Valerie Treyer

Glucocorticoid-induced impairment of declarative memory retrieval is associated with reduced blood flow in the medial temporal lobe

Previous work indicates that stress levels of circulating glucocorticoids can impair retrieval of declarative memory in human subjects. Several studies have reported that declarative memory retrieval relies on the medial temporal lobe. The present study used \mathrm{H}^{15}_{2}O‐positron emission tomography to investigate whether acutely elevated glucocorticoid levels affect regional cerebral blood flow in the medial temporal lobe, as well as in other brain regions, during declarative memory retrieval in healthy male human subjects. When measured over four different declarative memory retrieval tasks, a single, stress‐level dose of cortisone (25 mg) administered orally 1 h before retention testing, induced a large decrease in regional cerebral blood flow in the right posterior medial temporal lobe, the left visual cortex and the cerebellum. The decrease in the right posterior medial temporal lobe was maximal in the parahippocampal gyrus, a region associated with successful verbal memory retrieval. Cortisone administration also significantly impaired cued recall of word pairs learned 24 h earlier, while drug effects on performance in the other tasks (verbal recognition, semantic generation and categorization) were not significant. The present results provide further evidence that acutely elevated glucocorticoid levels can impair declarative memory retrieval processes and suggest that such impairments may be related to a disturbance of medial temporal lobe function.

Electromagnetic fields, such as those from mobile phones, alter regional cerebral blood flow and sleep and waking EEG

Usage of mobile phones is rapidly increasing, but there is limited data on the possible effects of electromagnetic field (EMF) exposure on brain physiology. We investigated the effect of EMF vs. sham control exposure on waking regional cerebral blood flow (rCBF) and on waking and sleep electroencephalogram (EEG) in humans. In Experiment 1, positron emission tomography (PET) scans were taken after unilateral head exposure to 30‐min pulse‐modulated 900 MHz electromagnetic field (pm‐EMF). In Experiment 2, night‐time sleep was polysomnographically recorded after EMF exposure. Pulse‐modulated EMF exposure increased relative rCBF in the dorsolateral prefrontal cortex ipsilateral to exposure. Also, pm‐EMF exposure enhanced EEG power in the alpha frequency range prior to sleep onset and in the spindle frequency range during stage 2 sleep. Exposure to EMF without pulse modulation did not enhance power in the waking or sleep EEG. We previously observed EMF effects on the sleep EEG (A. A. Borbély, R. Huber, T. Graf, B. Fuchs, E. Gallmann and P. Achermann. Neurosci. Lett., 1999, 275: 207–210; R. Huber, T. Graf, K. A. Cote, L. Wittmann, E. Gallmann, D. Matter, J. Schuderer, N. Kuster, A. A. Borbély, and P. Achermann. Neuroreport, 2000, 11: 3321–3325), but the basis for these effects was unknown. The present results show for the first time that (1) pm‐EMF alters waking rCBF and (2) pulse modulation of EMF is necessary to induce waking and sleep EEG changes. Pulse‐modulated EMF exposure may provide a new, non‐invasive method for modifying brain function for experimental, diagnostic and therapeutic purposes.

Nuclear Myocardial Perfusion Imaging with a Cadmium-Zinc-Telluride Detector Technique: Optimized Protocol for Scan Time Reduction

We aimed at establishing the optimal scan time for nuclear myocardial perfusion imaging (MPI) on an ultrafast cardiac γ-camera using a novel cadmium-zinc-telluride (CZT) solid-state detector technology. Methods: Twenty patients (17 male; BMI range, 21.7–35.5 kg/m2) underwent 1-d 99mTc-tetrofosmin adenosine stress and rest MPI protocols, each with a 15-min acquisition on a standard dual-detector SPECT camera. All scans were immediately repeated on an ultrafast CZT camera over a 6-min acquisition time and reconstructed from list-mode raw data to obtain scan durations of 1 min, 2 min, etc., up to a maximum of 6 min. For each of the scan durations, the segmental tracer uptake value (percentage of maximum myocardial uptake) from the CZT camera was compared by intraclass correlation with standard SPECT camera data using a 20-segment model, and clinical agreement was assessed per coronary territory. Scan durations above which no further relevant improvement in uptake correlation was found were defined as minimal required scan times, for which Bland–Altman limits of agreement were calculated. Results: Minimal required scan times were 3 min for low dose (r = 0.81; P < 0.001; Bland–Altman, −11.4% to 12.2%) and 2 min for high dose (r = 0.80; P < 0.001; Bland–Altman, −7.6% to 12.9%), yielding a clinical agreement of 95% and 97%, respectively. Conclusion: We have established the minimal scan time for a CZT solid-state detector system, which allows 1-d stress/rest MPI with a substantially reduced acquisition time resulting in excellent agreement with regard to uptake and clinical findings, compared with MPI from a standard dual-head SPECT γ-camera.

