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Biomedical subjects

Klaus P Ebmeier

Publications and source records attributed to Klaus P Ebmeier.

15 recordsLinked to original sources
PubMed2006

The effects of escitalopram on working memory and brain activity in healthy adults during performance of the n-back task.

RATIONALE: Psychotropic medication affects cognition and brain function, making it a potential confounder in functional neuroimaging studies of psychiatric patients. OBJECTIVE: To determine whether the sub-acute administration of an antidepressant (escitalopram) would induce differences in cognitive performance and associated brain function, which could be observed within the normal power of a functional imaging study. MATERIALS AND METHODS: Healthy adults (N=10) received a short course of escitalopram (10 mg/day for 7 days). Participants performed a parametric working memory (WM) task during BOLD fMRI, both while medication-free and after medication. To control for order effects, the medication-free examination was completed by half the subjects before starting medication and by the other half at least one week after medication. RESULTS: Escitalopram had no significant effect on WM accuracy or reaction time. Preliminary analysis of the imaging data revealed no significant (p(corrected)<0.05) differences in memory-load-dependent activation between conditions. However, small volume correction analysis of regions that were significant prior to correction for multiple comparisons highlighted between condition differences in regions likely to be susceptible to antidepressant effects (i.e. thalamus, anterior cingulate and inferior frontal gyrus). CONCLUSIONS: These results suggest that the sub-acute administration of antidepressants in healthy controls does not affect cognitive or hemodynamic function in healthy adults to a magnitude greater than one standard deviation unit. Therefore, the confounding effect of antidepressants on signal intensity in imaging studies of medicated, depressed individuals may be limited.

Adult↗
PubMed2006

Functional imaging as a predictor of schizophrenia.

BACKGROUND: Prospective studies of young individuals at high risk of schizophrenia allow the investigation of whether neural abnormalities predate development of illness and, if present, have the potential to identify those who may become ill. METHODS: We studied young individuals with at least two relatives with the disorder. At baseline functional magnetic resonance imaging (fMRI) scan, none met criteria for any psychiatric disorder, but four subjects subsequently developed schizophrenia. We report the baseline functional imaging findings in these subjects performing a sentence completion task compared with normal control subjects (n = 21) and those at high risk with (n = 21) and without (n = 41) psychotic symptoms who have not developed the disorder. RESULTS: High-risk subjects who became ill demonstrated increased activation of the parietal lobe, decreased activation of the anterior cingulate, and smaller increases in activation with increasing task difficulty in the right lingual gyrus and bilateral temporal regions. The hypothesized predictive power of parietal activation was supported only in combination with lingual gyrus activity, which gave a positive predictive value in this sample of .80. CONCLUSIONS: Although these findings should be considered cautiously, as only four subjects who had an fMRI scan subsequently became ill, they suggest functional abnormalities are present in high-risk subjects who later became ill, which distinguish them not only from normal control subjects but also those at high risk who had not developed the disorder. These differences are detectable with fMRI and may have clinical utility.

Adolescent↗
PubMed2006

Recent developments and current controversies in depression.

In this review of the last 5 years' developments in research into depression we focus on recent advances and current controversies. We cover epidemiology and basic science as well as the treatment of depression in adults in all its forms. Depression in , as well as in has been covered in recent Seminars in The Lancet. Depression in adulthood remains a very common and under-treated condition, resulting in a high degree of disability. Increasingly detailed knowledge about impairment of information processing in depression is being supplemented by quantitative studies of the brain processes underlying these impairments. Most patients improve with present treatments. The mechanisms of action of antidepressants are not fully understood; the hypothesis that reversing hippocampal cell loss in depression may be their active principle is a fascinating new development. Moral panic about the claim that antidepressant serotonin reuptake inhibitors cause patients to commit suicide and become addicted to their medication may have disconcerted the public and members of the medical profession. We will try to describe the considerable effort that has gone into collecting evidence to enlighten this debate.

Adult↗
PubMed2006

Factors modifying the efficacy of transcranial magnetic stimulation in the treatment of depression: a review.

