Thomas Dierks

Spatial pattern of cerebral glucose metabolism (PET) correlates with localization of intracerebral EEG-generators in Alzheimer's disease

BACKGROUND Since the measurement of human cerebral glucose metabolism (GluM) by positron emission tomography (PET) and that of human cerebral electrical activity by EEG reflect synaptic activity, both methods should be related in their cerebral spatial distribution. Healthy subjects do indeed demonstrate similar metabolic and neuroelectric spatial patterns. OBJECTIVE The aim of the study was to show that this similarity of GluM and EEG spatial patterns holds true in a population with a high variability of glucose metabolism. METHODS We investigated healthy control subjects and patients with varying degrees of cognitive dysfunction and varying GluM patterns by applying [18F]FDG PET and EEG. RESULTS We demonstrated that the localization of intracerebral generators of EEG correlates with spatial indices of GluM. CONCLUSION These results indicates that EEG provides similar spatial information about brain function as GluM-PET. Since EEG is a non-invasive technique, which is more widely available and can be repeated more often than PET, this may have important implications both for neuropsychiatric research and for clinical diagnosis. However, further studies are required to determine whether equivalent EEG dipole generators can yield a diagnostic specificity and sensitivity similar to that of GluM-PET.

Clinical efficacy of Ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type

Among the psychiatric illnesses associated with old age primary degenerative dementia of the Alzheimer type (DAT) has gained increasing importance in recent years. Even though a curative treatment of the disease is currently impossible, various drugs can be used to slow down its progression. In the present study the influence of oral treatment with 240 mg/day of Ginkgo bilabo special extract EGb 761 (Tebonin forte, manufactured by Dr Willmar Schwabe, Karlsruhe) on the clinical course of DAT was investigated in a double-blind, randomized, placebo-controlled parallel-group design in 20 outpatients. The duration of treatment was 3 months. The primary outcome variable was the sum score in the SKT-test for the determination of attention and memory. Other psychometric tests (trailmaking test, ADAS, CGI) and electrophysiological investigations (EEG topography) were evaluated descriptively. Although the active-treatment group, with a mean sum score of 19.67 points in the, S.K.T., had a poorer baseline level than the placebo group (18.11 points), it experienced an improvement to 16.78 points under treatment with EGb 761 whereas the placebo group deteriorated to 18.89 points. The differences between the baseline and final values formed the basis for a statistical group comparison, which gave a result favourable to EGb 761, at a significance level of p < .013. In addition to this psychometric confirmation of efficacy, certain descriptive trends were found at the psychopathological (Clinical Global Impression) and dynamic functional (EEG findings) levels, which can be interpreted as evidence of effectiveness of Ginkgo biloba special extract EGb 761 in mild to moderate dementia and of local effects in the central nervous system. Inter-group differences in the ADAS cognitive and non-cognitive subscales did not reach statistical significance, probably because of the small sample size.

Dementia of the alzheimer type: Effects on the spontaneous EEG described by dipole sources

The present study on brain electrical activity in healthy subjects (n = 35) and patients suffering from dementia of the Alzheimer type (DAT; n = 35) used Fast Fourier Transformation-dipole approximation to quantify differences between the two groups. DAT patients showed a shift of alpha and beta activity toward frontal brain regions. The amount of this shift correlated with the degree of dementia. The relative distribution of magnitude of activity between the frequency bands differed between DAT patients and control subjects. DAT patients had higher magnitudes in the slow frequency range, correlating with the severity of dementia, and lower ones in the alpha and beta range compared with findings in age-matched control subjects.

Amplitudes of auditory P300 in remitted and residual schizophrenics : correlations with clinical features

The parameters of auditory P300 were studied with reference-independent methods in a group of 18 remitted and residual schizophrenics, and in 18 age- and sex-matched controls. In the schizophrenic group, significant inverse correlations were found between P300 amplitudes and level of psychopathology assessed with the Scale for Assessment of Negative Symptoms and with the Brief Psychiatric Rating Scale. Clinical variables regarding social functioning and adaptation, assessed with the Schedule for Affective Disorders and Schizophrenia, and with axis V of DSM-III-R, correlated significantly with low amplitudes. The scalp locations of the maxima and minima of the P300 potentials had the tendency to be dislocated to the right in schizophrenics compared with controls. The results indicate low P300 amplitudes to be associated with pervasive cognitive impairment. Future studies will determine whether low P300 amplitudes have prognostic validity for course and outcome of schizophrenic disorders.

