Biomedical subjects

T Dierks

Publications and source records attributed to T Dierks.

At least 55 records · Page 3Linked to original sources

PubMed1997

EEG-microstates in mild memory impairment and Alzheimer's disease: possible association with disturbed information processing.

The only available functional neuroimaging methods reaching the time resolution of human information processing are EEG and MEG. Since spectral analysis implies analysis of longer time epochs, the high temporal resolution of EEG is partly lost. By dividing the EEG in the time-domain into segments of similar spatial distribution on the scalp (microstates) it has been possible to assess patterns of neuronal activity representing the information process currently performed by the brain. In the present study alterations of EEG microstates in subjective (n = 31) and objective (n = 38) memory impairment as well as in probable Alzheimer disease (DAT: n = 64) compared to healthy controls (n = 21) were investigated. The main findings were reduced segment durations and a more anterior center of gravity of the microstate topography in DAT. With more pronounced cognitive dysfunction larger window sizes were found. Shorter microstates and larger windows reflect more rapidly changing spatial activation patterns, and are interpreted as an impaired capability to establish stable brain states necessary for normal brain function. The anteriorization of the microstates is consistent with results in the frequency domain and may reflect neuropathological changes in DAT.

Aged↗

PubMed1997

A comparison of qEEG and HMPAO-SPECT in relation to the clinical severity of Alzheimer's disease.

Electroencephalographical studies have disclosed correlations between topographical features of Fast Fourier Transformation maps and the severity of Alzheimer's disease (DAT). The object of the present study was to explore the relations of HMPAO-SPECT and quantitative EEG (qEEG) with the severity of dementia. Twenty-three patients were included in the study. Spectral and topographical EEG parameters were compared with global and regional cerebral blood flow, and with psychometric measures of clinical severity. None of the regions of interest of the SPECT scans were significantly correlated with clinical severity. Low values in delta- and theta bands, however, were related to high scores on the Mini-Mental-State examination (P < 0.01), whereas the Syndrome-Kurz test correlated inversely with the power values in the alpha and beta band. The global decrease in cerebral blood flow (CBF) was associated with a shift on the topographical alpha-centroids in the posterior direction (P < 0.01). In previous studies correlations between CBF and clinical severity were weak, indicating a high interindividual variance, or interactions with concomitant vascular lesions. Whereas SPECT is a well-established tool for the diagnosis of dementia, the present study indicates qEEG as a potential marker for the staging of the cognitive decline in DAT.

Aged↗

PubMed1997

The AMDP modules I-IV: recommendations for a standardized acquisition of EEG data in psychiatry. Association for Methodology and Documentation in Psychiatry.

During the last few years, the working group 'Psychophysiology' of the Association for Methodology and Documentation in Psychiatry (AMDP) discussed the possibility of the establishment of defined EEG modules in psychiatry. It was the aim to create a common data pool in order to be able to have access to larger data sets. The installation of such a common data pool was regarded as an important prerequisite for a future diagnostic application of EEG and EP data in clinical practice. The most relevant arguments are: From a statistical point of view, multivariate investigations can be improved when relatively large data sets are available. Subgrouping of patients is facilitated. Different centers have access to different populations of patients. Furthermore, compliance with the recommendations contributes to a reduction in misunderstanding and false interpretation of other investigators' results. The working group 'Psychophysiology' of the AMDP now recommends EEG modules to be registered in psychiatry. The recommendations are based on investigations using these modules in clinical research and practice as well as several years of discussion within the working group. Four AMDP modules (I-IV) are presented: MI: resting EEG (closed eyes), MII: resting EEG (eyes open), MIII: EEG during videotracking, and MIV: EEG during choice reaction time. Recommendations for additional modules are planned in the near future: MV: EEG during geometry test, MVI: EEG during labyrinth test, and MVII: amplitude stimulus intensity function. MIII-MVI is paralleled by an EEG recording so that psychomotor performance can be measured and EEG data under different activation conditions are available. Compliance with the recommendations guarantees the possibility of access to the common data pool. Computer software is available in Berlin.

Electroencephalography↗

PubMed1996

A microsomal ATP-binding protein involved in efficient protein transport into the mammalian endoplasmic reticulum.

