Change in quantified electroencephalography (QEEG) with medication and altered clinical state in the same subjects with schizophrenia.
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Antipsychotic Agents↗
Biomedical subjects
E Gordon
Publications and source records attributed to E Gordon.
Decomposing skin conductance into tonic and phasic components.
Overlapping phasic skin conductance responses (SCRs) obtained using short interstimulus interval (ISI) paradigms such as those employed in cognitive research, confound measurement of each discrete phasic SCR as well as the tonic skin conductance level (SCL). We report a method of resolving this problem using a modelling technique that takes advantage of the stereotyped nature of the within-subject SCR waveform. A four-parameter sigmoid-exponential SCR model that describes the entire response, was developed and extended to five-, six- and eight-parameter skin conductance (SC) models. These SC models were successfully curve-fitted to more than 60 SC segments, each containing one SCR or two overlapping SCRs on a sloping baseline obtained from 20 normal subjects. The SC segments were consequently decomposed into their components: the tail of the previous response, one or two SCRs and the SCL. The SCRs free of the complication of overlap were then quantified. The raw SCRs of the same data set were also measured using a standard method. The standard measurement showed a significant reduction of 15% in amplitude and 140 ms in peak latency compared to our method. The basic four SCR model parameters--onset time, rise time, decay time constant and gain--showed increasing inter-subject variability in that order. These SCR model parameters may be studied as variables in normal and patient groups and as indices of treatment response. This quantitative method also provides a means to assess the relationships between central and autonomic psychophysiologic measures.
Adult↗
Is postictal electrical silence a predictor of response to electroconvulsive therapy?
Electroconvulsive therapy (ECT) is an established effective treatment modality for patients with severe depression. Recent studies have focused on developing predictors of response. In this prospective study, using percent decrease in Hamilton Depression Scale (21 items) as the outcome measure, we blindly evaluated 33 inpatients with major depression to determine whether postictal suppression, the electrical silence following induced seizure, would predict treatment response to ECT. A significant relationship was observed between degree of postictal suppression and likelihood of clinical improvement. Postictal suppression should be explored in more controlled studies as a predictor of ECT response.
Brain↗
[Therapeutic results in acute skull injuries at KS (Karolinska Hospital) during 25 years. Improved outcome with hyperventilation].
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Adolescent↗
Pain: ethics, culture, and informed consent to relief.
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Cultural Characteristics↗
Numbers of preceding nontargets differentially affect responses to targets in normal volunteers and patients with schizophrenia: a study of event-related potentials.
This event-related potential study systematically varied the number of nontargets (1, 3, 5, 7, 9) preceding the target tone in an oddball experiment and examined the effect of this on N2, P3, and reaction time measures in schizophrenic patients and normal volunteers. Schizophrenic patients were found to have reduced P3 amplitudes, but this reduction was restricted to series when the targets followed an intermediate number (3-7) of nontargets, and not when targets followed a short (1) or long series (9) of nontargets. Although other interpretations of this finding are possible, the pattern of results could be explained by the hypothesis that the refractory period governing the generation of the P3 component was prolonged in schizophrenia.
Adult↗
Regional differentiation of cortical activity in schizophrenia: a complementary approach to conventional analysis of regional cerebral blood flow.
This study examines an alternative to a narrow locus-of-dysfunction cortical pathophysiology in schizophrenia, which in turn suggests a modified approach to the analysis of data from regional cerebral blood flow studies. The results provide qualified support for a model of impaired differentiation of cortical activity in schizophrenia. As an index of the differentiation of cortical fields, regional gradients of cortical blood flow were examined. Medicated patients (n = 15) failed to show the differentiation of networks in frontal areas during a verbal memory recognition task observed in normal comparison subjects (n = 15). Unmedicated patients (n = 15) at rest tended to lose normal lateralization and had increased gradients in the right frontal area compared with normal comparison subjects.
Adult↗
Maximum variance of late component event related potentials (190-240 ms) in unmedicated schizophrenic patients.
The averaging of individual late component event related potential (ERP) responses, particularly P300, has revealed significant differences between schizophrenic patients and normal subjects. However, the averaging process removes the variability of the individual epochs that constitute that average. The response-variance-curve (RVC) method quantifies the variability of the individual epochs and allows examinations of windows of maximum variance. In this study, we examine the complementary nature of the RVC method to the traditional averaging approach. The averaged N200 and P300 ERP components differed significantly between the schizophrenic and normal groups, but not between the unmedicated and medicated schizophrenic patients. The RVC measure, on the other hand, revealed systematic differences in variability, maximal between 190 and 240 ms, between the unmedicated and medicated schizophrenic patients. The RVC measure therefore provides a focused time frame in which to examine dysfunctions in information processing and macroscopic scale changes in brain function due to medication.
Acoustic Stimulation↗
Event related response variability in schizophrenia: effect of intratrial target subsets.
