No effect of auditory–visual spatial disparity on temporal recalibration

It is known that the brain adaptively recalibrates itself to small (∼100 ms) auditory–visual (AV) temporal asynchronies so as to maintain intersensory temporal coherence. Here we explored whether spatial disparity between a sound and light affects AV temporal recalibration. Participants were exposed to a train of asynchronous AV stimulus pairs (sound-first or light-first) with sounds and lights emanating from either the same or a different location. Following a short exposure phase, participants were tested on an AV temporal order judgement (TOJ) task. Temporal recalibration manifested itself as a shift of subjective simultaneity in the direction of the adapted audiovisual lag. The shift was equally big when exposure and test stimuli were presented from the same or different locations. These results provide strong evidence for the idea that spatial co-localisation is not a necessary constraint for intersensory pairing to occur.     

The mirror antisaccade task: direction–amplitude interaction and spatial accuracy characteristics

In this study we examined the performance of human subjects in three oculomotor tasks: a visually guided saccade task (VST), a simple antisaccade task (SAT) and a mirror antisaccade task (MAT). The stimulus presentation was identical for all three tasks, and the differentiation of the tasks was based on the instruction given to the subjects. Subjects were instructed to either look at a visually presented target location (visually triggered saccade task), or to look at the opposite direction of the visually presented target (simple antisaccade task) or finally to look at the mirror location opposite to the location of the visually presented target (mirror antisaccade task). The loading of the simple antisaccade task with the addition of the amplitude requirement did not affect the percentage of directional errors but slowed down the onset of antisaccade execution by 19 ms. The amplitude of the directionally correct antisaccade in the mirror antisaccade task showed a significant distortion of the true mirror target location. This dysmetria followed the same qualitative pattern to that observed for the visually guided saccades, i.e., a near-target hypermetria together with a far-target hypometria, but both these features were exaggerated in the mirror antisaccade task. This distorted amplitude modulation of mirror antisaccade amplitude was completely lost in corrected antisaccades that followed a directional error.     

The relation of motion sickness to the spatial–temporal properties of velocity storage

Tilting the head in roll to or from the upright while rotating at a constant velocity (roll while rotating, RWR) alters the position of the semicircular canals relative to the axis of rotation. This produces vertical and horizontal nystagmus, disorientation, vertigo, and nausea. With recurrent exposure, subjects habituate and can make more head movements before experiencing overpowering motion sickness. We questioned whether promethazine lessened the vertigo or delayed the habituation, whether habituation of the vertigo was related to the central vestibular time constant, i.e., to the time constant of velocity storage, and whether the severity of the motion sickness was related to deviation of the axis of eye velocity from gravity. Sixteen subjects received promethazine and placebo in a double-blind, crossover study in two consecutive 4-day test series 1 month apart, termed series I and II. Horizontal and vertical eye movements were recorded with video-oculography while subjects performed roll head movements of approx. 45° over 2 s to and from the upright position while being rotated at 138°/s around a vertical axis. Motion sickness was scaled from 1 (no sickness) to an endpoint of 20, at which time the subject was too sick to continue or was about to vomit. Habituation was determined by the number of head movements that subjects made before reaching the maximum motion sickness score of 20. Head movements increased steadily in each session with repeated testing, and there was no difference between the number of head movements made by the promethazine and placebo groups. Horizontal and vertical angular vestibulo-ocular reflex (aVOR) time constants declined in each test, with the declines being closely correlated to the increase in the number of head movements. The strength of vertiginous sensation was associated with the amount of deviation of the axis of eye velocity from gravity; the larger the deviation of the eye velocity axis from gravity, the more severe the motion sickness. Thus, promethazine neither reduced the nausea associated with RWR, nor retarded or hastened habituation. The inverse relationship between the aVOR time constants and number of head movements to motion sickness, and the association of the severity of motion sickness with the extent, strength, and time of deviation of eye velocity from gravity supports the postulate that the spatiotemporal properties of velocity storage, which are processed between the nodulus and uvula of the vestibulocerebellum and the vestibular nuclei, are likely to represent the source of the conflict responsible for producing motion sickness.     

