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

Hemispheric Differences in Numerical Cognition: A Comparative Investigation of how Primates Process Numerosity

Four experiments, using both humans and monkeys as participants, were conducted to investigate the similarities and differences in human and nonhuman primate numerical cognition. In Experiment 1 it was determined that both humans and monkeys display a SNARC effect, with similar symbolic distance effects for both species. In addition, both species were found to respond faster to congruent stimulus pairs. In Experiment 2 both species were found accurately to recognize quantitative stimuli when presented for durations of 150 msec in a divided visual field paradigm. Performance for humans and monkeys for numerals and dot-patterns was almost identical in terms of accuracy and response times. In Experiment 3 participants were required to make relative numerousness judgments in a divided visual field paradigm. Both species responded faster and more accurately to stimuli presented to the right visual field. Species differences appeared, with monkeys performing equally well on both trial types whereas the humans performed better on numeral trials than on dot trials. In Experiment 4 repetitive transcranial magnetic stimulation (rTMS) was combined with the divided visual field paradigm. Accuracy was significantly disrupted for both species when compared to a no stimulation condition. A facilitation effect was also evident with both species exhibiting significant decreases in response time for all trials. Right-handed participants took longer to respond to stimuli presented to the left visual field. These findings add to the body of knowledge regarding both the similarities and differences of how quantitative stimuli are processed by humans and monkeys

Hemispatial neglect and deficits of verticality perception after stroke - neuropsychological results and modulation via galvanic vestibular stimulation

