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Biomedical subjects

Valerie Treyer

Publications and source records attributed to Valerie Treyer.

At least 19 recordsLinked to original sources

Diminishing reciprocal fairness by disrupting the right prefrontal cortex.

Humans restrain self-interest with moral and social values. They are the only species known to exhibit reciprocal fairness, which implies the punishment of other individuals' unfair behaviors, even if it hurts the punisher's economic self-interest. Reciprocal fairness has been demonstrated in the Ultimatum Game, where players often reject their bargaining partner's unfair offers. Despite progress in recent years, however, little is known about how the human brain limits the impact of selfish motives and implements fair behavior. Here we show that disruption of the right, but not the left, dorsolateral prefrontal cortex (DLPFC) by low-frequency repetitive transcranial magnetic stimulation substantially reduces subjects' willingness to reject their partners' intentionally unfair offers, which suggests that subjects are less able to resist the economic temptation to accept these offers. Importantly, however, subjects still judge such offers as very unfair, which indicates that the right DLPFC plays a key role in the implementation of fairness-related behaviors.

Adult↗

Disruption of right prefrontal cortex by low-frequency repetitive transcranial magnetic stimulation induces risk-taking behavior.

Decisions require careful weighing of the risks and benefits associated with a choice. Some people need to be offered large rewards to balance even minimal risks, whereas others take great risks in the hope for an only minimal benefit. We show here that risk-taking is a modifiable behavior that depends on right hemisphere prefrontal activity. We used low-frequency, repetitive transcranial magnetic stimulation to transiently disrupt left or right dorsolateral prefrontal cortex (DLPFC) function before applying a well known gambling paradigm that provides a measure of decision-making under risk. Individuals displayed significantly riskier decision-making after disruption of the right, but not the left, DLPFC. Our findings suggest that the right DLPFC plays a crucial role in the suppression of superficially seductive options. This confirms the asymmetric role of the prefrontal cortex in decision-making and reveals that this fundamental human capacity can be manipulated in normal subjects through cortical stimulation. The ability to modify risk-taking behavior may be translated into therapeutic interventions for disorders such as drug abuse or pathological gambling.

Adult↗

Uptake of 18F-fluorocholine, 18F-fluoro-ethyl-L: -tyrosine and 18F-fluoro-2-deoxyglucose in F98 gliomas in the rat.

INTRODUCTION: The positron emission tomography (PET) tracers (18)F-fluoro-ethyl-L: -tyrosine (FET), (18)F-fluorocholine (N,N-dimethyl-N-[(18)F]fluoromethyl-2-hydroxyethylammonium (FCH]) and (18)F-fluoro-2-deoxyglucose (FDG) are used in the diagnosis of brain tumours. The aim of this study was threefold: (a) to assess the uptake of the different tracers in the F98 rat glioma, (b) to evaluate the impact of blood-brain barrier (BBB) disruption and microvessel density (MVD) on tracer uptake and (c) to compare the uptake in the tumours to that in the radiation injuries (induced by proton irradiation of healthy rats) of our previous study. METHODS: F98 gliomas were induced in 26 rats. The uptake of FET, FCH and FDG was measured using autoradiography and correlated with histology, disruption of the BBB and MVD. RESULTS: The mean FET, FCH and FDG standardised uptake values (SUVs) in the tumour and the contralateral normal cortex (in parentheses) were 4.19+/-0.86 (1.32+/-0.26), 2.98+/-0.58 (0.51+/-0.11) and 11.02+/-3.84 (4.76+/-1.77) respectively. MVD was significantly correlated only with FCH uptake. There was a trend towards a negative correlation between the degree of BBB disruption and FCH uptake and a trend towards a positive correlation with FET uptake. The ratio of the uptake in tumours to that in the radiation injuries was 1.97 (FCH), 2.71 (FET) and 2.37 (FDG). CONCLUSION: MVD displayed a significant effect only on FCH uptake. The degree of BBB disruption seems to affect the accumulation of FET and FCH, but not FDG. Mean tumour uptake for all tracers was significantly higher than the accumulation in radiation injuries.

Animals↗

Selection of currently relevant words: an auditory verbal memory study using positron emission tomography.

