Performance of different automatic photographic identification software for larvae and adults of the European fire salamander.

For many species, population sizes are unknown despite their importance for conservation. For population size estimation, capture-mark-recapture (CMR) studies are often used, which include the necessity to identify each individual, mostly through individual markings or genetic characters. Invasive marking techniques, however, can negatively affect the individual fitness. Alternatives are low-impact techniques such as the use of photos for individual identification, for species with stable distinctive phenotypic traits. For the individual identification of photos, a variety of different software, with different requirements, is available. The European fire salamander (Salamandra salamandra) is a species in which individuals, both at the larval stage and as adults, have individual specific patterns that allow for individual identification. In this study, we compared the performance of five different software for the use of photographic identification for the European fire salamander: Amphibian & Reptile Wildbook (ARW), AmphIdent, I3S pattern+, ManderMatcher and Wild-ID. While adults can be identified by all five software, European fire salamander larvae can currently only be identified by two of the five (ARW and Wild-ID). We used one dataset of European fire salamander larval pictures taken in the laboratory and tested this dataset in two of the five software (ARW and Wild-ID). We used another dataset of European fire salamander adult pictures taken in the field and tested this using all five software. We compared the requirements of all software on the pictures used and calculated the False Rejection Rate (FRR) and the Recognition Rate (RR). For the larval dataset (421 pictures) we found that the ARW and Wild-ID performed equally well for individual identification (99.6% and 100% Recognition Rate, respectively). For the adult dataset (377 pictures), we found the best False Rejection Rate in ManderMatcher and the highest Recognition Rate in the ARW. Additionally, the ARW is the only program that requires no image pre-processing. In times of amphibian declines, non-invasive photo identification software allowing capture-mark-recapture studies help to gain knowledge on population sizes, distribution, movement and demography of a population and can thus help to support species conservation.

Stress response of fire salamander larvae differs between habitat types.

The larvae of the European fire salamander (Salamandra salamandra) can inhabit two different habitats: streams and ponds. Streams are characterized by lower predation risks and higher food availability. Thus, ponds are considered a less suitable habitat. To investigate the differential impacts of these two habitats on larval physiology, we measured the stress response of larvae. After successfully validating the measure of water-borne corticosterone release rates in fire salamander larvae, we measured the baseline and stress-induced corticosterone of 64 larvae from ponds and streams in the field. We found that larvae in ponds have a higher baseline and stress-induced corticosterone levels. Additionally, we performed a reciprocal transplant experiment (RTE) and tested whether larvae can adapt their stress responses to changing habitats. After two weeks, we did not find an increase in corticosterone levels when comparing stress-induced corticosterone values with baseline corticosterone values in larvae transferred into ponds, irrespective of their habitat of origin. However, larvae transferred into streams still exhibited an increase in the stress-induced corticosterone response in comparison with the baseline values. These results show that non-invasive hormone measurements can provide information on the habitat quality and potential adaptation and thus emphasize the potential for its use in conservation efforts.

Tonic immobility behaviour does not differ between fire salamander larvae from ponds and streams.

Tonic immobility is an antipredator defence in which the prey animal remains motionless after physical contact with the predator, pretending to be dead. This behaviour has been observed among a variety of taxa but has received only little attention in amphibian larvae. During our field studies with fire salamander larvae, we observed that larvae from different habitats display tonic immobility after handling. In our study site, we find larvae in pond and stream habitats, that differ in several aspects such as their stress response and their risk-taking behaviour, likely caused by the very different habitat conditions. We measured the time that the tonic immobility behaviour was displayed but found no difference between larvae from the two habitat types. Likewise, we also found no correlation between the size of the larvae and the duration of displaying the behaviour. In conclusion, we found that fire salamander larvae show tonic immobility, but found no evidence that the different habitat conditions influence the tonic immobility behaviour.

Migraine prodromes and migraine triggers.

Migraine is characterized by a well-defined premonitory phase occurring hours or even days before the headache. Also, many migraineurs report typical triggers for their headaches. Triggers, however, are not consistent in their ability to precipitate migraine headaches. When looking at the clinical characteristics of both premonitory symptoms and triggers, a shared pathophysiological basis seems evident. Both seem to have their origin in basic homeostatic networks such as the feeding/fasting, the sleeping/waking, and the stress response network, all of which strongly rely on the hypothalamus as a hub of integration and are densely interconnected. They also influence the trigeminal pain processing system. Additionally, thalamic and hormonal mechanisms are involved. Activity within all those networks is influenced by various endogenous and external factors and might even cyclically change dependent on physiological internal rhythms. This might affect the threshold for the generation of migraine headaches. Premonitory symptoms thus appear as the result of an already ongoing alteration within those networks, whereas triggers might in this special situation only be able to further stress the system over the threshold for attack generation as catalysts of a process already in motion.