The response-variance-curve (RVC) method quantifies the variability of the individual epochs that constitute the average event related potential (ERP), providing complementary information to that offered by ERPs. Numerous studies have found that average ERP late components of an auditory "oddball" paradigm can differentiate schizophrenic patients from normal subjects. Our previous study of the RVC measure revealed significant differences between medicated and unmedicated schizophrenic patients in the maximum ERP variability from 190 to 240 ms. In the present study of unmedicated schizophrenic patients and normal control subjects, we examined the influence of intertarget intervals (generated by pseudorandom stimulus sequences in an auditory oddball paradigm) on the intratrial effects of ERP variability measured by the RVC. The ERPs of unmedicated schizophrenic patients were characterized by an instability in a latency window corresponding to the N200 component. The effect was particularly large at an intertarget interval of 7.8 s and was significantly reduced on either side of this intertarget interval.
Acoustic Stimulation↗
Projection onto centroids difference vectors: a new approach to determine between group topographical differences, applied to P3 amplitude in schizophrenia.
A common problem in electrophysiological research concerns between group analysis of EEG and ERP topography. This paper proposes a new technique for determining whether or not a significant difference exists between multiple scalp site measurements from two groups. The method requires no a priori assumptions about the data and is thus ideal for exploratory data analysis, and it also requires that only one statistical test need be performed (significantly reducing the possibility of type I errors). The Projection onto Centroids Difference Vectors (PCDV) method involves deriving a measure from each individual of whether their measurements across sites are closer overall to the mean measurements of the rest of their experimental group, or to the other group. These measures from each individual are then compared between groups using a Student's t test, which indicates whether one group's data is significantly spatially different from the other. In this study we describe the method in detail and apply it to both stimulated data and to real auditory P3 data in unmedicated, medicated schizophrenics and matched normal controls. The PCDV method was also compared with statistical probability mapping (SPM). The PCDV method revealed the differences between the normal and patient groups more unambiguously than SPM, and the simulated data revealed that it was not liable to type I errors. PCDV provides an appropriate method for testing any between group EEG and ERP topographical differences.
Adult↗
Classification of single-trial ERP sub-types: application of globally optimal vector quantization using simulated annealing.
Examination of the single trials which are traditionally averaged to form late-component ERPs reveals a number of different sub-types of response. This study introduces an automated and robust approach to objectively classify these ERP sub-types. Auditory oddball ERP (target tones) data were examined in 25 normal subjects. Globally optimal vector quantization using simulated annealing (the "Metropolis algorithm") was employed to determine the natural groupings of the single-trial responses that constitute the average ERP. No prior assumptions about the ERP patterns were imposed. This is the first study to employ a cluster analysis technique with globally optimal properties in ERP research. We demonstrate that, due to the presence of many different undesirable local minima, a globally optimal solution is crucial if the classification of the single-trial ERPs is to reflect their real structure. The results of this study showed that only around 40% of single trials had a morphology which resembled the averaged ERP wave form. The remaining single trials had a response morphology which was different from the average, in terms of the amplitude and latency of the components. Single-trial ERP response sub-types may provide fundamental complementary functional information to the ERP average.
Acoustic Stimulation↗
Consistency of the first fixation when viewing a standard geometric stimulus.
Eye movements in response to presentation of a standard geometric figure (Rey Complex Geometric Figure) were investigated in 33 normal subjects. The figure was presented to each subject for 20 s, with instructions to remember as much detail as possible. Stimulus display was managed by special software that ensured all subjects were focused on the centre of the monitor before presentation, thus controlling for the initial point of gaze. Subjects were instructed, after viewing the stimulus, to reproduce the figure to scale on a blank sheet of paper. Location of the first voluntary fixation during the viewing period was consistently near the same feature in 80% of subjects (cohort I, n = 20). Patterns of eye movement during the remainder of the period, however, were found to vary widely among individuals. A complementary experiment using a second group of subjects (cohort II, n = 13) was undertaken to examine possible effects of brain function lateralisation on processing a feature in the left hemi-field. No lateralisation effect was evident and consistent identification of the same feature in the first voluntary fixation was confirmed for all subjects. No systematic relationships were found between eye movement indices obtained from real-time viewing of the Rey Figure and subsequent recall by drawing.
Adolescent↗
Eye movement and electrodermal responses to threat stimuli in post-traumatic stress disorder.
A core feature of post-traumatic stress disorder (PTSD) is hypervigilence to threatening material. This study measured processing of threat material in PTSD with simultaneously acquired initial eye movements and electrodermal activity, following presentation of threatening and neutral words. Ten PTSD subjects and 10 controls were presented with 4 words in parafoveal range. On trials in which a threat word was present, PTSD subjects demonstrated initial eye fixations on the threat word more than controls. PTSD subjects also demonstrated more orienting responses on all trials than controls. These results suggest that processing of threat information in PTSD can be usefully investigated with convergent psychophysiological methodologies.
