developed a microarray technology suitable for detecting microRNAs and printed a microRNA microarray representing 138 mammalian microRNAs corresponding to the sequences of the microRNAs we cloned as well as to other known microRNAs. We used this microarray to determine the profile of microRNAs expressed in the developing mouse brain. We observed a temporal wave of expression of microRNAs, suggesting that microRNAs play important roles in the development of the mammalian brain. CONCLUSION: We describe a microarray technology that can be used to analyze the expression of microRNAs and of other small RNAs. MicroRNA microarrays offer a new tool that should facilitate studies of the biological roles of microRNAs. We used this method to determine the microRNA expression profile during mouse brain development and observed a temporal wave of gene expression of sequential classes of microRNAs.

Animals↗

PubMed2005

Radial frequency stimuli and sine-wave gratings seem to be processed by distinct contrast brain mechanisms.

An assumption commonly made in the study of visual perception is that the lower the contrast threshold for a given stimulus, the more sensitive and selective will be the mechanism that processes it. On the basis of this consideration, we investigated contrast thresholds for two classes of stimuli: sine-wave gratings and radial frequency stimuli (i.e., j0 targets or stimuli modulated by spherical Bessel functions). Employing a suprathreshold summation method, we measured the selectivity of spatial and radial frequency filters using either sine-wave gratings or j0 target contrast profiles at either 1 or 4 cycles per degree of visual angle (cpd), as the test frequencies. Thus, in a forced-choice trial, observers chose between a background spatial (or radial) frequency alone and the given background stimulus plus the test frequency (1 or 4 cpd sine-wave grating or radial frequency). Contrary to our expectations, the results showed elevated thresholds (i.e., inhibition) for sine-wave gratings and decreased thresholds (i.e., summation) for radial frequencies when background and test frequencies were identical. This was true for both 1- and 4-cpd test frequencies. This finding suggests that sine-wave gratings and radial frequency stimuli are processed by different quasi-linear systems, one working at low luminance and contrast level (sine-wave gratings) and the other at high luminance and contrast levels (radial frequency stimuli). We think that this interpretation is consistent with distinct foveal only and foveal-parafoveal mechanisms involving striate and/or other higher visual areas (i.e., V2 and V4).

Adult↗

PubMed1998

Metabolic activity is increased in discrete brain regions before the occurrence of spike-and-wave discharges in weanling rats with genetic absence epilepsy.

In the present study, we measured basal local cerebral metabolic rates for glucose (LCMRglcs) in immature genetic absence epilepsy rats from Strasbourg (GAERS) at postnatal day 21 (P21), at which age no spike-and-wave discharges can be recorded. LCMRglcs in GAERS were compared to those in control non-epileptic (NE) rats of the same age selected from our breeding colony. LCMRglcs were measured in 60 structures by the quantitative [14C]2-deoxyglucose (2DG) autoradiographic technique. In P21 GAERS, LCMRglcs were similar to those of P21 NE rats in 46 areas. They increased over NE control levels in two groups of structures. First, metabolic increases were recorded in limbic structures such as entorhinal and piriform cortex, lateral septum as well as all hippocampal subfields and basolateral amygdala, although no spike-and-wave discharges can be recorded from those areas in adult GAERS. On the other hand, increases in LCMRglcs were also recorded in substantia nigra pars reticulata, superior colliculus and globus pallidus which are structures involved in the control of seizure activity. Finally, significant metabolic decreases in P21 GAERS were recorded in two posterior auditory regions, the inferior colliculus and the superior olive. In conclusion, our data show that the genetic mutation(s) underlying the cellular and molecular events responsible for the expression of spike-and-wave discharges in adult GAERS is(are) able to increase metabolic activity in limbic structures and in the nigral inhibitory system before the occurrence of absence seizures. Conversely, the full electrocortical maturation seems necessary for the expression of spike-and-wave discharges with the concurrent increase in LCMRglcs in adult GAERS.

Animals↗

PubMed2002

Role of corticotropin-releasing hormone in stressor-induced alterations of sleep in rat.

