Moderating Effect of Cortical Thickness on BOLD Signal Variability Age-Related Changes

The time course of neuroanatomical structural and functional measures across the lifespan is commonly reported in association with aging. Blood oxygen-level dependent signal variability, estimated using the standard deviation of the signal, or BOLDSD , is an emerging metric of variability in neural processing, and has been shown to be positively correlated with cognitive flexibility. Generally, BOLDSD is reported to decrease with aging, and is thought to reflect age-related cognitive decline. Additionally, it is well established that normative aging is associated with structural changes in brain regions, and that these predict functional decline in various cognitive domains. Nevertheless, the interaction between alterations in cortical morphology and BOLDSD changes has not been modeled quantitatively. The objective of the current study was to investigate the influence of cortical morphology metrics [i.e., cortical thickness (CT), gray matter (GM) volume, and cortical area (CA)] on age-related BOLDSD changes by treating these cortical morphology metrics as possible physiological confounds using linear mixed models. We studied these metrics in 28 healthy older subjects scanned twice at approximately 2.5 years interval. Results show that BOLDSD is confounded by cortical morphology metrics. Respectively, changes in CT but not GM volume nor CA, show a significant interaction with BOLDSD alterations. Our study highlights that CT changes should be considered when evaluating BOLDSD alternations in the lifespan

Exploring aspects of memory in healthy ageing and following stroke

Memory is critical for everyday functioning. Remembering an event with rich detail requires the ability to remember the temporal order of occurrences within the event and spatial locations associated with it. But it remains unclear whether it also requires memory for the perspective from which we encoded the event, whether these three aspects of memory are affected following stroke, and which are the key brain regions upon which they rely. These questions are explored in this thesis. In the first study presented here, I examined young and elderly healthy subjects with an autobiographical memory interview and a 2D spatial memory task assessing self-perspective, and found no correlation between performance on these tasks. In the second experimental study, by assessing stroke patients on a 3D spatio-temporal memory task, I found that damage to the right intraparietal sulcus was associated with poorer memory for temporal order. However, voxelwise analyses detected no association between parietal lobe regions and accuracy in the egocentric condition of this task, or between medial temporal lobe regions and accuracy in the allocentric condition, one possible reason being that performance was near ceiling. In the third experimental study, by assessing a considerably larger group of stroke patients on a spatial memory task, I found that, as a group, patients performed worse than healthy controls, and performance was correlated with an activities of daily living scale. A spatial memory network was identified in right (but not left) hemisphere stroke patients. These findings provide evidence that spatial memory impairment is common after stroke, highlight its potential functional relevance, and increase our understanding of which regions are critical for remembering temporal order and spatial information. Furthermore, they suggest a dissociation between the mechanisms underpinning recall of 2D scenes over relatively short intervals versus remembering of real-life events across periods of many years.Open Acces

Quantifying gaze and mouse interactions on spatial visual interfaces with a new movement analytics methodology

This research was supported by the Royal Society International Exchange Programme (grant no. IE120643).Eye movements provide insights into what people pay attention to, and therefore are commonly included in a variety of human-computer interaction studies. Eye movement recording devices (eye trackers) produce gaze trajectories, that is, sequences of gaze location on the screen. Despite recent technological developments that enabled more affordable hardware, gaze data are still costly and time consuming to collect, therefore some propose using mouse movements instead. These are easy to collect automatically and on a large scale. If and how these two movement types are linked, however, is less clear and highly debated. We address this problem in two ways. First, we introduce a new movement analytics methodology to quantify the level of dynamic interaction between the gaze and the mouse pointer on the screen. Our method uses volumetric representation of movement, the space-time densities, which allows us to calculate interaction levels between two physically different types of movement. We describe the method and compare the results with existing dynamic interaction methods from movement ecology. The sensitivity to method parameters is evaluated on simulated trajectories where we can control interaction levels. Second, we perform an experiment with eye and mouse tracking to generate real data with real levels of interaction, to apply and test our new methodology on a real case. Further, as our experiment tasks mimics route-tracing when using a map, it is more than a data collection exercise and it simultaneously allows us to investigate the actual connection between the eye and the mouse. We find that there seem to be natural coupling when eyes are not under conscious control, but that this coupling breaks down when instructed to move them intentionally. Based on these observations, we tentatively suggest that for natural tracing tasks, mouse tracking could potentially provide similar information as eye-tracking and therefore be used as a proxy for attention. However, more research is needed to confirm this.Publisher PDFPeer reviewe