Clinical and imaging studies have shown that the posterior and anterior parts of the limbic system make distinct contributions to memory processing. Whereas the medial temporal lobes and connected structures are important for learning and recognition of new information, the posterior orbitofrontal cortex appears to be crucial for the selection of currently relevant memories, that is, the ability to distinguish between memories that pertain to ongoing reality and memories that do not. Previous studies demonstrating this dissociation used repeated continuous recognition tasks with visual stimuli. In this H2O positron emission tomography study, we demonstrate that this same organizing principle also applies to auditory verbal information, that is, to the processing of auditorily presented words.

Acoustic Stimulation↗

Radioimmunotherapy targeting the extra domain B of fibronectin in C6 rat gliomas: a preliminary study about the therapeutic efficacy of iodine-131-labeled SIP(L19).

UNLABELLED: Despite aggressive treatment protocols, patients suffering from glioblastoma multiforme still experience poor outcome. Therefore, new adjuvant therapeutic options such as radioimmunotherapy (RIT) have been studied and have resulted in significant survival benefit. In this study, we assessed the efficacy of a novel radioimmunotherapeutic approach targeting the extra domain B (EDB) of fibronectin, a marker of angiogenesis, in glioma-bearing rats. METHODS: C6 gliomas were induced intracerebrally in Wistar rats. Ten to 11 days later, 220-360 MBq of iodine-131-labeled anti-EDB SIP(L19) ("small immunoprotein") was administered intravenously into nine animals, yielding a radiation dose of 13-21 Gy. Another nine rats served as controls. Then the following parameters were compared: median survival time, tumor size and histology. RESULTS: Histological examination of the tumors revealed typical glioblastoma characteristics. Eleven of 18 rats developed a tumor size bigger than 150 mm(3). When these animals were used for survival analysis, median survival did significantly differ between groups [22 days (therapy; n=7) vs. 16 days (control; n=4); P<.0176]. CONCLUSIONS: In this preliminary trial, (131)I-SIP(L19)-RIT showed promising potential in treating C6 gliomas, warranting further studies. However, larger trials with preferentially higher doses are needed to confirm this finding and, potentially, to further increase the efficacy of this treatment.

Animals↗

Changes in cerebral glucose metabolism after an expedition to high altitudes.

The possibility of persistent cerebral impairment due to exposure to extreme altitude and resulting hypoxic conditions is of great concern to both high altitude mountaineers and researchers. The aim of the present study was to investigate the effect of prolonged exposure to hypoxia on cerebral glucose metabolism, which probably precedes structural and functional impairment. Positron emission tomography (PET) employing [18F]-2-deoxy-2-fluoro-D-glucose (FDG) was performed, and the normobaric hypoxic ventilatory response (HVR) was assessed in 11 mountaineers before (pre) and after (post) climbing Mount Shisha Pangma (8048 m). During the climb, acute mountain sickness (AMS) symptoms were recorded and heart rate and oxygen saturation (SaO2) were measured daily. Neuropsychological evaluations were conducted at different heights. The difference FDGpost- FDGpre was analyzed voxel by voxel using statistical parametric mapping (SPM) and volumes of interest (VOI). SPM revealed two areas of increased cerebral FDG uptake after the expedition, one localized in the left cerebellum (+9.4%) and one in the white matter lateral of the left thalamus (+8.3%). The VOI analysis revealed increased postexpeditional metabolism in an area of the right cerebellum (+11%) and of the thalamus bilaterally (+3.7% on the left, +4.6% on the right). FDG-PET alterations did not correlate with changes in SaO2, HVR, or AMS scores. All neuropsychological test results during the climb were unremarkable. We conclude that a prolonged stay at an extreme altitude leads to regional specific changes in the cerebral glucose metabolism without any signs of neuropsychological impairment during the climb.

Acute Disease↗

F-18 FDG whole-body PET for the assessment of disease activity in patients with rheumatoid arthritis.