Aura phenomena do not initiate migraine attacks-Findings from neuroimaging.

OBJECTIVES/BACKGROUND: As cortical spreading depolarization (CSD) has been suggested to be the cause of migraine aura and as CSD can activate trigeminal nociceptive neurons in animals, it has been suggested that CSD may be the cause of migraine attacks. This raises the question of how migraine pain is generated in migraine attacks without aura and has led to the hypothesis that CSD may also occur in subcortical regions in the form of "silent" CSDs, and accordingly "silent auras". METHODS: In this case study, we provide evidence for common neuronal alterations preceding headache attacks with and without aura in a male patient with migraine, who underwent daily event-correlated functional magnetic resonance imaging of trigeminal nociception for a period of 30 days. During these days the man experienced migraine attacks with and without aura. RESULTS: Comparing the preictal phases between both attack types revealed a common hyperactivation of the hypothalamus (p < 0.01), which was already present 2 days before the actual attack. CONCLUSION: The time frame of the central pathophysiological orchestration of migraine attacks, irrelevant of the presence of later aura, strongly suggests that the aura is an epiphenomenon that is unrelated and does not initiate headache attacks.

Physical activity monitoring-based interventions in geriatric patients: a scoping review on intervention components and clinical applicability.

OBJECTIVE: To identify and analyze the components applied in interventions using physical activity (PA) monitoring in geriatric patients and determine their feasibility and applicability. METHODS: A systematic search in six databases (PubMed, Embase, SPORTDiscus, CINAHL, Web of Science, and GeroLit) was conducted to identify studies reporting interventions that included the application of a PA monitor in adults aged ≥ 60 years with a clinical diagnosis. PA monitor interventions were analyzed regarding their feedback, goal-setting and behavior change technique (BCT) components. To determine the feasibility and applicability of interventions, the participants' adherence to the intervention, their experience as well as adverse events were analyzed. RESULTS: Seventeen eligible studies, applying 22 interventions, were identified. Studies included a total of 827 older patients with a median age of 70.2 years. In thirteen interventions (59%), the PA monitor was embedded in a structured behavioral intervention, an indication-specific intervention or usual care. Most frequently applied intervention components were goal setting and self-monitoring (n = 18), real-time PA monitor feedback complemented by feedback from the study team (n = 12), use of further BCTs (n = 18), and regular counseling with the study team (n = 19). Comprehensive information on the participants' intervention adherence and experience were reported for 15 (68%) and 8 (36%) interventions, respectively. CONCLUSION: The components included in PA monitoring-based interventions varied considerably especially regarding the extent, frequency, and content of feedback, goal setting and BCTs counseling. Future research should evaluate which components are most effective and clinically applicable to promote physical activity in geriatric patients. To be able to precisely analyze the effects, trials should seek to report details on intervention components, adherence and adverse events, while future reviews may use the findings of this scoping review to conduct analyses with less heterogeneity in study characteristics and intervention strategies.

Short-term aerobic exercise for depression in acute geriatric psychiatry: study protocol for a randomized controlled trial.

BACKGROUND: Major depression is one of the main mental illnesses in old age, with acute exacerbated episodes requiring treatment in geriatric psychiatry. A meta-analysis showed that aerobic exercise in moderate intensity has large effects in older adults with major depression, but there is no evidence of aerobic exercise in geriatric psychiatry. Therefore, this study aims to analyze the feasibility and effects of an ergometer-based aerobic exercise on depressive symptoms. METHODS: A single-center randomized controlled trial will be conducted in an acute geriatric psychiatric hospital. Inpatients allocated to the intervention group will receive a 2-week aerobic ergometer program. The control group will receive seated flexibility exercise in addition to usual care. The overall effects on the patients' depressive symptoms will be measured by clinical global impression of change (CGI) as the primary outcome. Changes in depressive symptom domains, physical (in)activity, and aerobic performance as well as the dosage of applied antidepressants will be examined as secondary outcomes. DISCUSSION: This short-term aerobic exercise program is expected to decrease depressive symptoms in acute exacerbated periods in older adults. The results may increase the evidence for implementing physical activity interventions in acute hospital settings. The disease-related motivation for exercise in acute exacerbated depressive periods will be the most challenging aspect. The treatment of depression requires new cost-effective approaches, especially in acute geriatric psychiatry with potential benefits for patients, family members, and clinicians. TRIAL REGISTRATION: German Clinical Trial Register ID: DRKS00026117 TRIAL STATUS: Protocol Version 1.2 dated February 23, 2022. By February 23, 2022, the trial had recruited a total of 15 participants in two wards at the Department of Geriatric Psychiatry at the LVR-Hospital Cologne. Recruitment started on November 12, 2021. The recruitment is expected to continue for at least 12 months.