Protein transport into the mammalian endoplasmic reticulum depends on nucleoside triphosphates. Photoaffinity labelling of microsomes with azido-ATP prevents protein transport at the level of association of precursor proteins with the components of the transport machinery, Sec61alpha and TRAM proteins. The same phenotype of inactivation was observed after depleting a microsomal detergent extract of ATP-binding proteins by passage through ATP-agarose and subsequent reconstitution of the pass-through into proteoliposomes. Transport was restored by co-reconstitution of the ATP eluate. This eluate showed eight distinct bands in SDS gels. We identified five lumenal proteins (Grp170, Grp94, BiP/Grp78, calreticulin and protein disulfide isomerase), one membrane protein (ribophorin I) and two ribosomal proteins (L4 and L5). In addition to BiP (Grp78), Grp170 was most efficiently retained on ATP-agarose. Purified BiP did not stimulate transport activity. Sequence analysis revealed a striking similarity of Grp170 and the yeast microsomal protein Lhs1p which was recently shown to be involved in protein transport into yeast microsomes. We suggest that Grp170 mediates efficient insertion of polypeptides into the microsomal membrane at the expense of nucleoside triphosphates.

Adenosine Triphosphate↗

PubMed1996

Luciferase assembly after transport into mammalian microsomes involves molecular chaperones and peptidyl-prolyl cis/trans-isomerases.

The assembly of a heterodimeric luciferase was studied after de novo synthesis of corresponding precursor proteins in reticulocyte lysate and concomitant transport into dog pancreas microsomes. This cytosolic luciferase from a prokaryotic organism (Vibrio harveyi) was specifically used as a model protein to investigate (i) whether the eukaryotic cytosol and the microsomal lumen have similar folding capabilities and (ii) whether the requirements of a polypeptide for certain molecular chaperones and folding catalysts are determined by the polypeptide or the intracellular compartment. The two luciferase subunits were fused to the preprolactin signal peptide. Data indicate that efficient assembly of luciferase occurs in the mammalian microsomes. Furthermore, it was observed that luciferase assembly can be separated in time from synthesis and membrane transport, depends on ATP hydrolysis, is partially sensitive to cyclosporin A and FK506, and in the absence of lumenal proteins is less efficient as compared with the presence of lumenal proteins. Thus, heterodimeric luciferase depends on functionally related molecular chaperones and folding catalysts during its assembly in either the eukaryotic cytosol or the microsomal lumen.

Adenosine Triphosphate↗

PubMed1996

Efficient folding of firefly luciferase after transport into mammalian microsomes in the absence of luminal chaperones and folding catalysts.

Folding of polypeptides emerging from the protein translocase in the membrane of mammalian microsomes was analyzed after synthesis of corresponding precursor proteins in a mammalian translation system. Firefly luciferase was used as a model protein; the corresponding hybrid precursor contained the preprolactin signal peptide. The rates and efficiencies of folding of luciferase in microsomes were compared with those of folding of luciferase in the cytosol. Furthermore, folding of luciferase in microsomes was compared with that in proteoliposomes, i.e. in the absence of luminal molecular chaperones and folding catalysts. Folding in microsomes was less efficient compared with folding in the cytosol. Folding in the absence of luminal proteins was more efficient compared with folding in their presence and identical to folding in the cytosol. Thus, firefly luciferase emerging from translocase can efficiently fold to its native conformation without chaperoning by any luminal proteins. There may be molecular chaperones present in the microsomal membrane that can efficiently substitute for the cytosolic chaperone machinery comprising Hsp40, Hsp60, and Hsp70 with respect to folding of firefly luciferase.

Adenosine Triphosphate↗

PubMed1996

Cyclosporin A inhibits the degradation of signal sequences after processing of presecretory proteins by signal peptidase.

Targeting of presecretory proteins to, and insertion into, the microsomal membrane are mediated by signal sequences. These signal sequences are removed from presecretory proteins by signal peptidase. We demonstrate that the signal sequence of preprolactin, after translocation into microsomes and cleavage by signal peptidase, is converted to an intermediate form. This intermediate was found outside the microsomes, where it was degraded in the presence of cytosol. Degradation of the signal sequence of another presecretory protein, preprocecropinA, occurred even in the absence of cytosol. The immunosuppressant cyclosporin A inhibited trimming of the preprolactin signal sequence and degradation of the preprocecropinA signal sequence. We observed by cross-linking studies that cleaved signal sequences are bound to two microsomal proteins prior to degradation.

