Biomedical subjects

J A den Boer

Publications and source records attributed to J A den Boer.

At least 19 recordsLinked to original sources

PubMed2006

Detecting fearful and neutral faces: BOLD latency differences in amygdala-hippocampal junction.

Evolutionary survival and procreation are augmented if an individual organism quickly detects environmental threats and rapidly initiates defensive behavioral reactions. Thus, facial emotions signaling a potential threat, e.g., fear or anger, should be perceived rapidly and automatically, possibly through a subcortical processing route which includes the amygdala. Using event-related functional magnetic resonance imaging (fMRI), we investigated the time course of the response in the amygdala to neutral and fearful faces, which appear from dynamically decreasing random visual noise. We aimed to detect differences of the amygdala response between fearful and neutral faces by estimating the latency of the blood oxygenation level-dependent (BOLD) response. We found that bilateral amygdala-hippocampal junction activation occurred earlier for fearful than for neutral faces. Our findings support the theory of a dual route architecture in which the subcortical thalamic-hippocampal-amygdala route serves fast preconscious threat perception.

Amygdala↗

PubMed2006

Clinical efficacy of agomelatine in depression: the evidence.

Despite the advances of recent decades, there is still an urgent need for antidepressants with improved efficacy, safety and tolerability. Agomelatine is a new antidepressant with an innovative pharmacological profile. It is the first melatonergic antidepressant, and is a potent agonist of melatonin receptors (MT1 and MT2) with 5-HT2C antagonist properties. The efficacy of 25 mg/day agomelatine in treating major depressive disorder (MDD) has been demonstrated in a number of placebo-controlled studies. Evidence of improvement in depressive symptoms was observed in a dose-ranging study in which 25 mg/day agomelatine was significantly better than placebo, whatever the rating scale used (Hamilton Rating Scale for Depression, Clinical Global Impression, and Montgomery-Asberg Depression Rating Scale). These results have been confirmed in two similarly designed placebo-controlled studies. Agomelatine also produces a significant improvement in anxiety compared to placebo, according to Hamilton Rating Scale for Anxiety scores. The efficacy of agomelatine has been studied in subpopulations with more severe depression, demonstrating its efficacy in these difficult-to-treat patients. In view of the available data on agomelatine, this antidepressant can be regarded as an innovative treatment for MDD patients, offering a new approach in the management of depressed patients.

Acetamides↗

PubMed2006

Fear conditioning and shock intensity: the choice between minimizing the stress induced and reducing the number of animals used.

Many fear conditioning studies use electric shock as the aversive stimulus. The intensity of shocks varies throughout the literature. In this study, shock intensities ranging from 0 to 1.5 mA were used, and the effects on the rats assessed by both behavioural and biochemical stress parameters. Results indicated a significant difference with respect to defaecation and freezing behaviour between controls and those animals that received a shock. Significant differences in corticosterone levels were also noted between controls and those groups that received a shock. No significant differences were found between the shock groups with regards to the stress parameters measured in our fear conditioning paradigm, indicating that the two shock groups were similarly stressed. Increased significance levels were noted for freezing behaviour as well as a lower standard error of means was found in the highest shock intensity group. We therefore recommend using the higher shock intensity (1.5 mA) as the rats in the higher shock intensity group were more homogeneously fear-conditioned and therefore the results should be more reproducible and robust than in the lower shock intensity group. This would allow for fewer rats to be used in order to gain an accurate impression of the conditioning paradigm employed.

Animals↗

PubMed2005

Assessment of methylphenidate-induced changes in binding of continuously infused [(11)C]-raclopride in healthy human subjects: correlation with subjective effects.

