Playing with temptation: Stopping abilities to chocolate are superior, but also more extensive.

Cue-specific inhibitory control is assumed to support balanced food intake, but previous studies with established measures showed inconsistent results. We developed a novel kinematic stop task in virtual reality (VR) and report results from trajectory recordings. The primary objective of this explorative study was to assess the interrelationships between validated measures of food-related inhibitory control and novel measures from the VR task. We hypothesized that healthy female participants show worse inhibitory control when grasping attractive virtual chocolate, compared to non-edible color-and-shape matched objects. We further aimed to quantify the construct validity of kinematic measures (e.g., reaching extent/spatial displacement, movement time after stop-signal, velocity) with established measures of inhibitory control in a keyboard-based adaptive stop-signal task (SST). In total, 79 females with varying levels of chocolate craving participated in an experimental study consisting of self-report questionnaires, subjective chocolate craving, the conventional SST and the kinematic task in VR. Results showed superior stopping ability to chocolate in both tasks. In VR, participants successfully interrupted an initiated approach trajectory but terminated slightly closer to chocolate targets. Stop-signal delay (SSD) was adapted relative to movement onset and appeared later in chocolate trials, during which participants still stopped faster, as was also confirmed by shorter stop-signal reaction time (SSRT) in the conventional task. Yet, SSRT did not correlate with stopping in VR. Moreover, SSRT was related to depressive symptoms whereas measures from VR were related to chocolate craving and subjective hunger. Thus, VR stopping can provide deeper insights into healthy weight individuals' capacity to inhibit cue-specific approach behavior towards appetitive stimuli in simulated interactions. Furthermore, the results support a multi-faceted view of food-specific inhibitory control and behavioral impulsivity.

Critical View of Novel Treatment Strategies for Glioblastoma: Failure and Success of Resistance Mechanisms by Glioblastoma Cells.

According to the invasive nature of glioblastoma, which is the most common form of malignant brain tumor, the standard care by surgery, chemo- and radiotherapy is particularly challenging. The presence of glioblastoma stem cells (GSCs) and the surrounding tumor microenvironment protects glioblastoma from recognition by the immune system. Conventional therapy concepts have failed to completely remove glioblastoma cells, which is one major drawback in clinical management of the disease. The use of small molecule inhibitors, immunomodulators, immunotherapy, including peptide and mRNA vaccines, and virotherapy came into focus for the treatment of glioblastoma. Although novel strategies underline the benefit for anti-tumor effectiveness, serious challenges need to be overcome to successfully manage tumorigenesis, indicating the significance of developing new strategies. Therefore, we provide insights into the application of different medications in combination to boost the host immune system to interfere with immune evasion of glioblastoma cells which are promising prerequisites for therapeutic approaches to treat glioblastoma patients.

Motor Cortex Causally Contributes to Vocabulary Translation following Sensorimotor-Enriched Training.

The role of the motor cortex in perceptual and cognitive functions is highly controversial. Here, we investigated the hypothesis that the motor cortex can be instrumental for translating foreign language vocabulary. Human participants of both sexes were trained on foreign language (L2) words and their native language translations over 4 consecutive days. L2 words were accompanied by complementary gestures (sensorimotor enrichment) or pictures (sensory enrichment). Following training, participants translated the auditorily presented L2 words that they had learned. During translation, repetitive transcranial magnetic stimulation was applied bilaterally to a site within the primary motor cortex (Brodmann area 4) located in the vicinity of the arm functional compartment. Responses within the stimulated motor region have previously been found to correlate with behavioral benefits of sensorimotor-enriched L2 vocabulary learning. Compared to sham stimulation, effective perturbation by repetitive transcranial magnetic stimulation slowed down the translation of sensorimotor-enriched L2 words, but not sensory-enriched L2 words. This finding suggests that sensorimotor-enriched training induced changes in L2 representations within the motor cortex, which in turn facilitated the translation of L2 words. The motor cortex may play a causal role in precipitating sensorimotor-based learning benefits, and may directly aid in remembering the native language translations of foreign language words following sensorimotor-enriched training. These findings support multisensory theories of learning while challenging reactivation-based theories.SIGNIFICANCE STATEMENT Despite the potential for sensorimotor enrichment to serve as a powerful tool for learning in many domains, its underlying brain mechanisms remain largely unexplored. Using transcranial magnetic stimulation and a foreign language (L2) learning paradigm, we found that sensorimotor-enriched training can induce changes in L2 representations within the motor cortex, which in turn causally facilitate the translation of L2 words. The translation of recently acquired L2 words may therefore rely not only on auditory information stored in memory or on modality-independent L2 representations, but also on the sensorimotor context in which the words have been experienced.