Corticotropin-releasing hormone (CRH) mediates responses to a variety of stressors. We subjected rats to a 1-h period of an acute stressor, physical restraint, and determined the impact on subsequent sleep-wake behavior. Restraint at the beginning of the light period, but not the dark period, increased waking and reduced rapid eye movement sleep without dramatically altering slow-wave sleep (SWS). Electroencephalogram (EEG) slow-wave activity during SWS and brain temperature were increased by this manipulation. Central administration of the CRH receptor antagonist astressin blocked the increase in waking after physical restraint, but not during the period of restraint itself. Blockade of CRH receptors with astressin attenuated the restraint-induced elevation of brain temperature, but not the increase of EEG slow-wave activity during subsequent SWS. Although corticosterone increased after restraint in naive animals, it was not altered by this manipulation in rats well habituated to handling and injection procedures. These results suggest that under these conditions central CRH, but not the hypothalamic-pituitary-adrenal axis, is involved in the alterations in sleep-wake behavior and the modulation of brain temperature of rats exposed to physical restraint.

Animals↗

PubMed1980

Interference effect of 3 Hz brain stimulation on kindling behavior induced by 60 Hz stimulation.

Experiments were conducted to evaluate the effect of 3 Hz brain stimulation on kindling behavior induced by 60 Hz sine waves stimulation. In Experiment 1, 12 rats were subjected to 40 or 60 convulsion trials with 60 Hz stimulation and then given 36 trials of 3 Hz stimulation. When these rats were stimulated again with 60 Hz sine wave current at the same brain site, none of the rats showed a convulsion in nine test trials. The intensity of stimulation had to be increased on test trial 10 to elicit convulsions for each rat. Of 10 rats in two control groups, only 1 did not convulse during the nine test trials. In Experiment 2 the effective threshold intensity (ETI) to elicit a convulsion was determined on five separate occasions with 10 days of daily trials between determinations. On each day experimental rats were stimulated with 3 Hz current on the first and third trials and with 60 Hz current on the second trial (3-60-3 group). A steady increase in the intensity required to elicit a convulsion with 60 Hz current from ETI1 to ETI5 resulted. Rats stimulated only with 60 Hz sine waves on the second trial each day (X-60-X grou,) maintained relatively stable values from ETI1 to ETI5. In the four, 10-day blocks of trials, convulsions were suppressed in 20% to 80% of the trials over the 10 day period for the 3-60-3 group, with the greatest effect occurring after about 4 days of stimulation. This suppressive effect was prominent both with rats that were at the convulsion stage prior to the first application of 3 Hz stimulation and with rats that were at preconvulsion stages. In Experiment 3 the permanency of the suppressive effect was evaluated. Eight suppressed rats from the experimental group in Experiment 2 and 4 control rats were stimulated for 90 trials over 30 days with 60 Hz current, and ETI values were determined after each set of six trials. Four of the 8 experimental rats were convulsing at ETI1 within 20 days.

Amygdala↗

PubMed1980

The 500 Hz frequency-following potential in kangaroo rat: an evaluation with noise masking.

This study on kangaroo rat has shown that the volume-conducted 500 Hz FFP can be recorded at stimulus levels which are near behavioral threshold. The response is a complex, double-peaked wave form, indicating that multiple brain stem sources are involved in its generation. The FFP wave form changes in a complex manner with intensity. Recordings of the FFP in the presence of broadband noise demonstrate that the response is neural in origin at suprathreshold stimulus levels. The various configurations of the FFP in the presence of noise, high-pass or broadband, are dependent upon the level of the tone, the level of the noise, and the frequency at which the noise high-pass is set. High-pass masking experiments near threshold levels have demonstrated that the FFP is initiated at a restricted region of the apical cochlea. From all of the results, we conclude that the FFP at moderate and low levels (55--65 dB SPL) is generated primarily by neurons with best frequencies below 1.5--2.0 kHz. The onset component of the FFP is similarly affected by noise, indicating that it too is low frequency in origin.

Animals↗

PubMed2005

Characterization of EEG--a comparative study.