The neurocognitive underpinnings of the Simon effect: An integrative review of current research

Published online: 7 October 2020For as long as half a century the Simon task – in which participants respond to a nonspatial stimulus feature while ignoring its position – has represented a very popular tool to study a variety of cognitive functions, such as attention, cognitive control, and response preparation processes. In particular, the task generates two theoretically interesting effects: the Simon effect proper and the sequential modulations of this effect. In the present study, we review the main theoretical explanations of both kinds of effects and the available neuroscientific studies that investigated the neural underpinnings of the cognitive processes underlying the Simon effect proper and its sequential modulation using electroencephalogram (EEG) and event-related brain potentials (ERP), transcranial magnetic stimulation (TMS), and functional magnetic resonance imaging (fMRI). Then, we relate the neurophysiological findings to the main theoretical accounts and evaluate their validity and empirical plausibility, including general implications related to processing interference and cognitive control. Overall, neurophysiological research supports claims that stimulus location triggers the creation of a spatial code, which activates a spatially compatible response that, in incompatible conditions, interferes with the response based on the task instructions. Integration of stimulus-response features plays a major role in the occurrence of the Simon effect (which is manifested in the selection of the response) and its modulation by sequential congruency effects. Additional neural mechanisms are involved in supporting the correct and inhibiting the incorrect response.This research was supported by the Basque Government through the BERC 2018-2021 program and by the Spanish State Research Agency through BCBL Severo Ochoa excellence accreditation SEV-2015-0490 This study was also funded by Juan de la Cierva-Incorporación (Spanish government; JC) and European Commission (Marie Skłodowska-Curie actions 838536_BILINGUALPLAS; JC), by post-doctoral funding of the University of Bremen (DG; ZF 11/876/08), and by an ERC Advanced Grant (BH: ERC-2015-AdG-694722)

Modulation of the central vestibular networks through aging and high-strength magnetic fields