CK1δ-Derived Peptides as Novel Tools Inhibiting the Interactions between CK1δ and APP695 to Modulate the Pathogenic Metabolism of APP.

Alzheimer's disease (AD) is the major cause of dementia, and affected individuals suffer from severe cognitive, mental, and functional impairment. Histologically, AD brains are basically characterized by the presence of amyloid plaques and neurofibrillary tangles. Previous reports demonstrated that protein kinase CK1δ influences the metabolism of amyloid precursor protein (APP) by inducing the generation of amyloid-ß (Aß), finally contributing to the formation of amyloid plaques and neuronal cell death. We therefore considered CK1δ as a promising therapeutic target and suggested an innovative strategy for the treatment of AD based on peptide therapeutics specifically modulating the interaction between CK1δ and APP. Initially, CK1δ-derived peptides manipulating the interactions between CK1δ and APP695 were identified by interaction and phosphorylation analysis in vitro. Selected peptides subsequently proved their potential to penetrate cells without inducing cytotoxic effects. Finally, for at least two of the tested CK1δ-derived peptides, a reduction in Aß levels and amyloid plaque formation could be successfully demonstrated in a complex cell culture model for AD. Consequently, the presented results provide new insights into the interactions of CK1δ and APP695 while also serving as a promising starting point for further development of novel and highly innovative pharmacological tools for the treatment of AD.

Flow parsing and biological motion.

Flow parsing is a way to estimate the direction of scene-relative motion of independently moving objects during self-motion of the observer. So far, this has been tested for simple geometric shapes such as dots or bars. Whether further cues such as prior knowledge about typical directions of an object's movement, e.g., typical human motion, are considered in the estimations is currently unclear. Here, we adjudicated between the theory that the direction of scene-relative motion of humans is estimated exclusively by flow parsing, just like for simple geometric objects, and the theory that prior knowledge about biological motion affects estimation of perceived direction of scene-relative motion of humans. We placed a human point-light walker in optic flow fields that simulated forward motion of the observer. We introduced conflicts between biological features of the walker (i.e., facing and articulation) and the direction of scene-relative motion. We investigated whether perceived direction of scene-relative motion was biased towards biological features and compared the results to perceived direction of scene-relative motion of scrambled walkers and dot clouds. We found that for humans the perceived direction of scene-relative motion was biased towards biological features. Additionally, we found larger flow parsing gain for humans compared to the other walker types. This indicates that flow parsing is not the only visual mechanism relevant for estimating the direction of scene-relative motion of independently moving objects during self-motion: observers also rely on prior knowledge about typical object motion, such as typical facing and articulation of humans.

Visual Sensory Cortices Causally Contribute to Auditory Word Recognition Following Sensorimotor-Enriched Vocabulary Training.