The Electroencephalogram (EEG) is a representative signal containing information about the condition of the brain. The shape of the wave may contain useful information about the state of the brain. However, the human observer cannot directly monitor these subtle details. Besides, since bio-signals are highly subjective, the symptoms may appear at random in the time scale. Therefore, the EEG signal parameters, extracted and analyzed using computers, are highly useful in diagnostics. Chaotic measures like correlation dimension (CD), largest Lyapunov exponent (LLE), Hurst exponent (H) and entropy are used to characterize the signal. Results indicate that these nonlinear measures are good discriminators of normal and epileptic EEG signals. These measures distinguish epileptic EEG and alcoholic from normal EEG with an accuracy of more than 90%. The dynamical behavior is less random for alcoholic and epileptic compared to normal. This indicates less of information processing in the brain due to the hyper-synchronization of the EEG. Hence, the application of nonlinear time series analysis to EEG signals offers insight into the dynamical nature and variability of the brain signals. As a pre-analysis step, the EEG data is tested for nonlinearity using surrogate data analysis and the results exhibited a significant difference in the correlation dimension measure of the actual data and the surrogate data.

Alcoholism↗

PubMed2005

Entropies for detection of epilepsy in EEG.

The electroencephalogram (EEG) is a representative signal containing information about the condition of the brain. The shape of the wave may contain useful information about the state of the brain. However, the human observer cannot directly monitor these subtle details. Besides, since bio-signals are highly subjective, the symptoms may appear at random in the time scale. Therefore, the EEG signal parameters, extracted and analyzed using computers, are highly useful in diagnostics. The aim of this work is to compare the different entropy estimators when applied to EEG data from normal and epileptic subjects. The results obtained indicate that entropy estimators can distinguish normal and epileptic EEG data with more than 95% confidence (using t-test). The classification ability of the entropy measures is tested using ANFIS classifier. The results are promising and a classification accuracy of about 90% is achieved.

Algorithms↗

PubMed2004

Nonlinear analysis of EEG signals at different mental states.

BACKGROUND: The EEG (Electroencephalogram) is a representative signal containing information about the condition of the brain. The shape of the wave may contain useful information about the state of the brain. However, the human observer can not directly monitor these subtle details. Besides, since bio-signals are highly subjective, the symptoms may appear at random in the time scale. Therefore, the EEG signal parameters, extracted and analyzed using computers, are highly useful in diagnostics. This work discusses the effect on the EEG signal due to music and reflexological stimulation. METHODS: In this work, nonlinear parameters like Correlation Dimension (CD), Largest Lyapunov Exponent (LLE), Hurst Exponent (H) and Approximate Entropy (ApEn) are evaluated from the EEG signals under different mental states. RESULTS: The results obtained show that EEG to become less complex relative to the normal state with a confidence level of more than 85% due to stimulation. CONCLUSIONS: It is found that the measures are significantly lower when the subjects are under sound or reflexologic stimulation as compared to the normal state. The dimension increases with the degree of the cognitive activity. This suggests that when the subjects are under sound or reflexologic stimuli, the number of parallel functional processes active in the brain is less and the brain goes to a more relaxed state

Adolescent↗

PubMed2000

[A case of brain stem infarction with bilateral hearing loss].

The study case was a 66-year-old man who had bilateral neurosensory hearing impairment due to brain stem infarctions. He noticed mild hearing loss, frequent vertigo and tinnitus. About one month later, his hearing took a sudden turn for the worse, and he suffered from dysarthria, dysphagea and abasia. Neurological examination revealed pseudobulber palsy, left hemiparesis, cerebeller ataxia, disturbance of pain and temperature sensation on the right face and left side of the body. Brain stem auditory evoked potentials (BAEPs) showed a delayed small wave V with the abscence of previous waves on the right side and no significant waves on the left side. Brain magnetic resonance images (MRI) revealed infarctions in the bilateral middle cerebellar peduncles, including in the right lateral portions of pons, and the right lower pontine base. We believe that not only peripheral, but also central auditory pathways adjacent to infarctions were damaged. Magnetic resonance angiography (MRA) showed severe stenosis or occlusion of left vertebral artery and basilar artery. We concluded that hypoperfusion of the vertebrobasilar artery territories caused ischemia of the cochlear nerve and the auditory tracts in the brain stem, which resulted in bilateral hearing loss.

Aged↗

PubMedDate not supplied

Influence of aspirin on the contingent negative wave in healthy subjects.