Hemispatial neglect is a multimodal syndrome that often follows unilateral right-brain damage. Patients with hemispatial neglect fail to notice or respond to sensory stimuli presented in the contralesional hemispace, which is not caused by primary motor or sensory deficits. Associated disorders often co-occurring with hemispatial neglect are deficits of verticality perception. Patients with those deficits show significant deviations in their subjective visual or haptic vertical away from the objective physical vertical when being asked to indicate whether a stepwise rotatable rod in the frontal plane is vertical, either by seeing the rod (visual modality) or by touching it when blindfolded (haptic modality). Both, hemispatial neglect and disorders of verticality perception are very frequent and strongly related to substantial impairments in daily life. Thus, research on the subserving mechanisms and potential treatment methods is of high significance. Four studies were conducted, first addressing the potential benefits and risks of a new treatment method for patients with hemispatial neglect, and second investigating the multimodality of disorders of verticality perception and their occurrence in different spatial planes (frontal, sagittal). Study 1 to 3 of the present doctoral thesis focus on a potential new treatment technique of hemispatial neglect and related disorders, the so-called galvanic vestibular stimulation (GVS). GVS uses weak direct current delivered via electrodes placed on the mastoids behind the ears. The direct current leads to polarization effects of the vestibular nerves and activations of multisensory vestibular brain areas, which are often lesioned in patients with hemispatial neglect and deficits of verticality perception. In order to obtain a broad overview over the technique of GVS and the available evidence of its potential to modulate different neuropsychological phenomena, in Study 1 the scientific literature on GVS and the related technique of transcranial direct current stimulation (tDCS; electrodes are attached to the skull over the target cortical area) in the field of neuropsychology was reviewed. Both GVS and tDCS over the parietal cortex were proven to be able to modulate neglect and related disorders, with little evidence showing GVS-induced modulation of deficits of verticality perception. Study 2 was concerned with the frequency and intensity of adverse effects during and after GVS in persons with stroke and healthy individuals, recorded via a questionnaire. The results indicate only very few and slight adverse effects like mild itching and tingling underneath the electrodes during and after stimulation in both groups. Hence, GVS was shown to be a suitable and easily applicable technique for modulation with only minimal adverse effects. In Study 3, the question was addressed whether GVS modulates a frequent neglect phenomenon, namely the rightward error in horizontal line bisection. GVS significantly decreased the rightward line bisection error during stimulation in right-brain-damaged patients with but not without neglect in contrast with sham stimulation. Right-cathodal GVS was more effective than left-cathodal GVS. Finally, in Study 4 the subjective verticality judgments in two modalities (visual, haptic) and two spatial planes (frontal, sagittal) of right-brain-damaged patients with neglect, right-brain-damaged patients without neglect and age-matched healthy individuals were investigated using a novel testing device for all these tasks. We observed greater unsigned errors and significant perceptual tilts in the verticality judgments of right-brain-damaged patients with neglect in contrast to the other two groups. Tilts of the neglect patients were directed counterclockwise in the roll plane, and towards the observer in the sagittal plane for both modalities. In summary, the studies presented in this work suggest that GVS is a promising treatment method which is able to modulate neglect phenomena and related disorders and is furthermore well-tolerated by persons with stroke and healthy individuals. The beneficial effects of GVS are most likely induced by activation of surviving remnants of the otherwise lesioned multimodal vestibular brain areas in neglect patients, thereby re-calibrating their disturbed spatial representations. Furthermore the present thesis shows that deficits of verticality perception in neglect patients are multimodal and multispatial in nature. These impairments are presumably due to lesions of temporoparietal cortical regions involved in multisensory integration which leads to a disturbed representation of the vertical.Hemispatialer Neglect ist ein multimodales Syndrom, das häufig nach unilateralen rechtshemisphärischen Hirnschädigungen auftritt. Patienten mit hemispatialem Neglect beachten keine oder reagieren nicht auf sensorische Reize, die im kontraläsionalen Halbraum auftreten. Assoziierte Störungen, die häufig das Neglect-Syndrom begleiten, sind Störungen der Vertikalenwahrnehmung. Davon betroffene Patienten zeigen signifikante Abweichungen von der physikalischen Vertikalen in ihrer subjektiven visuellen oder haptischen Vertikalen. Hierbei müssen die Patienten angeben, wann ein in der Frontalebene schrittweise drehbarer Stab vertikal ist (visuelle Modalität) oder den Stab mit verbunden Augen vertikal ausrichten (haptische Modalität). Beide Störungsbilder kommen häufig vor und gehen mit beträchtlichen Einschränkungen im Alltagsleben einher. Aus diesem Grund ist die Erforschung der zugrundeliegenden Mechanismen und möglicher Behandlungsmethoden der Störungen von hoher Relevanz. Im Rahmen dieser Arbeit wurden vier Studien durchgeführt, um einerseits den potentiellen Nutzen und die Risiken einer neuen Behandlungsmethode für hemispatialen Neglect zu erfassen, und andererseits das Vorkommen von Störungen der Vertikalenwahrnehmung in verschiedenen Modalitäten und verschiedenen Raumebenen (frontal, sagittal) zu untersuchen. Studien 1 bis 3 der vorliegenden Dissertation widmen sich einer neuen potentiellen Behandlungsmethode von Patienten mit hemispatialem Neglect und verwandten Störungen, der sogenannten Galvanisch Vestibulären Stimulation (GVS). Hierbei wird Gleichstrom geringer Intensität mittels Elektroden appliziert, welche auf den Mastoiden hinter den Ohren platziert werden. Dies aktiviert multisensorische vestibuläre Hirnareale, welche häufig bei Patienten mit hemispatialem Neglect und Störungen der Vertikalenwahrnehmung geschädigt sind. Um einen breiten Überblick über die Methode der GVS und der vorhandenen Untersuchungen zur Modulation von neuropsychologischen Funktionen mittels dieser Methode zu erhalten, wurde in Studie 1 ein Literaturüberblick über die wissenschaftlichen Veröffentlichungen zur GVS und der verwandten Technik der Transkraniellen Gleichtstromstimulation (tDCS; Elektroden werden auf dem Schädel, über dem zu stimulierenden Kortexbereich, platziert) im Bereich der Neuropsychologie gegeben. Hierbei stellte sich heraus, dass beide Methoden, GVS und tDCS über dem Parietalkortex, in der Lage sind, Neglect und verwandte Störungen zu modulieren. In Studie 2 wurde die Häufigkeit und Intensität von Nebenwirkungen während und nach GVS bei Personen mit Schlaganfall und gesunden Individuen anhand eines Fragebogens erfasst. Die Befunde zeigen, dass GVS nur zu wenigen und leichten Nebenwirkungen, wie leichtes Jucken und Kribbeln der Haut unter den Elektroden, während und nach der Stimulation in beiden Probandengruppen führte. In Studie 3 wurde untersucht, ob GVS ein häufig vorkommendes Neglectphänomen, nämlich die Rechtsabweichung im horizontalen Linienhalbieren, moduliert. GVS verringerte während der Stimulation die Rechtsabweichung von Patienten mit rechtshemisphärischen Hirnschädigungen mit Neglect, nicht aber die von rechtshemisphärisch geschädigten Patienten ohne Neglect. Rechts-kathodale GVS war hierbei effektiver als links-kathodale GVS. Schließlich wurde in Studie 4 die Beurteilung der Vertikalen in zwei Modalitäten (visuell, haptisch) und zwei Raumebenen (frontal, sagittal) von rechtshemisphärisch geschädigten Patienten mit Neglect, ohne Neglect, sowie von altersentsprechenden gesunden Individuen erfasst. Dabei wurde ein neues Untersuchungsgerät eingesetzt, welches für alle Aufgaben verwendet wurde. Wir beobachteten größere ungerichtete Fehler und signifikante Verkippungen in den Vertikalitäts-Urteilen von rechtshemisphärisch geschädigten Patienten mit Neglect im Vergleich zu den anderen beiden Probandengruppen. Die Abweichungen der Neglectpatienten waren in der Frontalebene gegen den Uhrzeigersinn gerichtet und zeigten in der Sagittalebene in Richtung des Beobachters. Dieses Muster wurde in beiden Modalitäten beobachtet. Zusammengefasst legen die hier dargestellten Studien nahe, dass GVS eine vielversprechende Methode zur Modulation von Neglectphänomenen und verwandten Störungen ist und darüber hinaus gut vertragen wird. Die positiven Effekte von GVS bei Neglectpatienten basieren höchstwahrscheinlich auf der Aktivierung erhaltener Bereiche in ansonsten geschädigten multisensorischen vestibulären Hirnbereichen, wodurch gestörte räumliche Repräsentationen rekalibriert werden. Darüber hinaus zeigt die vorliegende Dissertation, dass Störungen der Vertikalenwahrnehmung von Neglectpatienten multimodal sind und in verschiedenen Raumebenen auftreten. Diese Störungen sind vermutlich bedingt durch Läsionen temporo-parietaler Kortexareale, welche an der multisensorischen Integration beteiligt sind und folglich zu gestörten Repräsentationen der Vertikalen führen

