Investigating the interplay of the human attentional and vestibular systems using transcranial magnetic stimulation

The aim of this doctoral thesis was to investigate the relationship between the processing of vestibular information, on the one hand, and higher cognitive functions such as visual (spatial) attention and perceptual decision making, on the other. In order to draw causal inference about the role of specific cortical regions in this interplay, two experimental studies were conducted which combined psychophysical task designs using verticality judgment tasks with transcranial magnetic stimulation (TMS). The first study employed a simultaneous TMS-EEG approach to examine the role of the right intraparietal sulcus (IPS) within the dorsal parietal cortex in verticality judgments – a cortical area that has repeatedly been associated with both the visual attention and vestibular systems. Facilitatory effects of right IPS TMS on the bias of verticality perception were reported and mirrored by EEG results, which pointed to a normalization of individual perceptual biases reflected in a fronto-central ERP component following the stimulation. In contrast, no effects of left IPS TMS on either behavioural or electrophysiological measures were observed and right IPS TMS did not modulate performance in a control task that used the same set of stimuli (vertical Landmark task). These findings point to a causal role of the right IPS in the neuronal implementation of upright perception and strengthen the notion of vestibular-attentional coupling. In the second study verticality judgments had to be made under different levels of perceptual demand to address the question of how perceptual decision making interacts with vestibular processing. Stimuli adapted from those used in the first study were presented in a visual search setting, which required perceptual and response switches, in a way that varied attentional demands. This task was combined with offline theta-burst TMS applied to the dorsal medial frontal cortex (dMFC). The dMFC has been found to crucially contribute to perceptual decision making and is connected to core parts of the vestibular cortical network. Analysis of distinct features of behavioural performance before as compared to following dMFC TMS revealed a specific involvement of the dMFC in establishing the precision and accuracy of verticality judgments, particularly under conditions of high perceptual load. In summary, the results of the two studies support the idea of a functional link between the processing of vestibular information, (spatial) attention, and perceptual decision making, giving rise to higher vestibular cognition. Moreover, they suggest that on a cortical level this interplay is achieved within a network of multimodal processing regions such as the parietal and frontal cortices

Ecological drivers of mercury accumulation in threespine stickleback fish

Thesis (Ph.D.) University of Alaska Fairbanks, 2013I utilized the ecological diversity displayed in the Cook Inlet adaptive radiation of threespine stickleback (Gasterosteus aculeatus species complex, hereafter 'stickleback') to examine the drivers of intra- and inter-population variation in total mercury (THg) concentrations. I examined the importance of sex, trophic position (TP), and habitat-specific foraging (measured as the proportion of the diet derived from benthic sources; a) in stickleback from Benka Lake, Alaska, a lake with both benthic and limnetic ecotypes. The results demonstrate that both sex and habitat-specific foraging are important determinants of THg concentrations in this threespine stickleback population. Specifically, male stickleback and stickleback foraging in limnetic habitats had higher THg concentrations than females or benthic foraging individuals. Further, I found that the relationships between THg concentration, TP, and a differed between the sexes such that TP and a were of approximately equal importance in female fish but TP was more important than a in male fish. I assessed the relative importance of these same factors in determining THg concentrations of stickleback from six lakes spanning a range of trophic ecologies. Across populations, I found sex and TP to be more important determinants of THg concentrations than reliance on benthic prey; however, there was substantial variation in the relative importance of these parameters in individual lakes. Across lakes I also found a positive correlation between THg concentrations in stickleback and the reliance on benthic prey, and my data suggest that differences in the bioavailability of Hg in the lakes were responsible for this relationship. I investigated temporal variation in the THg concentrations of Benka Lake stickleback. The temporal patterns observed in stickleback likely result from numerous physiological and ecological processes. I found that the importance and magnitude of these factors acting upon THg concentrations varied between sexes, ecotypes, or both, though the directions of the relationships were consistent across groups. Despite this variation, TP was consistently the most important determinant of Hg concentrations. Collectively, the results of this dissertation demonstrate that the ecological factors driving THg concentrations in stickleback are complex, likely integrate multiple confounding interactions, and often vary by sex, ecotype, and population (lake). To improve our understanding of the mechanisms underlying Hg bioaccumulation, future research should utilize experimental studies and larger numbers of wild populations to examine the independent effects of these variables within the context of varying physiologies and ecologies

Reducing variability of perceptual decision making with offline theta-burst TMS of dorsal medial frontal cortex.