A study was made of the alterations of the parameters of the slow brain potential, the contingent negative wave, under the influence of aspirin in healthy individuals, using the double blind method. The early and late wave of the CNW were investigated. A statistically significant decrease in the early CN wave was obtained after the ingestion of aspirin, and an increase in the late wave after the ingestion of aspirin and placebo. A central effect of aspirin, affecting the noradrenergic and dopaminergic brain systems, is hypothesized to explain the changes described.

Adult↗

PubMedDate not supplied

[Evaluation of heat production during propagation of the depression wave].

A mathematical model is proposed to describe a heat wave accompanying the spreading cortical depression wave in the large brain. The model takes into account heat production of neurons, thermal transmission with thermoconductivity and volume thermal losses. The model fits well for the wave shape and permits one to estimate heat production which is about 4-20 J/g X min.

Animals↗

PubMed1986

Cerebrovascular accident alters P300 event-related potential characteristics.

P300 event-related potentials to counted (target) and uncounted (background) visual stimuli were recorded from subjects who had sustained either a right or a left middle cerebral artery cerebrovascular accident (CVA) and from appropriate normal control subjects. Subjects were asked to count target stimuli and to ignore non-target stimuli. Standard measurements of the amplitude and latency of P300 components as well as intercorrelations among P300 wave forms from 3 brain regions (Fz, Cz, Pz) were collected. Amplitudes of N1-P2 and N2-P3 components as well as overall amplitude of the ERP wave form were reliably reduced by a CVA, but component latencies were not significantly affected. The amplitude reduction associated with a CVA cannot be simply interpreted as evidence for reduced cognitive efficiency because overall amplitudes and intercorrelations between brain regions of CVA patients were reduced for both counted and uncounted stimuli. The intercorrelations between brain regions were particularly reduced if the CVA was localized in the right hemisphere. For CVA patients, reduced component amplitudes may reflect decreased cortical intercommunication associated with damage to subcortical brain structures.

Activities of Daily Living↗

PubMed1996

Auditory evoked brain stem responses to trains of stimuli in human adults.

OBJECTIVE: This study describes the effect of train length, interstimulus interval, intertrain interval (ITI), and stimulus duration on the transition from the unadapted to the adapted wave V auditory evoked brain stem response (ABR). DESIGN: ABRs were recorded to stimuli presented at two different rates: a slow rate characterizing the unadapted response and a fast rate characterizing the adapted response. Trains of stimuli (a sequence of stimuli separated by intervals of silence) also were presented. Different stimulus parameters defining the trains were varied. RESULTS: Given a sufficiently long ITI, the latency prolongation to the first three or four stimuli in a train was rapid. It was similar for trains differing in number of stimuli. After the first three or four stimuli, there was a more gradual latency prolongation as a function of stimulus number. Shorter ITIs had the effect of prolonging the latencies to all the stimuli in the trains, reducing the rate of latency prolongation over the first few stimuli, and causing responses to trains of different length to differ (e.g., two click train responses were shorter latency than four click train responses). An unexpected result was the latency prolongation of wave Vs after the presentation of the stimulus trains. CONCLUSIONS: In response to a train of clicks, there seems to be a rapid increase in wave V latency to the first few clicks in the train followed by a more gradual latency prolongation to subsequent clicks in the train.

Adult↗

PubMed2003

Possible involvement of Wiskott-Aldrich syndrome protein family in aberrant neuronal sprouting in Alzheimer's disease.

One of the pathological characteristics of Alzheimer's disease (AD) is the formation of dystrophic neurites accompanied by aberrant neuronal sprouting. Although a number of studies have focussed on the formation of amyloid plaques and neurofibrillary tangles, the mechanism of neuronal sprouting in AD is not fully understood. The protein levels of neural Wiskott-Aldrich syndrome protein (N-WASP), WASP interacting SH3 protein (WISH) and WASP family verprolin-homologous protein (WAVE) were significantly increased in AD brains. In addition, N-WASP, WISH and WAVE were co-localized with filamentous actin in abnormal dendrite-like processes sprouting from staurosporine-treated human SH-SY5Y cells. These results suggest that N-WASP, WISH and WAVE may participate in the neurodegenerative aberrant sprouting in AD neurons.

