A demonstration of 'broken' visual space

It has long been assumed that there is a distorted mapping between real and ‘perceived’ space, based on demonstrations of systematic errors in judgements of slant, curvature, direction and separation. Here, we have applied a direct test to the notion of a coherent visual space. In an immersive virtual environment, participants judged the relative distance of two squares displayed in separate intervals. On some trials, the virtual scene expanded by a factor of four between intervals although, in line with recent results, participants did not report any noticeable change in the scene. We found that there was no consistent depth ordering of objects that can explain the distance matches participants made in this environment (e.g. A > B > D yet also A < C < D) and hence no single one-to-one mapping between participants’ perceived space and any real 3D environment. Instead, factors that affect pairwise comparisons of distances dictate participants’ performance. These data contradict, more directly than previous experiments, the idea that the visual system builds and uses a coherent 3D internal representation of a scene

Abscess Formation Following Spilled Gallstones During Laparoscopic Cholecystectomy

A review of the English literature concerning spilled gallstones during laparoscopic cholecystectomy is compared with one institution's experience of four cases during 1,726 laparoscopic cholecystectomies performed over a four-year period. Strategies regarding management and treatment are discussed

Evidence for the predictive remapping of visual attention

When attending an object in visual space, perception of the object remains stable despite frequent eye movements. It is assumed that visual stability is due to the process of remapping, in which retinotopically organized maps are updated to compensate for the retinal shifts caused by eye movements. Remapping is predictive when it starts before the actual eye movement. Until now, most evidence for predictive remapping has been obtained in single cell studies involving monkeys. Here, we report that predictive remapping affects visual attention prior to an eye movement. Immediately following a saccade, we show that attention has partly shifted with the saccade (Experiment 1). Importantly, we show that remapping is predictive and affects the locus of attention prior to saccade execution (Experiments 2 and 3): before the saccade was executed, there was attentional facilitation at the location which, after the saccade, would retinotopically match the attended location

Distribution of Attention Modulates Salience Signals in Early Visual Cortex

Previous research has shown that the extent to which people spread attention across the visual field plays a crucial role in visual selection and the occurrence of bottom-up driven attentional capture. Consistent with previous findings, we show that when attention was diffusely distributed across the visual field while searching for a shape singleton, an irrelevant salient color singleton captured attention. However, while using the very same displays and task, no capture was observed when observers initially focused their attention at the center of the display. Using event-related fMRI, we examined the modulation of retinotopic activity related to attentional capture in early visual areas. Because the sensory display characteristics were identical in both conditions, we were able to isolate the brain activity associated with exogenous attentional capture. The results show that spreading of attention leads to increased bottom-up exogenous capture and increased activity in visual area V3 but not in V2 and V1

Movement of environmental threats modifies the relevance of the defensive eye-blink in a spatially-tuned manner.

Subcortical reflexive motor responses are under continuous cortical control to produce the most effective behaviour. For example, the excitability of brainstem circuitry subserving the defensive hand-blink reflex (HBR), a response elicited by intense somatosensory stimuli to the wrist, depends on a number of properties of the eliciting stimulus. These include face-hand proximity, which has allowed the description of an HBR response field around the face (commonly referred to as a defensive peripersonal space, DPPS), as well as stimulus movement and probability of stimulus occurrence. However, the effect of stimulus-independent movements of objects in the environment has not been explored. Here we used virtual reality to test whether and how the HBR-derived DPPS is affected by the presence and movement of threatening objects in the environment. In two experiments conducted on 40 healthy volunteers, we observed that threatening arrows flying towards the participant result in DPPS expansion, an effect directionally-tuned towards the source of the arrows. These results indicate that the excitability of brainstem circuitry subserving the HBR is continuously adjusted, taking into account the movement of environmental objects. Such adjustments fit in a framework where the relevance of defensive actions is continually evaluated, to maximise their survival value

When Right Feels Left: Referral of Touch and Ownership between the Hands

Feeling touch on a body part is paradigmatically considered to require stimulation of tactile afferents from the body part in question, at least in healthy non-synaesthetic individuals. In contrast to this view, we report a perceptual illusion where people experience “phantom touches” on a right rubber hand when they see it brushed simultaneously with brushes applied to their left hand. Such illusory duplication and transfer of touch from the left to the right hand was only elicited when a homologous (i.e., left and right) pair of hands was brushed in synchrony for an extended period of time. This stimulation caused the majority of our participants to perceive the right rubber hand as their own and to sense two distinct touches – one located on the right rubber hand and the other on their left (stimulated) hand. This effect was supported by quantitative subjective reports in the form of questionnaires, behavioral data from a task in which participants pointed to the felt location of their right hand, and physiological evidence obtained by skin conductance responses when threatening the model hand. Our findings suggest that visual information augments subthreshold somatosensory responses in the ipsilateral hemisphere, thus producing a tactile experience from the non-stimulated body part. This finding is important because it reveals a new bilateral multisensory mechanism for tactile perception and limb ownership