OBJECTIVE: So far no convincing answer has emerged to the question of whether transcranial magnetic stimulation (TMS) can make a clinically useful contribution to the treatment of depression. Here we examine whether multiple sensitivity analyses can highlight parameters that predict a favorable treatment response. DATA SOURCES: Medline, Embase, and the Cochrane database for controlled trials were searched for relevant randomized controlled trials using the expression (transcranial magnetic stimulation or TMS) and depression. STUDY SELECTION: Thirty-three studies were identified and included in the random-effects meta-analysis, and between 17 and 31 studies were included in the secondary analyses comparing outcome of studies with different parameters. DATA EXTRACTION: Study data were extracted with a standardized data sheet. A meta-analysis based on Cohen d effect size measure was done for all studies and various subsets. Regression analysis of effect sizes with study parameters was done in 24 studies. DATA SYNTHESIS: Active TMS treatment was more effective than sham, but variability was too great to take any single study design as paradigmatic. No significant predictors of study effect size were found. Mean effect sizes were reduced, although still significant, in studies with stimulation intensity below 90% of motor threshold and new medication starting within 7 days before to 7 days after start of TMS. CONCLUSIONS: The absence of significant outcome predictors in the presence of significant variability of outcome measures can be interpreted in 2 ways: either study sizes and numbers and designs are insufficient to afford the power necessary to detect such predictors or TMS has a nonspecific effect on depression that is not influenced by study parameters. Large-scale comparative trials are necessary to decide between these interpretations.

Depressive Disorder↗
PubMed2005

Predicting schizophrenia: findings from the Edinburgh High-Risk Study.

BACKGROUND: The hypothesis that schizophrenia is neurodevelopmental was investigated in a prospective study of young people with a postulated 10-15% risk for the development of schizophrenia. AIMS: To determine premorbid variables distinguishing high-risk people who will go on to develop schizophrenia from those who will not. METHOD: A high-risk sample of 163 young adults with two relatives with schizophrenia was recruited. They and 36 controls were serially examined. Baseline measures were compared between those who did develop schizophrenia, a well control group, a well high-risk group and high-risk participants with partial or isolated psychotic symptoms. RESULTS: Of those at high risk, 20 developed schizophrenia within 2(1/2) years. More experienced isolated or partial psychotic symptoms. Those who developed schizophrenia differed from those who did not on social anxiety, withdrawal and other schizotypal features. The whole high-risk sample differed from the control group on developmental and neuropsychological variables. CONCLUSIONS: The genetic component of schizophrenia affects many more individuals than will develop the illness, and partial impairment can be found in them. Highly significant predictors of the development of schizophrenia are detectable years before onset.

Adolescent↗
PubMed2004

Repeatability of motor and working-memory tasks in healthy older volunteers: assessment at functional MR imaging.

PURPOSE: To prospectively determine the repeatability of functional magnetic resonance (MR) imaging brain activation tasks in a group of healthy older male volunteers. MATERIALS AND METHODS: Local research ethics committee approval and informed consent were obtained. Sixteen men with a mean age of 69 years +/- 3 (standard deviation) performed finger-tapping and N-back (number of screens back) working-memory tasks. Each subject underwent MR imaging three times in weekly intervals. Within-subject task repeatability was analyzed in terms of the number of voxels classified as activated (activation extent), the mean activation amplitude, and (for finger tapping) the center of the mass of the activated region. A repeatability index was calculated to compare test-retest repeatability between subjects and between functional MR imaging tasks. Within-session, between-session, and between-subject variability was assessed by using analysis of variance testing of activation amplitude and extent. RESULTS: Nine of the 16 subjects generated useful data at all three MR imaging-functional task sessions. At single-subject, single-session analysis, cortical activation was identified in most subjects and at most sessions. The centers of the masses of motor cortex activation were highly reproducible (within 3 mm). Patterns of activation were qualitatively repeatable, but there was substantial variability in the amplitudes and extents of activated regions. Within-session coefficients of variation (CVs) for left- versus right-hand and right- versus left-hand finger tapping were, respectively, 65% and 43% for activation amplitude and 75% and 121% for activation extent. The between-session CVs for activation amplitude were similar to the within-session values, whereas between-session CVs for activation extent were much greater than within-session values, up to 206%. CONCLUSION: The generally poor quantitative task repeatability highlights the need for further methodologic developments before much reliance can be placed on functional MR imaging results of single-session experiments.