Reduced Metabotropic Glutamate Receptor 5 Density in Major Depression Determined by [11C]ABP688 PET and Postmortem Study

OBJECTIVE Clinical and preclinical evidence suggests a hyperactive glutamatergic system in clinical depression. Recently, the metabotropic glutamate receptor 5 (mGluR5) has been proposed as an attractive target for novel therapeutic approaches to depression. The goal of this study was to compare mGluR5 binding (in a positron emission tomography [PET] study) and mGluR5 protein expression (in a postmortem study) between individuals with major depressive disorder and psychiatrically healthy comparison subjects. METHOD Images of mGluR5 receptor binding were acquired using PET with [(11)C]ABP688, which binds to an allosteric site with high specificity, in 11 unmedicated individuals with major depression and 11 matched healthy comparison subjects. The amount of mGluR5 protein was investigated using Western blot in postmortem brain samples of 15 depressed individuals and 15 matched comparison subjects. RESULTS The PET study revealed lower levels of regional mGluR5 binding in the prefrontal cortex, the cingulate cortex, the insula, the thalamus, and the hippocampus in the depression group relative to the comparison group. Severity of depression was negatively correlated with mGluR5 binding in the hippocampus. The postmortem study showed lower levels of mGluR5 protein expression in the prefrontal cortex (Brodmanns area 10) in the depression group relative to the comparison group, while prefrontal mGluR1 protein expression did not differ between groups. CONCLUSIONS The lower levels of mGluR5 binding observed in the depression group are consonant with the lower levels of protein expression in brain tissue in the postmortem depression group. Thus, both studies suggest that basal or compensatory changes in excitatory neurotransmission play roles in the pathophysiology of major depression.

Exposure to pulse‐modulated radio frequency electromagnetic fields affects regional cerebral blood flow

We investigated the effects of radio frequency electromagnetic fields (RF EMF) similar to those emitted by mobile phones on waking regional cerebral blood flow (rCBF) in 12 healthy young men. Two types of RF EMF exposure were applied: a ‘base‐station‐like’ and a ‘handset‐like’ signal. Positron emission tomography scans were taken after 30 min unilateral head exposure to pulse‐modulated 900 MHz RF EMF (10 g tissue‐averaged spatial peak‐specific absorption rate of 1 W/kg for both conditions) and sham control. We observed an increase in relative rCBF in the dorsolateral prefrontal cortex on the side of exposure. The effect depended on the spectral power in the amplitude modulation of the RF carrier such that only ‘handset‐like’ RF EMF exposure with its stronger low‐frequency components but not the ‘base‐station‐like’ RF EMF exposure affected rCBF. This finding supports our previous observation that pulse modulation of RF EMF is necessary to induce changes in the waking and sleep EEG, and substantiates the notion that pulse modulation is crucial for RF EMF‐induced alterations in brain physiology.

