Timetables of neurogenesis in the human brain based on experimentally determined patterns in the rat.
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Detailed protocols for the application of two different metal salt perfusion procedures are described for the production of superior catecholamine histofluorescence in the brains of immature rats up to 2 weeks of age. As in the adult, both magnesium and aluminum salts are highly advantageous for catecholamine histofluorescence in developing animals, and yield marked increases in sensitivity. In the magnesium-perfusion technique, animals are perfused in a simple one-step process using a hand-held syringe with cold buffer containing magnesium sulphate, formaldehyde and glyoxylic acid. The aluminum-perfusion (ALFA) technique provides even greater sensitivity and richness of detail, but requires a controlled-pressure perfusion system and a two-step perfusion process. Animals are first perfused with a room-temperature buffer containing magnesium sulphate and procain (to prevent vasoconstriction) followed by cold buffer containing aluminum sulphate and formaldehyde. In both methods, tissue pieces are subsequently freeze-dried, reacted with formaldehyde vapour and paraffin-sectioned according to the standard Falck-Hillarp procedure. Tissue pieces can also be taken from aluminum-perfused brains for simultaneous catecholamine assay using radioenzymatic methods, thereby permitting correlated histochemical and neurochemical analyses on the same brains. Many catecholamine terminal systems can be visualized in the rat brain even at birth with the ALFA procedure following pargyline pretreatment. However, the endogenous intraaxonal catecholamine concentration is so low in immature brains that the full anatomical extent of these systems cannot be reliably seen without recourse to pre-loading with an exogenously administered amine. For this purpose systemic injections of alpha-methyl-noradrenaline were extensively investigated. In combination with the ALFA procedure, such pretreatment was found to cause a dramatic increase in both the intensity and number of terminal and preterminal fibers throughout the brain. Control experiments with 6-hydroxydopamine and the catecholamine uptake blocker, nomifensine, indicate that this loading is specific for catecholamine systems. This approach has indicated that certain of the forebrain noradrenergic and dopaminergic systems are very extensive at birth, and in some regions an intermediate stage of hyperinnervation is a normal feature of ontogeny. Some of these findings are illustrated here and will also be presented in greater detail in further reports.
This paper attempts to quantitatively characterize the cerebral arterial circle in the chinchilla using a computerized image-analysis system. The sole source of the blood supply to the brain in this animal is the vertebral arteries and the basilar arteries. It was found that the diameter and volume of the basilar artery were over twofold larger than those of cerebral-circle arteries. The total length of the cerebral-circle arteries was approximately two times greater than the length of the basilar artery. A strong correlation between the parameters of the basilar artery and the total volume of the arterial circle was observed, as might be expected. These results suggest that if appropriate geometrical parameters are maintained, the brain can be adequately vascularized, even in the absence of additional blood supply.
While characterization of pathogenetic mechanisms underlying major depression is a fundamental aim of neuroscience research, an equally critical clinical goal is to identify biomarkers that might improve diagnostic accuracy and guide treatment selection for individual patients. To this end, a synthesis of functional neuroimaging studies examining regional metabolic and blood flow changes in depression is presented in the context of a testable limbic-cortical network model. 'Network' dysfunction combined with active intrinsic compensatory processes is seen to explain the heterogeneity of depressive symptoms observed clinically, as well as variations in pretreatment scan patterns described experimentally. Furthermore, the synchronized modulation of these dysfunctional limbic-cortical pathways is considered critical for illness remission, regardless of treatment modality. Testing of response-specific functional relationships among regional 'nodes' within this network using multivariate approaches is discussed, with a perspective aimed at identifying biomarkers of treatment non-response, relapse risk and disease vulnerability. Characterization of adaptive and maladaptive functional interactions among these pathways is seen as a critical step towards future development of evidenced-based algorithms that will optimize the diagnosis and treatment of individual depressed patients.
Fast, reliable and easy-to-use methods to quantify brain atrophy are of increasing importance in clinical studies on neuro-degenerative diseases. Here, ILAB 4, a new volumetry software that uses a fast semi-automated 3D segmentation of thin-slice T1-weighted 3D MR images based on a modified watershed transform and an automatic histogram analysis was evaluated. It provides the cerebral volumes: whole brain, white matter, gray matter and intracranial cavity. Inter- and intra-rater reliability and scan-rescan reproducibility were excellent in measuring whole brain volumes (coefficients of variation below 0.5%) of volunteers and patients. However, gray and white matter volumes were more susceptible to image quality. High accuracy of the absolute volume results (+/-5 ml) were shown by phantom and preparation measurements. Analysis times were 6 min for processing of 128 slices. The proposed technique is reliable and highly suitable for quantitative studies of brain atrophy, e.g., in multiple sclerosis.