Abstract Background Recent evidence suggests that the dorsal medial frontal cortex (dMFC) may make an important contribution to perceptual decision-making, and not only to motor control. Objective/hypothesis By fitting psychometric functions to behavioural data after TMS we tested whether the dMFC is critical specifically for the precision and/or bias of perceptual judgements. Additionally we aimed to disentangle potential roles of the dMFC in dealing with perceptual versus response switching. Methods A subjective visual vertical task (SVV) was used in which participants weight visual (and other, e.g., vestibular) information to establish whether a line is oriented vertically. To ensure a high perceptual demand (putatively necessary to demonstrate a dMFC involvement) SVV lines were presented inside pop-out targets within a visual search array. Distinct features of perceptual performance were analysed before as compared to following theta-burst TMS stimulation of the dMFC, a control site, or no stimulation, in three groups, each of 20 healthy participants. Results dMFC stimulation improved the precision of verticality judgments. Moreover, dMFC stimulation improved accuracy, selectively when response switches occurred with perceptual repeats. Conclusion These findings point to a causal role of the dMFC in establishing the precision of perceptual decision making, demonstrably dissociable from an additional role in motor control in attentionally demanding contexts

Body shape differences in a pair of closely related Malawi cichlids and their hybrids: Effects of genetic variation, phenotypic plasticity, and transgressive segregation

Citation: Husemann, M., Tobler, M., McCauley, C., Ding, B., & Danley, P. D. (2017). Body shape differences in a pair of closely related Malawi cichlids and their hybrids: Effects of genetic variation, phenotypic plasticity, and transgressive segregation. Ecology and Evolution. doi:10.1002/ece3.2823Phenotypic differences may have genetic and plastic components. Here, we investigated the contributions of both for differences in body shape in two species of Lake Malawi cichlids using wild-caught specimens and a common garden experiment. We further hybridized the two species to investigate the mode of gene action influencing body shape differences and to examine the potential for transgressive segregation. We found that body shape differences between the two species observed in the field are maintained after more than 10 generations in a standardized environment. Nonetheless, both species experienced similar changes in the laboratory environment. Our hybrid cross experiment confirmed that substantial variation in body shape appears to be genetically determined. The data further suggest that the underlying mode of gene action is complex and cannot be explained by simple additive or additive-dominance models. Transgressive phenotypes were found in the hybrid generations, as hybrids occupied significantly more morphospace than both parentals combined. Further, the body shapes of transgressive individuals resemble the body shapes observed in other Lake Malawi rock-dwelling genera. Our findings indicate that body shape can respond to selection immediately, through plasticity, and over longer timescales through adaptation. In addition, our results suggest that hybridization may have played an important role in the diversification of Lake Malawi cichlids through creating new phenotypic variation. © 2017 Published by John Wiley & Sons Ltd

Effect of robotic tilt table verticalization on recovery in patients with disorders of consciousness: a randomized controlled trial

AbstractVerticalization is a common therapeutic intervention during rehabilitation of patients with disorders of consciousness (DoC). The Erigo®Pro is a robotic tilt-table (RTT) with built-in stepping unit for the lower extremities to prevent orthostatic hypotension during verticalization. In addition, the system also provides functional electrical stimulation (FES) of muscles of the lower extremities. In this randomized controlled clinical trial (RCT), 47 patients with subacute DoC received a 4-week verticalization regime (16 verticalization sessions) and were allocated to one of three experimental groups: (1) verticalization by means of RTT with FES, (2) by means of RTT without FES, or (3) by conventional physiotherapy (CPT). Level of consciousness (LoC), spasticity, functional independence in daily activities, and functional brain connectivity measured by means of high-density quantitative EEG were assessed at baseline, directly after the verticalization program and after 6 months. There was a similar clinical improvement in all three experimental groups. RTT was not associated with an effect on any of the clinical outcomes. Verticalization or mobilization time during the study period was significantly positively correlated with recovery of consciousness (rho = 0.494, p &lt; 0.001) in the short term and showed a statistical trend at the 6 months follow-up (rho = 0.244, p = 0.078). In conclusion, RTT treatment is not more effective in promoting recovery of consciousness than CPT in subacute DoC patients. Yet, our data suggest, that verticalization may be an important and feasible rehabilitation intervention in this group of patients. ClinicalTrials.gov NCT Number NCT02639481, registered on December 24, 2015.</jats:p

Riparian Methylmercury Production Increases Riverine Mercury Flux and Food Web Concentrations.