RATIONALE: The dopaminergic system has been implicated in the pathogenesis and treatment of a variety of neuropsychiatric disorders. It has been shown that information on endogenous dopamine (DA) release can be obtained noninvasively by combining positron emission tomography with a dopaminergic challenge. This approach is based on the assumption that an injected radiolabeled ligand competes with the neurotransmitter for the same receptor. Increases in DA release will therefore result in a decreased binding of the radioligand. OBJECTIVES: We investigated the effect of the DA reuptake blocker methylphenidate (MP) on the binding of the D(2) receptor ligand [(11)C]-raclopride (RAC). METHODS: The effect of a 0.25 mg/kg intravenous dose of MP was studied in six healthy volunteers. RAC was administered as a bolus followed by constant infusion, and subjective effects were assessed using verbal rating scales. RESULTS: Control scans without MP administration showed that the mean RAC binding reached stable values approximately 30 min after start of the infusion. MP administration induced a 24% decrease in RAC binding in the total striatum. Correlations were found between the MP-induced change in euphoria and the percent change in binding potential (DeltaBP) in the dorsal striatum and between baseline anxiety and DeltaBP in the dorsal and middle striatum. We also found a negative correlation between baseline BP in the dorsal striatum and change in euphoria. CONCLUSIONS: Our results comply with previous findings, indicating the feasibility of the bolus infusion design combined with a relatively low MP dose to study dopaminergic (dys)function.

Adolescent↗

PubMed2005

Pair-housing of male and female rats during chronic stress exposure results in gender-specific behavioral responses.

UNLABELLED: Social support has a positive influence on the course of a depression and social housing of rats could provide an animal model for studying the neurobiological mechanisms of social support. Male and female rats were subjected to chronic footshock stress for 3 weeks and pair-housing of rats was used to mimic social support. Rats were isolated or housed with a partner of the opposite sex. A plastic tube was placed in each cage and subsequently used as a 'safe' area in an open field test. Time spent in the tube was used as a measurement of anxiety levels. Chronic stress increased adrenal weights in all groups, except for isolated females who showed adrenal hypertrophy in control conditions. In isolated males, chronic stress resulted in an increase in the time the animals spent in the tube. While stress did not affect this parameter in socially housed males, males with a stressed partner showed a similar response as isolated stressed males. Even though adrenal weights showed that isolated females were more affected by stress, after chronic stress exposure, they spent less time in the tube than socially housed females. Socially housed stressed females spent less time in the 'safe' tube compared to control counterparts, indicating that stress has a gender-specific behavioral effect. IN CONCLUSION: pair-housing had a stress-reducing effect on behavior in males. Isolation of females was stressful by itself. Pair housing of females was not able to prevent stress-induced behavioral changes completely, but appeared to reduce the effects of chronic stress.

Adrenal Glands↗

PubMed2005

The robustness of perception.

The natural environment around us, which is often crowded, cluttered or even foggy, is subject to a dynamically changing composition of objects and events. The human brain is continuously perceiving, recognizing and evaluating this dynamic scene composition. If the perception of degraded visual objects is important, e.g. in the case of potential threat stimuli, the brain needs to be more sensitive in detecting these objects from the natural environment. It is therefore hypothesized that reacting to the dynamically changing environment involves a robust and quick processing of salient information, which can be either with or without conscious awareness. We investigated the dynamics and robustness of perception using pictures of three salience levels, i.e. fearful faces (most salient), neutral faces (salient) and houses (nonsalient), which appear from dynamically decreasing random visual noise. Stimuli were matched for luminance, contrast, brightness and spatial frequency information. Reaction times show a significantly earlier response for faces than for houses. Fearful faces were significantly more quickly detected than neutral faces. The neural correlates sustaining robust perception were investigated with event-related functional magnetic resonance imaging (fMRI). The amygdala showed a significant perception-related response for faces, as compared to houses, that was further enhanced for fearful faces as compared to neutral faces. Our data indicate that emotionally salient information processing is (i) mediated by the amygdala and (ii) more robust than for nonsalient stimuli as it shows a significantly lower perceptual threshold.

Adolescent↗

PubMed2005

Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology.

These British Association for Psychopharmacology guidelines cover the range and aims of treatment for anxiety disorders. They are based explicitly on the available evidence and are presented as recommendations to aid clinical decision making in primary and secondary medical care. They may also serve as a source of information for patients and their carers. The recommendations are presented together with a more detailed review of the available evidence. A consensus meeting involving experts in anxiety disorders reviewed the main subject areas and considered the strength of evidence and its clinical implications. The guidelines were constructed after extensive feedback from participants and interested parties. The strength of supporting evidence for recommendations was rated. The guidelines cover the diagnosis of anxiety disorders and key steps in clinical management, including acute treatment, relapse prevention and approaches for patients who do not respond to first-line treatments.

