Neurophysiological effects of sleep deprivation in healthy adults, a pilot study

Total sleep deprivation (TSD) may induce fatigue, neurocognitive slowing and mood changes, which are partly compensated by stress regulating brain systems, resulting in altered dopamine and cortisol levels in order to stay awake if needed. These systems, however, have never been studied in concert. At baseline, after a regular night of sleep, and the next morning after TSD, 12 healthy subjects performed a semantic affective classification functional magnetic resonance imaging (fMRI) task, followed by a [11C]raclopride positron emission tomography (PET) scan. Saliva cortisol levels were acquired at 7 time points during both days. Affective symptoms were measured using Beck Depression Inventory (BDI), Spielberger State Trait Anxiety Index (STAI) and visual analogue scales. After TSD, perceived energy levels, concentration, and speed of thought decreased significantly, whereas mood did not. During fMRI, response speed decreased for neutral words and positive targets, and accuracy decreased trendwise for neutral words and for positive targets with a negative distracter. Following TSD, processing of positive words was associated with increased left dorsolateral prefrontal activation. Processing of emotional words in general was associated with increased insular activity, whereas contrasting positive vs. negative words showed subthreshold increased activation in the (para)hippocampal area. Cortisol secretion was significantly lower after TSD. Decreased voxel-by-voxel [11 C]raclopride binding potential (BPND) was observed in left caudate. TSD induces widespread cognitive, neurophysiologic and endocrine changes in healthy adults, characterized by reduced cognitive functioning, despite increased regional brain activity

Accelerated brain aging as a biomarker for staging in bipolar disorder:An exploratory study

Background:Two established staging models outline the longitudinal progression in bipolar disorder (BD) based on episode recurrence or inter-episodic functioning. However, underlying neurobiological mechanisms and corresponding biomarkers remain unexplored. This study aimed to investigate if global and (sub)cortical brain structures, along with brain-predicted age difference (brain-PAD) reflect illness progression as conceptualized in these staging models, potentially identifying brain-PAD as a biomarker for BD staging. Methods:In total, 199 subjects with bipolar-I-disorder and 226 control subjects from the Dutch Bipolar Cohort with a high-quality T1-weighted magnetic resonance imaging scan were analyzed. Global and (sub)cortical brain measures and brain-PAD (the difference between biological and chronological age) were estimated. Associations between individual brain measures and the stages of both staging models were explored. Results:A higher brain-PAD (higher biological age than chronological age) correlated with an increased likelihood of being in a higher stage of the inter-episodic functioning model, but not in the model based on number of mood episodes. However, after correcting for the confounding factors lithium-use and comorbid anxiety, the association lost significance. Global and (sub)cortical brain measures showed no significant association with the stages. Conclusions:These results suggest that brain-PAD may be associated with illness progression as defined by impaired inter-episodic functioning. Nevertheless, the significance of this association changed after considering lithium-use and comorbid anxiety disorders. Further research is required to disentangle the intricate relationship between brain-PAD, illness stages, and lithium intake or anxiety disorders. This study provides a foundation for potentially using brain-PAD as a biomarker for illness progression.</p

Neurophysiological Effects of Sleep Deprivation in Healthy Adults, a Pilot Study

textabstractTotal sleep deprivation (TSD) may induce fatigue, neurocognitive slowing and mood changes, which are partly compensated by stress regulating brain systems, resulting in altered dopamine and cortisol levels in order to stay awake if needed. These systems, however, have never been studied in concert. At baseline, after a regular night of sleep, and the next morning after TSD, 12 healthy subjects performed a semantic affective classification functional magnetic resonance imaging (fMRI) task, followed by a [11C]raclopride positron emission tomography (PET) scan. Saliva cortisol levels were acquired at 7 time points during both days. Affective symptoms were measured using Beck Depression Inventory (BDI), Spielberger State Trait Anxiety Index (STAI) and visual analogue scales. After TSD, perceived energy levels, concentration, and speed of thought decreased significantly, whereas mood did not. During fMRI, response speed decreased for neutral words and positive targets, and accuracy decreased trendwise for neutral words and for positive targets with a negative distracter. Following TSD, processing of positive words was associated with increased left dorsolateral prefrontal activation. Processing of emotional words in general was associated with increased insular activity, whereas contrasting positive vs. negative words showed subthreshold increased activation in the (para)hippocampal area. Cortisol secretion was significantly lower after TSD. Decreased voxel-by-voxel [11 C]raclopride binding potential (BPND) was observed in left caudate. TSD induces widespread cognitive, neurophysiologic and endocrine changes in healthy adults, characterized by reduced cognitive functioning, despite increased regional brain activity. The blunted HPA-axis response together with altered [11C]raclopride binding in the basal ganglia indicate that sustained wakefulness requires involvement of additional adaptive biological systems

Reduced parahippocampal and lateral temporal GABA(A)-[C-11]flumazenil binding in major depression: preliminary results

Purpose: Major depressive disorder (MDD) has been related to both a dysfunctional γ-amino butyric acid (GABA) system and to hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA). Although GABA has been suggested to inhibit HPA axis activity, their relationship has never been studied at the level of the central GAB

Perfectionisme in de gezondheidszorg: handig of handicap?