The production and uptake of toxic methylmercury (MeHg) impacts aquatic ecosystems globally. Rivers can be dynamic and difficult systems to study for MeHg production and bioaccumulation, hence identifying sources of MeHg to these systems is both challenging and important for resource management within rivers and main-stem reservoirs. Riparian zones, which are known biogeochemical hotspots for MeHg production, are understudied as potential sources of MeHg to rivers. Here, we present a comprehensive quantification of the hydrologic and biogeochemical processes governing MeHg concentrations, loads, and bioaccumulation at 16 locations along 164 km of the agriculturally intensive Snake River (Idaho, Oregon USA) during summer baseflow conditions, with emphasis on riparian production of MeHg. Approximately one-third of the MeHg load of the Snake River could not be attributed to inflowing waters (upgradient, tributaries, or irrigation drains). Across the study reach, increases in MeHg loads in surface waters were significantly correlated with MeHg concentrations in riparian porewaters, suggesting riparian zones were likely an important source of MeHg to the Snake River. Across all locations, MeHg concentrations in surface waters positively correlated with MeHg concentrations in benthic snails and clams, supporting that riparian produced MeHg was assimilated into local aquatic food webs. This study contributes new insights into riparian MeHg production within rivers which can inform mitigation efforts to reduce MeHg bioaccumulation in fish

Contrasting Magnitude and Timing of Pulsed Aqueous Methylmercury Bioaccumulation across a Reservoir Food Web.

Water column hypoxia is a key process influencing methylmercury (MeHg) production and availability in waterbodies worldwide. During seasonal destratification, large, short-lived pulses of aqueous MeHg may be released into the subsequently mixed water column, but little is known about the fate of these pulses, particularly whether there are concomitant increases in MeHg uptake into aquatic food webs. We examined the magnitude and timing of MeHg uptake across several trophic guilds relative to the reservoir stratification status using biweekly mercury data from water, zooplankton, and fish (Bluegill, Lepomis macrochirus and Smallmouth Bass, Micropterus dolomieu). Zooplankton MeHg concentrations increased by up to 250% during destratification, concurrent with increases in aqueous MeHg concentrations. Zooplankton and filter-passing MeHg concentrations were positively correlated when the reservoir was mixed (R2 = 0.95) and destratifying (R2 = 0.57) but not while the reservoir was stratified (R2 = 0.21). Mercury concentrations in adult bluegill and juveniles of both fish species increased 20-70% following destratification, with responses lagging 4-8 weeks behind those in water and zooplankton MeHg. Mercury concentrations in piscivorous adult bass varied little over the course of the study. Our findings demonstrate the responsiveness of reservoir food webs to pulses in MeHg availability, suggesting that these pulses could play an important role in biotic MeHg exposure within and downstream of reservoirs

Informal Caregivers of Patients with Disorders of Consciousness: a Qualitative Study of Communication Experiences and Information Needs with Physicians

