Left Cerebellar Lesions may be Associated with an Increase in Spatial Neglect-like Symptoms.

Each cerebellar hemisphere projects to the contralateral cerebral hemisphere. Previous research suggests a lateralization of cognitive functions in the cerebellum that mirrors the cerebral cortex, with attention/visuospatial functions represented in the left cerebellar hemisphere, and language functions in the right cerebellar hemisphere. Although there is good evidence supporting the role of the right cerebellum with language functions, the evidence supporting the notion that attention and visuospatial functions are left lateralized is less clear. Given that spatial neglect is one of the most common disorders arising from right cortical damage, we reasoned that damage to the left cerebellum would result in increased spatial neglect-like symptoms, without necessarily leading to an official diagnosis of spatial neglect. To examine this disconnection hypothesis, we analyzed neglect screening data (line bisection, cancellation, figure copying) from 20 patients with isolated unilateral cerebellar stroke. Results indicated that left cerebellar patients (n = 9) missed significantly more targets on the left side of cancellation tasks compared to a normative sample. No significant effects were observed for right cerebellar patients (n = 11). A lesion overlap analysis indicated that Crus II (78% overlap), and lobules VII and IX (66% overlap) were the regions most commonly damaged in left cerebellar patients. Our results are consistent with the notion that the left cerebellum may be important for attention and visuospatial functions. Given the poor prognosis typically associated with neglect, we suggest that screening for neglect symptoms, and visuospatial deficits more generally, may be important for tailoring rehabilitative efforts to help maximize recovery in cerebellar patients.

Direction of visual shift and hand congruency enhance spatial realignment during visuomotor adaptation.

Although prism adaptation has been studied extensively for over 100 years to better understand how the motor system adapts to sensory perturbations, very few studies have systematically studied how the combination of the hand used to adapt, and the direction of visual shift, might influence adaptation. Given that sensory inputs and motor outputs from the same side are processed (at least initially) in the same hemisphere, we wondered whether there might be differences in how people adapt when the hand used and the direction of visual shift were congruent (e.g., adapting to rightward shifting prisms with the right hand), compared to incongruent (e.g., adapting to rightward shifting prisms with the left hand). In Experiment 1 we re-analyzed a previously published dataset (Striemer, Enns, and Whitwell Striemer et al., Cortex 115:201-215, 2019a) in which healthy adults (n = 17) adapted to 17° leftward or rightward optically displacing prisms using their left or right hand (tested in separate sessions, counterbalanced). Our results revealed a "congruency effect" such that adaptation aftereffects were significantly larger for reaches performed without visual feedback (i.e., straight-ahead pointing) when the direction of prism shift and the hand used were congruent, compared to incongruent. We replicated this same congruency effect in Experiment 2 in a new group of participants (n = 25). We suggest that a better understanding of the cognitive and neural mechanisms underlying the congruency effect will allow researchers to build more precise models of visuomotor learning, and may lead to the development of more effective applications of prism adaptation for the treatment of attentional disorders following brain damage.

StaphAIR: A Label-Free Antigen Microarray Approach to Detecting Anti-Staphylococcus aureus Antibody Responses in Orthopedic Infections.

Arrayed imaging reflectometry (AIR) is an optical biosensor platform for simple, multiplex measurement of antigen-specific antibody responses in patient blood samples. Here, we report the development of StaphAIR, an 8-plex Staphylococcus aureus antigen array on the AIR platform for profiling antigen-specific anti-S. aureus humoral immune responses. Initial validation experiments with mouse and humanized monoclonal antibodies against the S. aureus autolysin glucosaminidase (Gmd) domain, and subsequent testing with dilution series of pooled positive human serum confirmed analytically robust behavior of the array, with all antigens displaying Langmuir-type dose-response curves. Testing a cohort of 82 patients with S. aureus musculoskeletal infections (MSKI) and 30 healthy individuals enabled discrimination of individual patient responses to different S. aureus antigens, with statistical significance between osteomyelitis patients and controls obtained overall for four individual antigens (IsdA, IsdB, Gmd, and SCIN). Multivariate analyses of the antibody titers obtained from StaphAIR revealed its utility as a potential diagnostic tool for detecting S. aureus MSKI (area under the receiver operating characteristic curve (AUC) > 0.85). We conclude that StaphAIR has utility as a high-throughput immunoassay for studying and diagnosing osteomyelitis in patients.

