Real world management of individuals with severe FXI deficiency and its impact on clinical outcomes: Experience from a haemophilia treatment centre.

INTRODUCTION: The management of Factor XI deficiency is challenged by a variable association between FXI level and bleeding phenotype. Additionally, there is scarce data describing management strategies and their outcomes, specifically bleeding, thrombosis, and other complications. AIMS: To evaluate bleeding, thrombosis, and other complications in individuals with severe FXI deficiency seen in our comprehensive haemophilia treatment centre (HTC). Peri-procedural management strategies and the resulting impact on bleeding and other clinically relevant outcomes were reported. METHODS: Retrospective review of the electronic medical record of adult patients with severe FXI deficiency (< 20% activity) seen at a New York City comprehensive HTC between 2017 and 2022. Procedures, haemostatic management, and outcomes were collected and analysed. RESULTS: We identified 38 individuals (64%) females with severe FXI deficiency. The mean age was 56 ± 21 years (SD). The median FXI activity level was 3% (IQR: 1-8%). The mean BAT score was 3.1 ± 2.4; (52%) individuals did not have a history of bleeding. A total of 256 surgeries and procedures were performed. There was reduced bleeding with preventative or reactive treatment during procedures. Arterial but not venous thrombotic complications were observed. Plasma was mostly used for procedures associated with higher risk of bleeding and antifibrinolytics for procedures at sites of high fibrinolysis. CONCLUSIONS: Current management strategies pose a burden of care for these patients and manifested as nonbleeding adverse events and changes in clinical management. These findings highlight the need for novel investigation in predicting and managing bleeding for individuals with severe FXI deficiency.

Electrical stimulation thresholds differ between V1 and V2.

Cortical visual prostheses are designed to treat blindness by restoring visual perceptions through artificial electrical stimulation of the primary visual cortex (V1). Intracortical microelectrodes produce the smallest visual percepts and thus higher resolution vision - like a higher density of pixels on a monitor. However, intracortical microelectrodes must maintain a minimum spacing to preserve tissue integrity. One solution to increase the density of percepts is to implant and stimulate multiple visual areas, such as V1 and V2, although the properties of microstimulation in V2 remain largely unexplored. We provide a direct comparison of V1 and V2 microstimulation in two common marmoset monkeys. We find similarities in response trends between V1 and V2 but differences in threshold, neural activity duration, and spread of activity at the threshold current. This has implications for using multi-area stimulation to increase the resolution of cortical visual prostheses.

LIRcentral: a manually curated online database of experimentally validated functional LIR motifs.

Several selective macroautophagy receptor and adaptor proteins bind members of the Atg8 (autophagy related 8) family using short linear motifs (SLiMs), most often referred to as Atg8-family interacting motifs (AIMs) or LC3-interacting regions (LIRs). AIM/LIR motifs have been extensively studied during the last fifteen years, since they can uncover the underlying biological mechanisms and possible substrates for this key catabolic process of eukaryotic cells. Prompted by the fact that experimental information regarding LIR motifs can be found scattered across heterogeneous literature resources, we have developed LIRcentral (https://lircentral.eu), a freely available online repository for user-friendly access to comprehensive, high-quality information regarding LIR motifs from manually curated publications. Herein, we describe the development of LIRcentral and showcase currently available data and features, along with our plans for the expansion of this resource. Information incorporated in LIRcentral is useful for accomplishing a variety of research tasks, including: (i) guiding wet biology researchers for the characterization of novel instances of LIR motifs, (ii) giving bioinformaticians/computational biologists access to high-quality LIR motifs for building novel prediction methods for LIR motifs and LIR containing proteins (LIRCPs) and (iii) performing analyses to better understand the biological importance/features of functional LIR motifs. We welcome feedback on the LIRcentral content and functionality by all interested researchers and anticipate this work to spearhead a community effort for sustaining this resource which will further promote progress in studying LIR motifs/LIRCPs.Abbreviations: AIM, Atg8-family interacting motif; Atg8, autophagy related 8; GABARAP, GABA type A receptor-associated protein; LIR, LC3-interacting region; LIRCP, LIR-containing protein; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; PMID, PubMed identifier; PPI, protein-protein interaction; SLiM, short linear motif.

Accelerated absorption of regular insulin administered via a vascularizing permeable microchamber implanted subcutaneously in diabetic Rattus norvegicus.