Due to improvements in medicine, the figures of patients with disorders of consciousness (DoC) are increasing. Diagnostics of DoC and prognostication of rehabilitation outcome is challenging but necessary to evaluate recovery potential and to decide on treatment options. Such decisions should be made by doctors and patients’ surrogates based on medico-ethical principles. Meeting information needs and communicating effectively with caregivers as the patients´ most common surrogate-decision makers is crucial, and challenging when novel tech-nologies are introduced. This qualitative study aims to explore information needs of informal DoC caregivers, how they manage the obtained information and their perceptions and experiences with caregiver-physician communication in facilities that implemented innovative neurodiagnostics studies. In 2021, we conducted semi-structured interviews with nine caregivers of clinically stable DoC patients in two rehabilitation centers in Italy and Germany. Participants were selected based on consecutive purposeful sampling. Caregivers were recruited at the facilities after written informed consent. All interviews were recorded, transcribed verbatim and translated. For analysis, we used reflexive thematic analysis according to Braun & Clarke (2006). Caregivers experienced the conversations emotionally, generally based on the value of the information provided. They reported to seek positive information, comfort and empathy with-in the communication of results of examinations. They needed detailed information to gain a deep understanding and a clear picture of their loved-one’s condition. The results suggest a mismatch between the perspectives of caregivers and the perspectives of medical profession-als, and stress the need for more elaborate approaches to the communication of results of neu-rodiagnostics studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12152-022-09503-0

Participatory development of an international information brochure on the multimodal assessment of disorders of consciousness

Background Disorders of consciousness (DoC) refers to a group of clinical conditions of altered consciousness. To improve their diagnosis and prognosis, multimodal assessment can be of great importance. Informal caregivers of people with DoC who are confronted with new technologies as such can benefit from interventions to expand their health literacy, i.e., the ability to use information to make health decisions for oneself and others. Methods We developed an information brochure on multimodal assessment for DoC in a participatory process, with decisions made by a steering group. The process was based on a methodological framework for the development of patient decision aids that built on the International Patient Decision Aid Standards (IPDAS). Results On the background of a broad variety of needs, the priority was to focus on the explanation of multimodal testing and provide information about its uncertainty. Its development aimed at enhancing informal caregivers' understanding of implications of results from multimodal assessment and its relevance for prognosis. It should avoid the portrayal of information that could lead to the impression of false hope or suboptimal rehabilitation care. Informal caregivers rated its usability and acceptability highly, though they preferred less technical language. Conclusion The participatory process was crucial to the project. Future studies should investigate the effectiveness of the brochure in fostering informal caregivers' health literacy. Patient or Public Contribution Informal caregivers of people with DoC were deliberately included in the steering group and they participated in a field test of the prototype brochure

PerBrain: a multimodal approach to personalized tracking of evolving state-of-consciousness in brain-injured patients: protocol of an international, multicentric, observational study

BACKGROUND: Disorders of consciousness (DoC) are severe neurological conditions in which consciousness is impaired to various degrees. They are caused by injury or malfunction of neural systems regulating arousal and awareness. Over the last decades, major efforts in improving and individualizing diagnostic and prognostic accuracy for patients affected by DoC have been made, mainly focusing on introducing multimodal assessments to complement behavioral examination. The present EU-funded multicentric research project “PerBrain” is aimed at developing an individualized diagnostic hierarchical pathway guided by both behavior and multimodal neurodiagnostics for DoC patients. METHODS: In this project, each enrolled patient undergoes repetitive behavioral, clinical, and neurodiagnostic assessments according to a patient-tailored multi-layer workflow. Multimodal diagnostic acquisitions using state-of-the-art techniques at different stages of the patients’ clinical evolution are performed. The techniques applied comprise well-established behavioral scales, innovative neurophysiological techniques (such as quantitative electroencephalography and transcranial magnetic stimulation combined with electroencephalography), structural and resting-state functional magnetic resonance imaging, and measurements of physiological activity (i.e. nasal airflow respiration). In addition, the well-being and treatment decision attitudes of patients’ informal caregivers (primarily family members) are investigated. Patient and caregiver assessments are performed at multiple time points within one year after acquired brain injury, starting at the acute disease phase. DISCUSSION: Accurate classification and outcome prediction of DoC are of crucial importance for affected patients as well as their caregivers, as individual rehabilitation strategies and treatment decisions are critically dependent on the latter. The PerBrain project aims at optimizing individual DoC diagnosis and accuracy of outcome prediction by integrating data from the suggested multimodal examination methods into a personalized hierarchical diagnosis and prognosis procedure. Using the parallel tracking of both patients’ neurological status and their caregivers’ mental situation, well-being, and treatment decision attitudes from the acute to the chronic phase of the disease and across different countries, this project aims at significantly contributing to the current clinical routine of DoC patients and their family members. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04798456. Registered 15 March 2021 – Retrospectively registered