Absolute quantification of cerebral blood flow with magnetic resonance, reproducibility of the method, and comparison with H215O positron emission tomography

While H215O positron emission tomography (PET) is still the gold standard in the quantitative assessment of cerebral perfusion (rCBF), its technical challenge, limited availability, and radiation exposure are disadvantages of the method. Recent work demonstrated the feasibility of magnetic resonance (MR) for quantitative cerebral perfusion imaging. There remain open questions, however, especially regarding reproducibility. The main purpose of this study was to assess the accuracy and reproducibility of MR-derived flow values to those derived from H215O PET. Positron emission tomography and MR perfusion imaging was performed in 20 healthy male volunteers, who were chronic smokers, on day 1 and day 3 of a 4-day hospitalization. Subjects were randomly assigned to one of two groups, each with 10 subjects. One group was allowed to smoke as usual during the hospitalization, while the other group stopped smoking from day 2. Positron emission tomography and MR images were coregistered and rCBF was determined in two regions of interest, defined over gray matter (gm) and white matter (wm), yielding rCBFPETgm, rCBFMRgm, rCBFPETwm, and rCBFMRwm. Bland-Altman analysis was used to investigate reproducibility by assessing the difference rCBFday3 - rCBFday1 in eight continual-smoker volunteers. The analysis showed a good reproducibility for PET, but not for MR. Mean ± SD of the difference rCBFday3 - rCBFday1 in gray matter was 6.35 ± 21.06 and 0.49 ± 5.27 mL · min−1 · 100 g−1 for MR and PET, respectively; the corresponding values in white matter were 2.60 ± 15.64 and −1.14 ± 4.16 mL · min−1 · 100 g−1. The Bland-Altman analysis was also used to assess MRI and PET agreement comparing rCBF measured on day 1. The analysis demonstrated a reasonably good agreement of MR and PET in white matter (rCBFPETwm - rCBFMRwm; −0.09 ± 7.23 mL · min−1 · 100 g−1), while in gray matter a reasonable agreement was only achieved after removing vascular artifacts in the MR perfusion maps (rCBFPETgm - rCBFMRgm; −11.73 ± 14.52 mL · min−1 · 100 g−1). In line with prior work, these results demonstrate that reproducibility was overall considerably better for PET than for MR. Until reproducibility is improved and vascular artifacts are efficiently removed, MR is not suitable for reliable quantitative perfusion measurements.

Nonconscious formation and reactivation of semantic associations by way of the medial temporal lobe

A successful strategy to memorize unrelated items is to associate them semantically. This learning method is typical for declarative memory and depends on the medial temporal lobe (MTL). Yet, only a small fraction of perceived items emerge into conscious awareness and receive the status of representations in declarative memory. This functional magnetic resonance imaging (fMRI) study tackled the mnemonic fate of unrelated item pairs processed without conscious awareness. Stimuli consisted of a face and a written profession (experimental condition) or of a face (control condition) exposed very briefly between pattern masks. Although the participants were unaware of the stimuli, activity in the hippocampus and perirhinal cortex was changed in the experimental versus the control condition; perirhinal activity changes correlated with the reaction time measure of the later nonconscious retrieval. For retrieval, the previously presented faces were shown again, this time for conscious inspection. The task was to guess the professional category of each face. This task was to induce a nonconscious retrieval of previously formed face-profession associations. Remarkably, activity in the hippocampus and perirhinal cortex was enhanced when subjects were confronted with faces from the experimental versus the control condition. The degree of hippocampal and perirhinal activation changes correlated with the reaction time measure of nonconscious retrieval. Together, our findings suggest that new semantic associations can be formed and retrieved by way of the medial temporal lobe without awareness of the associations or its components at encoding or any awareness that one is remembering at retrieval.

First head-to-head comparison of effective radiation dose from low-dose 64-slice CT with prospective ECG-triggering versus invasive coronary angiography

Background: Reduction of radiation burden of multidetector computed tomography coronary angiography (CTCA) has remained an important task. Objective: To compare effective radiation dose of low-dose 64-slice CTCA using prospective ECG-triggering versus diagnostic invasive coronary angiography (CA). Methods: 42 patients referred for elective invasive CA owing to suspected coronary artery disease (CAD) were prospectively enrolled to undergo a low-dose CTCA without calcium scoring within the same day before CA. Dose-area product of diagnostic invasive CA and dose-length product of CTCA were measured, converted into effective radiation dose and compared using Mann-Whitney U tests. In addition, accuracy of CTCA to detect CAD (coronary artery narrowing ⩾50%) was assessed using invasive CA as standard of reference. On an intention-to-diagnose basis all non-evaluative vessels were included in the analysis and censored as positive. Results: The estimated mean effective radiation dose was 8.5 (4.4) mSv (range 1.4–20.5 mSv) for diagnostic invasive CA, and 2.1 (0.7) mSv (range 1.0–3.3 mSv) for CTCA (p<0.001). 19 patients (42.9%) had no CAD by invasive CA. 40 (95.2%) patients have been correctly classified as having CAD (23/23) or no CAD (17/19). Over 97% (551/567) of segments were evaluable. Vessel-based analysis revealed sensitivity, specificity, positive and negative predictive value of 94.2% (CI 0.8% to 1.0%), 94.8% (CI 09% to 1.0%), 89.0% (CI 0.8% to 1.0%), 97.4% (CI 09% to 1.0%) and an accuracy of 94.6%. Conclusions: Low dose CTCA allows evaluation of CAD with high accuracy, but delivers a significantly less effective radiation dose to patients compared to diagnostic invasive CA.