Amino Acid Sequence↗

PubMed1996

Topography of the maximum of the amplitude of EEG frequency bands in dementia of the Alzheimer type.

The localization of the maxima of activity of 36 patients with dementia of the Alzheimer type and 36 age-matched controls was calculated after Fourier transformation of EEG data in six frequency bands (4 Hz steps between 1 and 24 Hz). Patients were divided into three groups of severity (BCRS mean < 3,9, 4.0-4.9, and > 4.9). Significant differences were found in the beta frequency band. In the distribution of the maxima of the activity, the maxima of patients were located more frontally than the maxima of controls. The alterations were staged dependent. The beta activity in EEG is said to be correlated with cognitive processes; the correlation between cognitive decline and decreasing beta activity in dementia of the Alzheimer type might support this assumption. Differences in the location of the maxima between patients and controls might allow for differentiation between both groups.

Aged↗

PubMed1996

The predictive value of P300-amplitudes in the course of schizophrenic disorders.

Auditory P300-amplitudes have been found to be correlated with the social functioning and with the impairment in daily life by negative symptoms in cross-sectional studies. In this prospective longitudinal study, the correlation of auditory P300-amplitudes registrated at the index examination was investigated with the clinical outcome after an average of 2.4 years. Based on previous studies, only schizophrenic patients who were in a stabilized residual state were included in the study. Reference-independent P300-parameters of the index examination were correlated with axis V of DSM-III-R (GAF), with the Brief Psychiatric Rating Scale (BPRS) and with the Scale for Assessment of Negative Symptoms (SANS) assessed at the follow-up examination. The correlation of index P300-amplitude with social functioning at follow-up was significant. No correlations of index P300 with the current symptomatology at follow-up, as expressed by BPRS and SANS was found, however. The results indicate a predictive value of the P300-amplitude on the clinical outcome in terms of social functioning of schizophrenic patients.

Acoustic Stimulation↗

PubMed1996

Early cerebral functional outcome after coronary artery bypass surgery using different acid-base management during hypothermic cardiopulmonary bypass.

BACKGROUND: Cerebral injury can render meaningless an otherwise successful cardiac operation. As carbon dioxide management during hypothermic cardiopulmonary bypass has a major impact on cerebral blood flow during bypass, it may also influence postoperative cerebral function. The objective of this prospective, controlled, double-blind study was to compare the effect of pH-stat (temperature correction of blood gas analyses) or alpha-stat (no temperature correction) on brain function. METHODS: Cerebral function was assessed non-invasively using neurological examination, a neuropsychological test battery, quantitative electroencephalogram and the cognitive evoked potential P300 preoperatively and on postoperative day 7 or 8. Forty-five patients undergoing elective aortocoronary bypass grafting in barbiturate/opiate anesthesia were randomised into a pH-stat-(n = 23) and an alpha-stat-group (n = 22). Membrane oxygenators with arterial line filtration and non-pulsatile flow at a perfussion pressure of 50-60 mmHg were used throughout. RESULTS: One patient in each group developed a new paresis. Among 49 comparisons of cerebral function parameters, only 3 showed significant differences at the 5%-level, i.e. exactly what is expected purely by chance. These differences were too small to be clinically relevant and favored either pH-stat (theta-amplitude) or alpha-stat (subtest 3 of syndrome-short-test, number of mistakes in aiming). CONCLUSION: Under the bypass conditions of this study there was no difference in early cerebral functional outcome between pH-or alpha-stat carbon dioxide management during hypothermic cardiopulmonary bypass.

Acid-Base Equilibrium↗

PubMed1995

Correlation between cognitive brain function and electrical brain activity in dementia of Alzheimer type.

Psychometric tests which assess cognitive brain function in dementia disorders are partly prone to artifacts, e.g., the experience of the investigator and the cooperation of the patient influences the results. An objective way to assess the degree of cognitive disturbance could be to measure neuronal activity represented by the electrical brain activity. The aim of the present study was to investigate how well cognitive function in dementia assessed by psychometric tests correlates with electrical brain activity (EEG). Multichannel EEG data was reduced into 3-D intracerebral equivalent dipole EEG generators allowing a more convenient statistical data management and valid physiological data interpretation. 35 patients suffering from dementia of Alzheimer type were investigated. An increase of dipole strength in the slow frequency bands, a more anterior equivalent dipole of alpha- and beta-activity, and a slowing of the EEG with increasing cognitive deterioration could be demonstrated. The results support the hypothesis that the amount of disturbance of cognitive function in dementia can be assessed by measuring the electrical activity of the brain.