Perfectionism is common amongst medical doctors and, further, it is becoming more frequently seen in young people. Factors associated with this include the rise of social media and the increasing focus on social performance. Whilst perfectionism can be associated with positive characteristics such as accuracy and perseverance, it may also have a dark side: it is associated with significant mental and physical health problems. In this context, developing greater insight into one's perfectionism and means to address it would be of benefit to doctors. Perfectionism can be divided into three forms - perfectionistic concerns (PC), perfectionistic strivings (PS), perfectionism oriented at others (PO) - each of which has a different relationship to health problems and can reinforce each other. High PC are associated with many health complaints. The relationship between PS and health complaints is possibly U-shaped: both too little and too much PS are associated with many health complaints. Doctors could benefit from more balance in their perfectionism and this could be achieved by understanding their own perfectionism as well as daring to show vulnerability and leniency towards themselves and those around them

Symposia in undergraduate medical education: tailoring training in competencies to students' needs

Introduction: In mastering competencies, it is a challenge to create training sessions which acknowledge individual students’ needs and are logistically feasible in the medical master’s program. Methods: Symposia were implemented in the medical master’s program to provide knowledge and training of skills in a number of topics, providing a positive contribution to students’ competencies and personal development. Each symposium contained a morning and afternoon program, structured around medical and societal themes addressing various competencies and covering current national and international events. Alternating interactive teaching methods were used. Students were asked to rate each daypart program on a 5-point Likert scale in terms of both teaching methods and content, and to comment on the best aspects of the symposium as well as areas for improvement. Scores higher than 3.5 were interpreted as a predominantly favourable outcome. Results: In 2016, 10 symposia were organized with an average of 108 attendees and a response rate of 63% (1,366 completed questionnaires). Mean overall scores on ‘teaching methods’ and ‘usefulness for professional development’ were 3.8 and 3.7, respectively. The overall results corresponded with a high level of student appreciation. Conclusion: Symposia offer a podium for training students in subject matter and competencies that is greatly appreciated. Using alternating interactive teaching methods, symposia are structured around medical and societal themes and adjusted to the latest developments and current events in healthcare. By allowing students to select the symposia they would like to participate in, a tailor-made medical master’s program in competencies is created

Responsivity to stress in chronic posttraumatic stress disorder due to childhood sexual abuse

The purpose of this study was to investigate psychological, cardiovascular, and neuroendocrine reactivity to standardized stress tests (orthostatic challenge, Stroop Color Word Test) in drug-free adult women with chronic PTSD due to repetitive childhood sexual abuse. At baseline, the 11 patients showed significantly higher mean scores on the Symptom Check List-90 and the Profile of Mood States than 13 healthy female controls, whereas baseline cardiovascular or hormonal parameters showed no differences between the groups. Also, no significant differences were found between the two groups in cardiovascular and hormonal responsivity to the stress tests. Thus, in the presence of robust psychological differences, the patients with chronic PTSD due to childhood sexual abuse did not show alterations in baseline values of neurobiological parameters, nor did they react differently to a physical and mental stress test when compared to healthy controls

Estimation of image derived input functions using a reconstruction based partial volume correction algorithm: Methodology and evaluation in [11C]flumazenil studies

Introduction: The availability of image derived input functions (IDIF) obviates the need for arterial blood sampling and thereby facilitates clinical use of quantitative PET studies. The aim of this study was to develop a method for deriving IDIFs using reconstruction-based partial volume correction (PVC) [1]. Methods: PET and arterial blood data from nine dynamic [11C]flumazenil scans, acquired using an ECAT EXACT HR+ scanner and an on-line blood sampler, were used to develop and evaluate the method. Scans were reconstructed using both standard (no PVC) ordered subset expectation maximization (OSEM, 2 iterations, 16 subsets) and a PVC-OSEM algorithm, which corrects for the spatial resolution of the scanner. Number of iterations and width of PVC kernel were varied. The following regions of interest (ROIs) Methods: were evaluated for defining cerebral arteries: (a) pixel value threshold, (b) variable number of 'hottest' pixels per plane, (c) region growing, (d) cluster analysis, and (e) MR-based ROI. ROIs were defined on a pseudo blood volume image, generated by summation of early frames (<60s). ROIs were copied to all frames and IDIFs were extracted from both OSEM and PVC-OSEM images. For each IDIF the following parameters were derived: (a) area under the curve (AUC) for peak (1-2 min), (b) AUC for tail (2-60 min), (c) volume of distribution (Vd) obtained from parametric Logan images, and (d) Vd and K1 obtained from parametric basis function method (BFM) images. In each case, Results: were compared with those using on-line measured arterial input functions. Results: For PVC-OSEM, the optimal trade-off between computational time and signal-to-noise ratio was obtained for 4 iterations and 16 subsets. A 5.5 mm Gaussian resolution kernel gave optimal recovery correction. The best IDIF was obtained using the 'four hottest pixels per plane' over the blood pool in the region below the base of the skull. Compared with standard OSEM, use of PVC-OSEM improved mean (SD) AUC from 0.46 (0.06) to 1.15 (0.11) for the peak and from 0.82 (0.06) to 0.94 (0.12) for the tail part of the input function, respectively. Results: of the comparison between OSEM and PVC-OSEM for Vd and K1 are shown in Table 1 and Figure 1. Discussion and Conclusions: Excellent correlations were obtained between Vd and K1 values based on IDIFs and those based on on-line sampled input functions. Definition of an accurate IDIF may be sensitive to patient movement and future studies need to focus on motion correction Methods:. Nevertheless, this study shows the feasibility of deriving accurate IDIFs from dynamic PET scans using reconstruction-based PVC