UNLABELLED: PURPOSE OF REPORT: F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used to image synovitis in patients with rheumatoid arthritis (RA). The aim of this study was to evaluate if a simple scoring system based on visual assessment of FDG joint uptake correlates with the clinical assessment of patients with RA undergoing antiinflammatory treatment. MATERIALS AND METHODS: Seven patients with active RA underwent whole-body FDG PET and clinical assessment before and after treatment with the antitumor necrosis factor alpha antibody (infliximab). A PET total joint score, ie, the sum of all scores based on FDG uptake intensity between zero and 4 in 28 joints, was correlated with a total joint score based on the clinical disease activity in the same joints using a Spearman rank correlation. RESULTS: The PET based total joint score was similarly high before onset as was the clinical total joint score. The decrease of FDG joint uptake in the follow-up PET scans correlated significantly with the clinical assessment. Additionally, synovial FDG uptake was found in extraarticular sites such as tendon sheaths and bursae. CONCLUSIONS: Visual assessment of FDG uptake shows a significant correlation with clinical evaluation of disease activity in patients with RA undergoing antiinflammatory treatment.

Adult↗

Male subjects who could not perceive the pheromone 5a-androst-16-en-3-one, produced similar orbitofrontal changes on PET compared with perceptible phenylethyl alcohol (rose).

BACKGROUND: The aim of this study was to evaluate in how far cerebral blood flow changes in male subjects when exposed to a pheromone that they cannot consciously smell. METHODS: We used a boar taint steroid (5a-Androst-16-en-3-one), which is similar to human axillary sweat but could not be detected by the human volunteers who participated in this study. RESULTS: The pheromone produced activation of the orbitofrontal and frontal cortex in comparison to a baseline condition. The same regions were activated when the subjects smelled a rose-like odour. CONCLUSION: This study shows that a pheromone, which is not consciously detected, can evoke a response in the brain that is similar to a detectable odour.

Adult↗

Effects of baseline task position on apparent activation in functional imaging of memory.

Brain activation dissociates during the repeated performance of memory tasks with decreasing medial temporal and increasing orbitofrontal activation. The impact of such adaptations on a baseline task is unknown. In this study, we used H2(15)O positron emission tomography (PET) in two groups of subjects performing a continuous recognition task and a baseline task. The group performing the baseline task after the main task showed significant medial temporal activation in the subtraction (recognition task-baseline). The group performing the baseline task at the beginning showed right orbitofrontal activation. These differences appeared to result primarily from different activations during the baseline task. It thus appears that the temporal context of a baseline task may fundamentally alter cognitive requirements and substantially influence apparent brain activation during a memory task. We suggest that the automatic filtration of memories according to their relevance for ongoing reality, a capacity mediated by the orbitofrontal cortex, is one such influence on apparent activation.

Adult↗

Processing content or location: distinct brain activation in a memory task.

Objects are defined by their content ("what") and by their location ("where"). In the visual system, processing of these two types of information is segregated into distinct anatomical and functional pathways. Using H2 (15)O positron emission tomography to measure cerebral blood flow, we examined the differences in processing of "what" when compared with "where" information in human memory. We found that the detection of deviations from a previously learned image sequence activates distinct brain regions depending on whether the image's content or its location has changed. When deviations of an image's content had to be detected, the left medial temporal lobe (MTL) activation increased. In contrast, detection of deviations from the learned locations of the objects induced increased activation in the right MTL and in the right parietal cortex. These data demonstrate distinct contributions of the left and right MTL to the processing of "what" vs. "where" in memory.

Adult↗

The human orbitofrontal cortex monitors outcomes even when no reward is at stake.

The orbitofrontal cortex (OFC) processes the occurrence or omission of anticipated rewards, but clinical evidence suggests that it might serve as a generic outcome monitoring system, independent of tangible reward. In this positron emission tomography (PET) study, normal human subjects performed a series of tasks in which they simply had to predict behind which one of two colored rectangles a drawing of an object was hidden. While all tasks involved anticipation in that they had an expectation phase between the subject's prediction and the presentation of the outcome, they varied with regards to the uncertainty of outcome. No comment on the correctness of the prediction, no record of ongoing performance, and no reward, not even a score, was provided. Nonetheless, we found strong activation of the OFC: in comparison with a baseline task, the left anterior medial OFC showed activation in all conditions, indicating a basic role in anticipation; the left posterior OFC was activated in all tasks with some uncertainty of outcome, suggesting a role in the monitoring of outcomes; the right medial OFC showed activation exclusively during guessing. The data indicate a generic role of the human OFC, with some topical specificity, in the generation of hypotheses and processing of outcomes, independent of the presence of explicit reward.