Cerebellar tDCS Alters the Perception of Optic Flow.

Studies have shown that the cerebellar vermis is involved in the perception of motion. However, it is unclear how the cerebellum influences motion perception. tDCS is a non-invasive brain stimulation technique that can reduce (through cathodal stimulation) or increase neuronal excitability (through anodal stimulation). To explore the nature of the cerebellar involvement on large-field global motion perception (i.e., optic flow-like motion), we applied tDCS on the cerebellar midline while participants performed an optic flow motion discrimination task. Our results show that anodal tDCS improves discrimination threshold for optic flow perception, but only for left-right motion in contrast to up-down motion discrimination. This result was evident within the first 10 min of stimulation and was also found post-stimulation. Cathodal stimulation did not have any significant effects on performance in any direction. The results show that discrimination of optic flow can be improved with tDCS of the cerebellar midline and provide further support for the role of the human midline cerebellum in the perception of optic flow.

The Ties that Bind: Agnosia, Neglect and Selective Attention to Visual Scale.

PURPOSE OF REVIEW: Historical and contemporary treatments of visual agnosia and neglect regard these disorders as largely unrelated. It is thought that damage to different neural processes leads directly to one or the other condition, yet apperceptive variants of agnosia and object-centered variants of neglect share remarkably similar deficits in the quality of conscious experience. Here we argue for a closer association between "apperceptive" variants of visual agnosia and "object-centered" variants of visual neglect. We introduce a theoretical framework for understanding these conditions based on "scale attention", which refers to selecting boundary and surface information at different levels of the structural hierarchy in the visual array. RECENT FINDINGS: We review work on visual agnosia, the cortical structures and cortico-cortical pathways that underlie visual perception, visuospatial neglect and object-centered neglect, and attention to scale. We highlight direct and indirect pathways involved in these disorders and in attention to scale. The direct pathway involves the posterior vertical segments of the superior longitudinal fasciculus that are positioned to link the established dorsal and ventral attentional centers in the parietal cortex with structures in the inferior occipitotemporal cortex associated with visual apperceptive agnosia. The connections in the right hemisphere appear to be more important for visual conscious experience, whereas those in the left hemisphere appear to be more strongly associated with the planning and execution of visually guided grasps directed at multi-part objects such as tools. In the latter case, semantic and functional information must drive the selection of the appropriate hand posture and grasp points on the object. This view is supported by studies of grasping in patients with agnosia and in patients with neglect that show that the selection of grasp points when picking up a tool involves both scale attention and semantic contributions from inferotemporal cortex. The indirect pathways, which include the inferior fronto-occipital and horizontal components of the superior longitudinal fasciculi, involve the frontal lobe, working memory and the "multiple demands" network, which can shape the content of visual awareness through the maintenance of goal- and task-based abstractions and their influence on scale attention. Recent studies of human cortico-cortical pathways necessitate revisions to long-standing theoretical views on visual perception, visually guided action and their integrations. We highlight findings from a broad sample of seemingly disparate areas of research to support the proposal that attention to scale is necessary for typical conscious visual experience and for goal-directed actions that depend on functional and semantic information. Furthermore, we suggest that vertical pathways between the parietal and occipitotemporal cortex, along with indirect pathways that involve the premotor and prefrontal cortex, facilitate the operations of scale attention.

Prism adaptation speeds reach initiation in the direction of the prism after-effect.