Very Small Home Ranges of Two Gravid European Brown Bears during Hyperphagia.

In September 2019, two gravid female brown bears (Ursus arctos) were captured and equipped with GPS/GSM collars in Paklenica National Park (Croatia). Home ranges during hyperphagia were analyzed to describe the spatiotemporal requirements. Mean seasonal home ranges were very small with 9.2 km2 and 7.5 km2 (Brownian Bridge Movement Model 95%). During the tracking period, both bears used different territories and showed little to no use of overlapping area. The bears in our study spent a considerable time in proximity of artificial feeding sites, indicating a probable use of these structures as a food resource (mean 15.7% and 30.7%). Furthermore, the bears approached very close to human structures such as 8.9 m and 4.4 m. As most encounters between humans and bears occur during hyperphagia, it is important to offer refugia from human disturbance, especially as the National Park is not only used by residents, but also by tourists. To adapt management according to the animal's needs, further studies should include more individuals from different age and sex classes. Both females were gravid. It remains unclear whether gravidity has an effect on the home range and should be further investigated.

Migraine: disease characterisation, biomarkers, and precision medicine.

Migraine is a disabling neurological disorder, diagnosis of which is based on clinical criteria. A shortcoming of these criteria is that they do not fully capture the heterogeneity of migraine, including the underlying genetic and neurobiological factors. This complexity has generated momentum for biomarker research to improve disease characterisation and identify novel drug targets. In this Series paper, we present the progress that has been made in the search for biomarkers of migraine within genetics, provocation modelling, biochemistry, and neuroimaging research. Additionally, we outline challenges and future directions for each biomarker modality. We also discuss the advances made in combining and integrating data from multiple biomarker modalities. These efforts contribute to developing precision medicine that can be applied to future patients with migraine.

Altered trigeminal pain processing on brainstem level in persistent idiopathic facial pain.

ABSTRACT: Persistent idiopathic facial pain (PIFP) is a poorly understood chronic pain syndrome of the face, formerly known as atypical facial pain. It is characterized by a constant painful sensation without neurological abnormalities and without clinically objectifiable cause. Similarities to neuropathic pain conditions have been discussed and are currently thought to be relevant for the pathophysiology of this disease. In this study, we aim to characterize the trigeminal pain processing in PIFP using functional magnetic resonance imaging of the brainstem. Twenty-five patients suffering from PIFP and 25 healthy controls underwent a standardized and well-established paradigm of painful stimulation of the trigeminal nerve using gaseous ammonia. Functional images were acquired within a 3T magnetic resonance imaging scanner using an optimized protocol for high-resolution echo planar brainstem imaging. Patients with PIFP show exclusively a stronger activation to painful stimulation in the spinal trigeminal nucleus when contrasted against healthy controls. Our data suggest that abnormal central pain processing plays a role in the pathophysiology of PIFP. An integration of these findings into neuropathic pain models might help to gain a better general understanding of the pathophysiology of PIFP.

Partial Similarity Reveals Dynamics in Brainstem-Midbrain Networks during Trigeminal Nociception.

Imaging studies help us understand the important role of brainstem and midbrain regions in human trigeminal pain processing without solving the question of how these regions actually interact. In the current study, we describe this connectivity and its dynamics during nociception with a novel analytical approach called Partial Similarity (PS). We developed PS specifically to estimate the communication between individual hubs of the network in contrast to the overall communication within that network. Partial Similarity works on trial-to-trial variance of neuronal activity acquired with functional magnetic resonance imaging. It discovers direct communication between two hubs considering the remainder of the network as confounds. A similar method to PS is Representational Similarity, which works with ordinary correlations and does not consider any external influence on the communication between two hubs. Particularly the combination of Representational Similarity and Partial Similarity analysis unravels brainstem dynamics involved in trigeminal pain using the spinal trigeminal nucleus (STN)-the first relay station of peripheral trigeminal input-as a seed region. The combination of both methods can be valuable tools in discovering the network dynamics in fMRI and an important instrument for future insight into the nature of various neurological diseases like primary headaches.