Frontal Lobe↗

The neural basis of altruistic punishment.

Many people voluntarily incur costs to punish violations of social norms. Evolutionary models and empirical evidence indicate that such altruistic punishment has been a decisive force in the evolution of human cooperation. We used H2 15O positron emission tomography to examine the neural basis for altruistic punishment of defectors in an economic exchange. Subjects could punish defection either symbolically or effectively. Symbolic punishment did not reduce the defector's economic payoff, whereas effective punishment did reduce the payoff. We scanned the subjects' brains while they learned about the defector's abuse of trust and determined the punishment. Effective punishment, as compared with symbolic punishment, activated the dorsal striatum, which has been implicated in the processing of rewards that accrue as a result of goal-directed actions. Moreover, subjects with stronger activations in the dorsal striatum were willing to incur greater costs in order to punish. Our findings support the hypothesis that people derive satisfaction from punishing norm violations and that the activation in the dorsal striatum reflects the anticipated satisfaction from punishing defectors.

Adult↗

Constant-infusion H(2)15O PET and acetazolamide challenge in the assessment of cerebral perfusion status.

UNLABELLED: Assessing the baseline perfusion and perfusion reserve after acetazolamide (ACZ) challenge is a common method for the evaluation of patients with cerebrovascular disease. Most previous studies using H(2)(15)O PET applied the bolus injection technique. There is considerable discrepancy regarding the optimal time point of imaging after ACZ injection. The purpose of this study was to continuously monitor cerebral blood flow (CBF) after ACZ using constant-infusion H(2)(15)O PET. METHODS: Four patients with stenoses of an internal carotid artery and 6 with moyamoya disease were studied. H(2)(15)O was continuously infused, and data were recorded in 1-min frames. After equilibration of H(2)(15)O, 5 min of baseline data were acquired, and then 1 g of ACZ was administered intravenously and data collection continued for 10-22 min. Arterial blood was continuously drawn for absolute quantification of CBF. RESULTS: The arterial (15)O concentration remained generally stable during scanning, and the cerebellar blood flow fluctuations of the 5 baseline scans were small. The scan-to-scan difference was 6% (difference of 2 successive scans/mean). In the nonpathologic areas, the increase in CBF started 1-2 min after administration of ACZ. The largest fraction of the increase occurred from 0 to 10 min. The ratio of CBF in pathologic areas to CBF in cerebellum showed an initial decrease that stabilized after 5 min. CONCLUSION: A continuous-infusion protocol is a viable alternative to single bolus injections for the assessment of cerebral perfusion status. Such a protocol is advantageous when the time course of CBF after an intervention is not known. With continuous monitoring, the optimal time point for evaluation of a certain parameter can be chosen post hoc. Furthermore, the time course of CBF itself may allow the definition of new parameters for evaluating perfusion status in cerebrovascular patients, both for assessment before a revascularization procedure and for follow-up. A limitation of the present study is the relatively small number of patients with each type of cerebrovascular disease and the lack of healthy subjects.

Acetazolamide↗

Functional neuroimaging predicts individual memory outcome after amygdalohippocampectomy.

We examined memory-related activity within to-be-resected medial temporal lobe (MTL) structures in 12 epilepsy patients with PET before amygdalohippocampectomy and studied the reallocation of memory functions to the contralateral MTL before and after surgery. Learning tasks were designed to activate predominantly the right or left MTL. Those patients who significantly activated to-be-resected ipsilateral MTL structures during the ipsilateral learning task (i.e. the left MTL during verbal learning or the right MTL during nonverbal learning) experienced a postoperative memory decline. Preoperative activation in the contralateral MTL during the ipsilateral learning task positively correlated with the postoperative outcome for ipsilateral memory. There was no significant postoperative reallocation of ipsilateral memory functions to the contralateral MTL.

Adolescent↗

Subcortical loop activation during selection of currently relevant memories.

