Event-related potentials (ERPs) represent the cortical processing of sensory, motor or cognitive functions invoked by particular events or stimuli. A current theory posits that the catecholaminergic ...neurotransmitters dopamine (DA) and norepinephrine (NE) modulate a number of endogenous ERPs during various cognitive processes. This manuscript aims to evaluate a leading neurotransmitter hypothesis with a systematic overview and meta-analysis of pharmacologic DA and NE manipulation of specific ERPs in healthy subjects during executive function. Specifically, the frontally-distributed P3a, N2, and Ne/ERN (or error-related negativity) are supposedly modulated primarily by DA, whereas the parietally-distributed P3b is thought to be modulated by NE. Based on preceding research, we refer to this distinction between frontally-distributed DA-sensitive and parietally-distributed NE-sensitive ERP components as the Extended Neurobiological Polich (ENP) hypothesis. Our systematic review and meta-analysis indicate that this distinction is too simplistic and many factors interact with DA and NE to influence these specific ERPs. These may include genetic factors, the specific cognitive processes engaged, or elements of study design, i.e. session or sequence effects or data-analysis strategies.
•Polich proposed norepinephrine (NE) modulation of the parietally-distributed P3b.•Dopamine (DA) reputedly modulates the frontally-distributed P3a/nP3, N2 and Ne/ERN.•We examine pharmacologic DA/NE ERP modulation in healthy subjects.•Our systematic literature review does not wholly support the DA/NE dichotomy.•The meta-analysis showed heterogeneity of effect sizes and publication bias of the P3b component.
Wine faults threaten brand recognition and consumer brand loyalty. The objective of this study was to compare the acuteness of e‐tongue and human sensory evaluation of wine fault development in ...Riesling wine over 42 days of storage. Riesling wines uninoculated (control) or inoculated with 104 CFU/mL cultures of Wickerhamomyces anomalus, Acetobacter aceti, Lactobacillus brevis, or Pediococcus parvulus were assessed every 7 days with the e‐tongue and a rate‐all‐that‐apply (RATA) sensory panel. After 7 days of storage, the e‐tongue detected differences in all four wine spoilage microorganism treatments, compared to control wine, with discrimination indices over 86%. The RATA sensory panel detected significant differences beginning on day 35 of storage, 28 days after the e‐tongue detected differences. This study showed that the e‐tongue was more sensitive than the human panel as a detection tool, without sensory fatigue.
Practical Application
This research is useful for winemakers seeking additional instrumental methods in the early detection of wine faults. Given the results of this study, the e‐tongue can be a useful tool for detecting early chemical changes in white wines that have undergone microbial spoilage, providing winemakers with time to mitigate faults before they surpass sensory thresholds.
Abstract
Background
Antidepressant discontinuation is associated with a broad range of adverse effects. Debilitating discontinuation symptoms can impede the discontinuation process and contribute to ...unnecessary long-term use of antidepressants. Antidepressant trials reveal large placebo effects, indicating a potential use of open-label placebo (OLP) treatment to facilitate the discontinuation process. We aim to determine the effect of OLP treatment in reducing antidepressant discontinuation symptoms using a series of N-of-1 trials.
Methods
A series of randomized, single-blinded N-of-1 trials will be conducted in 20 patients with fully remitted DSM-V major depressive disorder, experiencing moderate to severe discontinuation symptoms following antidepressant discontinuation. Each N-of-1 trial consists of two cycles, each comprising two-week alternating periods of OLP treatment and of no treatment in a random order, for a total of eight weeks. Our primary outcome will be self-reported discontinuation symptoms rated twice daily via the smartphone application ‘StudyU’. Secondary outcomes include expectations about discontinuation symptoms and (depressed) mood. Statistical analyses will be based on a Bayesian multi-level random effects model, reporting posterior estimates of the overall and individual treatment effects.
Discussion
Results of this trial will provide insight into the clinical application of OLP in treating antidepressant discontinuation symptoms, potentially offering a new cost-effective therapeutic tool. This trial will also determine the feasibility and applicability of a series of N-of-1 trials in a clinical discontinuation trial.
Trial registration
ClinicalTrials.gov: NCT05051995, first registered September 20, 2021.