Attention and Interhemispheric Transfer: A Behavioral and fMRI Study

When both detections and responses to visual stimuli are performed within one and the same hemisphere, manual reaction times (RTs) are faster than when the two operations are carried out in different hemispheres. A widely accepted explanation for this difference is that it reflects the time lost in callosal transmission. Interhemispheric transfer time can be estimated by subtracting RTs for uncrossed from RTs for crossed responses (crossed uncrossed difference, or CUD). In the present study, we wanted to ascertain the role of spatial attention in affecting the CUD and to chart the brain areas whose activity is related to these attentional effects on interhemispheric transfer. To accomplish this, we varied the proportion of crossed and uncrossed trials in different blocks. With this paradigm subjects are likely to focus attention either on the hemifield contralateral to the responding hand (blocks with 80 crossed trials) or on the ipsilateral hemifield (blocks with 80 uncrossed trials). We found an inverse correlation between the proportion of crossed trials in a block and the CUD and this effect can be attributed to spatial attention. As to the imaging results, we found that in the crossed minus uncrossed subtraction, an operation that highlights the neural processes underlying interhemispheric transfer, there was an activation of the genu of the corpus callosum as well as of a series of cortical areas. In a further commonality analysis, we assessed those areas which were activated specifically during focusing of attention onto one hemifield either contra- or ipsilateral to the responding hand. We found an activation of a number of cortical and subcortical areas, notably, parietal area BA 7 and the superior colliculi. We believe that the main thrust of the present study is to have teased apart areas important in interhemispheric transmission from those involved in spatial attention.

Low-dose computed tomography coronary angiography with prospective electrocardiogram triggering: feasibility in a large population.

OBJECTIVES We sought to assess the feasibility of prospective electrocardiogram triggering for achieving low-dose computed tomography coronary angiography (CTCA) in a large population. BACKGROUND Prospective electrocardiogram triggering dramatically reduces radiation exposure for CTCA but requires heart rate (HR) control to obtain diagnostic image quality. Its feasibility in daily clinical routine has therefore remained to be elucidated. METHODS We evaluated 612 patients consecutively referred for CTCA by 64-slice computed tomography. Intravenous metoprolol (2 to 30 mg) was administered if necessary to achieve a target HR below 65 beats/min. Image quality was assessed on a semiquantitative 4-point scale for each coronary segment. RESULTS Forty-six (7.5%) patients were deemed ineligible due to irregular heart rhythm (n = 19), insufficient response to metoprolol (n = 21), renal insufficiency (n = 3), or inability to follow breath-hold commands (n = 3). Mean effective radiation dose was 1.8 ± 0.6 mSv with a diagnostic image quality in 96.2% of segments. Finally, low-dose CTCA allowed a firm diagnosis with regard to the presence or absence of coronary artery disease in 527 (86.1%) patients. Intravenous metoprolol to achieve an HR below 65 beats/min was used in 64.4% of patients. Incidence of nondiagnostic segments was inversely related to HR (r = -0.809, p < 0.001). Below an HR cutoff of 62 beats/min, only 1.2% of coronary segments were nondiagnostic. CONCLUSIONS Low-dose CTCA by electrocardiogram triggering is feasible in the vast majority of an every-day population. However, HR control is crucial, as an HR below 62 beats/min favors diagnostic image quality.