Aged↗
PubMed2004

Predicting the accuracy of a diagnosis of Alzheimer's disease with 99mTc HMPAO single photon emission computed tomography.

The current clinical practice of reporting images obtained with single photon emission computed tomography (SPECT) with 99mTc-d,l-hexamethylpropylene amine oxime (99mTc HMPAO) images was examined by having 16 experts evaluate the appearance of SPECT images in patients with probable Alzheimer type dementia (ATD), patients with major depressive episode (DSM-IV), and healthy volunteers. The experts rated diagnostic criteria of scan appearance in respect of importance for their individual diagnostic practice. Experts were nuclear medicine specialists, psychiatrists and physicists taking part in a European multi-centre collaborative project. They examined 158 perfusion scans and then the same perfusion scans together with statistical parametric maps (SPMs). The sensitivity of experts' diagnostic judgments was significantly and negatively correlated with the importance they attributed to reduced regional perfusion in the parietal lobes. A corresponding positive correlation was observed for diagnostic specificity against depressed and healthy volunteers. Similar results were observed with SPMs, where in addition area under the receiver operating characteristic (ROC) curve was significantly reduced with raters' increased diagnostic reliance on frontal lobe perfusion deficits. Sensitivity was greater with SPM for patients younger than 70 years and with dementia severity. The more importance experts placed on parietal (symmetrical) perfusion deficits, the less sensitive and the more specific their diagnostic judgment was. Using multiple raters in large patient samples may provide a way of identifying successful explicit diagnostic strategies for clinical image analysis.

Aged↗
PubMed2004

Transcranial magnetic stimulation for auditory hallucinations in schizophrenia.

It has been suggested that low frequency transcranial magnetic stimulation (TMS) over left temporo-parietal cortex may reduce the frequency and intensity of auditory hallucinations in schizophrenia. Sixteen patients with hallucinations, treatment-resistant for at least 2 months, were randomised into a placebo-controlled crossover study of TMS at 1 Hz and 80% of motor threshold over left temporo-parietal cortex. Treatment periods lasted for 4 days, with daily duration escalating from 4 to 8, 12 and 16 min on subsequent days. Each minute of stimulation was followed by 15 s of rest to check coil position and allow the patient to move, if necessary. Both patients and symptom raters were unaware of the treatment condition. Patients' hallucination scores improved from baseline with both real and sham TMS, and there was no significant difference between real and sham treatments. There was a trend for second treatments, whether sham or real, to be more effective than first treatments. Other psychopathology scales (apart from positive symptoms) and verbal memory were not affected by real or sham TMS. Previous positive studies could not be replicated with these parameters. TMS is safe if applied within the protocol used.

Adolescent↗
PubMed2004

Reduction of cingulate gray matter density in poor outcome bipolar illness.

Structural brain abnormalities are associated with poor outcome unipolar depressive disorder. Gray matter density can be assessed with an automated, operator independent analysis (SPM99). We thus compared 11 poor outcome bipolar patients with 15 age-, sex- and IQ-matched healthy volunteers with a standard neuropsychological examination and an Elscint 2.0 Tesla MRI scanner. At the time of examination, patients were neither hypomanic nor significantly depressed, but were significantly impaired on the McGlashan scale. Their memory function was characterized by reduced performance in the California verbal learning and digit-symbol substitution tests. Statistical parametric mapping revealed abnormal gray matter density, mainly in fronto-limbic cortex, but particularly widespread in cingulate cortex. Although causality of these changes is difficult to resolve, the results offer useful insights into the neural correlates of severe bipolar disorder.

Adolescent↗
PubMed2002

Right and left prefrontal transcranial magnetic stimulation at 1 Hz does not affect mood in healthy volunteers.