In Type 1 diabetes patients, even ultra-rapid acting insulins injected subcutaneously reach peak concentrations in 45 minutes or longer. The lag time between dosing and peak concentration, as well as intra- and inter-subject variability, render prandial glucose control and dose consistency difficult. We postulated that insulin absorption from subcutaneously implantable vascularizing microchambers would be significantly faster than conventional subcutaneous injection. Male athymic nude R. norvegicus rendered diabetic with streptozotocin were implanted with vascularizing microchambers (single chamber; 1.5 cm2 surface area per side; nominal volume, 22.5 µl). Plasma insulin was assayed after a single dose (1.5 U/kg) of diluted insulin human (Humulin®R U-100), injected subcutaneously or via microchamber. Microchambers were also implanted in additional animals and retrieved at intervals for histologic assessment of vascularity. Following conventional subcutaneous injection, the mean peak insulin concentration was 22.7 (SD 14.2) minutes. By contrast, when identical doses of insulin were injected via subcutaneous microchamber 28 days after implantation, the mean peak insulin time was shortened to 7.50 (SD 4.52) minutes. Peak insulin concentrations were similar by either route; however, inter-subject variability was reduced when insulin was administered via microchamber. Histologic examination of tissue surrounding microchambers showed mature vascularization on days 21 and 40 post-implantation. Implantable vascularizing microchambers of similar design may prove clinically useful for insulin dosing, either intermittently by needle, or continuously by pump including in "closed loop" systems, such as the artificial pancreas.

Ocular following responses of the marmoset monkey are dependent on postsaccadic delay, spatiotemporal frequency, and saccade direction.

Ocular following is a short-latency, reflexive eye movement that tracks wide-field visual motion. It has been studied extensively in humans and macaques and is an appealing behavior for studying sensory-motor transformations in the brain because of its rapidity and rigidity. We explored ocular following in the marmoset, an emerging model in neuroscience because their lissencephalic brain allows direct access to most cortical areas for imaging and electrophysiological recordings. In three experiments, we tested ocular following responses in three adult marmosets. First, we varied the delay between saccade end and stimulus motion onset, from 10 to 300 ms. As in other species, tracking had shorter onset latencies and higher eye speeds with shorter postsaccadic delays. Second, using sine-wave grating stimuli, we explored the dependence of eye speed on spatiotemporal frequency. The highest eye speed was evoked at ∼16 Hz and ∼0.16 cycles per degree (cpd); however, the highest gain was elicited at ∼1.6 Hz and ∼1.2 cpd. The highest eye speed for each spatial frequency was observed at a different temporal frequency, but this interdependence was not consistent with complete speed tuning of the ocular following response. Finally, we found the highest eye speeds when saccade and stimulus motion directions were identical, although latencies were unaffected by direction difference. Our results showed qualitatively similar ocular following in marmosets, humans, and macaques, despite over an order of magnitude variation in body and eye size across species. This characterization will help future studies examining the neural basis of sensory-motor transformations.NEW & NOTEWORTHY Previous ocular following studies focused on humans and macaques. We examined the properties of ocular following responses in marmosets in three experiments, in which postsaccadic delay, spatial-temporal frequency of stimuli, and congruence of saccade and motion directions were manipulated. We have demonstrated short-latency ocular following in marmosets and discuss the similarities across three species that vary markedly in eye and head size. Our findings will help future studies examining the neural mechanism of sensory-motor transformations.

Cortical layering disrupts multi-electrode current steering.

Objective.Blindness affects approximately 40 million people worldwide and has inspired the development of cortical visual prostheses for restoring sight. Cortical visual prostheses electrically stimulate neurons of the visual cortex to artificially evoke visual percepts. Of the 6 layers of the visual cortex, layer 4 contains neurons that are likely to evoke a visual percept. Intracortical prostheses therefore aim to target layer 4; however, this can be difficult due to cortical curvature, inter-subject cortical variability, blindness-induced anatomical changes in cortex, and electrode placement variations. We investigated the feasibility of using current steering to stimulate specific cortical layers between electrodes in the laminar column.Approach.We explored whether the multiunit neural activity peak can be manipulated between two simultaneously stimulating electrodes in different layers of the cortical column. A 64-channel, 4-shank electrode array was implanted into the visual cortex of Sprague-Dawley rats (n= 7) orthogonal to the cortical surface. A remote return electrode was positioned over the frontal cortex in the same hemisphere. Charge was supplied to two stimulating electrodes along a single shank. Differing ratios of charge (100:0, 75:25, 50:50) and separation distances (300-500µm) were tested.Results.Current steering across the cortical layers did not result in a consistent shift of the neural activity peak. Both single-electrode and dual-electrode stimulation induced activity throughout the cortical column. This contrasts observations that current steering evoked a controllable peak of neural activity between electrodes implanted at similar cortical depths. However, dual-electrode stimulation across the layers did reduce the stimulation threshold at each site compared to single-electrode stimulation.Significance.Multi-electrode stimulation is not suitable for targeted activation of layers using current steering. However, it can be used to reduce activation thresholds at adjacent electrodes within a given cortical layer. This may be applied to reduce the stimulation side effects of neural prostheses, such as seizures.