Damage to the temporal-parietal cortex in the right hemisphere often leads to spatial neglect-a disorder in which patients are unable to attend to sensory input from their contralesional (left) side. Neglect has been associated with both attentional and premotor deficits. That is, in addition to having difficulty with attending to the left side, patients are often slower to initiate leftward vs. rightward movements (i.e., directional hypokinesia). Previous research has indicated that a brief period of adaptation to rightward shifting prisms can reduce symptoms of neglect by adjusting the patient's movements leftward, toward the neglected field. Although prism adaptation has been shown to reduce spatial attention deficits in patients with neglect, very little work has examined the effects of prisms on premotor symptoms. In the current study, we examined this in healthy individuals using leftward shifting prisms to induce a rightward shift in the egocentric reference frame, similar to neglect patients prior to prism adaptation. Specifically, we examined the speed with which healthy participants initiated leftward and rightward reaches (without visual feedback) prior to and following adaptation to either 17° leftward (n = 16) or 17° rightward (n = 15) shifting prisms. Our results indicated that, following adaptation, participants were significantly faster to initiate reaches towards targets located in the direction opposite the prism shift. That is, participants were faster to initiate reaches to right targets following leftward prism adaptation and were faster to initiate reaches to left targets following rightward prism adaptation. Overall, these results are consistent with the idea that prism adaptation can influence the speed with which a reach can be initiated toward a target in the direction opposite the prism shift, possibly through altering activity in neural circuits involved in reach planning.

Prism adaptation magnitude has differential influences on perceptual versus manual responses.

Previous research has indicated that rightward prism adaptation can reduce symptoms of spatial neglect following right brain damage. In addition, leftward prism adaptation can create "neglect-like" patterns of performance in healthy adults on tasks that measure attention and spatial biases. Although a great deal of research has focused on which behaviors are influenced by prism adaptation, very few studies have focused directly on how the magnitude of visual shift induced by prisms might be related to the observed aftereffects, or the effects of prisms on measures of attentional and spatial biases. In the current study, we examined these questions by having groups of healthy adult participants complete manual line bisection and landmark tasks prior to and following adaptation to either 8.5° (15 diopter; n = 22) or 17° (30 diopter; n = 25) leftward shifting prisms. Our results demonstrated a significantly larger rightward shift in straight-ahead pointing (a measure of prism aftereffect) following adaptation to 17°, compared to 8.5° leftward shifting prisms. In addition, only 17° leftward shifting prisms resulted in a significant rightward shift in line bisection following adaptation. However, there was a significant change in performance on the landmark task pre- versus post-adaptation in both the 8.5° and 17° leftward shifting prism groups. Interestingly, correlation analyses indicated that changes in straight-ahead pointing pre- versus post-adaptation were positively correlated with changes in performance on the manual line bisection task, but not the landmark task. These data suggest that larger magnitudes of prism adaptation seem to have a greater influence on tasks that require a response with the adapted hand (i.e., line bisection), compared to tasks that only require a perceptual judgment (i.e., the landmark task). In addition, these data provide further evidence that the effects of prisms on manual and perceptual responses are not related to one another.

High-performance, low-voltage electroosmotic pumps with molecularly thin silicon nanomembranes.

We have developed electroosmotic pumps (EOPs) fabricated from 15-nm-thick porous nanocrystalline silicon (pnc-Si) membranes. Ultrathin pnc-Si membranes enable high electroosmotic flow per unit voltage. We demonstrate that electroosmosis theory compares well with the observed pnc-Si flow rates. We attribute the high flow rates to high electrical fields present across the 15-nm span of the membrane. Surface modifications, such as plasma oxidation or silanization, can influence the electroosmotic flow rates through pnc-Si membranes by alteration of the zeta potential of the material. A prototype EOP that uses pnc-Si membranes and Ag/AgCl electrodes was shown to pump microliter per minute-range flow through a 0.5-mm-diameter capillary tubing with as low as 250 mV of applied voltage. This silicon-based platform enables straightforward integration of low-voltage, on-chip EOPs into portable microfluidic devices with low back pressures.

Influence of silicon dioxide capping layers on pore characteristics in nanocrystalline silicon membranes.