•All participants showed robust novelty P3 waveforms during both testing sessions.•Patients who were tested on medication during a first session, showed enhanced novelty P3 amplitudes during a second ...session (off medication).•Our results demonstrate the necessity for properly controlled repeated-measures designs to isolate diagnosis or medication effects and novelty or repetition effects.
Parkinson’s Disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons. Cognitive impairments have been reported using the event-related potential (ERP) technique. Patients show reduced novelty P3 (nP3) amplitudes in oddball experiments, a response to infrequent, surprising stimuli, linked to the orienting response of the brain. The nP3 is thought to depend on dopaminergic neuronal pathways though the effect of dopaminergic medication in PD has not yet been investigated.
Twenty-two patients with PD were examined “on” and “off” their regular dopaminergic medication in a novelty 3-stimulus-oddball task. Thirty-four healthy controls were also examined over two sessions, but received no medication. P3 amplitudes were compared throughout experimental conditions.
All participants showed sizeable novelty difference ERP effects, i.e. ndP3 amplitudes, during both testing sessions. An interaction of diagnosis, medication and testing order was also found, indicating that dopaminergic medication modulated ndP3 in patients with PD across the two testing sessions: We observed enhanced ndP3 amplitudes from PD patients who were off medication on the second testing session.
Patients with PD ‘off’ medication showed ERP evidence for repetition-related enhancement of novelty responses. Dopamine depletion in neuronal pathways that are affected by mid-stage PD possibly accounts for this modulation of novelty processing.
The data in this study potentially suggest that repetition effects on novelty processing in patients with PD are enhanced by dopaminergic depletion.
Transcutaneous auricular Vagal Nerve Stimulation (taVNS) is a non-invasive brain stimulation technique associated with possible modulation of norepinephrinergic (NE) activity. NE is suspected to ...contribute to generation of the P3 event-related potential. Recent evidence has produced equivocal evidence whether taVNS influences the P3 in healthy individuals during oddball tasks. We examined the effect of taVNS on P3 amplitudes using a novel visual Bayesian oddball task, which presented 200 sequences of three stimuli. The three consecutive stimuli in each sequence are labelled Draw 1, Draw 2 and Draw 3. In total, 47 Subjects completed this visual Bayesian oddball task under randomised sham and active taVNS stimulation in parallel with an electroencephalographic (EEG) recording. We conducted exploratory analyses of the effect of taVNS on P3 amplitudes separately for Draws. We found typical oddball effects on P3 amplitudes at Draws 1 and 2, but not Draw 3. At Draw 2, the oddball effect was enhanced during active compared to sham taVNS stimulation. These data provide evidence that taVNS influences parietal P3 amplitudes under specific circumstances. Only P3 amplitudes at Draw 2 were affected, which may relate to closure of Bayesian inference after Draw 2. Our findings seemingly support previously reported links between taVNS and the NE system.
Antidepressants are established as an evidence-based, guideline-recommended treatment for Major Depressive Disorder. Prescriptions have markedly increased in past decades, with a specific surge in ...maintenance prescribing. Patients often remain on antidepressants longer than clinically necessary. When attempting to stop, many patients experience adverse discontinuation symptoms. Discontinuation symptoms can be debilitating and hinder successful discontinuation. While discontinuation symptoms can result from pharmacological effects, evidence on nocebo-induced side effects of antidepressant use suggests that patients' expectations may also influence occurrence.
To disentangle pharmacological and expectation effects in antidepressant discontinuation, patients with fully remitted Major Depressive Disorder who fulfill German guideline recommendations to discontinue will either remain on or discontinue their antidepressant. Participants' expectations will be manipulated by varying verbal instructions using an open-hidden paradigm. Within the open trial arms, participants will receive full information about treatment, i.e., high expectation. Within the hidden trial arms, participants will be informed about a 50% chance of discontinuing versus remaining on their antidepressant, i.e., moderate expectation. A total of N = 196 participants will be randomly assigned to either of the four experimental groups: open discontinuation (OD; n = 49), hidden discontinuation (HD; n = 49), open continuation (OC; n = 49), or hidden continuation (HC; n = 49). Discontinuation symptom load during the 13-week experimental phase will be our primary outcome measure. Secondary outcome measures include discontinuation symptom load during the subsequent 39-week clinical observation phase, recurrence during the 13-week experimental period, recurrence over the course of the complete 52-week trial evaluated in a time-to-event analysis, and stress, anxiety, and participants' attentional and emotional processing at 13 weeks post-baseline. Blood and saliva samples will be taken as objective markers of antidepressant blood serum level and stress. Optional rsfMRI measurements will be scheduled.