Adult↗

PubMed1995

Larger topographical variance and decreased duration of brain electric microstates in depression.

The topographical configuration of the spontaneous brain electric fields is considered to contain relevant information about the pattern of the generating cortical electrochemical activation and the associated cognitive processes. Space oriented segmentation allows to break down the stream of the spontaneous EEG into brain electric microstates with stable configuration of the fields. It has been shown that the mean duration of the microstates was consistent with the duration of elementary steps of cognitive processes, and that different topographies of the microstates are associated with different cognitive modalities. Space-oriented segmentation was applied to the resting EEG of 22 depressive patients and of 22 controls. The topographical variance was larger, and the most prominent brain electrical microstates of the EEG epochs were significantly shorter in the depressive group than in controls. No differences were found for the shortest microstates. This result cannot be explained by group differences in the frequency domain of the EEG. No topographical differences were found between the microstates of depressives and those of controls. Based on previous results in healthy volunteers during spontaneous cognition and in schizophrenic patients, the findings indicate that formal aspects rather than the modalities of the stream of cognition are altered in depression. Automatic and schematic processing, and attentional deficits as described in depressive patients might account for the finding of less sustained brain electrical microstates.

Adult↗

PubMed1995

Electrical brain activity in schizophrenia described by equivalent dipoles of FFT-data.

Since results of conventional FFT-power-analysis are reference-dependent, only unambiguous neurophysiological data should be used for a functional physiological interpretation of EEG-data. FFT-approximation with successive center-of-gravity-dipole calculation gives unambiguous EEG-data with regard to recording reference. In the present investigation 22 medicated schizophrenic patients were compared with 22 healthy age- and sex-matched controls with regard to spontaneous resting EEG. More anterior and superficial equivalent-dipoles were found in the beta-bands for schizophrenic patients compared to healthy control subjects. There was a tendency of increased beta-activity in schizophrenic subjects. With more severe schizophrenic symptoms (higher BPRS-score), the more anterior was the equivalent-dipole localization in the beta 1-band, and the deeper in the theta-band. The different locations of the beta-band dipoles in schizophrenic patients suggest that different neuronal populations generate beta-activity in schizophrenia compared to healthy controls. FFT-approximation allows a substantial and meaningful data reduction in multichannel recordings and will hopefully help in understanding pathological brain functions in schizophrenia.

Adolescent↗

PubMed1995

P300-mapping--a neurophysiological tool to quantify cerebral dysfunction after coronary artery bypass grafting.

Objective parameters are needed to quantify cerebral dysfunction following cardiac surgery in outcome and comparative studies. In this investigation we assessed the value of the late auditory evoked potentials N100 and P300 to measure the neuropsychological deficit after coronary artery bypass grafting (CABG). N100, an exogenous potential is influenced by the stimulus pattern (frequency, intensity and stimulus presentation rate). P300, an endogenous potential, depends on the cognitive processing invoked by the stimulus. With approval of the Human Investigation Committee and the patients' consents, 52 subjects undergoing elective CABG were enrolled. Operation, extracorporal circulation, anesthesia and postoperative intensive care were standardized. Twenty-channel recordings of N100 and P300 were obtained for off-line analysis. P300 was elicited using an oddball paradigm with rare target tones interspersed among frequent non-target tones. Additionally, neuropsychological tests (syndrome short test SKT and letter cancellation test) were carried out. Neurological examination and all tests were compared preoperatively and one week postoperatively. A significant deterioration in cerebral function was documented by the SKT score (P = 0.04), an increase in P300 latency (P = 0.004) and an increase of mistake rate in counting the P300 target tone (P = 0.02). No differences between preoperative and postoperative testing were found for letter cancellation, P300 amplitude and any N100 parameter. No correlation was found between the preoperative/postoperative changes in SKT score and P300 latency. P300 was proved to be an objective neurophysiological parameter that allows for the quantification of cerebral function after CABG.