Porous nanocrystalline silicon (pnc-Si) membranes are a new class of membrane material with promising applications in biological separations. Pores are formed in a silicon film sandwiched between nm thick silicon dioxide layers during rapid thermal annealing. Controlling pore size is critical in the size-dependent separation applications. In this work, we systematically studied the influence of the silicon dioxide capping layers on pnc-Si membranes. Even a single nm thick top oxide layer is enough to switch from agglomeration to pore formation after annealing. Both the pore size and porosity increase with the thickness of the top oxide, but quickly reach a plateau after 10 nm of oxide. The bottom oxide layer acts as a barrier layer to prevent the a-Si film from undergoing homo-epitaxial growth during annealing. Both the pore size and porosity decrease as the thickness of the bottom oxide layer increases to 100 nm. The decrease of the pore size and porosity is correlated with the increased roughness of the bottom oxide layer, which hinders nanocrystal nucleation and nanopore formation.

Highly porous silicon membranes fabricated from silicon nitride/silicon stacks.

Nanopore formation in silicon films has previously been demonstrated using rapid thermal crystallization of ultrathin (15 nm) amorphous Si films sandwiched between nm-thick SiO2 layers. In this work, the silicon dioxide barrier layers are replaced with silicon nitride, resulting in nanoporous silicon films with unprecedented pore density and novel morphology. Four different thin film stack systems including silicon nitride/silicon/silicon nitride (NSN), silicon dioxide/silicon/silicon nitride (OSN), silicon nitride/silicon/silicon dioxide (NSO), and silicon dioxide/silicon/silicon dioxide (OSO) are tested under different annealing temperatures. Generally the pore size, pore density, and porosity positively correlate with the annealing temperature for all four systems. The NSN system yields substantially higher porosity and pore density than the OSO system, with the OSN and NSO stack characteristics fallings between these extremes. The higher porosity of the Si membrane in the NSN stack is primarily due to the pore formation enhancement in the Si film. It is hypothesized that this could result from the interfacial energy difference between the silicon/silicon nitride and silicon/silicon dioxide, which influences the Si crystallization process.

Methods for testing Zernike phase plates and a report on silicon-based phase plates with reduced charging and improved ageing characteristics.

Imaging with Zernike phase plates is increasingly being used in cryo-TEM tomography and cryo-EM single-particle applications. However, rapid ageing of the phase plates, together with the cost and effort in producing them, present serious obstacles to widespread adoption. We are experimenting with phase plates based on silicon chips that have thin windows; such phase plates could be mass-produced and made available at moderate cost. The windows are coated with conductive layers to reduce charging, and this considerably extends the useful life of the phase plates compared to traditional pure-carbon phase plates. However, a compromise must be reached between robustness and transmission through the phase-plate film. Details are given on testing phase-plate performance by means of imaging an amorphous thin film and evaluating the power spectra of the images.

Charge- and size-based separation of macromolecules using ultrathin silicon membranes.

Commercial ultrafiltration and dialysis membranes have broad pore size distributions and are over 1,000 times thicker than the molecules they are designed to separate, leading to poor size cut-off properties, filtrate loss within the membranes, and low transport rates. Nanofabricated membranes have great potential in molecular separation applications by offering more precise structural control, yet transport is also limited by micrometre-scale thicknesses. This limitation can be addressed by a new class of ultrathin nanostructured membranes where the membrane is roughly as thick (approximately 10 nm) as the molecules being separated, but membrane fragility and complex fabrication have prevented the use of ultrathin membranes for molecular separations. Here we report the development of an ultrathin porous nanocrystalline silicon (pnc-Si) membrane using straightforward silicon fabrication techniques that provide control over average pore sizes from approximately 5 nm to 25 nm. Our pnc-Si membranes can retain proteins while permitting the transport of small molecules at rates an order of magnitude faster than existing materials, separate differently sized proteins under physiological conditions, and separate similarly sized molecules carrying different charges. Despite being only 15 nm thick, pnc-Si membranes that are free-standing over 40,000 microm2 can support a full atmosphere of differential pressure without plastic deformation or fracture. By providing efficient, low-loss macromolecule separations, pnc-Si membranes are expected to enable a variety of new devices, including membrane-based chromatography systems and both analytical and preparative microfluidic systems that require highly efficient separations.

Assessment and recovery of visually guided reaching deficits following cerebellar stroke.

