IFCN guidelines for topographic and frequency analysis of EEGs and EPs.The International Federation of Clinical Neurophysiology.
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Publications and source records attributed to D Lehmann.
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BACKGROUND: Schizophrenic symptoms commonly are felt to indicate a loosened coordination, i.e. a decreased connectivity of brain processes. METHODS: To address this hypothesis directly, global and regional multichannel electroencephalographic (EEG) complexities (omega complexity and dimensional complexity) and single channel EEG dimensional complexities were calculated from 19-channel EEG data from 9 neuroleptic-naive, first-break, acute schizophrenics and 9 age- and sex-matched controls. Twenty artifact-free 2 second EEG epochs during resting with closed eyes were analyzed (2-30 Hz bandpass, average reference for global and regional complexities, local EEG gradient time series for single channels). RESULTS: Anterior regional Omega-Complexity was significantly increased in schizophrenics compared with controls (p < 0.001) and anterior regional Dimensional Complexity showed a trend for increase. Single channel Dimensional Complexity of local gradient waveshapes was prominently increased in the schizophrenics at the right precentral location (p = 0.003). CONCLUSIONS: The results indicate a loosened cooperativity or coordination (vice versa: an increased independence) of the active brain processes in the anterior brain regions of the schizophrenics.
This paper describes the methodologies used to develop a prediction model to assist health workers in developing countries in facing one of the most difficult health problems in all parts of the world: the presentation of an acutely ill young infant. Statistical approaches for developing the clinical prediction model faced at least two major difficulties. First, the number of predictor variables, especially clinical signs and symptoms, is very large, necessitating the use of data reduction techniques that are blinded to the outcome. Second, there is no uniquely accepted continuous outcome measure or final binary diagnostic criterion. For example, the diagnosis of neonatal sepsis is ill-defined. Clinical decision makers must identify infants likely to have positive cultures as well as to grade the severity of illness. In the WHO/ARI Young Infant Multicentre Study we have found an ordinal outcome scale made up of a mixture of laboratory and diagnostic markers to have several clinical advantages as well as to increase the power of tests for risk factors. Such a mixed ordinal scale does present statistical challenges because it may violate constant slope assumptions of ordinal regression models. In this paper we develop and validate an ordinal predictive model after choosing a data reduction technique. We show how ordinality of the outcome is checked against each predictor. We describe new but simple techniques for graphically examining residuals from ordinal logistic models to detect problems with variable transformations as well as to detect non-proportional odds and other lack of fit. We examine an alternative type of ordinal logistic model, the continuation ratio model, to determine if it provides a better fit. We find that it does not but that this model is easily modified to allow the regression coefficients to vary with cut-offs of the response variable. Complex terms in this extended model are penalized to allow only as much complexity as the data will support. We approximate the extended continuation ratio model with a model with fewer terms to allow us to draw a nomogram for obtaining various predictions. The model is validated for calibration and discrimination using the bootstrap. We apply much of the modelling strategy described in Harrell, Lee and Mark (Statist. Med. 15, 361-387 (1998)) for survival analysis, adapting it to ordinal logistic regression and further emphasizing penalized maximum likelihood estimation and data reduction.
The present study shows that different neural activity during mental imagery and abstract mentation can be assigned to well-defined steps of the brain's information-processing. During randomized visual presentation of single, imagery-type and abstract-type words, 27 channel event-related potential (ERP) field maps were obtained from 25 subjects (sequence-divided into a first and second group for statistics). The brain field map series showed a sequence of typical map configurations that were quasi-stable for brief time periods (microstates). The microstates were concatenated by rapid map changes. As different map configurations must result from different spatial patterns of neural activity, each microstate represents different active neural networks. Accordingly, microstates are assumed to correspond to discrete steps of information-processing. Comparing microstate topographies (using centroids) between imagery- and abstract-type words, significantly different microstates were found in both subject groups at 286-354 ms where imagery-type words were more right-lateralized than abstract-type words, and at 550-606 ms and 606-666 ms where anterior-posterior differences occurred. We conclude that language-processing consists of several, well-defined steps and that the brain-states incorporating those steps are altered by the stimuli's capacities to generate mental imagery or abstract mentation in a state-dependent manner.