Despite a rise in the use of "learning by doing" pedagogical methods in praxis, little is known as to how the brain benefits from these methods. Learning by doing strategies that utilize complementary information ("enrichment") such as gestures have been shown to optimize learning outcomes in several domains including foreign language (L2) training. Here we tested the hypothesis that behavioral benefits of gesture-based enrichment are critically supported by integrity of the biological motion visual cortices (bmSTS). Prior functional neuroimaging work has implicated the visual motion cortices in L2 translation following sensorimotor-enriched training; the current study is the first to investigate the causal relevance of these structures in learning by doing contexts. Using neuronavigated transcranial magnetic stimulation and a gesture-enriched L2 vocabulary learning paradigm, we found that the bmSTS causally contributed to behavioral benefits of gesture-enriched learning. Visual motion cortex integrity benefitted both short- and long-term learning outcomes, as well as the learning of concrete and abstract words. These results adjudicate between opposing predictions of two neuroscientific learning theories: While reactivation-based theories predict no functional role of specialized sensory cortices in vocabulary learning outcomes, the current study supports the predictive coding theory view that these cortices precipitate sensorimotor-based learning benefits.

Comparable search efficiency for human and animal targets in the context of natural scenes.

In a previous series of studies, we have shown that search for human targets in the context of natural scenes is more efficient than search for mechanical targets. Here we asked whether this search advantage extends to other categories of biological objects. We used videos of natural scenes to directly contrast search efficiency for animal and human targets among biological or nonbiological distractors. In visual search arrays consisting of two, four, six, or eight videos, observers searched for animal targets among machine distractors, and vice versa (Exp. 1). Another group searched for animal targets among human distractors, and vice versa (Exp. 2). We measured search slope as a proxy for search efficiency, and complemented the slope with eye movement measurements (fixation duration on the target, as well as the proportion of first fixations landing on the target). In both experiments, we observed no differences in search slopes or proportions of first fixations between any of the target-distractor category pairs. With respect to fixation durations, we found shorter on-target fixations only for animal targets as compared to machine targets (Exp. 1). In summary, we did not find that the search advantage for human targets over mechanical targets extends to other biological objects. We also found no search advantage for detecting humans as compared to other biological objects. Overall, our pattern of findings suggests that search efficiency in natural scenes, as elsewhere, depends crucially on the specific target-distractor categories.

Concurrent processing of optic flow and biological motion.

The concurrent processing of optic flow and biological motion is crucial for navigating to a destination without colliding with others. Neuroimaging studies and formal models have provided evidence for distinct neural mechanisms involved in processing the 2 types of motion. It may, therefore, be possible to process both types of motions independently. To test for possible interferences at the behavioral level, we conducted a dual task paradigm in which we presented a point-light walker in a flow field that simulated forward motion. Observers judged both the articulation of the walker and the heading direction. We found that varying the difficulty of one task had no effect on the performance of the other task, arguing against interferences. Performance in the biological motion task was similar in dual and single task conditions. For the heading task, concurrence costs were observed when the heading task was difficult but not when it was easy. Concurrence costs did not depend on practice effects, effects of specific motor responses, and incidental processing of biological motion. In line with neuroimaging studies and formal models, our results argue not only for independent processing of optic flow and biological motion but also for concurrence costs affecting heading performance. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Recently learned foreign abstract and concrete nouns are represented in distinct cortical networks similar to the native language.

In the native language, abstract and concrete nouns are represented in distinct areas of the cerebral cortex. Currently, it is unknown whether this is also the case for abstract and concrete nouns of a foreign language. Here, we taught adult native speakers of German 45 abstract and 45 concrete nouns of a foreign language. After learning the nouns for 5 days, participants performed a vocabulary translation task during functional magnetic resonance imaging. Translating abstract nouns in contrast to concrete nouns elicited responses in regions that are also responsive to abstract nouns in the native language: the left inferior frontal gyrus and the left middle and superior temporal gyri. Concrete nouns elicited larger responses in the angular gyri bilaterally and the left parahippocampal gyrus than abstract nouns. The cluster in the left angular gyrus showed psychophysiological interaction (PPI) with the left lingual gyrus. The left parahippocampal gyrus showed PPI with the posterior cingulate cortex. Similar regions have been previously found for concrete nouns in the native language. The results reveal similarities in the cortical representation of foreign language nouns with the representation of native language nouns that already occur after 5 days of vocabulary learning. Furthermore, we showed that verbal and enriched learning methods were equally suitable to teach foreign abstract and concrete nouns. Hum Brain Mapp 38:4398-4412, 2017. © 2017 Wiley Periodicals, Inc.