The cerebellum is known to play an important role in the coordination and timing of limb movements. The present study focused on how reach kinematics are affected by cerebellar lesions to quantify both the presence of motor impairment, and recovery of motor function over time. In the current study, 12 patients with isolated cerebellar stroke completed clinical measures of cognitive and motor function, as well as a visually guided reaching (VGR) task using the Kinarm exoskeleton at baseline (∼2 weeks), as well as 6, 12, and 24-weeks post-stroke. During the VGR task, patients made unassisted reaches with visual feedback from a central 'start' position to one of eight targets arranged in a circle. At baseline, 6/12 patients were impaired across several parameters of the VGR task compared to a Kinarm normative sample (n = 307), revealing deficits in both feed-forward and feedback control. The only clinical measures that consistently demonstrated impairment were the Purdue Pegboard Task (PPT; 9/12 patients) and the Montreal Cognitive Assessment (6/11 patients). Overall, patients who were impaired at baseline showed significant recovery by the 24-week follow-up for both VGR and the PPT. A lesion overlap analysis indicated that the regions most commonly damaged in 5/12 patients (42% overlap) were lobule IX and Crus II of the right cerebellum. A lesion subtraction analysis comparing patients who were impaired (n = 6) vs. unimpaired (n = 6) on the VGR task at baseline showed that the region most commonly damaged in impaired patients was lobule VIII of the right cerebellum (40% overlap). Our results lend further support to the notion that the cerebellum is involved in both feedforward and feedback control during reaching, and that cerebellar patients tend to recover relatively quickly overall. In addition, we argue that future research should study the effects of cerebellar damage on visuomotor control from a perception-action theoretical framework to better understand how the cerebellum works with the dorsal stream to control visually guided action.

"Real-time" obstacle avoidance in the absence of primary visual cortex.

When we reach toward objects, we easily avoid potential obstacles located in the workspace. Previous studies suggest that obstacle avoidance relies on mechanisms in the dorsal visual stream in the posterior parietal cortex. One fundamental question that remains unanswered is where the visual inputs to these dorsal-stream mechanisms are coming from. Here, we provide compelling evidence that these mechanisms can operate in "real-time" without direct input from primary visual cortex (V1). In our first experiment, we used a reaching task to demonstrate that an individual with a dense left visual field hemianopia after damage to V1 remained strikingly sensitive to the position of unseen static obstacles placed in his blind field. Importantly, in a second experiment, we showed that his sensitivity to the same obstacles in his blind field was abolished when a short 2-s delay (without vision) was introduced before reach onset. These findings have far-reaching implications, not only for our understanding of the time constraints under which different visual pathways operate, but also in relation to how these seemingly "primitive" subcortical visual pathways can control complex everyday behavior without recourse to conscious vision.

Pore size control of ultrathin silicon membranes by rapid thermal carbonization.

Rapid thermal carbonization in a dilute acetylene (C(2)H(2)) atmosphere has been used to chemically modify and precisely tune the pore size of ultrathin porous nanocrystalline silicon (pnc-Si). The magnitude of size reduction was controlled by varying the process temperature and time. Under certain conditions, the carbon coating displayed atomic ordering indicative of graphene layer formation conformal to the pore walls. Initial experiments show that carbonized membranes follow theoretical predictions for hydraulic permeability and retain the precise separation capabilities of untreated membranes.

Blindsight.

For over a century, research has demonstrated that damage to primary visual cortex does not eliminate all capacity for visual processing in the brain. From Riddoch's (1917) early demonstration of intact motion processing for blind field stimuli, to the iconic work of Weiskrantz et al. (1974) showing reliable spatial localization, it is clear that secondary visual pathways that bypass V1 carry information to the visual brain that in turn influences behavior. In this chapter, we briefly outline the history and phenomena associated with blindsight, before discussing the nature of the secondary visual pathways that support residual visual processing in the absence of V1. We finish with some speculation as to the functional characteristics of these secondary pathways.

Cerebellar lesions disrupt spatial and temporal visual attention.