Neural mechanisms of spatial stimulus–response compatibility: the effect of crossed-hand position

Previous psychological experiments have indicated the existence of a visual-proprioceptive interaction in spatial stimulus-response compatibility (SSRC) tasks, but there is little specific information on the neural basis of such interaction in humans. Using functional magnetic resonance imaging (fMRI), we compared the neural activity associated with two different aspects of spatial coding: the coding of the "internal" spatial position of motor-response effectors (i.e., the position of body parts) as obtained through proprioception, and the coding of "external" positions, i.e., the positions of visual stimuli. A 2 x 2 factorial design was used to investigate the spatial compatibility (incompatible versus compatible) between a visual stimulus and hand position (crossed versus uncrossed). The subjects were instructed to respond to stimuli presented to the right or left visual field with either the ipsilateral (compatible condition) or the contralateral hand (incompatible condition). The incompatible condition produced stronger activation in the bilateral superior parietal lobule, inferior parietal lobule, and bilateral superior frontal gyrus than the compatible condition. The crossed-hand condition produced stronger activation in the bilateral precentral gyrus, superior frontal gyrus, superior parietal lobule, and superior temporal gyrus than the uncrossed-hand condition. These results suggest that activity in the frontal-parietal regions is related to two functions: (1) representation of the visual stimulus-motor response spatial configuration in an SSRC task, and (2) integration between external visual and internal proprioceptive sensory information. The activation in the superior temporal gyrus was not affected by the visual stimulus-motor response spatial configuration in an SSRC task; rather, it was affected by the crossed-hand posture. Thus, it seems to be related to representing internal proprioceptive sensory information necessary to carry out motor actions.     

Atypical signed language development: A case study of challenges with visual–spatial processing

In signed languages, the articulatory space in front of the signer is used grammatically, topographically, and to depict a real or imagined space around a signer and thus is an important consideration in signed language acquisition. It has been suggested that children who acquire signed languages rely on concomitant visual–spatial development to support their linguistic development. We consider the case of a native-signing deaf adolescent female with average intelligence who had been reported to struggle with spatial aspects of American Sign Language (ASL) as a child. Results of a battery of linguistic and nonlinguistic tests suggest that she has relatively good ASL skills with the exception of some specific difficulties on spatial tasks that require attention to ASL and nonlinguistic topographic space or changes in visual perspective (e.g., classifiers and referential shift). This child has some difficulties with visual–spatial abilities, and we suggest that this has affected her acquisition of those aspects of ASL that are heavily dependent on visual–spatial processing.     

Visual–spatial and anatomical constraints interact in a bimanual coordination task with transformed visual feedback

There is a debate in the literature about the influence of spatial and anatomical constraints on bimanual coordination dynamics. In the present experiment, participants swung hand-held pendulums about the wrist while attending to visual feedback about relative phase (superimposed phase plots of each pendulum) that was displayed on a screen. Participants were instructed to maintain in-phase or anti-phase coordination in the visual display. Visual–spatial and anatomical constraints were dissociated by introducing a phase shift in the visual display so that visual feedback differed from the movements being performed by the participants in 15° increments from −180° to +180°. Analysis of mean relative phase and its variability suggested that visual–spatial and anatomical constraints interact in bimanual coordination dynamics.     

The reduction of anti-cancer drug antagonism by the spatial protection of drugs with PLA–TPGS nanoparticles

Docetaxel (DCL) and tamoxifen (TAM) individually are potent drugs in the fight against breast cancer. However when used in combination, they become antagonistic because of differential metabolism of both drugs. We reasoned that by spatially protecting them from metabolizing enzymes with poly (lactide)-d-α-tocopheryl polyethylene glycol succinate (PLA–TPGS) nanoparticles (NPs), we might reduce this drug antagonism. We now report that the drug antagonism between DCL and TAM in MCF7 cell line, was significantly reduced when co-delivered in PLA–TPGS NPs. In addition, this effect of NPs attenuated at high drug concentrations. To investigate the role of NPs in the reduction of drug antagonism, we quantified cellular uptake of the fluorescent model drug coumarin 6 (C6) encapsulated in a rigorous permutation of drugs-nanoparticles ratios. NPs carrying C6 exhibited enhanced cellular uptake over their free C6 counterparts at correspondingly low drug concentrations. This led us to conclude that the reduction of drug antagonism by NPs is correlated to cellular uptake and being in NPs therefore protects both drugs until they are released intracellular for therapeutic anti-cancer effect.     