Where now for infection services in the NHS? How lessons from the pandemic should drive long-overdue integration of microbiology and infectious diseases.

In its first 2 decades, the NHS witnessed the near eradication of life-threatening community-acquired infections. However, medical advances have created different challenges (such as antimicrobial resistance and healthcare-associated infections) against a background of an increasingly ageing population. The recent COVID-19 pandemic has highlighted a lack of parity with regards to provision of NHS 'infection services' (infectious diseases, microbiology and virology) across the UK, which urgently needs to be addressed. We recommend a fundamental review of NHS infection service provision: divided into four key areas. Firstly, there should be a consideration of a single multidisciplinary specialty of infection medicine removing barriers to training and service delivery. Secondly, streamline infection training via a single pathway through to certificate of completion of training, encompassing all aspects of infection service provision, for example, infection diagnostics, clinical care (including inpatient, outpatient and community based care), and infection prevention and control. There should be flexibility within the training curriculum to facilitate combined training with general internal medicine (GIM) as well as out of programme activities. Innovative ways of providing clinical experience should be considered, acknowledging the roles that medical microbiologists working closely with GIM colleagues in district general hospitals can play in managing patients with infections. Thirdly, formally commission a national network of specialised infectious diseases units with the creation of service standards. This can facilitate future pandemic resilience using a hub-and-spoke model utilising local infection expertise. Lastly, standardise the NHS framework to lead and coordinate development of integrated infection services at the local level.

Real-world effectiveness of steroids in severe COVID-19: a retrospective cohort study.

INTRODUCTION: Randomised controlled trials have shown that steroids reduce the risk of dying in patients with severe Coronavirus disease 2019 (COVID-19), whilst many real-world studies have failed to replicate this result. We aim to investigate real-world effectiveness of steroids in severe COVID-19. METHODS: Clinical, demographic, and viral genome data extracted from electronic patient record (EPR) was analysed from all SARS-CoV-2 RNA positive patients admitted with severe COVID-19, defined by hypoxia at presentation, between March 13th 2020 and May 27th 2021. Steroid treatment was measured by the number of prescription-days with dexamethasone, hydrocortisone, prednisolone or methylprednisolone. The association between steroid > 3 days treatment and disease outcome was explored using multivariable cox proportional hazards models with adjustment for confounders (including age, gender, ethnicity, co-morbidities and SARS-CoV-2 variant). The outcome was in-hospital mortality. RESULTS: 1100 severe COVID-19 cases were identified having crude hospital mortality of 15.3%. 793/1100 (72.1%) individuals were treated with steroids and 513/1100 (46.6%) received steroid ≤ 3 days. From the multivariate model, steroid > 3 days was associated with decreased hazard of in-hospital mortality (HR: 0.47 (95% CI: 0.31-0.72)). CONCLUSION: The protective effect of steroid treatment for severe COVID-19 reported in randomised clinical trials was replicated in this retrospective study of a large real-world cohort.

Genome-wide polymorphism and genic selection in feral and domesticated lineages of Cannabis sativa.