BACKGROUND: Prefrontal repetitive transcranial magnetic stimulation (rTMS) has been used to induce side-specific mood changes in volunteers and patients. To clarify inconsistencies between reports that used different stimulation frequencies, we conducted a controlled study with a low (1 Hz) frequency, comparing left with right-sided stimulation METHODS: Nineteen healthy volunteers received randomised left or right prefrontal rTMS at a frequency of 1 Hz and 100% of motor threshold in two sessions two weeks apart. RESULTS: There were significant improvements with TMS for performance in the digit symbol substitution and verbal fluency tests, but no change of mood on a number of measures. There was also a reduction of pulse rate after TMS. The only side-specific TMS-effect was on mean arterial pressure, which decreased pressure after left, but not after right prefrontal TMS. CONCLUSIONS: Apart from the unexpected and so far unreplicated effect on mean arterial pressure, there were no side-specific effects on mood in volunteers. It is unlikely that a simple laterality model of mood together with the assumed activating effect of higher and 'quenching' effect of lower stimulation frequency can account for the effects of TMS on mood.

Adult↗
PubMed2002

Statistical parametric mapping of (99m)Tc-HMPAO-SPECT images for the diagnosis of Alzheimer's disease: normalizing to cerebellar tracer uptake.

BACKGROUND: For a quantitative comparison of images obtained during (99m)Tc-hexamethylpropylene amine oxime (HMPAO) single-photon emission computed tomography (SPECT), brain activity values are usually normalized to a reference region. In studies of Alzheimer-type dementia (ATD), the cerebellum is often used as a reference region, assuming that it is spared any major pathological involvement. Statistical parametric mapping (SPM) may enhance the evaluation of SPECT scans in ATD patients. However, current SPM software only allows scaling to average whole brain activity (i.e., global normalization). The aim of this study was to develop an easily applied, objective, and reproducible method for determining average cerebellar tracer uptake so that images can be scaled specifically to cerebellar activity prior to the performance of SPM analysis. We also investigated whether cerebellar normalization increases the sensitivity and specificity of SPM analysis of ATD patients compared with global normalization. METHODS: Image files were taken from a parallel study investigating the use of SPECT as a diagnostic tool for early onset of ATD. Two methods for determining cerebellar activity were developed: one manually, using templates, the other automated, using specified coordinates entered into a Matlab routine. Group comparison of ATD patients versus controls (= healthy volunteers and depressed patients) was performed on a voxel-by-voxel basis using SPM 96 on Windows 95. Receiver operator characteristics (ROC) were computed for 20 student raters examining patient and control scans with and without single-subject SPMs. RESULTS: The reduction of cerebral blood flow in the group of ATD patients appeared 1.7 times greater in spatial extent when the tracer uptake was normalized to cerebellum rather than to average whole brain activity. Computing the reverse contrast (reductions in the control group compared with ATD patients) produced clusters of significance in globally normalized images which were not manifest after normalizing to cerebellum. This is consistent with the notion that the cerebellum is spared in ATD. Analysis of the area under the ROC curve showed that cerebellar-normalized SPM produced significantly improved accuracy over perfusion scans alone. CONCLUSION: An easily applied, objective, reproducible method was developed for normalizing images to cerebellum prior to the performance of SPM analysis. Cerebellar normalization produced more extensive abnormalities in SPM analyses of ATD patients than global normalization. Furthermore, cerebellar normalization produced marginally more accurate diagnostic results in single-scan SPM analysis of ATD patients than did global normalization.

Aged↗
PubMed2002

Left dorso-lateral repetitive transcranial magnetic stimulation affects cortical excitability and functional connectivity, but does not impair cognition in major depression.