Adult↗
Outcome of head injury in 2298 patients treated in a single clinic during a 21-year period.
Between 1968 and 1988, 2298 head-injured patients of all grades of severity were registered in the data bank of a single clinic. The majority of patients were admitted to a community hospital and transferred later to the neurosurgical clinic. The data included mechanism of injury and clinical status at admission, including the level of consciousness according to the Glasgow Coma Score (GCS) before and after resuscitation. After admission, nearly all patients below a score of 8 were intubated and treated with controlled ventilation until the patient awakened, died, or had remained in a steady state for approximately 3 weeks. Assessment of the final outcome was made according to the Glasgow Outcome Scale (GOS) both at discharge and again after the patient's status was stabilized. The results show a stable yearly outcome during the 21 years of recording but a significantly improved good recovery and mortality rate when compared with our previous results. Outcome was significantly correlated to age and type and severity of lesion, as judged by the postresuscitation GCS. The outcome of the 1264 most severely injured, comatose patients (GCS < 9) shows a good recovery rate of 55%, a severely disabled rate of 14%, a vegetative rate of 7%, and a mortality rate of 24%. We attribute these results, which compare favorably with others, to prompt airway control and controlled ventilation in unconscious patients.
Accidental Falls↗
Antiviral properties of aminodiol inhibitors against human immunodeficiency virus and protease.
A series of aminodiol inhibitors of human immunodeficiency virus type 1 (HIV-1) protease were identified by using an in vitro peptide cleavage assay. BMS 182,193, BMS 186,318, and BMS 187,071 protected cells against HIV-1, HIV-2, and simian immunodeficiency virus infections, with 50% effective doses ranging from 0.05 to 0.33 microM, while having no inhibitory effect on cells infected with unrelated viruses. These compounds were also effective in inhibiting p24 production in peripheral blood mononuclear cells infected with HIV-1 IIIB and against the zidovudine-resistant HIV-1 strain A018C. Time-of-addition studies indicated that BMS 182,193 could be added as late as 27 h after infection and still retain its antiviral activity. To directly show that the activity of these compounds in culture was due to inhibition of proteolytic cleavage, the levels of HIV-1 gag processing in chronically infected cells were monitored by Western blot (immunoblot) analysis. All compounds blocked the processing of p55 in a dose-dependent manner, with 50% effective doses of 0.4 to 2.4 microM. To examine the reversibility of BMS 186,318, chronically infected CEM-SS cells were treated with drug and virions purified from the culture medium. Incubation of HIV-1 particles in drug-free medium indicated that inhibition of p55 proteolysis was slowly reversible. The potent inhibition of HIV-1 during both acute and chronic infections indicates that these aminodiol compounds are effective anti-HIV-1 compounds.
Antiviral Agents↗
Aminodiol HIV protease inhibitors. 1. Design, synthesis, and preliminary SAR.
A series of HIV protease inhibitors containing a novel C2 symmetrical "aminodiol" core structure were prepared from amino acid starting materials. The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds. Optimization of the structure-activity in this series led to aminodiol 9a (Ki = 100 nM; ED50 (HIV-1) = 80 nM) containing P1/P1 benzyl and P2/P2 Boc substituents. Compound 9a is a selective inhibitor of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin. In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs. After i.v. and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40%) and a promising plasma elimination half-life (4 h).
Amino Alcohols↗
The P300 ERP component: an index of cognitive dysfunction in depression?
A number of measures of brain function have suggested that depression is associated with cerebral hypoactivity. This study examines the late components of the event-related potential (ERP), in particular the P300 component, in depression. The P300 component is thought to index the updating of neurocognitive models which are concerned with the prediction of future events. Cognitive theories of depression include the proposition that depression may be characterized by abnormalities in the prediction of future events. The P300 component may therefore provide one neurophysiological index of cognitive dysfunction in depression. Twenty-seven subjects (14 medicated, 13 drug-free) fulfilling DSM-III criteria for Major Depression were compared to 27 age- and sex-matched normal controls. The amplitudes and latencies of N100, P200, N200 and P300 ERP components, reaction time and task accuracy were recorded during a standard auditory discrimination task. No significant differences were found in any ERP component measure or in reaction-time between the groups. Depressed subjects performed the experimental task significantly less accurately than normal controls, but this was not reflected in the ERPs.
Antidepressive Agents, Tricyclic↗
Single photon emission computed tomography (SPECT) measures of brain function in schizophrenia.
This study explores SPECT measured in schizophrenic patients at rest. Left temporal lobe activity was found to be decreased with increasing positive symptoms' scores scores. Medicated patients showed a reversal of this pattern underlying this positive symptom effect. Patients with a recent history of auditory hallucinations showed an atypical right temporal lobe dominance, which occurred independently of medication status. These preliminary data are suggestive of the potential utility of SPECT to elucidate symptom/medication/brain activity interrelationships in schizophrenia.
Antipsychotic Agents↗