Adolescent↗

PubMed2004

Five-minute recordings of heart rate variability in obsessive-compulsive disorder, panic disorder and healthy volunteers.

BACKGROUND: Recent studies have used spectral analysis of heart rate variability (HRV) to study autonomous nervous system (ANS) function in panic disorder (PD). Most studies reported a reduced HRV in resting PD patients, suggesting increased sympathetic and decreased parasympathetic tone. In obsessive-compulsive disorder (OCD) inconsistent findings have been reported on ANS function and to date no studies have been carried out with spectral analysis of HRV. In this HRV study we compared ANS function in patients with PD, OCD and normal controls. METHODS: Standardized HRV measurement was carried out in 24 PD patients, 26 OCD patients and 24 age-matched normal controls. All patients were drug free. As this comparison yielded unexpected results, the PD and normal control samples were enlarged to 53 and 54 subjects, respectively, to verify our first measurement. RESULTS: OCD patients were not characterized by a reduced HRV, as compared to normal controls. This was also found in PD patients, even in the enlarged sample. CONCLUSIONS: HRV analysis in patients with OCD or PD showed that these patients were not characterized by ANS abnormalities, as no evidence was found of diminished HRV in a large sample of resting OCD and PD patients, measured sitting on a hospital bed.

Adult↗

PubMed2003

Neuropsychological investigation into the carcinoid syndrome.

RATIONALE: In patients suffering from metastatic carcinoid tumors, chronic disturbances of serotonergic metabolism are frequently present. Serotonin is supposed to influence a range of cognitive functions. OBJECTIVES: The present study evaluated the cognitive performance of carcinoid patients. METHODS: In 14 patients with proven carcinoid syndrome, neuropsychological functioning was studied. Visual search, sustained attention, set shifting ability and spatial working memory were assessed using tests from the CANTAB neuropsychological battery. This was compared with the performance of matched healthy controls. RESULTS: Plasma tryptophan levels were lower than controls. Patients showed an enhanced ability to learn new stimulus-response associations. Sustained visual attention, however, was impaired. CONCLUSION: Cognitive patterns were different from those found in depressive patients and partly mimicked those found in tryptophan depletion experiments. Further investigation has to point out the role of serotonergic changes in the accomplishment of affective states.

Aged↗

PubMed2003

Immunohistochemical changes induced by repeated footshock stress: revelations of gender-based differences.

As a growing literature has proven, adverse experiences, particularly when severe and persistent, play a pivotal role in the development of neuronal dysfunctions and psychopathology. In the present study, the neurochemical changes induced by acute and repeated footshock exposure were investigated at the molecular and cellular level, using c-fos and phospho-ERK1/2 immunoreactivity and gene expression arrays. Marked gender-related differences were found following both acute and prolonged footshock exposure. Acute aversive conditioning resulted in significant immunohistochemical changes that might be critically involved in the modulation of fear-related responses, especially in males. Prolonged footshock exposure, on the contrary, was associated with sustained hypothalamic-pituitary-adrenal axis hyperactivity, differential gender-related patterns of cortical-limbic activity, and abnormal neuronal plasticity, especially in medial prefrontocortical regions. These data may provide additional insights into the understanding of the neural circuits underlying the effects of acute and repeated footshock exposure as well as clarify some of the mechanisms involved in the development of stress-related neuronal abnormalities.

Animals↗

PubMed2003

One brain, two selves.

Having a sense of self is an explicit and high-level functional specialization of the human brain. The anatomical localization of self-awareness and the brain mechanisms involved in consciousness were investigated by functional neuroimaging different emotional mental states of core consciousness in patients with Multiple Personality Disorder (i.e., Dissociative Identity Disorder (DID)). We demonstrate specific changes in localized brain activity consistent with their ability to generate at least two distinct mental states of self-awareness, each with its own access to autobiographical trauma-related memory. Our findings reveal the existence of different regional cerebral blood flow patterns for different senses of self. We present evidence for the medial prefrontal cortex (MPFC) and the posterior associative cortices to have an integral role in conscious experience.

