Impaired top-down modulation of saccadic latencies in patients with schizophrenia but not in first-degree relatives

Impaired eye movements have a long history in schizophrenia research and meet the criteria of a reliable biomarker. However, the effects of cognitive load and task difficulty on saccadic latencies (SL) are less understood. Recent studies showed that SL are strongly task dependent: SL are decreased in tasks with higher cognitive demand, and increased in tasks with lower cognitive demand. The present study investigates SL modulation in patients with schizophrenia and their first-degree relatives. A group of 13 patients suffering from ICD-10 schizophrenia, 10 first-degree relatives, and 24 control subjects performed two different types of visual tasks: a color task and a Landolt ring orientation task. We used video-based oculography to measure SL. We found that patients exhibited a similar unspecific SL pattern in the two different tasks, whereas controls and relatives exhibited 20–26% shorter average latencies in the orientation task (higher cognitive demand) compared to the color task (lower cognitive demand). Also, classification performance using support vector machines suggests that relatives should be assigned to the healthy controls and not to the patient group. Therefore, visual processing of different content does not modulate SL in patients with schizophrenia, but modulates SL in the relatives and healthy controls. The results reflect a specific oculomotor attentional dysfunction in patients with schizophrenia that is a potential state marker, possibly caused by impaired top-down disinhibition of the superior colliculus by frontal/prefrontal areas such as the frontal eye fields.

Universal ontology: attentive tracking of objects and substances across languages and over development

Previous research has demonstrated that adults are successful at visually tracking rigidly moving items, but experience great difficulties when tracking substance-like ‘‘pouring’’ items. Using a comparative approach, we investigated whether the presence/absence of the grammatical count–mass distinction influences adults and children’s ability to attentively track objects versus substances. More specifically, we aimed to explore whether the higher success at tracking rigid over substance-like items appears universally or whether speakers of classifier languages (like Japanese, not marking the object–substance distinction) are advantaged at tracking substances as compared to speakers of non-classifier languages (like Swiss German, marking the object–substance distinction). Our results supported the idea that language has no effect on low-level cognitive processes such as the attentive visual processing of objects and substances. We concluded arguing that the tendency to prioritize objects is universal and independent of specific characteristics of the language spoken.

A Vertical Asymmetry in Saccades

Visual exploration of natural scenes imposes demands that differ between the upper and the lower visual hemifield. Yet little is known about how ocular motor performance is affected by the location of visual stimuli or the direction of a behavioural response. We compared saccadic latencies between upper and lower hemifield in a variety of conditions, including short-latency prosaccades, long-latency prosaccades, antisaccades, memory-guided sac- cades and saccades with increased attentional and selection demand. All saccade types, except memory guided saccades, had shorter latencies when saccades were directed to- wards the upper field as compared to downward saccades (p<0.05). This upper field reaction time advantage probably arises in ocular motor rather than visual processing. It may originate in structures involved in motor preparation rather than execution.

Exploring the emotional brain: Neural correlates of homeostatic and sensory-evoked emotions and their interaction in emotional rivalry

Human emotions are essential for survival. They are vital for the satisfaction of basic needs, the regulation of personal life and successful integration into social structures. Depending on which aspect of an emotion is used in its definition, many different theories offer possible answers to the questions of what emotions are and how they can be distinguished. The systematic investigation of emotions in cognitive neuroscience is relatively new, and neuroimaging studies specifically focussing on the neural correlates of different categories of emotions are still lacking. Therefore, the current thesis aimed at investigating the behavioural and neurophysiological correlates of different human emotional levels and their interaction in healthy subjects. We differentiated between emotions according to their cerebral entry site and neural processing pathways: homeostatic emotions, which are elicited by metabolic changes and processed by the interoceptive system (such as thirst, hunger, and need for air), and sensory-evoked emotions, which are evoked by external inputs via the eyes, ears or nose, or their corresponding mental representations and processed in the brain as sensory perception (e.g. fear, disgust, or pride). Using functional magnetic resonance imaging (fMRI) and behavioural parameters, we examined both the specific neural underpinnings of a homeostatic emotion (thirst) and a sensory-evoked emotion (disgust), and their interaction in a situation of emotional rivalry when both emotions were perceived simultaneously. This thesis comprises three research articles reporting the results of this research. The first paper presents disgust-related brain imaging data in a thirsty and a satiated condition. We found that disgust mainly activated the anterior insular cortex. In the thirsty condition, however, we observed an interaction effect between disgust and thirst: when thirsty, the subjects rated the disgusting stimulus as less repulsive. On the neurobiological level, this reduction of subjective disgust was accompanied by significantly reduced neural activity in the insular cortex. These results provide new neurophysiological evidence for a hierarchical organization among homeostatic and sensory-evoked emotions, revealing that in a situation of emotional conflict, homeostatic emotions are prioritized over sensory-evoked emotions. In the second paper, findings on brain perfusion over four different thirst stages are reported, with a special focus on the parametric progression of thirst. Cerebral perfusion differences over all thirst stages were found in the posterior insular cortex. Taking this result together with the findings of the first paper, the insular cortex seems to be a key player in human emotional processing, since it comprises specific representations of homeostatic and sensory-evoked emotions and also represents the site of cortical interaction between the two levels of emotions. Finally, although this thesis focussed on the homeostatic modulation of disgust, we were also interested in whether dehydration modulates taste perception. The results of this behavioural experiment are described in the third paper, where we show that dehydration alters the perception of neutral taste stimuli.