The migraineur's brain networks: Continuous resting state fMRI over 30 days.

OBJECTIVE: The aim of the current study was to identify typical alterations in resting state connectivity within different stages of the migraine cycle and to thus explore task-free mechanisms of headache attack generation in migraineurs. BACKGROUND: Recent evidence in migraine pathophysiology suggests that hours and even days before headache certain changes in brain activity take place, ultimately leading to an attack. Here, we investigate changes before headache onset using resting state functional magnetic resonance imaging (fMRI). METHODS: Nine episodic migraineurs underwent daily resting state functional magnetic resonance imaging for a minimum period of 30 consecutive days, leading to a cumulative number of 282 total days scanned. Thus, data from 15 spontaneous headache attacks were acquired. This allows analysing not only the ictal and the interictal phase of migraine but also the preictal phase. ROI-to-ROI (region of interest) and ROI-to-voxel connectivity was calculated over the migraine cycle. RESULTS: Within the ROI-to-ROI analysis, the right nucleus accumbens showed enhanced functional connectivity to the left amygdala, hippocampus and gyrus parahippocampalis in the preictal phase compared to the interictal phase. ROI-to-voxel connectivity of the right accumbens with the dorsal rostral pons was enhanced during the preictal phase compared to interictally. Regarding custom defined ROIs, the dorsal pons was ictally functionally more strongly coupled to the hypothalamic area than interictally. CONCLUSIONS: This unique data set suggests that particularly connectivity changes in dopaminergic centres and between the dorsal pons and the hypothalamus are important within migraine attack generation and sustainment.

Phase dependent hypothalamic activation following trigeminal input in cluster headache.

BACKGROUND: Task-free imaging approaches using PET have shown the posterior hypothalamus to be specifically activated during but not outside cluster headache attacks. Evidence from task related functional imaging approaches however is scarce. METHODS: Twenty-one inactive cluster headache patients (episodic cluster headache out of bout), 16 active cluster headache patients (10 episodic cluster headache in bout, 6 chronic cluster headache) and 18 control participants underwent high resolution brainstem functional magnetic resonance imaging of trigeminal nociception using gaseous ammonia as a painful stimulus. RESULTS: Following trigeminonociceptive stimulation with ammonia there was a significantly stronger activation within the posterior hypothalamus in episodic cluster headache patients out of bout when compared to controls. When contrasting estimates of the pain contrast, active cluster headache patients where in between the two other groups but did not differ significantly from either. CONCLUSION: The posterior hypothalamus might thus be hyperexcitable in cluster headache patients outside the bout while excitability to external nociceptive stimuli decreases during in bout periods, probably due to frequent hypothalamic activation and possible neurotransmitter exhaustion during cluster attacks.

Longitudinal Neuroimaging over 30 Days: Temporal Characteristics of Migraine.

OBJECTIVE: Although migraine is defined by the headache and headache-associated symptoms, the true beginning of a migraine attack lies in the premonitory phase. To understand the generation of attacks, one needs to investigate the phase before headache starts. The premonitory phase of migraine is characterized by a well-described complex of symptoms. Its duration, however, is not clearly defined, and there are no biomarkers to help define when this phase starts. METHODS: Here, we used functional magnetic resonance imaging (MRI) to elucidate the duration of the premonitory phase in spontaneous human migraine attacks. Because migraine attacks are hardly predictable and thereby the premonitory phase is difficult to catch, we scanned 9 patients daily over a minimum period of 30 days using a well-established paradigm for functional MRI of trigeminal nociception. RESULTS: Seven patients were included in the analysis, thus providing cumulative data of 27 spontaneous human migraine attacks including scans before, during, and after migraine pain as well as interictal scans. As a response to painful trigeminal stimulation, activation of the hypothalamus was present within the last 48 hours before headache onset but not earlier. INTERPRETATION: Using hypothalamic activation as a potential marker for the premonitory phase of migraine in this unique dataset, our data corroborated a duration of 48 hours for the premonitory phase of migraine. We suggest applying this time criterion in future studies when focusing on this phase of the migraine cycle. ANN NEUROL 2020;87:646-651.