The current study represents the first comprehensive examination of spatial, temporal and sustained attention following cerebellar damage. Results indicated that, compared to controls, cerebellar damage resulted in a larger cueing effect at the longest SOA - possibly reflecting a slowed the onset of inhibition of return (IOR) during a reflexive covert attention task, and reduced the ability to detect successive targets during an attentional blink task. However, there was little evidence to support the notion that cerebellar damage disrupted voluntary covert attention or the sustained attention to response task (SART). Lesion overlay data and supplementary voxel-based lesion symptom mapping (VLSM) analyses indicated that impaired performance on the reflexive covert attention and attentional blink tasks were related to damage to Crus II of the left posterior cerebellum. In addition, subsequent analyses indicated our results are not due to either general motor impairments or to damage to the deep cerebellar nuclei. Collectively these data demonstrate, for the first time, that the same cerebellar regions may be involved in both spatial and temporal visual attention.

Ion-selective permeability of an ultrathin nanoporous silicon membrane as probed by scanning electrochemical microscopy using micropipet-supported ITIES tips.

We report on the application of scanning electrochemical microscopy (SECM) to the measurement of the ion-selective permeability of porous nanocrystalline silicon membrane as a new type of nanoporous material with potential applications in analytical, biomedical, and biotechnology device development. The reliable measurement of high permeability in the molecularly thin nanoporous membrane to various ions is important for greater understanding of its structure-permeability relationship and also for its successful applications. In this work, this challenging measurement is enabled by introducing two novel features into amperometric SECM tips based on the micropipet-supported interface between two immiscible electrolyte solutions (ITIES) to reveal the important ion-transport properties of the ultrathin nanopore membrane. The tip of a conventional heat-pulled micropipet is milled using the focused ion beam (FIB) technique to be smoother, better aligned, and subsequently, approach closer to the membrane surface, which allows for more precise and accurate permeability measurement. The high membrane permeability to small monovalent ions is determined using FIB-milled micropipet tips to establish a theoretical formula for the membrane permeability that is controlled by free ion diffusion across water-filled nanopores. Moreover, the ITIES tips are rendered selective for larger polyions with biomedical importance, i.e., polyanionic pentasaccharide Arixtra and polycationic peptide protamine, to yield the membrane permeability that is lower than the corresponding diffusion-limited permeability. The hindered transport of the respective polyions is unequivocally ascribed to electrostatic and steric repulsions from the wall of the nanopores, i.e., the charge and size effects.

Can intention override the "automatic pilot"?

Previous research has suggested that the visuomotor system possesses an "automatic pilot" which allows people to make rapid online movement corrections in response to sudden changes in target position. Importantly, the automatic pilot has been shown to operate in the absence of visual awareness, and even under circumstances in which people are explicitly asked not to correct their ongoing movement. In the current study, we investigated the extent to which the automatic pilot could be "disengaged" by explicitly instructing participants to ignore the target jump (i.e., "NO-GO"), by manipulating the order in which the two tasks were completed (i.e., either "GO" or NO-GO first), and by manipulating the proportion of trials in which the target jumped. The results indicated that participants made fewer corrections in response to the target jump when they were asked not to correct their movement (i.e., NO-GO), and when they completed the NO-GO task prior to the task in which they were asked to correct their movement when the target jumped (i.e., the GO task). However, increasing the proportion of jumping targets had only a minimal influence on performance. Critically, participants still made a significant number of unintended corrections (i.e., errors) in the NO-GO tasks, even under explicit instructions not to correct their movement if the target jumped. Overall these data suggest that, while the automatic pilot can be influenced to some degree by top-down strategies and previous experience, the pre-potent response to correct an ongoing movement cannot be completely disengaged.

Covert face priming reveals a 'true face effect' in a case of congenital prosopagnosia.

Previous research indicates that individuals with congenital prosopagnosia (CP) fail to demonstrate significant priming from faces to related names in covert recognition tasks. The interpretation has been that CP precludes the ability to acquire face representations. In the current study we replicated this important finding. In addition, we also demonstrated significant 'true face effect' in a CP patient, where face primes that matched the probe names facilitated reaction times compared to unrelated face primes. These data suggest that some individuals with CP may possess degraded face representations that facilitate the priming of a person's identity, but not semantic associates.