Self-motion direction discrimination in the visually impaired

Despite the close interrelation between vestibular and visual processing (e.g., vestibulo-ocular reflex), surprisingly little is known about vestibular function in visually impaired people. In this study, we investigated thresholds of passive whole-body motion discrimination (leftward vs. rightward) in nine visually impaired participants and nine age-matched sighted controls. Participants were rotated in yaw, tilted in roll, and translated along the interaural axis at two different frequencies (0.33 and 2 Hz) by means of a motion platform. Superior performance of visually impaired participants was found in the 0.33 Hz roll tilt condition. No differences were observed in the other motion conditions. Roll tilts stimulate the semicircular canals and otoliths simultaneously. The results could thus reflect a specific improvement in canal–otolith integration in the visually impaired and are consistent with the compensatory hypothesis, which implies that the visually impaired are able to compensate the absence of visual input.

Processing-dependent and -independent pathways for recognition of iodinated contrast media by specific human T cells

One to three percent of patients exposed to intravenously injected iodinated contrast media (CM) develop delayed hypersensitivity reactions. Positive patch test reactions, immunohistological findings, and CM-specific proliferation of T cells in vitro suggest a pathogenetic role for T cells. We have previously demonstrated that CM-specific T cell clones (TCCs) show a broad range of cross-reactivity to different CM. However, the mechanism of specific CM recognition by T cell receptors (TCRs) has not been analysed so far.

Impaired performance on the rapid visual information processing task (RVIP) could be an endophenotype of schizophrenia

The aim of the present study was to investigate whether healthy first-degree relatives of schizophrenia patients show reduced sensitivity performance, higher intra-individual variability (IIV) in reaction time (RT), and a steeper decline in sensitivity over time in a sustained attention task. Healthy first-degree relatives of schizophrenia patients (n=23) and healthy control subjects (n=46) without a family history of schizophrenia performed a demanding version of the Rapid Visual Information Processing task (RVIP). RTs, hits, false alarms, and the sensitivity index A' were assessed. The relatives were significantly less sensitive, tended to have higher IIV in RT, but sustained the impaired level of sensitivity over time. Impaired performance on the RVIP is a possible endophenotype for schizophrenia. Higher IIV in RT, apparently caused by impaired context representations, might result in fluctuations in control and lead to more frequent attentional lapses.

Stimulus predictability reduces responses in primary visual cortex

In this functional magnetic resonance imaging study we tested whether the predictability of stimuli affects responses in primary visual cortex (V1). The results of this study indicate that visual stimuli evoke smaller responses in V1 when their onset or motion direction can be predicted from the dynamics of surrounding illusory motion. We conclude from this finding that the human brain anticipates forthcoming sensory input that allows predictable visual stimuli to be processed with less neural activation at early stages of cortical processing.

Investigating human audio-visual object perception with a combination of hypothesis-generating and hypothesis-testing fMRI analysis tools

Primate multisensory object perception involves distributed brain regions. To investigate the network character of these regions of the human brain, we applied data-driven group spatial independent component analysis (ICA) to a functional magnetic resonance imaging (fMRI) data set acquired during a passive audio-visual (AV) experiment with common object stimuli. We labeled three group-level independent component (IC) maps as auditory (A), visual (V), and AV, based on their spatial layouts and activation time courses. The overlap between these IC maps served as definition of a distributed network of multisensory candidate regions including superior temporal, ventral occipito-temporal, posterior parietal and prefrontal regions. During an independent second fMRI experiment, we explicitly tested their involvement in AV integration. Activations in nine out of these twelve regions met the max-criterion (A < AV > V) for multisensory integration. Comparison of this approach with a general linear model-based region-of-interest definition revealed its complementary value for multisensory neuroimaging. In conclusion, we estimated functional networks of uni- and multisensory functional connectivity from one dataset and validated their functional roles in an independent dataset. These findings demonstrate the particular value of ICA for multisensory neuroimaging research and using independent datasets to test hypotheses generated from a data-driven analysis.