Topography of the quantitative electroencephalogram in dementia of the Alzheimer type : relation to severity of dementia

Conventional electroencephalographic (EEG) frequency bands and peak frequency were investigated in patients with probable dementia of the Alzheimer type (DAT). Measures of EEG topography and activity were also related to the severity of dementia, as assessed by neuropsychological tests. EEG activity measured in conventional frequency bands proved to be the most sensitive parameter for the quantitative differentiation of DAT, whereas the topography of peak frequency was the better qualitative discriminator between healthy subjects and DAT patients.

Intensity dependence of auditory evoked potentials (AEPs) as biological marker for cerebral serotonin levels: effects of tryptophan depletion in healthy subjects.

Abstract Rationale: The intensity dependence of the auditory evoked potentials (AEP) has been suggested to be a specific biological marker of central serotonergic activity. Objective: While previous studies used circumstantial evidence to support this hypothesis, we manipulated (decreased) cerebral levels of serotonin directly by using tryptophan depletion. Methods: Twelve healthy young subjects were investigated using placebo and two different amino acid mixtures in a double blind cross over design on three different occasions. AEPs recorded during tryptophan depletion were analyzed by dipole analysis and regional sources using methods published in the literature. Results: For none of the mixtures a significant effect of tryptophan depletion was found. There was a trend towards reduced intensity dependency after tryptophan depletion, especially in the right hemisphere. This reduction correlated with the amount of reduced tryptophan in plasma. Conclusions: The results indicate, in contrast to earlier indirect studies, that the intensity dependence of AEPs is not a specific marker of central serotonergic activity.

Differences in P300 amplitudes and topography between cycloid psychosis and schizophrenia in Leonhard's classification

In a polydiagnostic approach, we investigated the parameters of auditory P300 in a group of 18 remitted schizophrenics and in 18 age‐ and sex‐matched controls. All patients fulfilled the criteria of schizophrenic disorder according to DSM‐III‐R. Applying Leonhards classification, patients were to be subdivided into 7 cycloid psychosis and 11 Leonhards schizophrenics. Patients with cycloid psychosis fulfilled the operational criteria of Brockington et al. We found significantly lower P300 amplitudes in the group of Leonhards schizophrenics than in controls and in cycloid psychosis, whereas no difference could be shown between patients with cycloid psychosis and controls. Both the maxima and the minima of the P300 field map were dislocated significantly to the right in the group of Leonhards schizophrenics but not in cycloid psychosis.

Longitudinal changes in quantitative EEG during long-term tacrine treatment of patients with Alzheimer's disease

Quantitative EEG is a potentially useful tool in demonstrating the effects of treatments with acetylcholinesterase (AChE) inhibitors on the progression of Alzheimers disease (AD). In order to define the profile of EEG changes during tacrine long-term treatment, for 12 months we followed 15 AD patients receiving an optimal individually tolerable dose. After 3 months theta global field power (GFP) was significantly reduced, and after 6 months both theta and delta GFP decreased. Theta GFP was still reduced after 12 months of treatment when compared to the baseline. Significant decreases in fast activities of beta 1 and beta 2 GFP were also observed. The untreated reference group (n = 10) did not show any significant changes in GFP after 12 months follow-up, although generators of theta activity had a significant shift towards posterior regions. These findings suggest that slowing in fast EEG frequencies during chronic treatment with AChE inhibitors may provide an early indicator of declining treatment efficiency.

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

SummaryThe 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.

Multimodal imaging of residual function and compensatory resource allocation in cortical atrophy: a case study of parietal lobe function in a patient with Huntington's disease

In a case of Huntingtons disease (HD) with dementia and pronounced parieto-frontal atrophy, the functional state of the affected regions was investigated using functional magnetic resonance imaging (fMRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET). It was observed that although parietal areas showed extensive atrophy and reduced resting glucose metabolism, the patient performed with similar accuracy but with longer response time in a visuospatial task compared with healthy control subjects. At the same time, the blood oxygen level-dependent (BOLD) fMRI signal in these areas, which are involved in visuospatial processing, showed a similar task-dependent modulation as in control subjects. The signal amplitude (signal percent change) of the task-dependent activation was even higher for the HD patient than in the control group. This residual functionality of parietal areas involved in visuospatial processing could account for the patients performance in the task concerned, which contrasted with his poor performance in other cognitive tasks. The increased percent-signal change suggests that a higher neuronal effort was necessary to reach a similar degree of accuracy as in control subjects, fitting well with the longer reaction time. We propose that fMRI should be considered as a tool for the assessment of functionality of morphologically abnormal cortex and for the investigation of compensatory resource allocation in neurodegenerative disorders.