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UNLABELLED: A wide range of techniques for registration of medical images has been devised in recent years. The aim of this study is to quantify the overall spatial registration error of 3 different methods for image registration: interactive matching, surface matching, and uniformity index matching as described by Woods. METHODS: MRI and ethylcysteinate dimer-SPECT images of the brain were registered for 15 patients. The matching error was assessed by determining intra- and interobserver variability of registrations. Quantification of the registration error was based on the mean spatial distance of 5000 voxels between 2 image positions. The mean position after repeated registrations in each patient was used as the gold standard. To evaluate the coherence of the 3 different registration methods, intermethod variability was determined. RESULTS: Interactive matching showed an intraobserver/interobserver variability of 1.5+/-0.3 mm/1.6+/-0.3 mm (mean +/- SD). The time demand for this method was 11+/-5 min. Surface matching revealed a variability of 2.6+/-1.1 mm/3.8+/-1.0 mm and a time demand of 26+/-12 min. Reproducibility of Woods' algorithm was 2.2+/-0.8 mm with a time demand of 9+/-3 min. In 4 of the 15 cases, Woods' method failed. The mean deviation between all 3 methods was 2.3+/-0.8 mm. CONCLUSION: With a suitable user interface, interactive matching had the lowest registration error. The influence of subjectivity was shown to be negligible. Therefore, interactive matching is our preferred technique for image fusion of the brain.
The review considers the advantages of Xenopus embryos as an experimental model to study the molecular-genetic mechanisms of embryo development. The results are described that were obtained with this model in studies on the early brain development within the framework of the Russian program Human Genome.
The model of treatment of mental disorders described by Peschel and Peschel (1990) raises the problem of medical patriarchy. The model does not consider the marked impact of cognition, volition, and affect on the physical realm. While a model of treatment based on a psychological matriarchy is no better, a model of training in health promotion with an appropriate balance of the physical, mental, and spiritual aspects of life gives more hope of training professionals who can see the larger picture of their patients' lives and a better record of success than presently exists.
Manganese is an essential nutrient required by the human body, but conversely, over exposure to the element may cause central nervous system damage. The technique of in vivo neutron activation analysis, using the McMaster KN-accelerator, is being investigated as a possible method of noninvasively determining manganese concentrations within the human body. Since the brain is the primary target of damage from exposure it would be the ideal site for measurements. Thus, Monte Carlo simulations have been undertaken to define the optimum experimental parameters for such a measurement, examining the use of possible moderator, reflector and collimator materials.
Magnetoencephalographic (MEG) auditory evoked fields produced by short tone pips were recorded from 34 normal adults (17 males, 17 females) and the 100 msec latency component (M100) localized in left and right hemispheres. Absolute M100 location in the antero-posterior dimension was calculated for each subject. M100 sources were significantly further anterior in the right hemisphere of males. Magnetic resonance (MR) based anatomy of the superior temporal gyri (STG) in a subset of 17 subjects showed that in the left STG of both males and females M100 sources were located approximately midway on the STG. In the right hemisphere of males, however, M100 sources were significantly further anterior on the STG than was the case for females. The findings are compatible with a sex based difference in right STG functional anatomy, with evidence of greater hemispheric lateralization in males compared to females based upon a predominantly right hemisphere contribution.
The objective is to increase the number of selections in brain computer interfaces (BCI) by recording and analyzing the steady state visual evoked potential response to dual stimulation. A BCI translates the VEP signals into user commands. The frequency band from which stimulation frequency can be selected is limited for SSVEP. This paper discusses a method to increase the number of commands by using a suitable combination of frequencies for stimulation. A biopotential amplifier based on the driven right leg circuit (DRL) is used to record 60 s epochs of the SSVEP (O(z)-A(1)) on 15 subjects using simultaneous overlapped stimulation (6, 7, 12, 13 and 14 Hzs and corresponding half frequencies). The power spectrum of each recording is obtained by frequency domain averaging of 400 ms SSVEPs and the spectral peaks were normalized. The spectral peaks of the combination frequencies of stimulation are predominant compared to individual stimulating frequencies. This method increases the number of selections by using a limited number of stimulating frequencies in BCI. For example, six selections are possible by generating only three frequencies.