Uncovering Multisensory Processing through Non-Invasive Brain Stimulation

Most of current knowledge about the mechanisms of multisensory integration of environmental stimuli by the human brain derives from neuroimaging experiments. However, neuroimaging studies do not always provide conclusive evidence about the causal role of a given area for multisensory interactions, since these techniques can mainly derive correlations between brain activations and behavior. Conversely, techniques of non-invasive brain stimulation (NIBS) represent a unique and powerful approach to inform models of causal relations between specific brain regions and individual cognitive and perceptual functions. Although NIBS has been widely used in cognitive neuroscience, its use in the study of multisensory processing in the human brain appears a quite novel field of research. In this paper, we review and discuss recent studies that have used two techniques of NIBS, namely transcranial magnetic stimulation and transcranial direct current stimulation, for investigating the causal involvement of unisensory and heteromodal cortical areas in multisensory processing, the effects of multisensory cues on cortical excitability in unisensory areas, and the putative functional connections among different cortical areas subserving multisensory interactions. The emerging view is that NIBS is an essential tool available to neuroscientists seeking for causal relationships between a given area or network and multisensory processes. With its already large and fast increasing usage, future work using NIBS in isolation, as well as in conjunction with different neuroimaging techniques, could substantially improve our understanding of multisensory processing in the human brain

Distinct contributions of extrastriate body area and temporoparietal junction in perceiving one's own and others' body.

The right temporoparietal cortex plays a critical role in body representation. Here, we applied repetitive transcranial magnetic stimulation (rTMS) over right extrastriate body area (EBA) and temporoparietal junction (TPJ) to investigate their causative roles in perceptual representations of one's own and others' body. Healthy women adjusted size-distorted pictures of their own body or of the body of another person according to how they perceived the body (subjective task) or how others perceived it (intersubjective task). In keeping with previous reports, at baseline, we found an overall underestimation of body size. Crucially, EBA-rTMS increased the underestimation bias when participants adjusted the images according to how others perceived their own or the other woman's body, suggesting a specific role of EBA in allocentric body representations. Conversely, TPJ-rTMS increased the underestimation bias when participants adjusted the body of another person, either a familiar other or a close friend, in both subjective and intersubjective tasks, suggesting an involvement of TPJ in representing others' bodies. These effects were body-specific, since no TMS-induced modulation was observed when participants judged a familiar object. The results suggest that right EBA and TPJ play active and complementary roles in the complex interaction between the perceptions of one's own and other people's body