The importance of the vestibular system usually goes unnoticed in our daily lives and its significance is only experienced by patients suffering from vestibular diseases. The vestibular system is essential for orientation in space, and perception of motion, as well as keeping balance, and maintaining stable visual perception while moving in a three-dimensional world. Functional imaging has long been used to study the multisensory vestibular network in healthy subjects, as well as in patients with diseases of the vestibular system. The majority of these previous studies sought to associate brain areas with vestibular processing, by evaluating increases or decreases in blood-oxygen-level dependent signal (BOLD-signal) during application of artificial vestibular stimulations. However, many basic network properties of the multisensory vestibular cortical network still remain unknown. Since it is now possible to infer networks from functional connectivity analysis, that associates areas into networks based on their spatiotemporal signal behavior, a few of the remaining questions can be addressed. The dynamics of the vestibular networks and other co-activated networks in regard to the processing of a multisensory stimulation remain largely unknown. Do subjects of different ages respond differently to a vestibular challenge? Furthermore, a new form of vestibular stimulation, termed magnetic vestibular stimulation (MVS), has recently been discovered. It occurs in strong magnetic fields (≥1.5 tesla), that are commonly used in functional magnetic resonance imaging (fMRI), and raises questions about a possible modulation of vestibular networks during fMRI, potentially biasing functional neuroimaging results. The purpose of this thesis is to develop suggestions for studying the multisensory vestibular network and the influence of vestibular modulations on resting-state networks with fMRI. The focus lies on basic scientific investigations of (1) the influence of aging on the ability of subjects to respond to a challenge of the multisensory vestibular network and (2) the modulatory influence of magnetic fields (the MR environment) on functional imaging and resting-state networks in general. To this end, we carried out two studies. The first study was a cross-sectional aging study investigating the modulation of vestibular, somatosensory and motor networks in healthy adults (N=39 of 45 in total, age 20 to 70 years, 17 males). We used galvanic vestibular stimulation (GVS) to stimulate all afferences of the peripheral vestibular end organs or vestibular nerve in order to activate the entire multisensory vestibular network, as age-associated changes might be specific to sensory processing. We also controlled for changes of the motor network, structural fiber integrity (fractional anisotropy – FA), and volume changes to simultaneously compare the effects of aging across structure and function. The second study investigated the influence of the static magnetic field of the MR environment in a group of healthy subjects (N=27 of 30 in total, age 21 to 38 years, 19 females), as it was recently shown that a strong magnetic field produces a vestibular imbalance in healthy subjects. We examined MVS at field strengths of 1.5 tesla and 3 tesla. The associated spontaneous nystagmus, the scaling of the nystagmus’ slow phase velocity (SPV) across field strengths, the between subject variance of the SPV were analysed, and the analogous scaling relationship was identified in the modulation of resting-state network amplitudes, like the default mode network (DMN), between 1.5 tesla and 3 tesla to reveal its effect on fMRI results. Aging and MVS modulated networks associated with vestibular function and resting-state networks known for vestibular interactions. The results from our aging study imply that the dynamics of vestibular networks is limited by the influence of aging even in healthy adults without any noticeable vestibular deficit. Vestibular networks show a decline of functional connectivity with age and an increase of temporal variability (in excess of stimulation induced changes) with age. In contrast somatosensory and motor networks did not show any significant linear relationship with age or any significant changes between the youngest and oldest participants. Age-associated structural changes (gray matter volume changes or structural connectivity changes) did not explain the decline in functional connectivity or increase in temporal variability. Furthermore, stimulation thresholds did not change with age (nor did they correlate with the functional connectivity amplitudes or temporal variability), indicating that the age-associated changes that were found for the vestibular network, were not dependent on peripheral decline, as GVS is thought to directly stimulate the vestibular nerve. The results from our study of the influence of the static magnetic field of the MR environment showed that MVS was already present at a field strength of 1.5 tesla, as evident from the induced nystagmus, indicating a state of vestibular imbalance. Furthermore, MVS scaled linearly with field strength between 1.5 tesla and 3 tesla, and identified the effects of MVS in the scaling of functional resting-state network fluctuations, showing that MVS does indeed influence resting-state networks due to vestibular imbalance. Specifically, MVS does influence DMN resting-state network dynamics in accordance with the predicted scaling of MVS based on the Lorentz-force model for MVS. These results taken together not only imply that subjects were in a vestibular state of imbalance, but also that the extent and direction of the state of imbalance showed more variance between subjects with increasing field strength. In summary, the following suggestions for vestibular research can be delineated to extend the kind of questions that can be answered by functional MRI experiments and to improve these investigations for the benefit of clinically relevant research of healthy controls and patients. Regarding the influence of age, we suggest that researchers comparing patients with vestibular deficits and healthy controls should separate the age-matched group into age-strata (non-overlapping subgroups with different age spans, e.g. 20-40 years, 40-60 years and above 60 years of age). Each stratum should be compared and interpreted separately given that different age-groups have different levels of vestibular network dynamics available for compensation (or responding to a challenge). This is particularly relevant when patients show a wide age-distribution, e.g. in the case of vestibular neuritis patients. With respect to the influence of magnetic fields, we suggest that MVS should be seen as a new way of manipulating networks that either process vestibular information or show vestibular interactions, by using strong magnetic fields (≥1.5 tesla), as commonly used in MRI. The potential of modulating vestibular influences on networks via MVS lies in being able to induce or manipulate vestibular imbalances. In the healthy this can be used to create states that are similar to the diseased state, but without peripheral or central lesions. In patients this will allow to extend or reduce vestibular imbalances. In both cases this can be done while performing functional MRI simply by using the magnetic field of the MRI scanner and adjusting the head position of the subject in question. In studies that need to avoid vestibular perturbations MVS should be controlled by adjusting the head position of the subject and measuring the resulting eye movements. This should then be seen as an effort to remove unwanted variance, i.e., as an effort to homogenize the group, and achieve better statistical results due to less (uncontrolled) MVS interference that increases bias and variance with increasing field strength. In summary, these suggestions result in three short questions that researchers could ask themselves when thinking about vestibular research projects in the future. Age-grouping: “Is the response to a challenge different for younger adults than older adults, i.e., does each age-group compensate differently?” MVS modulation: “Can a manipulation of the imbalance state of our subjects with MVS help us to reveal more about the vestibular network’s response to a challenge or should we avoid interference by MVS in the imbalance state of our subjects?” Sensitivity: “Is the measure that I want to use sensitive enough to show the differences that I am looking for?” Connectivity and temporal variability might be sensitive enough, but many clinical tests might not be sufficient