Magnetoencephalographic (MEG) auditory evoked fields (EF) were recorded from left and right hemispheres of 9 normal males and 12 normal females. Source location of the 100 ms latency component (M100) was localized to superior temporal lobes bilaterally using an inverse solution algorithm. All subjects also were administered the Wechsler block design and visual reproduction subtests, and the California Verbal Learning Test (CVLT). M100 source locations demonstrated significant sex differences in interhemispheric asymmetry. Males had source locations further anterior than females, with the differences most pronounced in the right hemisphere. Expected sex differences were found in neuropsychological test performance, with males performing better on block design ad visual reproduction, and females performing better on the CVLT. Across both sexes, block design scores correlated significantly with right hemisphere M100 location, with more anterior source locations associated with better performance. CVLT scores were negatively correlated with right hemisphere M100 source locations. These findings suggest MEG-based measures of interhemispheric asymmetry may be related to specific neuropsychological test performance measures.
Prior work proved that it is possible to find a unique solution to the problem of defining the configuration of electric current underlying observed extracranial magnetic fields, if sufficient priori knowledge of the source configuration is available. This minimum-norm least-squares (MNLS) inverse solution for a magnetic source image (MSI) is extended here to include temporal as well as spatial parameters of the underlying current pattern. This capitalizes on the temporal resolution of magnetoencephalography (MEG), which is on the order of milliseconds. Other forms of functional brain imaging are far less sensitive to the rate of change of states of the brain. Influences on the quality of the resulting MSI by measurement noise and errors in determining the image surface are characterized. A new technique for reducing noise in the inverse problem is developed by taking into consideration the spatial and time-dependence of the noise detected by the sensors. This new approach to regularization reduces the contribution from noisy measurements to the inverse calculation, and therefore improves the stability of the inverse.
Clinico-physiological studies of 426 healthy subjects revealed normal parameters of the blood flow linear velocity along the extra- and intracranial portions of major cerebral vessels as determined by means of transcranial dopplerography. Normal parameters of the systolic-diastolic coefficient, the reactivity of major vessels and their pial draining network were studied in respect to their responses to functional loads of physical and chemical character which enabled one to determine functional possibilities of the cerebral circulation system. The ability of the dopplerographic technique was assessed in respect to studying of separate control mechanisms of the brain circulation system.
OBJECTIVE: This study aimed to describe the use of the P300 event-related potential as a control signal in a brain computer interface (BCI) for healthy and paralysed participants. METHODS: The experimental device used the P300 wave to control the movement of an object on a graphical interface. Visual stimuli, consisting of four arrows (up, right, down, left) were randomly presented in peripheral positions on the screen. Participants were instructed to recognize only the arrow indicating a specific direction for an object to move. P300 epochs, synchronized with the stimulus, were analyzed on-line via Independent Component Analysis (ICA) with subsequent feature extraction and classification by using a neural network. RESULTS: We tested the reliability and the performance of the system in real-time. The system needed a short training period to allow task completion and reached good performance. Nonetheless, severely impaired patients had lower performance than healthy participants. CONCLUSIONS: The proposed system is effective for use with healthy participants, whereas further research is needed before it can be used with locked-in syndrome patients. SIGNIFICANCE: The P300-based BCI described can reliably control, in 'real time', the motion of a cursor on a graphical interface, and no time-consuming training is needed in order to test possible applications for motor-impaired patients.
We use functional magnetic resonance imaging (fMRI) and behavioral analyses to study the neural roots of biases in causal reasoning. Fourteen participants were given a task requiring them to interpret data relative to plausible and implausible causal theories. Encountering covariation-based data during the evaluation of a plausible theory as opposed to an implausible theory selectively recruited neural tissue in the prefrontal and occipital cortices. In addition, the plausibility of a causal theory modulated the recruitment of distinct neural tissue depending on the extent to which the data were consistent versus inconsistent with the theory provided. Specifically, evaluation of data consistent with a plausible causal theory recruited neural tissue in the parahippocampal gyrus, whereas evaluating data inconsistent with a plausible theory recruited neural tissue in the anterior cingulate, left dorsolateral prefrontal cortex, and precuneus. We suggest that these findings provide a neural instantiation of the mechanisms by which working hypotheses and evidence are integrated in the brain.
Age effects in the error negativity (Ne) and error positivity (Pe) were examined in a standard letter flanker task and an age-sensitive source memory exclusion task. Older adults made more errors and produced Ne and Pe components of lower amplitude in both tasks. The Ne was insensitive to task and error rate. The Pe, however, was reduced in the source memory relative to the flanker task and was correlated with error rate in both tasks. Ne and Pe dipoles were generally localized to anterior cingulate cortex, but dipoles associated with the Pe were more frontal for flanker errors and, for young adults, more posterior for source errors. These data suggest that the Ne reflects an automatic response to error as it occurs whereas the Pe, being more sensitive to age and task demands, and more closely linked to accuracy, reflects the allocation of attention to an error that has been made.