Current understanding of premonitory networks in migraine: A window to attack generation.

AIM: To describe neuronal networks underlying commonly reported migraine premonitory symptoms and to discuss how these might precipitate migraine pain. BACKGROUND: Migraine headache is frequently preceded by a distinct and well characterized premonitory phase including symptoms like yawning, sleep disturbances, alterations in appetite and food intake and hypersensitivity to certain external stimuli. Recent neuroimaging studies strongly suggest the hypothalamus as the key mediator of the premonitory phase and also suggested alterations in hypothalamic networks as a mechanism of migraine attack generation. When looking at the vast evidence from basic research within the last decades, hypothalamic and thalamic networks are most likely to integrate peripheral influences with central mechanisms, facilitating the precipitation of migraine headaches. These networks include sleep, feeding and stress modulating centers within the hypothalamus, thalamic pathways and brainstem centers closely involved in trigeminal pain processing such as the spinal trigeminal nucleus and the rostral ventromedial medulla, all of which are closely interconnected. CONCLUSION: Taken together, these networks represent the pathophysiological basis for migraine premonitory symptoms as well as a possible integration site of peripheral so-called "triggers" with central attack facilitating processes.

Visual processing in migraineurs depends on the migraine cycle.

We investigated changes of after-image duration in migraineurs and healthy controls (HCs) and throughout the migraine cycle to depict changes in the excitatory/inhibitory equilibrium within the visual cortex. Forty-seven episodic (EMs) and 39 chronic migraineurs (CMs; interictal) were compared to 34 HCs for visual after-image duration. Additionally, seven EMs were investigated every consecutive day over 20 to 32 days using the identical paradigm throughout the migraine cycle. Interictally, the after-image duration was shorter compared to HCs, but significantly longer in the ictal compared to interictal phase. These data suggest an altered excitatory/inhibitory equilibrium in migraineurs, which oscillates over the migraine cycle. ANN NEUROL 2019;85:280-283.

Visual stimulation leads to activation of the nociceptive trigeminal nucleus in chronic migraine.

OBJECTIVE: The visual system has often been described to be sensitized in migraineurs, with light being perceived as aversive or even painful. One possible explanation for this altered perception is crosslinks between the visual and the trigeminonociceptive system. Visual stimulation in chronic migraineurs on the level of the brainstem might lead to enhanced activity within the spinal trigeminal nucleus (sTN) as the main site of trigeminal pain processing within this area. METHODS: Eighteen episodic migraineurs (EM), 17 chronic migraineurs (CM), and 19 healthy controls (HC) underwent one session of high-resolution brainstem imaging during which a rotating checkerboard was presented repeatedly as a visual stimulus. Data were analyzed using SPM12 and MATLAB with the classic first-level-second-level approach of SPM. Analyses of variance were used for group comparisons. RESULTS: CM showed enhanced activation within the sTN as compared to HC. In addition, we observed enhanced activity within the right superior colliculus in CM as compared to HC. When comparing all migraineurs with headaches during scanning with all migraineurs without headaches during scanning and HC, we also found the sTN to be more strongly activated during headaches. CONCLUSION: Our data provide evidence for the existence of visual-nociceptive integration on brainstem level in chronic migraineurs.

Linear and inverted U-shaped dose-response functions describe estrogen effects on hippocampal activity in young women.

In animals, 17-beta-estradiol (E2) enhances hippocampal plasticity in a dose-dependent, monotonically increasing manner, but this relationship can also exhibit an inverted U-shaped function. To investigate E2's dose-response function in the human hippocampus, we pharmacologically increased E2 levels in 125 naturally cycling women (who were in their low-hormone menstruation phase) to physiological (equivalent to menstrual cycle peak) and supraphysiological (equivalent to levels during early pregnancy) concentrations in a placebo-controlled design. Twenty-four hours after first E2 intake, we measured brain activity during encoding of neutral and negative pictures and then tested recognition memory 24 h after encoding. Here we report that E2 exhibits both a monotonically increasing relationship with hippocampal activity as well as an inverted U-shaped relationship, depending on the hippocampal region. Hippocampal activity exhibiting a U-shaped relationship inflects at supraphysiological E2 levels, suggesting that while E2 within physiological ranges stimulates hippocampal activity, supraphysiological ranges show opposite effects.