Modulation of the central vestibular networks through aging and high-strength magnetic fields

The importance of the vestibular system usually goes unnoticed in our daily lives and its significance is only experienced by patients suffering from vestibular diseases. The vestibular system is essential for orientation in space, and perception of motion, as well as keeping balance, and maintaining stable visual perception while moving in a three-dimensional world. Functional imaging has long been used to study the multisensory vestibular network in healthy subjects, as well as in patients with diseases of the vestibular system. The majority of these previous studies sought to associate brain areas with vestibular processing, by evaluating increases or decreases in blood-oxygen-level dependent signal (BOLD-signal) during application of artificial vestibular stimulations. However, many basic network properties of the multisensory vestibular cortical network still remain unknown. Since it is now possible to infer networks from functional connectivity analysis, that associates areas into networks based on their spatiotemporal signal behavior, a few of the remaining questions can be addressed. The dynamics of the vestibular networks and other co-activated networks in regard to the processing of a multisensory stimulation remain largely unknown. Do subjects of different ages respond differently to a vestibular challenge? Furthermore, a new form of vestibular stimulation, termed magnetic vestibular stimulation (MVS), has recently been discovered. It occurs in strong magnetic fields (≥1.5 tesla), that are commonly used in functional magnetic resonance imaging (fMRI), and raises questions about a possible modulation of vestibular networks during fMRI, potentially biasing functional neuroimaging results. The purpose of this thesis is to develop suggestions for studying the multisensory vestibular network and the influence of vestibular modulations on resting-state networks with fMRI. The focus lies on basic scientific investigations of (1) the influence of aging on the ability of subjects to respond to a challenge of the multisensory vestibular network and (2) the modulatory influence of magnetic fields (the MR environment) on functional imaging and resting-state networks in general. To this end, we carried out two studies. The first study was a cross-sectional aging study investigating the modulation of vestibular, somatosensory and motor networks in healthy adults (N=39 of 45 in total, age 20 to 70 years, 17 males). We used galvanic vestibular stimulation (GVS) to stimulate all afferences of the peripheral vestibular end organs or vestibular nerve in order to activate the entire multisensory vestibular network, as age-associated changes might be specific to sensory processing. We also controlled for changes of the motor network, structural fiber integrity (fractional anisotropy – FA), and volume changes to simultaneously compare the effects of aging across structure and function. The second study investigated the influence of the static magnetic field of the MR environment in a group of healthy subjects (N=27 of 30 in total, age 21 to 38 years, 19 females), as it was recently shown that a strong magnetic field produces a vestibular imbalance in healthy subjects. We examined MVS at field strengths of 1.5 tesla and 3 tesla. The associated spontaneous nystagmus, the scaling of the nystagmus’ slow phase velocity (SPV) across field strengths, the between subject variance of the SPV were analysed, and the analogous scaling relationship was identified in the modulation of resting-state network amplitudes, like the default mode network (DMN), between 1.5 tesla and 3 tesla to reveal its effect on fMRI results. Aging and MVS modulated networks associated with vestibular function and resting-state networks known for vestibular interactions. The results from our aging study imply that the dynamics of vestibular networks is limited by the influence of aging even in healthy adults without any noticeable vestibular deficit. Vestibular networks show a decline of functional connectivity with age and an increase of temporal variability (in excess of stimulation induced changes) with age. In contrast somatosensory and motor networks did not show any significant linear relationship with age or any significant changes between the youngest and oldest participants. Age-associated structural changes (gray matter volume changes or structural connectivity changes) did not explain the decline in functional connectivity or increase in temporal