Acoustic droplet–hydrogel composites for spatial and temporal control of growth factor delivery and scaffold stiffness

Wound healing is regulated by temporally and spatially restricted patterns of growth factor signaling, but there are few delivery vehicles capable of the “on-demand” release necessary for recapitulating these patterns. Recently we described a perfluorocarbon double emulsion that selectively releases a protein payload upon exposure to ultrasound through a process known as acoustic droplet vaporization (ADV). In this study, we describe a delivery system composed of fibrin hydrogels doped with growth factor-loaded double emulsion for applications in tissue regeneration. Release of immunoreactive basic fibroblast growth factor (bFGF) from the composites increased up to 5-fold following ADV and delayed release was achieved by delaying exposure to ultrasound. Releasates of ultrasound-treated materials significantly increased the proliferation of endothelial cells compared to sham controls, indicating that the released bFGF was bioactive. ADV also triggered changes in the ultrastructure and mechanical properties of the fibrin as bubble formation and consolidation of the fibrin in ultrasound-treated composites were accompanied by up to a 22-fold increase in shear stiffness. ADV did not reduce the viability of cells suspended in composite scaffolds. These results demonstrate that an acoustic droplet–hydrogel composite could have broad utility in promoting wound healing through on-demand control of growth factor release and/or scaffold architecture.     

Segmentation of spatial experience by hippocampal θ sequences

The encoding and storage of experience by the hippocampus is essential for the formation of episodic memories and the transformation of individual experiences into semantic structures such as maps and schemas. The rodent hippocampus compresses ongoing experience into repeating theta sequences, but the factors determining the content of theta sequences are not understood. Here we first show that the spatial paths represented by theta sequences in rats extend farther in front of the rat during acceleration and higher running speeds and begin farther behind the rat during deceleration. Second, the length of the path is directly related to the length of the theta cycle and the number of gamma cycles in it. Finally, theta sequences represent the environment in segments or 'chunks'. These results imply that information encoded in theta sequences is subject to powerful modulation by behavior and task variables. Furthermore, these findings suggest a potential mechanism for the cognitive 'chunking' of experience.     

Composite pullulan–dextran polysaccharide scaffold with interfacial polyelectrolyte complexation fibers: A platform with enhanced cell interaction and spatial distribution

Hydrogels are highly preferred in soft tissue engineering because they recapitulate the hydrated extracellular matrix. Naturally derived polysaccharides, like pullulan and dextran, are attractive materials with which to form hydrophilic polymeric networks due to their non-immunogenic and non-antigenic properties. However, their inherent hydrophilicity prevents adherent cell growth. In this study, we modified pullulan–dextran scaffolds with interfacial polyelectrolyte complexation (IPC) fibers to improve their ability to support adherent cell growth. We showed that the pullulan–dextran–IPC fiber composite scaffold laden with extracellular matrix protein has improved cell adhesion and proliferation compared to the plain polysaccharide scaffold. We also demonstrated the zero-order release kinetics of the biologics bovine serum albumin and vascular endothelial growth factor (VEGF) incorporated in the composite scaffold. Lastly, we showed that the VEGF released from the composite scaffold retained its capacity to stimulate endothelial cell growth. The incorporation of IPC fibers in the pullulan–dextran hydrogel scaffold improved its functionality and biological activity, thus enhancing its potential in tissue engineering applications.     

Do head-on-trunk signals modulate disengagement of spatial attention?

Body schema is indispensable for sensorimotor control and learning, but whether it is associated with cognitive functions, such as allocation of spatial attention, remains unclear. Observations in patients with unilateral spatial neglect support this view, yet data from neurologically normal participants are inconsistent. Here, we investigated the influence of head-on-trunk positions (30° left or right, straight ahead) on disengagement of attention in healthy participants. Five experiments examined the effects of valid or invalid cues on spatial shifts of attention using the Posner paradigm. Experiment 1 used a forced-choice task. Participants quickly reported the location of a target that appeared left or right of the fixation point, preceded by a cue on the same (valid) or opposite side (invalid). Experiments 2, 3, and 4 also used valid and invalid cues but required participants to simply detect a target appearing on the left or right side. Experiment 5 used a speeded discrimination task, in which participants quickly reported the orientation of a Gabor. We observed expected influences of validity and stimulus onset asynchrony as well as inhibition of return; however, none of the experiments suggested that head-on-trunk position created or changed visual field advantages, contrary to earlier reports. Our results showed that the manipulations of the body schema did not modulate attentional processes in the healthy brain, unlike neuropsychological studies on neglect patients. Our findings suggest that spatial neglect reflects a state of the lesioned brain that is importantly different from that of the normally functioning brain.     