Covert brain activity related to task-free, spontaneous (i.e. unrequested), emotional evaluation of human face images was analysed in 27-channel averaged event-related potential (ERP) map series recorded from 18 healthy subjects while observing random sequences of face images without further instructions. After recording, subjects self-rated each face image on a scale from "liked" to "disliked". These ratings were used to dichotomize the face images into the affective evaluation categories of "liked" and "disliked" for each subject and the subjects into the affective attitudes of "philanthropists" and "misanthropists" (depending on their mean rating across images). Event-related map series were averaged for "liked" and "disliked" face images and for "philanthropists" and "misanthropists". The spatial configuration (landscape) of the electric field maps was assessed numerically by the electric gravity center, a conservative estimate of the mean location of all intracerebral, active, electric sources. Differences in electric gravity center location indicate activity of different neuronal populations. The electric gravity center locations of all event-related maps were averaged over the entire stimulus-on time (450 ms). The mean electric gravity center for disliked faces was located (significant across subjects) more to the right and somewhat more posterior than for liked faces. Similar differences were found between the mean electric gravity centers of misanthropists (more right and posterior) and philanthropists. Our neurophysiological findings are in line with neuropsychological findings, revealing visual emotional processing to depend on affective evaluation category and affective attitude, and extending the conclusions to a paradigm without directed task.
Prompted reports of recall of spontaneous, conscious experiences were collected in a no-input, no-task, no-response paradigm (30 random prompts to each of 13 healthy volunteers). The mentation reports were classified into visual imagery and abstract thought. Spontaneous 19-channel brain electric activity (EEG) was continuously recorded, viewed as series of momentary spatial distributions (maps) of the brain electric field and segmented into microstates, i.e. into time segments characterized by quasi-stable landscapes of potential distribution maps which showed varying durations in the sub-second range. Microstate segmentation used a data-driven strategy. Different microstates, i.e. different brain electric landscapes must have been generated by activity of different neural assemblies and therefore are hypothesized to constitute different functions. The two types of reported experiences were associated with significantly different microstates (mean duration 121 ms) immediately preceding the prompts; these microstates showed, across subjects, for abstract thought (compared to visual imagery) a shift of the electric gravity center to the left and a clockwise rotation of the field axis. Contrariwise, the microstates 2 s before the prompt did not differ between the two types of experiences. The results support the hypothesis that different microstates of the brain as recognized in its electric field implement different conscious, reportable mind states, i.e. different classes (types) of thoughts (mentations); thus, the microstates might be candidates for the 'atoms of thought'.
Acute respiratory infections (ARI) are a major cause of morbidity in children worldwide, and are estimated to cause four million deaths per year, mainly in the developing world. In those countries, bacterial infection with high case fatality is common, apparently following a primary viral infection. The case management strategy has had success in controlling severe outcomes. However, its dependence on the use of antibiotics and the advantage of primary prevention support the need for vaccines. Vaccines against viruses such as respiratory syncytial and parainfluenza would prevent what is often the initial infection and vaccines against Haemophilus influenzae and S. pneumoniae the major bacterial causes of mortality. Maternal immunization may have special relevance in developing countries where protection early in life is required. The development of combination vaccines would also be especially useful, since contacts with the medical system are often difficult. The introduction and use of new vaccines in those regions will require demonstration of cost effectiveness and acceptance by policy makers.
We investigated brain electric field signatures of subjective feelings after chewing regular gum or gum base without flavor. 19-channel eyes-closed EEG from 20 healthy males before and after 5 minutes of chewing the two gum types in random sequence was source modeled in the frequency domain using the FFT-Dipole-Approximation. 3-dimensional brain locations and strengths (Global Field Power, GFP) of the equivalent sources of five frequency bands were computed as changes from pre-chewing baseline. Gum types differed (ANOVA) in pre-post changes of source locations for the alpha-2 band (to anterior and right after regular gum, opposite after gum base) and beta-2 band (to anterior and inferior after regular gum, opposite after gum base), and of GFP for delta-theta, alpha-2 and beta-1 (regular gum: increase. gum base: decrease). Subjective feeling changed to more positive values after regular gum than gum base (ANOVA).--Thus, chewing gum with and without taste-smell activates different brain neuronal populations.
A morbidity study of diarrhoea covering 1926 children aged less than 5 years was carried out in Goroka town and the Lowa and Asaro Census Divisions, Eastern Highlands Province between 1986 and 1989. The study involved weekly demographic surveillance of the total population and morbidity surveillance of children by lay reporters who enquired about the presence or absence on any of the preceding 8 days of a range of symptoms associated with diarrhoeal and respiratory diseases. A three-day symptom-free period was used to define distinct episodes of diarrhoea. The average number of episodes/child-year for all children in the study population was 3.0. Boys suffered a significantly higher incidence of diarrhoea under 48 months of age than girls (4.4 episodes compared to 3.6/child-year). Incidence was highest among those aged 6-17 months (5.5/child-year) with a rapid decline after age 35 months. Incidence of diarrhoea was highest in the more remote Asaro Census Division and was higher in periurban areas than in Goroka town. Incidence also varied significantly between villages, some villages experiencing up to 10 times the incidence of diarrhoea found in Goroka town. The incidence of diarrhoea was significantly higher in January than at other times of year. Duration of diarrhoea varied with age, the longest duration being an average of 4.7 days in the 12-17 months age group. In order to reduce diarrhoea morbidity, it is necessary to improve access to water, encourage improved hygiene practices and breastfeeding and warn people about the risks of sleeping with pigs.