Do People "Pop Out"?

The human body is a highly familiar and socially very important object. Does this mean that the human body has a special status with respect to visual attention? In the current paper we tested whether people in natural scenes attract attention and "pop out" or, alternatively, are at least searched for more efficiently than targets of another category (machines). Observers in our study searched a visual array for dynamic or static scenes containing humans amidst scenes containing machines and vice versa. The arrays consisted of 2, 4, 6 or 8 scenes arranged in a circular array, with targets being present or absent. Search times increased with set size for dynamic and static human and machine targets, arguing against pop out. However, search for human targets was more efficient than for machine targets as indicated by shallower search slopes for human targets. Eye tracking further revealed that observers made more first fixations to human than to machine targets and that their on-target fixation durations were shorter for human compared to machine targets. In summary, our results suggest that searching for people in natural scenes is more efficient than searching for other categories even though people do not pop out.

Visual and motor cortices differentially support the translation of foreign language words.

At present, it is largely unclear how the human brain optimally learns foreign languages. We investigated teaching strategies that utilize complementary information ("enrichment"), such as pictures or gestures, to optimize vocabulary learning outcome. We found that learning while performing gestures was more efficient than the common practice of learning with pictures and that both enrichment strategies were better than learning without enrichment ("verbal learning"). We tested the prediction of an influential cognitive neuroscience theory that provides explanations for the beneficial behavioral effects of enrichment: the "multisensory learning theory" attributes the benefits of enrichment to recruitment of brain areas specialized in processing the enrichment. To test this prediction, we asked participants to translate auditorily presented foreign words during fMRI. Multivariate pattern classification allowed us to decode from the brain activity under which enrichment condition the vocabulary had been learned. The visual-object-sensitive lateral occipital complex (LOC) represented auditory words that had been learned with pictures. The biological motion superior temporal sulcus (bmSTS) and motor areas represented auditory words that had been learned with gestures. Importantly, brain activity in these specialized visual and motor brain areas correlated with behavioral performance. The cortical activation pattern found in the present study strongly supports the multisensory learning theory in contrast to alternative explanations. In addition, the results highlight the importance of learning foreign language vocabulary with enrichment, particularly with self-performed gestures.

Duration perception in crossmodally-defined intervals.

How humans perform duration judgments with multisensory stimuli is an ongoing debate. Here, we investigated how sub-second duration judgments are achieved by asking participants to compare the duration of a continuous sound to the duration of an empty interval in which onset and offset were marked by signals of different modalities using all combinations of visual, auditory and tactile stimuli. The pattern of perceived durations across five stimulus durations (ranging from 100 ms to 900 ms) follows the Vierordt Law. Furthermore, intervals with a sound as onset (audio-visual, audio-tactile) are perceived longer than intervals with a sound as offset. No modality ordering effect is found for visualtactile intervals. To infer whether a single modality-independent or multiple modality-dependent time-keeping mechanisms exist we tested whether perceived duration follows a summative or a multiplicative distortion pattern by fitting a model to all modality combinations and durations. The results confirm that perceived duration depends on sensory latency (summative distortion). Instead, we did not find evidence for multiplicative distortions. The results of the model and the behavioural data support the concept of a single time-keeping mechanism that allows for judgments of durations marked by multisensory stimuli.

TBSS and probabilistic tractography reveal white matter connections for attention to object features.