Dynamic Social Adaptation of Motion-Related Neurons in Primate Parietal Cortex

Social brain function, which allows us to adapt our behavior to social context, is poorly understood at the single-cell level due largely to technical limitations. But the questions involved are vital: How do neurons recognize and modulate their activity in response to social context? To probe the mechanisms involved, we developed a novel recording technique, called multi-dimensional recording, and applied it simultaneously in the left parietal cortices of two monkeys while they shared a common social space. When the monkeys sat near each other but did not interact, each monkey's parietal activity showed robust response preference to action by his own right arm and almost no response to action by the other's arm. But the preference was broken if social conflict emerged between the monkeys—specifically, if both were able to reach for the same food item placed on the table between them. Under these circumstances, parietal neurons started to show complex combinatorial responses to motion of self and other. Parietal cortex adapted its response properties in the social context by discarding and recruiting different neural populations. Our results suggest that parietal neurons can recognize social events in the environment linked with current social context and form part of a larger social brain network

In vivo functional neurochemistry of human cortical cholinergic function during visuospatial attention

Cortical acetylcholine is involved in key cognitive processes such as visuospatial attention. Dysfunction in the cholinergic system has been described in a number of neuropsychiatric disorders. Levels of brain acetylcholine can be pharmacologically manipulated, but it is not possible to directly measure it in vivo in humans. However, key parts of its biochemical cascade in neural tissue, such as choline, can be measured using magnetic resonance spectroscopy (MRS). There is evidence that levels of choline may be an indirect but proportional measure of acetylcholine availability in brain tissue. In this study, we measured relative choline levels in the parietal cortex using functional (event-related) MRS (fMRS) during performance of a visuospatial attention task, with a modelling approach verified using simulated data. We describe a task-driven interaction effect on choline concentration, specifically driven by contralateral attention shifts. Our results suggest that choline MRS has the potential to serve as a proxy of brain acetylcholine function in humans

Bifunctional Anti-Huntingtin Proteasome-Directed Intrabodies Mediate Efficient Degradation of Mutant Huntingtin Exon 1 Protein Fragments

Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disorder caused by a trinucleotide (CAG)n repeat expansion in the coding sequence of the huntingtin gene, and an expanded polyglutamine (>37Q) tract in the protein. This results in misfolding and accumulation of huntingtin protein (htt), formation of neuronal intranuclear and cytoplasmic inclusions, and neuronal dysfunction/degeneration. Single-chain Fv antibodies (scFvs), expressed as intrabodies that bind htt and prevent aggregation, show promise as immunotherapeutics for HD. Intrastriatal delivery of anti-N-terminal htt scFv-C4 using an adeno-associated virus vector (AAV2/1) significantly reduces the size and number of aggregates in HDR6/1 transgenic mice; however, this protective effect diminishes with age and time after injection. We therefore explored enhancing intrabody efficacy via fusions to heterologous functional domains. Proteins containing a PEST motif are often targeted for proteasomal degradation and generally have a short half life. In ST14A cells, fusion of the C-terminal PEST region of mouse ornithine decarboxylase (mODC) to scFv-C4 reduces htt exon 1 protein fragments with 72 glutamine repeats (httex1-72Q) by ∼80–90% when compared to scFv-C4 alone. Proteasomal targeting was verified by either scrambling the mODC-PEST motif, or via proteasomal inhibition with epoxomicin. For these constructs, the proteasomal degradation of the scFv intrabody proteins themselves was reduced<25% by the addition of the mODC-PEST motif, with or without antigens. The remaining intrabody levels were amply sufficient to target N-terminal httex1-72Q protein fragment turnover. Critically, scFv-C4-PEST prevents aggregation and toxicity of httex1-72Q fragments at significantly lower doses than scFv-C4. Fusion of the mODC-PEST motif to intrabodies is a valuable general approach to specifically target toxic antigens to the proteasome for degradation