Until today, no study has explored the interplay of pharmacological effects and patients' expectations during antidepressant discontinuation. Disentangling their effects has important implications for understanding mechanisms underlying adverse discontinuation symptoms. Results can inform strategies to manage discontinuation symptoms and optimize expectations in order to help patients and physicians discontinue antidepressants more safely and effectively.
ClinicalTrials.gov (NCT05191277), January 13, 2022.
Uptake of vaccination against COVID-19 is strongly affected by concerns about adverse effects. Research on nocebo effects suggests that these concerns can amplify symptom burden.
To investigate ...whether positive and negative expectations prior to COVID-19 vaccination are associated with systemic adverse effects.
This prospective cohort study analyzed the association of expected benefits and risks of vaccination, adverse effects at first vaccination, and observed adverse effects in close contacts with severity of systemic adverse effects among adults receiving a second dose of messenger RNA (mRNA)-based vaccines between August 16 and 28, 2021. A total of 7771 individuals receiving the second dose at a state vaccination center in Hamburg, Germany, were invited to participate; of these, 5370 did not respond, 535 provided incomplete information, and 188 were excluded retrospectively. The mobile application m-Path was used for data collection.
Primary outcome was a composite severity index of systemic adverse effects in 12 symptom areas measured once daily with an electronic symptom diary over 7 consecutive days. Data were analyzed by mixed-effects multivariable ordered logistic regression adjusted for prevaccine symptom levels and observation times.
A total of 10 447 observations from 1678 individuals receiving vaccinations (BNT162b2 Pfizer BioNTech in 1297 77.3% and mRNA-1273 Moderna in 381 22.7%) were collected. The participants' median age was 34 (IQR, 27-44) years, and 862 (51.4%) were women. The risk for more severe adverse effects was higher for persons expecting a lower benefit of vaccination (odds ratio OR for higher expectations, 0.72 95% CI, 0.63-0.83; P < .001), expecting higher adverse effects of vaccination (OR, 1.39 95% CI, 1.23-1.58; P < .001), having experienced higher symptom burden at the first vaccination (OR, 1.60 95% CI, 1.42-1.82; P < .001), scoring higher on the Somatosensory Amplification Scale (OR, 1.21 95% CI, 1.06-1.38; P = .004), and if the vaccine mRNA-1273 was given rather than BNT162b2 (OR, 2.45 95% CI, 2.01-2.99; P < .001). No associations were seen for observed experiences.
In this cohort study, several nocebo effects occurred in the first week after COVID-19 vaccination. The severity of systemic adverse effects was associated not only with vaccine-specific reactogenicity but also more negative prior experiences with adverse effects from the first COVID-19 vaccination, more negative expectations regarding vaccination, and tendency to catastrophize instead of normalize benign bodily sensations. Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines.
The enumeration and evaluation of bacteria and mold are important elements in the evaluation of hatchery sanitation programs. However, detection of bacteria and mold in fluff samples is time ...consuming and cumbersome. The PetrifilmTM aerobic count plate (ACP) and the Petrifilm yeast/mold count plate are ready-to-use alternatives to the traditional enumeration media used for bacteria and mold associated with environment and food. The purpose of this study was to evaluate the usefulness of Petrifilms for enumeration of aerobic bacteria and mold from hatchery fluff samples. Comparisons of ACP and mold counts were performed in 25 fluff samples. These samples were from 2 commercial hatcheries. ACP comparisons were made by evaluating the standard for pour plating with plate count agar versus aerobic count plate Petrifilm. Mold comparisons were made by evaluating Sabouraud dextrose agar versus yeast/mold plate count Petrifilm. Overall equivalent bacterial counts and mold counts were obtained by both enumeration methods. Because the Petrifilm method is convenient and gave comparative results, it offers a good alternative for fluff aerobic bacteria and mold counts.
Two patients with the same model of single-coil active fix implantable defibrillator lead presented with evidence of lead malfunction, in one case with an abrupt rise in pacing impedance and ...threshold and in the other with evidence of over-sensing. In both cases, the chest radiograph showed separation of conductors in the defibrillation lead from the main body of the lead.
PDF