Testosterone: Activation or organization of spatial cognition?

Previous studies in animals have revealed effects of both prenatal and current testosterone on brain organization and behavior. However, it is unclear how these effects translate to the human brain. Here, we refine previous procedures to clarify the relative contribution of prenatal versus current testosterone indices to cognitive function. Sixty-nine subjects performed four computerized tasks measuring mental rotation, targeting, figure-disembedding and perceptual discrimination. Using stepwise regression analyses, performance was related to free testosterone assayed in saliva samples and to second-to-fourth finger length ratios (2D:4D), a putative index of prenatal testosterone exposure. The exclusive predictor for mental rotation was found to be sex, while 2D:4D was found to be the sole predictor of targeting, exhibiting a curvilinear relation, and figure-disembedding performance, showing a linear relation. These findings suggest a substantial role for prenatal testosterone but not current testosterone in determining cognitive performance.     

Neuroprotective effect of alpha-asarone on spatial memory and nitric oxide levels in rats injected with amyloid-β(25–35)

The chemical α-asarone is an important active substance of the Acori graminei rhizome (AGR). It has pharmacological effects that include antihyperlipidemic, antiinflammatory, and antioxidant activity. Our aim was to study the effects α-asarone on nitric oxide (NO) levels in the hippocampus and temporal cortex of the rat after injection of the fraction 25–35 from amyloid-β (Aβ_(25–35)). In addition we examined the working spatial memory in an eight-arm radial maze. Our results showed a significant increase of nitrites in the hippocampus and temporal cortex of Aβ_(25–35)-treated rats. Other evidence of neuronal damage was the expression of a glial-fibrillar-acid protein and a silver staining. There were impairments in the spatial memory evaluated in the eight-arm radial maze. We wanted to determine whether α-asarone improves the memory correlated with NO overproduction and neuronal damage caused by the injection of Aβ_(25–35) into rats. Then animals received a 16-day treatment of α-asarone before the Aβ_(25–35) injection. Our results show a significant decrease of nitrite levels in the hippocampus and temporal cortex, without astrocytosis and silver-staining cells, which correlates with memory improvement in the α-asarone-treated group. Our results suggest that α-asarone may protect neurons against Aβ_(25–35)–caused neurotoxicity by inhibiting the effects of NO overproduction in the hippocampus and temporal cortex.     

Vogt–Koyanagi–Harada syndrome

Objectives

The objectives of this study are to review our current knowledge of the aetiopathogenesis of Vogt–Koyanagi–Harada syndrome, including viral infection, genetic factors and immunomediated mechanisms, and to discuss pathogenesis and its relevance to pharmacotherapy.

Systematic review methodology

Relevant publications from 1965 to 2012 on the aetiopathogenesis and pharmacotherapy of VKHS were analysed.

Results and conclusion

Vogt–Koyanagi–Harada syndrome (VKHS) is a rare multisystemic autoimmune disease that affects tissues containing melanin, including the eye, inner ear, meninges, and skin. The disease is characterised by bilateral uveitis associated with a varying constellation of auditory, neurological and cutaneous manifestations.The disease occurs more frequently among people with darker skin pigmentation. Asians, Native Americans, and Hispanics are most frequently affected. It predominates in patients aged between 20 and 50 years, and females are affected more frequently, with a female:male ratio of 2:1.The classic clinical course is characterised by bilateral panuveitis, hypoacusis, and meningitis, in addition to cutaneous involvement with poliosis, vitiligo, and alopecia.Although the exact cause of VKH disease remains unknown, it is thought to be a T-cell-mediated autoimmune process directed against melanocytes.VKHS classically begins with vague systemic symptoms suggestive of a viral infection, although a clear association between a specific viral agent and the disease has not been established.Genetic factors may play an important role in the loss of self-tolerance in VKHS. The HLA-DRB1*0405 allele is the main susceptibility allele for VKHS.Early and aggressive systemic corticosteroids are still the primary initial therapy for VKHS. Ocular complications may require an intravitreous injection of corticosteroids. Despite proper treatment with steroids, a number of patients experience recurrent attacks or steroid-associated complications. Thus, non steroid immunomodulatory therapy (IMT) has become necessary for the treatment of VKHS.     