Aged↗

PubMed1995

Plasma levels of the beta-carbolines harman and norharman in Parkinson's disease.

Several lines of evidence suggest that endogenous and exogenous toxins may play a major role in the pathogenesis of Parkinson's disease (PD). In vivo aromatic beta-carbolines, like harman or norharman, may easily be formed by cyclization of indoleamines with e.g. aldehydes. Because of the structural similarity to MPTP, beta-carbolines have been proposed as endogenous toxins. For further elucidation of the role of beta-carbolines in neurodegenerative disorders, harman and norharman plasma levels were measured in 36 patients with PD and compared to an age- and sex-matched control group. Plasma levels of norharman in PD were significantly higher compared to the control group. Harman in the plasma of Parkinsonian patients was also elevated compared to controls, but this difference was not significant. Correlation of beta-carbolines with plasma levels of L-dopa, oral doses of bromocriptine and selegiline in treated Parkinsonian patients showed no significant results. On the one hand these results may suggest a possible role of beta-carbolines in the pathophysiological processes initiating PD, by, e.g., inducing mitochondrial respiratory inhibition like MPP+. One may speculate, however, that elevated levels of norharman and harman are due to an endogenous upregulation caused by unknown metabolic processes.

Aged↗

PubMed1994

P300 in schizophrenia: interactions between amplitudes and topography.

Low P300 amplitudes and topographical asymmetries have been reported in schizophrenic patients, but reference-independent amplitude assessment failed to replicate reduced amplitudes. P300 amplitude is conventially assessed at midline electrodes (Pz), and asymmetric topography as reported in schizophrenics, may confound this measurement. We investigated the possible interaction between P300 topography and assessments of amplitudes. In 41 clinically stable schizophrenics and 31 normal controls, the general finding of reduced amplitudes at the Pz-electrode and topographical asymmetries in the patient group were replicated. In both groups, asymmetries of the P300 field (lateralized peaks) reduced the standard amplitude assessment at the midline parietal electrode, but did not affect the reference-independent, global amplitude assessment. This shows that asymmetry per se does not imply reduced field strength. In addition, in schizophrenics, but not in controls, there was a significant effect of the direction of asymmetry on both amplitude measures, amplitudes being lower with increasing shift of the P300 peak to the right side. Considering also the slightly left-lateralized peaks in the normal controls, this suggests that only right-lateralized P300 peaks express functional deficits in schizophrenics, whereas left-lateralized peaks fall within the physiological variability of the P300 field. The reference-independent amplitude assessment is proposed for unambiguous amplitude assessment in order to better define the clinical, psychological and physiopathological meaning of the P300 alterations in schizophrenics.

Adult↗

PubMed1994

P300 asymmetries in schizophrenia revisited with reference-independent methods.

Evidence of hemispheric asymmetries in schizophrenia has been reported from different research areas. Asymmetries in evoked potential P300 topography are still controversial because of inconsistent findings. In the present study, previous results of abnormal lateralization of P300 were replicated in stabilized residual schizophrenic patients. Auditory P300 was recorded during an oddball task in which subjects detected rare target stimuli. Schizophrenic patients had the P300 peak shifted to the right hemisphere and differed significantly from age- and sex-matched normal control subjects who had left-lateralized P300 peaks. A comparison of different methods of assessment and analysis of the topographical features of the P300 electric fields showed that the extraction of reference-independent descriptors of P300 topography is a reliable and sensitive method for statistical handling of the maps. The results suggest left hemispheric dysfunction during cognitive tasks in a subgroup of schizophrenic patients. Inconsistencies between previous studies are likely to be due to heterogeneous patient groups, which may have included patients in an acute schizophrenic episode or patients in clinical remission. Investigation of the clinical meaning of P300 alterations requires careful psychopathological definition of the patient groups.

Adult↗

PubMed1994

Event-related potentials and psychopharmacology. Cholinergic modulation of P300.

The event-related potential P300 probably reflects the encoding of information into short-term memory. Anatomical structures of the limbic system are involved in this process. Since the same structures are involved in the generation of the event-related potential P300, P300 is thus well suited to assess pharmacological influence on memory functions and cognitive processes, for example, by changing the availability of neurotransmitters like acetylcholine at their respective receptors.

Adult↗