Clinical studies on spontaneous confabulation and imaging studies with healthy subjects indicate that the anterior limbic system, in particular, the orbitofrontal cortex (OFC), is necessary to adjust thought and behavior to current reality. It appears to achieve this by continuously suppressing activated memories that do not pertain to ongoing reality, even before their content is consciously recognized. In the present study, we explored through what anatomical connections the OFC exerts this influence. Healthy subjects were scanned with H(2)(15)O PET as they performed four blocks of continuous recognition tasks, each block composed of a different type of stimuli (meaningful designs, geometric designs, words, nonwords). Within each block, three runs composed of exactly the same picture series, arranged in different order each time, were made. Subjects were asked to indicate item recurrences only within the currently ongoing run and to disregard familiarity from previous runs. In the combined first runs, in which all items were initially new and responses could be based on familiarity judgement (with repeated items) alone, we found medial temporal and right orbitofrontal activation. In the combined third runs, when all items were already known and selection of currently relevant memories was required, we found left orbitofrontal activation contingent with distinct activation of the ventral striatum, head and body of the caudate nucleus, substantia nigra, and medial thalamus. The study indicates that the OFC influences the cortical representation of memories through subcortical connections including the basal ganglia and the thalamus. The data are compatible with a role of the dopaminergic reward system in the monitoring of ongoing reality in thinking.

Adult↗

Quantitative cerebral H2(15)O perfusion PET without arterial blood sampling, a method based on washout rate.

The quantitative determination of regional cerebral blood flow (rCBF) is important in certain clinical and research applications. The disadvantage of most quantitative methods using H(2)(15)O positron emission tomography (PET) is the need for arterial blood sampling. In this study a new non-invasive method for rCBF quantification was evaluated. The method is based on the washout rate of H(2)(15)O following intravenous injection. All results were obtained with Alpert's method, which yields maps of the washin parameter K(1) (rCBF(K1)) and the washout parameter k(2) (rCBF(k2)). Maps of rCBF(K1) were computed with measured arterial input curves. Maps of rCBF(k2*) were calculated with a standard input curve which was the mean of eight individual input curves. The mean of grey matter rCBF(k2*) (CBF(k2*)) was then compared with the mean of rCBF(K1) (CBF(K1)) in ten healthy volunteer smokers who underwent two PET sessions on day 1 and day 3. Each session consisted of three serial H(2)(15)O scans. Reproducibility was analysed using the rCBF difference scan 3-scan 2 in each session. The perfusion reserve (PR = rCBF(acetazolamide)-rCBF(baseline)) following acetazolamide challenge was calculated with rCBF(k2*) (PR(k2*)) and rCBF(K1) (PR(K1)) in ten patients with cerebrovascular disease. The difference CBF(k2*)-CBF(K1) was 5.90+/-8.12 ml/min/100 ml (mean+/-SD, n=55). The SD of the scan 3-scan 1 difference was 6.1% for rCBF(k2*) and rCBF(K1), demonstrating a high reproducibility. Perfusion reserve values determined with rCBF(K1) and rCBF(k2*) were in high agreement (difference PR(k2*)-PR(K1)=-6.5+/-10.4%, PR expressed in percentage increase from baseline). In conclusion, a new non-invasive method for the quantitative determination of rCBF is presented. The method is in good agreement with Alpert's original method and the reproducibility is high. It does not require arterial blood sampling, yields quantitative voxel-by-voxel maps of rCBF, and is computationally efficient and easy to implement.

Adult↗

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.

Adult↗

Active hippocampus during nonconscious memories.

The hippocampal formation is known for its importance in conscious, declarative memory. Here, we report neuroimaging evidence in humans for an additional role of the hippocampal formation in nonconscious memory. We maskedly presented combinations of faces and written professions such that subjects were not aware of them. Nevertheless, the masked presentations activated many of the brain regions that unmasked presentations of these stimuli did. To induce a nonconscious retrieval of the faces and face-associated occupational information, subjects were instructed to view the previously masked faces and to guess the professional category of each person--academic, artist, and workman. Guessing the professional category of previously masked versus new faces activated the left and right hippocampal formation and right perirhinal cortex as well as bilateral fusiform areas and fronto-temporal areas known to mediate the retrieval of semantic information. These activations within the semantic processing system suggest that conceptual knowledge acquired during masking was nonconsciously retrieved. Our data provide clues to an analogous role of the hippocampus in conscious and nonconscious memory.

Adult↗