Selective attention to features of interest facilitates object processing in a cluttered and dynamic environment. Previous research found that distinct networks of regions across cortex are activated depending on the attended feature. These networks typically consist of posterior feature-preferring regions and anterior regions involved in attentional processes. In the current study, we investigated the role of white matter connections between the posterior and anterior regions within these networks for attention to features of novel colored dynamic objects. We asked participants to perform a 1-back feature-attention task while we acquired both functional and diffusion-weighted images. Using tract-based spatial statistics and probabilistic tractography, we found that the right superior longitudinal fasciculus (SLF) connected posterior and anterior object-processing regions and that voxels within the SLF correlated with response times on the task. Posterior and anterior regions that were anatomically connected also had increased functional connectivity relative to posterior and anterior regions that were not connected. Our results demonstrate that both functional and structural information has to be taken into account to understand selective attention and object perception.

Automatic processing of unattended object features by functional connectivity.

Observers can selectively attend to object features that are relevant for a task. However, unattended task-irrelevant features may still be processed and possibly integrated with the attended features. This study investigated the neural mechanisms for processing both task-relevant (attended) and task-irrelevant (unattended) object features. The Garner paradigm was adapted for functional magnetic resonance imaging (fMRI) to test whether specific brain areas process the conjunction of features or whether multiple interacting areas are involved in this form of feature integration. Observers attended to shape, color, or non-rigid motion of novel objects while unattended features changed from trial to trial (change blocks) or remained constant (no-change blocks) during a given block. This block manipulation allowed us to measure the extent to which unattended features affected neural responses which would reflect the extent to which multiple object features are automatically processed. We did not find Garner interference at the behavioral level. However, we designed the experiment to equate performance across block types so that any fMRI results could not be due solely to differences in task difficulty between change and no-change blocks. Attention to specific features localized several areas known to be involved in object processing. No area showed larger responses on change blocks compared to no-change blocks. However, psychophysiological interaction (PPI) analyses revealed that several functionally-localized areas showed significant positive interactions with areas in occipito-temporal and frontal areas that depended on block type. Overall, these findings suggest that both regional responses and functional connectivity are crucial for processing multi-featured objects.

The influence of unattended features on object processing depends on task demand.

Objects consist of features such as shape, motion and color, all of which can be selectively used for different object processing tasks. The present study investigated whether task demands influenced how well participants attended to features of novel colored dynamic objects that were task-relevant while ignoring those that were task-irrelevant. To address this, we used tasks which had different perceptual, learning and memory demands. The unattended features were systematically changed to measure their effects on how well participants could process the attended feature. In Experiment 1, participants discriminated simultaneously presented objects on the basis their shape or motion. We found that changes to unattended motion and color did not affect participants' sensitivity to discriminate the attended feature but changes to unattended shape did. We also found that changes to unattended motion impaired how quickly observers responded. In Experiment 2, participants identified learned objects at the individual level on the basis of their shape or motion. We found that changes to any unattended features affected accuracy and reaction times. Overall, these results point to an important role of task demands in object processing: Task demands can influence whether task-irrelevant features affect object-processing performance.

The neural mechanisms of reliability weighted integration of shape information from vision and touch.

Behaviourally, humans have been shown to integrate multisensory information in a statistically-optimal fashion by averaging the individual unisensory estimates according to their relative reliabilities. This form of integration is optimal in that it yields the most reliable (i.e. least variable) multisensory percept. The present study investigates the neural mechanisms underlying integration of visual and tactile shape information at the macroscopic scale of the regional BOLD response. Observers discriminated the shapes of ellipses that were presented bimodally (visual-tactile) or visually alone. A 2 × 5 factorial design manipulated (i) the presence vs. absence of tactile shape information and (ii) the reliability of the visual shape information (five levels). We then investigated whether regional activations underlying tactile shape discrimination depended on the reliability of visual shape. Indeed, in primary somatosensory cortices (bilateral BA2) and the superior parietal lobe the responses to tactile shape input were increased when the reliability of visual shape information was reduced. Conversely, tactile inputs suppressed visual activations in the right posterior fusiform gyrus, when the visual signal was blurred and unreliable. Somatosensory and visual cortices may sustain integration of visual and tactile shape information either via direct connections from visual areas or top-down effects from higher order parietal areas.