A comprehensive understanding of the degree to which genomic variation is maintained by selection versus drift and gene flow is lacking in many important species such as Cannabis sativa (C. sativa), one of the oldest known crops to be cultivated by humans worldwide. We generated whole genome resequencing data across diverse samples of feralized (escaped domesticated lineages) and domesticated lineages of C. sativa. We performed analyses to examine population structure, and genome wide scans for FST, balancing selection, and positive selection. Our analyses identified evidence for sub-population structure and further support the Asian origin hypothesis of this species. Feral plants sourced from the U.S. exhibited broad regions on chromosomes 4 and 10 with high F̄ST which may indicate chromosomal inversions maintained at high frequency in this sub-population. Both our balancing and positive selection analyses identified loci that may reflect differential selection for traits favored by natural selection and artificial selection in feral versus domesticated sub-populations. In the U.S. feral sub-population, we found six loci related to stress response under balancing selection and one gene involved in disease resistance under positive selection, suggesting local adaptation to new climates and biotic interactions. In the marijuana sub-population, we identified the gene SMALLER TRICHOMES WITH VARIABLE BRANCHES 2 to be under positive selection which suggests artificial selection for increased tetrahydrocannabinol yield. Overall, the data generated, and results obtained from our study help to form a better understanding of the evolutionary history in C. sativa.

Intracortical current steering shifts the location of evoked neural activity.

Objective.Intracortical visual prostheses are being developed to restore sight in people who are blind. The resolution of artificial vision is dictated by the location, proximity and number of electrodes implanted in the brain. However, increasing electrode count and proximity is traded off against tissue damage. Hence, new stimulation methods are needed that can improve the resolution of artificial vision without increasing the number of electrodes. We investigated whether a technique known as current steering can improve the resolution of artificial vision provided by intracortical prostheses without increasing the number of physical electrodes in the brain.Approach.We explored how the locus of neuronal activation could be steered when low amplitude microstimulation was applied simultaneously to two intracortical electrodes. A 64-channel, four-shank electrode array was implanted into the visual cortex of rats (n= 7). The distribution of charge ranged from single-electrode stimulation (100%:0%) to an equal distribution between the two electrodes (50%:50%), thereby steering the current between the physical electrodes. The stimulating electrode separation varied between 300 and 500µm. The peak of the evoked activity was defined as the 'virtual electrode' location.Main results.Current steering systematically shifted the virtual electrode on average between the stimulating electrodes as the distribution of charge was moved from one stimulating electrode to another. This effect was unclear in single trials due to the limited sampling of neurons. A model that scales the cortical response to each physical electrode when stimulated in isolation predicts the evoked virtual electrode response. Virtual electrodes were found to elicit a neural response as effectively and predictably as physical electrodes within cortical tissue on average.Significance.Current steering could be used to increase the resolution of intracortical electrode arrays without altering the number of physical electrodes which will reduce neural tissue damage, power consumption and potential heat dispersion issues.

Clinical features and management of human monkeypox: a retrospective observational study in the UK.

BACKGROUND: Cases of human monkeypox are rarely seen outside of west and central Africa. There are few data regarding viral kinetics or the duration of viral shedding and no licensed treatments. Two oral drugs, brincidofovir and tecovirimat, have been approved for treatment of smallpox and have demonstrated efficacy against monkeypox in animals. Our aim was to describe the longitudinal clinical course of monkeypox in a high-income setting, coupled with viral dynamics, and any adverse events related to novel antiviral therapies. METHODS: In this retrospective observational study, we report the clinical features, longitudinal virological findings, and response to off-label antivirals in seven patients with monkeypox who were diagnosed in the UK between 2018 and 2021, identified through retrospective case-note review. This study included all patients who were managed in dedicated high consequence infectious diseases (HCID) centres in Liverpool, London, and Newcastle, coordinated via a national HCID network. FINDINGS: We reviewed all cases since the inception of the HCID (airborne) network between Aug 15, 2018, and Sept 10, 2021, identifying seven patients. Of the seven patients, four were men and three were women. Three acquired monkeypox in the UK: one patient was a health-care worker who acquired the virus nosocomially, and one patient who acquired the virus abroad transmitted it to an adult and child within their household cluster. Notable disease features included viraemia, prolonged monkeypox virus DNA detection in upper respiratory tract swabs, reactive low mood, and one patient had a monkeypox virus PCR-positive deep tissue abscess. Five patients spent more than 3 weeks (range 22-39 days) in isolation due to prolonged PCR positivity. Three patients were treated with brincidofovir (200 mg once a week orally), all of whom developed elevated liver enzymes resulting in cessation of therapy. One patient was treated with tecovirimat (600 mg twice daily for 2 weeks orally), experienced no adverse effects, and had a shorter duration of viral shedding and illness (10 days hospitalisation) compared with the other six patients. One patient experienced a mild relapse 6 weeks after hospital discharge. INTERPRETATION: Human monkeypox poses unique challenges, even to well resourced health-care systems with HCID networks. Prolonged upper respiratory tract viral DNA shedding after skin lesion resolution challenged current infection prevention and control guidance. There is an urgent need for prospective studies of antivirals for this disease. FUNDING: None.