Adult↗

PubMed2003

Evidence of enhancement of spatial attention during inhibition of a visuo-motor response.

A visuo-motor task was used as the setting for a study into inhibition in six healthy volunteers using fMRI. The task involved responding to colored stimuli, which appeared at random positions in the left and right visual field, with the corresponding hand. The volunteers were asked to respond to green colored stimuli ("go" response) and to inhibit responses to red stimuli ("no-go" response). The task was presented in a block design with blocks of three types; only "go" trials, a pseudo-random mixture of "go" and "no-go" tasks ("go/no-go" block), and "visual control." ANCOVA analysis of the fMRI data was performed within the framework of SPM99. Increased activation in the go vs visual control comparison was found in the bilateral motor and medial premotor cortices associated with the action of the button press response, as well as parietal regions attending to the task of identifying the visual field. The go/no-go vs visual control comparison showed a similar pattern, plus additional prefrontal areas that have previously been shown to be associated with inhibition. The direct comparison of the go and go/no-go blocks highlighted large differences not only in the prefrontal cortices, associated with inhibition, but also particularly in the right parietal cortex. We interpret the increased parietal activation, during inhibition, as representing a heightened spatial attention required for the correct execution of the inhibition task.

Adult↗

PubMed2002

Iterative versus filtered backprojection reconstruction for statistical parametric mapping of PET activation measurements: a comparative case study.

The significance of task-induced cerebral blood flow responses, assessed using statistical parametric mapping, depends, among other things, on the signal-to-noise ratio (SNR) of these responses. Generally, positron emission tomography sinograms of H(2)(15)O activation studies are reconstructed using filtered backprojection (FBP). Alternatively, the acquired data can be reconstructed using an iterative reconstruction procedure. It has been demonstrated that the application of iterative reconstruction methods improves image SNR as compared with FBP. The aim of this study was to compare FBP with iterative reconstruction, to assess the statistical power of H(2)(15)O-PET activation studies using statistical parametric mapping. For this case study, PET data originating from a bimanual motor task were reconstructed using both FBP and maximum likelihood expectation maximization (ML-EM), an iterative algorithm. Both resulting data sets were statistically analyzed using statistical parametric mapping. It was found, with this dataset, that the statistical analysis of the iteratively reconstructed data confirm the a priori expected physiological response. In addition, increased Z scores were obtained in the iteratively reconstructed data. In particular, for the expected task-related response, activation of the posterior border of the left angular gyrus, the Z score increased from 3.00 to 3.96. Furthermore, the number of statistically significant clusters doubled while their volume increased by more than 50%. In conclusion, iterative reconstruction has the potential to increase the statistical power in H(2)(15)O-PET activation studies as compared with FBP reconstruction.

Brain Mapping↗

PubMed2002

Interscan displacement-induced variance in PET activation data is excluded by a scan-specific attenuation correction.

In PET activation studies, linear changes in regional cerebral blood flow may be caused by subject interscan displacements rather than by changes in cognitive state. The aim of this study was to investigate the impact of these artifacts and to assess whether they can be removed by applying a scan-specific calculated attenuation correction (CAC) instead of the default measured attenuation correction (MAC). Two independent data sets were analyzed, one with large (data I) and one with small (data II) interscan displacements. After attenuation correction (CAC or MAC), data were analyzed using SPM99. Interscan displacement parameters (IDP), obtained during scan realignment, were included as additional regressors in the General Linear Model and their impact was assessed by variance statistics revealing the affected brain volume. For data I, this volume reduced dramatically from 579 to 12 cm(3) (approximately 50-fold) at P(uncorr) </= 0.001 and from 100 to 0 cm(3) at P(corr) </= 0.05 when CAC was applied instead of MAC. Surprisingly, for data II, applying CAC instead of MAC still resulted in a substantial (approximately 10-fold) reduction of the affected volume from 23 to 2 cm(3) at P(uncorr) </= 0.001. We conclude that interscan displacement-induced variance can be prevented by applying a (realigned attenuation correction scan (e.g., CAC). With MAC data, introducing IDP covariates is not an alternative since they model only this variance. Even in data with minor interscan displacements, applying a (realigned attenuation correction method (e.g., CAC) is superior to a nonaligned MAC with IDP covariates.