Neural Mechanisms of Transsaccadic Integration of Visual Features

This thesis explores the neural mechanisms of transsaccadic integration of visual features. In the study, I investigated the cortical correlates of transsaccadic integration of object orientation in multiple reference frames. In a functional MRI adaptation (fMRIa) paradigm, participants viewed sets of two orientation stimuli in each trial and were asked to indicate if the orientations were the same (Repeat condition) or different (Novel condition). Stimuli were presented in one of three spatial conditions: 1) space-fixed, 2) retina-fixed and 3) frame-independent. Results indicate that, in addition to common activation in frontal motor cortical regions in all three spatial conditions, parietal and occipitotemporal regions are active in the space-fixed condition, parietofrontal regions are active in the retina-fixed condition, and parietofrontal and occipitotemporal regions are active in the frame-independent condition. In conclusion, these results indicate that transsaccadic integration involves differential activation of cortical areas, depending on the frame of reference

Transcranial Magnetic Stimulation of Early Visual Cortex During Transsaccadic Integration of Object Features

Visual information is integrated across saccades to maintain a continuous spatiotemporal representation of the world. This study investigated the role of early visual cortex (EVC) in trans-saccadic integration using functional magnetic resonance imaging guided repetitive transcranial magnetic stimulation (rTMS) protocol. Triple-pulse rTMS was applied over left and right EVC during the fixation task (participants maintained gaze), and saccade task (participants made an eye movement that either maintained or reversed the visual quadrant of the test stimulus). rTMS had no effect when 1) fixation was maintained, 2) saccades kept the stimulus in the same visual quadrant, or 3) quadrant corresponding to the first Gabor patch was stimulated. However, rTMS affected performance (relative to opposite EVC rTMS) when saccades brought the remembered visual stimulus into the magnetically stimulated quadrant. This effect increased with saccade amplitude. These results show that EVC is involved in the memory and ‘remapping’ of visual features across saccades

The left intraparietal sulcus modulates the selection of low salient stimuli

Neuropsychological and functional imaging studies have suggested a general right hemisphere advantage for processing global visual information and a left hemisphere advantage for processing local information. In contrast, a recent transcranial magnetic stimulation study [Mevorach, C., Humphreys, G. W., & Shalev, L. Opposite biases in salience-based selection for the left and right posterior parietal cortex. Nature Neuroscience, 9, 740-742, 2006b] demonstrated that functional lateralization of selection in the parietal cortices on the basis of the relative salience of stimuli might provide an alternative explanation for previous results. In the present study, we applied a whole-brain analysis of the functional magnetic resonance signal when participants responded to either the local or the global levels of hierarchical figures. The task (respond to local or global) was crossed with the saliency of the target level (local salient, global salient) to provide, for the first time, a direct contrast between brain activation related to the stimulus level and that related to relative saliency. We found evidence for lateralization of salience-based selection but not for selection based on the level of processing. Activation along the left intraparietal sulcus (IPS) was found when a low saliency stimulus had to be selected irrespective of its level. A control task showed that this was not simply an effect of task difficulty. The data suggest a specific role for regions along the left IPS in salience-based selection, supporting the argument that previous reports of lateralized responses to local and global stimuli were contaminated by effects of saliency

Perception, action and the cortical visual streams

Over a decade ago Milner and Goodale suggested that perception and action are subserved by two distinct cortical visual streams. The ventral stream projecting from striate cortex to inferotemporal cortex is involved in the perceptual identification of objects. The dorsal stream projecting from striate cortex to posterior parietal cortex is involved in visually guided actions. A series of experiments have been carried out and are presented within this thesis to investigate how various aspects of visuomotor behaviour fit into such a model. A range of techniques were employed, including: (1) behavioural studies with patients with optic ataxia (dorsal stream damage) and visual form agnosia (ventral stream damage); (2) transcranial magnetic stimulation (TMS) in healthy subjects; (3) functional magnetic resonance imaging (fMRI) in healthy subjects. The following conclusions were made: (1) obstacle avoidance behaviour is impaired in patients with optic ataxia due to damage to the dorsal stream; (2) obstacle avoidance is intact in patients with visual form agnosia as damage is restricted to the ventral stream; (3) obstacle avoidance is mediated by the dorsal stream when an immediate response is required, whereas under delayed conditions the ventral stream comes into play; (4) visual form agnosic patients can use looming information to catch moving objects and they are capable of responding to online perturbations due to an intact dorsal stream; (5) V5 / MT+ is involved in motion processing for perception and action and does not belong exclusively to the dorsal or ventral stream; (6) the dorsal stream is only sensitive to orientation changes if the stimuli are graspable. While some modifications of the original distinction are necessary, the experiments presented within this thesis suggest that this model has, for the most part, withstood the test of time and provides a useful framework for understanding various aspects of perception and action