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

Parametric [11C]flumazenil images

OBJECTIVE: This [C]flumazenil (FMZ) study evaluates the performance of various parametric analysis methods and their ability to detect statistically significant group differences. METHODS: Dynamic 60-min FMZ scans were performed in eight healthy and nine individuals with major depressive disorder. Parametric volume of distribution (VT) images were generated using a basis function method (BFM) implementation of the single tissue compartment model (1T) and Logan plot analysis, both with a metabolite-corrected arterial plasma input function. Parametric binding potential (BPND) images were generated using multilinear reference tissue methods (MRTM0-4), reference Logan and receptor parametric mapping (RPM1-2), with pons as a reference region. Standardized uptake value (SUV) and SUV ratio-to-pons (SUVr) images were calculated over the time interval 30-40 and 20-60 min postinjection. The resulting VT, BPND, SUV and SUVr values were compared with nonlinear regression values, using both the 1T model and the simplified reference tissue model. Statistical parametric mapping (SPM5) was used to detect group differences, with an emphasis on the bilateral parahippocampal gyri. RESULTS: BFM was more accurate than Logan, but showed more variability. Both RPM methods and MRTM2 showed the best average correlation with the simplified reference tissue model. In using SPM, SUV and SUVr images provided the best contrast between groups in the parahippocampal gyri, but provided large underestimation and overestimation in quantitative comparisons. BFM and RPM methods allowed for the determination of perfusion effects. CONCLUSION: Parametric Logan VT, MRTM2 and RPM1-2 BPND methods allow the best quantitative comparison of FMZ binding between groups and show good discriminating performance in SPM analysis

Clinical profiles of subsequent stages in bipolar disorder: Results from the Dutch Bipolar Cohort

Introduction: The manifestation of bipolar disorder (BD) is hypothesized to be determined by clinical characteristics such as familial loading, childhood abuse, age at onset, illness duration, comorbid psychiatric disorders, addiction, treatment resistance, and premorbid cognitive functioning. Which of these are associated with a more severe course and worse outcome is currently unknown. Our objective is to find a combination of clinical characteristics associated with advancement to subsequent stages in two clinical staging models for BD. Methods: Using cross-sectional data from the Dutch Bipolar Cohort, staging was applied to determine the progression of bipolar-I-disorder (BD-I; N = 1396). Model A is primarily defined by recurrence of mood episodes, ranging from prodromal to chronicity. Model B is defined by level of inter-episodic functioning, ranging from prodromal to inability to function autonomously. For both models, ordinal logistic regression was conducted to test which clinical characteristics are associated with subsequent stages. Results: For model A, familial loading, childhood abuse, earlier onset, longer illness duration, psychiatric comorbidity, and treatment resistance were all predictors for a higher stage in contrast to addiction and cognitive functioning. For model B, childhood abuse, psychiatric comorbidity, cognitive functioning, and treatment resistance were predictors for a more severe stage, whereas age at onset, illness duration, and addiction were not. Discussion/conclusions: Differences in clinical characteristics across stages support the construct validity of both staging models. Characteristics associated with a higher stage largely overlapped across both models. This study is a first step toward determining different clinical profiles, with a corresponding course and outcome

Comparison of plasma input and reference tissue models for analysing [(11)C]flumazenil studies

A single-tissue compartment model with plasma input is the established method for analysing [(11)C]flumazenil ([(11)C]FMZ) studies. However, arterial cannulation and measurement of metabolites are time-consuming. Therefore, a reference tissue approach is appealing, but this approach has not been fully validated for [(11)C]FMZ. Dynamic [(11)C]FMZ positron emission tomography scans with arterial blood sampling were performed in nine drug-free depressive patients and eight healthy subjects. Regions of interest were defined on co-registered magnetic resonance imaging scans and projected onto dynamic [(11)C]FMZ images. Using a Hill-type metabolite function, single (1T) and reversible two-tissue (2T) compartmental models were compared. Simplified reference tissue model (SRTM) and full reference tissue model (FRTM) were investigated using both pons and (centrum semiovale) white matter as reference tissue. The 2T model provided the best fit in 59% of cases. Two-tissue V(T) values were on average 1.6% higher than 1T V(T) values. Owing to the higher rejection rate of 2T fits (7.3%), the 1T model was selected as plasma input method of choice. SRTM was superior to FRTM, irrespective whether pons or white matter was used as reference tissue. BP(ND) values obtained with SRTM correlated strongly with 1T V(T) (r=0.998 and 0.995 for pons and white matter, respectively). Use of white matter as reference tissue resulted in 5.5% rejected fits, primarily in areas with intermediate receptor density. No fits were rejected using pons as reference tissue. Pons produced 23% higher BP(ND) values than white matter. In conclusion, for most clinical studies, SRTM with pons as reference tissue can be used for quantifying [(11)C]FMZ bindin

fMRI task conditions.

<p>fMRI task conditions.</p

Effects of TSD for fMRI and [¹¹C]raclopride PET.

<p><i>p</i> <0.005, extent threshold 10 voxels. A and B are task related fMRI results, showing increased prefrontal and limbic activation respectively, in the conditions (A) positive valence versus baseline and (B) both emotional valences. C is a [¹¹C]raclopride PET image, showing decreased voxel-by-voxel RPM2 binding potential (BP_ND) in nucleus caudatus in <i>n</i> = 8. At the bottom right is the Z-score scale depicted.</p