TIME- AND FREQUENCY-BASED INDEPENDENT EVALUATION OF QRST CANCELLATION TECHNIQUES FOR SINGLE-LEAD ELECTROCARDIOGRAMS DURING ATRIAL FIBRILLATION.

With the increased prevalence of atrial fibrillation (AF) - a rhythm disturbance in heart's top chambers - there is growing interest in accurate non-invasive diagnosis of atrial activity to improve its therapy. A key component in non-invasive analysis of atrial activity is a successful removal of the ventricular QRST complexes from electrocardiograms (ECGs). In this study, we have developed a new approach for an objective and physiologically-based evaluation of QRST cancellation methods based on comparisons with the power spectra of the AF. Three commonly used QRST cancellation methods were evaluated; namely, average beat subtraction, singular value cancellation, and principal component analysis. These methods were evaluated in time and frequency domains using a set of synthesized ECGs preserving the atrial-specific temporal and spectral properties. It was observed that the ABS method provided the best estimation when QRST morphological variability is low, while PCA produces an overall best estimate when a large QRST morphological variability is present.

Filling in the Visual Gaps: Shifting Cortical Activity using Current Steering.

Cortical vision prostheses are being developed to restore sight in blind patients. Existing electrode arrays that electrically stimulate cortical tissue to artificially induce neural activity are difficult to position directly next to each other. Leaving space between implants creates gaps in the visual field where no visual percepts can be created. Here, we propose current steering as a solution to elicit a neural response between physical electrode locations. We assessed the centroid of neural activity produced by dual-electrode stimulation in the visual cortex of Sprague-Dawley rats. We determined that this centroid could be shifted between physical electrodes by altering the ratio of charge delivered to each electrode. This centroidal shift could enable better environmental perception for cortical implant patients by creating a complete visual field representation while maintaining safe array spacing.

Marmosets: a promising model for probing the neural mechanisms underlying complex visual networks such as the frontal-parietal network.

The technology, methodology and models used by visual neuroscientists have provided great insights into the structure and function of individual brain areas. However, complex cognitive functions arise in the brain due to networks comprising multiple interacting cortical areas that are wired together with precise anatomical connections. A prime example of this phenomenon is the frontal-parietal network and two key regions within it: the frontal eye fields (FEF) and lateral intraparietal area (area LIP). Activity in these cortical areas has independently been tied to oculomotor control, motor preparation, visual attention and decision-making. Strong, bidirectional anatomical connections have also been traced between FEF and area LIP, suggesting that the aforementioned visual functions depend on these inter-area interactions. However, advancements in our knowledge about the interactions between area LIP and FEF are limited with the main animal model, the rhesus macaque, because these key regions are buried in the sulci of the brain. In this review, we propose that the common marmoset is the ideal model for investigating how anatomical connections give rise to functionally-complex cognitive visual behaviours, such as those modulated by the frontal-parietal network, because of the homology of their cortical networks with humans and macaques, amenability to transgenic technology, and rich behavioural repertoire. Furthermore, the lissencephalic structure of the marmoset brain enables application of powerful techniques, such as array-based electrophysiology and optogenetics, which are critical to bridge the gaps in our knowledge about structure and function in the brain.

Insulinoma-derived pseudo-islets for diabetes research.

The islets of Langerhans of the pancreas are the primary endocrine organ responsible for regulating whole body glucose homeostasis. The use of isolated primary islets for research development and training requires organ resection, careful digestion, and isolation of the islets from nonendocrine tissue. This process is time consuming, expensive, and requires substantial expertise. For these reasons, we sought to develop a more rapidly obtainable and consistent model system with characteristic islet morphology and function that could be employed to train personnel and better inform experiments prior to using isolated rodent and human islets. Immortalized ß cell lines reflect several aspects of primary ß cells, but cell propagation in monolayer cell culture limits their usefulness in several areas of research, which depend on islet morphology and/or functional assessment. In this manuscript, we describe the propagation and characterization of insulinoma pseudo-islets (IPIs) from a rat insulinoma cell line INS832/3. IPIs were generated with an average diameter of 200 µm, consistent with general islet morphology. The rates of oxygen consumption and mitochondrial oxidation-reduction changes in response to glucose and metabolic modulators were similar to isolated rat islets. In addition, the dynamic insulin secretory patterns of IPIs were similar to primary rat islets. Thus, INS832/3-derived IPIs provide a valuable and convenient model for accelerating islet and diabetes research.