Examining the influence of ‘noise’ on judgements of spatial extent

The line bisection task--commonly used as a clinical measure of unilateral neglect--requires participants to place a mark on a horizontal line to indicate where they think centre is. In general, results suggest that the allocation of attention mediates bisection. In addition, previous research shows that participants rarely explore the endpoints of lines, suggesting that peripheral visual information informs bisection. Here, we examined bisection performance under conditions in which differing levels of 'noise' were introduced to the line to examine the hypothesis that the fidelity and symmetry of peripheral information would inform performance. Contrary to our expectations, results showed that symmetrically introducing noise to the line biased bisection further leftward compared to a 'no-noise' condition. Furthermore, asymmetrical noise increased leftward bisection errors primarily when lines were presented in left space or when the greater amount of noise was on the left half of the line. These results indicate that the fidelity of peripheral visual information mediates bisection behaviour that is already biased leftwards probably due to right hemisphere attentional mechanisms.     

Uneven spatial distribution of surface EMG: what does it mean?

The aim of this work is to show how changes in surface electromyographic activity (sEMG) during a repetitive, non-constant force contraction can be detected and interpreted on the basis of the amplitude distribution provided by high-density sEMG techniques. Twelve healthy male subjects performed isometric shoulder elevations, repeating five times a force ramp profile up to 25 % of the maximal voluntary contraction (MVC). A 64-electrode matrix was used to detect sEMG from the trapezius muscle. The sEMG amplitude distribution was obtained for the force levels in the range 5–25 % MVC with steps of 5 % MVC. The effect of force level, subject, electrode position and ramp repetition on the sEMG amplitude distribution was tested. The sEMG amplitude was significantly smaller in the columns of the electrode grid over the tendons (repeated measures ANOVA, p < 0.01). The barycentre of the distribution of sEMG amplitude was subject-specific (Kruskal–Wallis test, p < 0.01), and shifted caudally with the increase of force levels and cranially with the repetition of the motor task (both p < 0.01, repeated measures ANOVA). The results are discussed in terms of motor unit recruitment in different muscle sub-portions. It is concluded that the sEMG amplitude distribution obtained by multichannel techniques provides useful information in the study of muscle activity, and that changes in the spatial distribution of the recruited motor units during a force varying isometric contraction might partially explain the variability observed in the activation pattern of the upper trapezius muscle.     

Sustained expression of interleukin-1β in mouse hippocampus impairs spatial memory

Glial activation and neuroinflammation occur in neurodegenerative disease and brain injury, however their presence in normal brain aging suggests that chronic neuroinflammation may be a factor in age-related dementia. Few studies have investigated the impact of sustained elevation of hippocampal interleukin-1β, a pro-inflammatory cytokine upregulated during aging and Alzheimer's disease, on cognition in mice. We utilized the IL-1β^XAT transgenic mouse to initiate bilateral hippocampal overexpression of interleukin-1β to determine the influence of sustained neuroinflammation independent of disease pathology. Fourteen days following transgene induction, adult male and female IL-1β^XAT mice were tested on non-spatial and spatial versions of the Morris water maze. For the spatial component, one retention trial was conducted 48 h after completion of a 3 day acquisition protocol (eight trials per day). Induction of IL-1β did not impact non-spatial learning, but was associated with delayed acquisition and decreased retention of the spatial task. These behavioral impairments were accompanied by robust reactive gliosis and elevated mRNA expression of inflammatory genes in the hippocampus. Our results suggest that prolonged neuroinflammation response per se may impact mnemonic processes and support the future application of IL-1β^XAT transgenic mice to investigate chronic neuroinflammation in age- and pathology-related cognitive dysfunction.