PURPOSE: Transcranial magnetic stimulation (TMS) has been used for over a decade to investigate cortical function. More recently, it has been employed to treat conditions such as major depression. This study was designed to explore the effects of differential treatment parameters, such as stimulation frequency. In addition, the data were examined to determine whether a change in connectivity occurred following TMS. METHOD: Fifteen patients with major depression were entered into a combined imaging and treatment experiment with single photon emission computed tomography (SPECT) and repetitive transcranial magnetic stimulation (rTMS) over left dorso-lateral prefrontal cortex (DLPFC). Brain perfusion during a verbal fluency task was compared between pre- and poststimulation conditions. Patients were then treated with 80% of motor threshold for a total of 10 days, using 5000 stimuli at 5, 10 or 20 Hz. Tests of cortical excitability and neuropsychological tests were done throughout the trial. FINDINGS: Patients generally improved with treatment. There was no perceptible difference between stimulation frequencies, which may have reflected low study power. An increase in rostral anterior cingulate activation after the treatment day was associated with increased functional connectivity in the dorso-lateral frontal loop on the left and the limbic loop on both sides. No noticeable deterioration in neuropsychological function was observed. CONCLUSION: TMS at the stimulation frequencies used seems to be safe over a course of 5000 stimuli. It appears to have an activating effect in anterior limbic structures and increase functional connectivity in the neuroanatomical networks under the stimulation coil within an hour of stimulation.

Adult↗
PubMed2001

The effects of noradrenergic re-uptake inhibition on memory encoding in man.

RATIONALE: Animal and human evidence implicate the central noradrenergic system in the process of memory modulation for emotional material. Blockade of the beta-adrenergic system in humans has been shown to result in decreased recall and recognition memory performance, relative to placebo, for the emotional elements of a series of slides accompanied by a narrative. Stimulation of the noradrenergic system with yohimbine has also been shown to result in increased recall and recognition performance relative to placebo for the same stimulus materials. OBJECTIVES: The present study tested the hypothesis that stimulating the central noradrenergic system using the new noradrenaline re-uptake inhibitor reboxetine would result in a dose-dependent enhancement of memory for emotional material in man. METHODS: The central noradrenergic system was manipulated using reboxetine in a double-blind, randomised between-group, placebo-controlled design with 36 healthy adult subjects in each of three groups (placebo, 4 and 8 mg reboxetine). Free recall and recognition memory performance were assessed in a 'surprise' memory test following a 7-day interval. RESULTS: We found no memory enhancing effect of reboxetine. In contrast we observed a dose-dependent effect on memory opposite to the predicted direction. There were no significant differences between groups in self-rated stress and arousal scores or self-rated emotional reactions to the stimuli. All groups showed the expected increased memory performance for the middle 'emotive' phase of the story. CONCLUSION: Selective stimulation of the central noradrenergic system at encoding did not result in enhanced long-term memory for emotional material in man.

Adrenergic Uptake Inhibitors↗
PubMedDate not supplied

Systematic review of the diagnostic accuracy of 99mTc-HMPAO-SPECT in dementia.

OBJECTIVE: The authors sought to determine the diagnostic accuracy of 99mTc-HMPAO-SPECT in discriminating between Alzheimer disease (AD) and other dementias. METHODS: Articles published between 1985 and 2002 were retrieved systematically from MEDLINE and EMBASE, cross-referencing with personal collections and 13 narrative reviews. Of 301 studies identified, 48 survived exclusion criteria and contained extractable data. Two authors independently assessed and graded the methodology of all included studies. Diagnostic comparison groups included vascular dementia (VD; 13 studies), fronto-temporal dementia (FTD; 7 studies), normal healthy volunteers (27 studies), and non-dementia patients (13 studies). Where statistically justified, groups were pooled in a metaanalysis; summary receiver operating curves were constructed; and heterogeneity across studies examined by regression of the diagnostic odds ratio. RESULTS: The pooled weighted sensitivity of 99mTc-HMPAO-SPECT in discriminating clinically defined AD from VD was 71.3%; its specificity was 75.9%. The pooled weighted sensitivity and specificity for AD versus FTD were 71.5% and 78.2%, respectively. Variation in outcome across studies was not found to be attributable to any single factor. CONCLUSION: Pathological verification studies suggest that clinical criteria may be more sensitive in detecting AD than brain SPECT (81% versus 74%). However, SPECT studies provide a higher specificity against other types of dementia than clinical criteria (91% versus 70%). SPECT may, therefore, be helpful in the differential diagnosis of AD. Clinical follow-up studies are urgently required to establish its predictive validity with regard to natural history and treatment response.

Aged↗