variability. Furthermore, stimulation thresholds did not change with age (nor did they correlate with the functional connectivity amplitudes or temporal variability), indicating that the age-associated changes that were found for the vestibular network, were not dependent on peripheral decline, as GVS is thought to directly stimulate the vestibular nerve. The results from our study of the influence of the static magnetic field of the MR environment showed that MVS was already present at a field strength of 1.5 tesla, as evident from the induced nystagmus, indicating a state of vestibular imbalance. Furthermore, MVS scaled linearly with field strength between 1.5 tesla and 3 tesla, and identified the effects of MVS in the scaling of functional resting-state network fluctuations, showing that MVS does indeed influence resting-state networks due to vestibular imbalance. Specifically, MVS does influence DMN resting-state network dynamics in accordance with the predicted scaling of MVS based on the Lorentz-force model for MVS. These results taken together not only imply that subjects were in a vestibular state of imbalance, but also that the extent and direction of the state of imbalance showed more variance between subjects with increasing field strength. In summary, the following suggestions for vestibular research can be delineated to extend the kind of questions that can be answered by functional MRI experiments and to improve these investigations for the benefit of clinically relevant research of healthy controls and patients. Regarding the influence of age, we suggest that researchers comparing patients with vestibular deficits and healthy controls should separate the age-matched group into age-strata (non-overlapping subgroups with different age spans, e.g. 20-40 years, 40-60 years and above 60 years of age). Each stratum should be compared and interpreted separately given that different age-groups have different levels of vestibular network dynamics available for compensation (or responding to a challenge). This is particularly relevant when patients show a wide age-distribution, e.g. in the case of vestibular neuritis patients. With respect to the influence of magnetic fields, we suggest that MVS should be seen as a new way of manipulating networks that either process vestibular information or show vestibular interactions, by using strong magnetic fields (≥1.5 tesla), as commonly used in MRI. The potential of modulating vestibular influences on networks via MVS lies in being able to induce or manipulate vestibular imbalances. In the healthy this can be used to create states that are similar to the diseased state, but without peripheral or central lesions. In patients this will allow to extend or reduce vestibular imbalances. In both cases this can be done while performing functional MRI simply by using the magnetic field of the MRI scanner and adjusting the head position of the subject in question. In studies that need to avoid vestibular perturbations MVS should be controlled by adjusting the head position of the subject and measuring the resulting eye movements. This should then be seen as an effort to remove unwanted variance, i.e., as an effort to homogenize the group, and achieve better statistical results due to less (uncontrolled) MVS interference that increases bias and variance with increasing field strength. In summary, these suggestions result in three short questions that researchers could ask themselves when thinking about vestibular research projects in the future. Age-grouping: “Is the response to a challenge different for younger adults than older adults, i.e., does each age-group compensate differently?” MVS modulation: “Can a manipulation of the imbalance state of our subjects with MVS help us to reveal more about the vestibular network’s response to a challenge or should we avoid interference by MVS in the imbalance state of our subjects?” Sensitivity: “Is the measure that I want to use sensitive enough to show the differences that I am looking for?” Connectivity and temporal variability might be sensitive enough, but many clinical tests might not be sufficient

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 335)

This bibliography lists 143 reports, articles and other documents introduced into the NASA Scientific and Technical Information System during March, 1990. Subject coverage includes: aerospace medicine and psychology, life support systems and controlled environments, safety equipment, exobiology and extraterrestrial life, and flight crew behavior and performance