Adaptor Proteins, Signal Transducing↗

PubMed1979

Combined dynamics of EEG and evoked potentials. II. Studies of simultaneously recorded EEG-EPograms in the auditory pathway, reticular formation, and hippocampus of the cat brain during sleep.

This study is carried out on single (not averaged) recordings combining the spontaneous activity preceding the stimulus onset and the EP recorded upon acoustical stimulation. These recordings, which we call EEG-EPograms, are measured simultaneously from different subdural structures, such as the auditory cortex, medial geniculate nucleus, inferior colliculus, reticular formation and the hippocampus of the cat brain during the slow wave sleep stage. Using a combined analysis procedure (C.A.P.), the relevant frequency components of spontaneous EEG and EPs, recorded simultaneously from these brain nuclei, are analyzed according to the consistent selectivity bands depicted by the determined amplitude-frequency characteristics for the SWS-stage. In parallel with the results which we obtained for the waking stage, these analyses provide also the following information: (1) there is an important congruency in the time courses of simultaneous response components in common frequency bands, especially in the alpha and beta frequency ranges; (2) there exist significant coupling and synchrony between the evoked amplitude enhancements in the simultaneously recorded single response components; (3) the inter-nuclei coherency in the brain's electrical activity is enormously increased upon stimulation;(4) the evoked response magnitude can be predicted, with reasonable accuracy, from the spontaneous activity preceding the stimulus. All these findings are discussed with reference to those obtained for the waking stage.

Animals↗

PubMed1994

Intraoperative SEP monitoring in neurosurgery around the brain stem and cervical spinal cord: differential recording of subcortical components.

The results of intraoperative monitoring of median nerve somatosensory evoked potentials (SEP's) were evaluated in 75 neurosurgical patients in order to assess the role of differential derivation of brain stem (P14) and spinal cord (N13) wave activity. These components were compared with the conventionally recorded neck potential ("N13") that reflects overlap of P14 and N13. The spinal cord N13 wave was recorded from the posterior to anterior lower aspect of the neck and the brain stem P14 wave from the midfrontal scalp to the nasopharynx; both derivations enabled isolated low-artifact recording of these components. In 18.7% of patients, moderate to major latency and/or amplitude shifts of N13 or P14 were found that were masked in conventional neck-scalp recordings of "N13". There was a 6.7% false-negative rate in this series. Using a neck-scalp derivation alone, a 14.7% false-negative rate would have resulted and an isolated worsening of the P14 component (with stable neck potential) in six cases would have been overlooked. It is concluded that the proposed SEP recording technique allows independent assessment of spinal cord and brain stem activity. It is, therefore, superior to the conventional neck-scalp derivation technique, in which important information may be concealed or even lost due to the overlap of the brain stem P14 and spinal cord N13 potentials.

Adolescent↗

PubMed1997

Human brain functional imaging with reflectance CWS.

Continuous Wave Spectroscopy (CWS) has been used in human subjects to detect brain function by observation of brain oxygenation and blood volume changes. In this research, we have developed a device for imaging brain oxygenation and blood volume with multiple sources and detectors in an area of 10 x 12 cm. Twelve, 1 watt tungsten bulbs were used as a light source, together with 8 detectors consisting of silicon-photodiodes with band-pass filters at 760 and 850 nms. The detectors were placed on a model system of the human head, providing 16 source-detector combinations with 4 cm separation. Eight to 16 seconds were required to image a brain function. Models using resin and a black object which have similar optical characteristics to a brain were studied. The model study showed that we can detect changes in absorption as deep as 2 cm from the surface. Human subjects with relatively thin hair, who volunteered for this study, were asked to tap fingers and rest, or to observe light flashing and darkness alternatively for 10 to 20 minutes while the images were being taken. In the finger tapping, the blood volume increased in a small, 1-2 cm area, while in the light stimulation, a much larger area was affected with a greater increased blood volume. Oxygenation occurred also in the area where blood volume increased. We concluded that the CWS can be used to image the location of brain activity by means of blood volume increase and oxygenation. In addition, brain disfunction and diseases, such as learning disability and brain hematoma may be detected with this imaging device.

Adolescent↗