Adverse drug events secondary to iodinated contrast agents are of particular concern to all clinicians. Despite the availability of newer agents, the mortality rates remain unchanged. We describe a fatal adverse event secondary to use of the high osmolality agent iothalmate meglumine 30%. A 58-y-old healthy female with no previous history of drug or food allergy had cardiac arrest toward the end of the i.v. infusion of the contrast agent during a CT scan. The patient expired despite aggressive therapeutic measures.
27-Channel EEG potential map series were recorded from 12 normals with closed and open eyes. Intracerebral dipole model source locations in the frequency domain were computed. Eye opening (visual input) caused centralization (convergence and elevation) of the source locations of the seven frequency bands, indicative of generalized activity; especially, there was clear anteriorization of alpha-2 (10.5-12 Hz) and beta-2 (18.5-21 Hz) sources (alpha-2 also to the left). Complexity of the map series' trajectories in state space (assessed by Global Dimensional Complexity and Global OMEGA Complexity) increased significantly with eye opening, indicative of more independent, parallel, active processes. Contrary to PET and fMRI, these results suggest that brain activity is more distributed and independent during visual input than after eye closing (when it is more localized and more posterior).
In a recent double-blind, phase II study, conducted in our department, we showed that Linomide-treated MS patients had significantly less active lesions (in serial monthly MRI tests) and a tendency for clinical stabilization. Here we present the immunological evaluation of the patients who participated in this study and propose a novel mechanism by which Linomide downregulates autoreactivity. Peripheral blood leukocytes (PBLs), serum, and CSF samples were obtained at two to four time points over the 6 months of the trial. Flow cytometric analysis (FACS) of the CD5/CD19, CD4/CD8, CD14/CD3, CD16/CD3, CD45RA/CD4, and CD45RO/CD4 surface markers on PBLs was performed and the levels of the IL-1beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma, and IL-2R were also examined. White blood counts of Linomide-treated patients were consistently elevated throughout the treatment period (P = 0.002-0.04). Cytokines levels in serum and CSF were highly fluctuating and we could not detect any clear trend as a result of Linomide treatment. FACS analysis showed that Linomide treatment significantly increased the percentage of the CD4+/CD45RA+ cells (from 35.5% at baseline to 42.3% at week 24; P = 0.02), and decreased CD4+/CD45RO+ lymphocytes (62.6% at baseline vs 53.7% at week 24, P = 0.02). Linomide also induced a transient increase in the NK-cells, the NK 1.1 cells, and the CD5 B-cells (P = 0.02). Upregulation of naive CD45RA T-lymphocytes and parallel downregulation of memory CD45RO cells seems to be one of the main mechanisms by which Linomide inhibits MS activity and may represent an alternative immunomodulating approach for the treatment of MS and autoimmunity in general.
The influence of the immediate prestimulus EEG microstate (sub-second epoch of stable topography/map landscape) on the map landscape of visually evoked 47-channel event-related potential (ERP) microstates was examined using the frequent, non-target stimuli of a cognitive paradigm (12 volunteers). For the two frequent prestimulus microstate classes (oriented left anterior-right posterior and right anterior-left posterior), ERP map series were selectively averaged. The post-stimulus ERP grand average map series was segmented into microstates; 10 were found. The centroid locations of positive and negative map areas extracted as landscape descriptors. Significant differences (MANOVAs and t-tests) between the two prestimulus classes were found in four of the ten ERP microstates. The relative orientation of the two ERP microstate classes was the same as prestimulus in some ERP microstates, but reversed in others. Thus, brain electric microstates at stimulus arrival influence the landscapes of the post-stimulus ERP maps and therefore, information processing; prestimulus microstate effects differed for different post-stimulus ERP microstates.
Linomide (quinoline-3-carboxamide, LS-2616), a synthetic immunomodulator, protects animals against a variety of experimental autoimmune diseases. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS), linomide blocks both the clinical and histological signs of the disease, without inducing generalized immunosuppression. In the first clinical trial in patients with MS, linomide was shown to inhibit the progression of the disease. In the present study we investigated several aspects of the mechanisms of action of this immunomodulator. We found that linomide can inhibit acute EAE even when given as pretreatment, prior to induction of disease (days - 10 to 0). This inhibitory effect was reversed by adoptive transfer of naive spleen cells. A short course (7 days) of linomide treatment also inhibited EAE, especially when administered immediately after disease induction. Spleen cells from linomide-treated mice failed to present myelin antigens to T-cell lines in vitro. The defective antigen presentation was normalized by anti-oxidants such as 2-mercaptoethanol. The proportion of Mac1+ cells in the spleens of linomide-treated mice was significantly reduced and macrophage growth was inhibited in long term cultures of spleen cells derived from linomide-treated animals. Our findings suggest that the effect of linomide on EAE may be attributed, at least in part, to inactivation of antigen presenting cells, possibly following a short period of over-stimulation and increased oxidant production. This mechanism may play a universal role in the regulation of autoimmune reactivity and merits further investigation.