Adult↗

PubMed2002

Decision making performance in obsessive compulsive disorder.

BACKGROUND: Neuro-imaging studies in OCD report the orbitofrontal cortex to be functionally abnormal. As these areas are presumed to be involved in decision making, studying this behavior in OCD may provide further insight into the cognitive deficits accompanying the disorder. METHODS: Performance of 27 drug-free OCD patients and 26 healthy volunteers was compared on the decision making task of Bechara et al. [Cognition, 50 (1994) 7-15]. RESULTS: OCD patients and volunteers displayed comparable decision-making behavior. Within OCD patients, risk taking was independently related to both anxiety and OCD severity. LIMITATIONS: Results must be regarded as preliminary, due to the limited number of OCD patients included and the lack of a clinical control group. CONCLUSIONS: Although VMpfc function is not generally impaired, it seems to be involved in OCD; possibly in another way than could be measured with this task. CLINICAL RELEVANCE: Clarification of cognitive distortions underlying OCD may guide development of new strategies for cognitive-behavioral therapy.

Adult↗

PubMed2002

Evaluation of two cortical fraction estimation algorithms for the calculation of dynamic magnetic resonance renograms.

With the high resolution of dynamic magnetic resonance imaging (MRI) scans it is possible to measure cortical renograms directly, but due to partial volume effects this is impossible for medullary renograms. With weighted subtraction of the cortical renogram from a mixed renogram it becomes possible to extract the medullary renogram. For this subtraction the fraction of cortical tissue, present in the region of interest in which the mixed renogram is determined, has to be calculated. We have evaluated two algorithms for calculation of the cortical fraction. Both algorithms use the fact that during an interval after the start of the cortical enhancement no medullary enhancement occurs. One algorithm calculates the ratio between the slopes of both enhancement curves. The other is based on minimising the medullary signal values using a least squares error (LSE) method. Using a computer model of the renograms and measurements on real patients we analysed the accuracy of both methods and determined the best parameters for each.

Algorithms↗

PubMed2002

Heart rate variability as predictor of nonresponse to mirtazapine in panic disorder: a preliminary study.

Using spectral analysis of heart rate, several studies have shown that panic disorder patients are characterized by a reduced heart rate variability (HRV), indicative of abnormalities in autonomous nervous system (ANS) function. We recently reported that patients with panic disorder, who did not respond to pharmacotherapy, were characterized at baseline by a higher heart rate. In this study, ANS functioning is investigated as a possible predictor of nonresponse to pharmacotherapy. Twenty-eight medication-free panic disorder patients entered a 12-week open-label treatment study with mirtazapine. Five-minute HRV recordings were obtained before treatment and were analysed using spectral analysis. The data of 17 patients could be used. The total spectrum and low frequency power of responders to mirtazapine were significantly higher than those of nonresponders. Our findings suggest that nonresponders to short-term mirtazapine treatment are characterized at baseline by a lowered output of the ANS. The results are preliminary in view of the small sample studied.

Adult↗

PubMed2002

Differential effects of olanzapine and risperidone on cognition in schizophrenia? A saccadic eye movement study.

Recent studies suggest that novel antipsychotics have positive effects on certain cognitive functions in schizophrenia. The present study investigated this claim by means of saccadic paradigms, which provide a selective index of cognitive function. Thirty-three first-episode schizophrenic patients were randomly assigned to either olanzapine or risperidone treatment and compared with healthy control subjects for three saccadic paradigms. The influence of symptom profile, extrapyramidal symptoms, age, education, gender, hospitalization, and medication dose on cognitive performance was also investigated. Although the two patient groups did not differ from each other in task performance, both patient groups showed substantial problems in inhibitory control of saccades. A high level of education appeared to be protective for this impairment.

Adolescent↗