Linomide is a synthetic compound that affects various immunological functions and inhibits experimental autoimmune encephalomyelitis (EAE). In the present study we evaluated the effect of linomide on the HPA axis functions under basal and stress-induced conditions and examined whether the effect of linomide on the HPA axis is involved in linomide-induced amelioration of EAE in rats. Linomide caused a significant increase of serum ACTH and corticosterone (CS). The adrenocortical response to various stress modalities as well as the negative feedback exerted by glucocorticoids was not affected. The marked reduction of thymus weight following linomide treatment was abrogated in adrenalectomized rats. The induction of EAE in adrenalectomized rats was completely inhibited by linomide treatment. These results suggest that the increased CS levels induced by linomide are responsible for the decrease in thymus weight but do not play a role in the therapeutic effect of this drug in EAE.
Brain electric activity is viewed as sequences of momentary maps of potential distribution. Frequency-domain source modeling, estimation of the complexity of the trajectory of the mapped brain field distribution in state space, and microstate parsing were used as analysis tools. Input-presentation as well as task-free (spontaneous thought) data collection paradigms were employed. We found: Alpha EEG field strength is more affected by visualizing mentation than by abstract mentation, both input-driven as well as self-generated. There are different neuronal populations and brain locations of the electric generators for different temporal frequencies of the brain field. Different alpha frequencies execute different brain functions as revealed by canonical correlations with mentation profiles. Different modes of mentation engage the same temporal frequencies at different brain locations. The basic structure of alpha electric fields implies inhomogeneity over time-alpha consists of concatenated global microstates in the sub-second range, characterized by quasi-stable field topographics, and rapid transitions between the microstates. In general, brain activity is strongly discontinuous, indicating that parsing into field landscape-defined microstates is appropriate. Different modes of spontaneous and induced mentation are associated with different brain electric microstates; these are proposed as candidates for psychophysiological 'atoms of thought'.
The present study investigates the threonine requirements of British United Turkey (BUT) Big 6 turkey toms from 0 to 4, 8 to 12, and 16 to 20 wk of age. Growth, feed conversion, and carcass quality responses to increasing dietary threonine levels were measured. From 0 to 4 wk of age (57 g to 1.1 kg live weight), a dietary threonine level of about 0.95% (3.3 g/Mcal ME) was found to be adequate to obtain optimum growth and feed conversion. From 8 to 12 wk of age (4.0 to 8.6 kg live weight), there was no significant response to dietary threonine beyond the basal level of 0.69% (2.2 g/ Mcal ME). From 16 to 20 wk of age (13.1 to 18.7 kg live weight), a threonine level of about 0.58% (1.8 g/Mcal ME) appeared to be adequate to obtain optimum growth. For optimum breast meat deposition, a higher level in the range of 0.64% (2.0 g/Mcal ME) dietary threonine was required. The present findings may point to the importance of threonine as potentially third limiting amino acid after methionine and lysine in cereal-based turkey diets.
OBJECTIVE: Because of its practical importance for public health monitoring in developing countries, we aimed to determine whether susceptibility to penicillin of pneumococci isolated from the upper respiratory tract (URT) is representative of the susceptibility of pneumococci causing pneumonia in children. METHOD: The serogroup distribution and minimum inhibitory concentration of penicillin for 56 and 90 isolates from blood and cerebrospinal fluid, respectively, were compared with those of 833 pneumococcal carriage isolates from Papua New Guinean children. These included 154 and 98 strains from bacteremic and nonbacteremic hospitalized patients with pneumonia, respectively, 350 from outpatients with respiratory infections and 176 and 55, respectively, from children in a community-based study who were healthy or sick with pneumonia. RESULTS: Proportions of pneumococci intermediately resistant to penicillin were comparable in the URT and blood (60%) in 1985 through 1987 when serogroup distributions in the two sites were similar. However, penicillin resistance was higher in the URT (75%) than blood (44%) in 1980 through 1984 when the less frequently carried, less resistant serogroups (1 to 5, 7 to 12, 45 and 46) accounted for a high proportion of bacteremic strains. CONCLUSIONS: URT isolates from any group of sick or healthy children could provide a conservative estimate of antimicrobial susceptibility of invasive strains and is a practical way of monitoring susceptibility as well as evaluating the continued effectiveness of standard antibiotic therapy. If there was cause for concern, it would then be necessary to examine invasive isolates.