Microstimulation-evoked neural responses in visual cortex are depth dependent.

BACKGROUND: Cortical visual prostheses often use penetrating electrode arrays to deliver microstimulation to the visual cortex. To optimize electrode placement within the cortex, the neural responses to microstimulation at different cortical depths must first be understood. OBJECTIVE: We investigated how the neural responses evoked by microstimulation in cortex varied with cortical depth, of both stimulation and response. METHODS: A 32-channel single shank electrode array was inserted into the primary visual cortex of anaesthetized rats, such that it spanned all cortical layers. Microstimulation with currents up to 14 µA (single biphasic pulse, 200 µs per phase) was applied at depths spanning 1600 µm, while simultaneously recording neural activity on all channels within a response window 2.25-11 ms. RESULTS: Stimulation elicited elevated neuronal firing rates at all depths of cortex. Compared to deep sites, superficial stimulation sites responded with higher firing rates at a given current and had lower thresholds. The laminar spread of evoked activity across cortical depth depended on stimulation depth, in line with anatomical models. CONCLUSION: Stimulation in the superficial layers of visual cortex evokes local neural activity with the lowest thresholds, and stimulation in the deep layers evoked the most activity across the cortical column. In conjunction with perceptual reports, these data suggest that the optimal electrode placement for cortical microstimulation prostheses has electrodes positioned in layers 2/3, and at the top of layer 5.

Visual responses in the dorsolateral frontal cortex of marmoset monkeys.

The marmoset monkey (Callithrix jacchus) has gained attention in neurophysiology research as a new primate model for visual processing and behavior. In particular, marmosets have a lissencephalic cortex, making multielectrode, optogenetic, and calcium-imaging techniques more accessible than other primate models. However, the degree of homology of brain circuits for visual behavior with those identified in macaques and humans is still being ascertained. For example, whereas the location of the frontal eye fields (FEF) within the dorsolateral frontal cortex has been proposed, it remains unclear whether neurons in the corresponding areas show visual responses-an important characteristic of FEF neurons in other species. Here, we provide the first description of receptive field properties and neural response latencies in the marmoset dorsolateral frontal cortex, based on recordings using Utah arrays in anesthetized animals. We find brisk visual responses in specific regions of the dorsolateral prefrontal cortex, particularly in areas 8aV, 8C, and 6DR. As in macaque FEF, the receptive fields were typically large (10°-30° in diameter) and the median responses latency was brisk (60 ms). These results constrain the possible interpretations about the location of the marmoset FEF and suggest that the marmoset model's significant advantages for the use of physiological techniques may be leveraged in the study of visuomotor cognition.NEW & NOTEWORTHY Behavior and cognition in humans and other primates rely on networks of brain areas guided by the frontal cortex. The marmoset offers exciting new opportunities to study links between brain physiology and behavior, but the functions of frontal cortex areas are still being identified in this species. Here, we provide the first evidence of visual receptive fields in the marmoset dorsolateral frontal cortex, an important step toward future studies of visual cognitive behavior.

Local field potential phase modulates neural responses to intracortical electrical stimulation.

Cortical visual prostheses could one day help restore sight to the blind by targeting the visual cortex with electrical stimulation. However, power consumption and limited spatial resolution impose limits on performance, while large amounts of electrical charge sometimes necessary to evoke phosphenes can cause seizures. Here, we propose the use of the local field potential as a control signal for the timing of stimulation to reduce charge requirements. In Sprague-Dawley rats, visual cortex was electrically stimulated at random times, and neural responses recorded. Electrical stimulation at specific phases of the local field potential required smaller amounts of charge to elicit spikes than naïve stimulation. Incorporating this into prosthesis design could improve their safety and efficacy.

A twisted visual field map in the primate dorsomedial cortex predicted by topographic continuity.

Adjacent neurons in visual cortex have overlapping receptive fields within and across area boundaries, an arrangement theorized to minimize wiring cost. This constraint is traditionally thought to create retinotopic maps of opposing field signs (mirror and nonmirror visual field representations) in adjacent areas, a concept that has become central in current attempts to subdivide the extrastriate cortex. We simulated the formation of retinotopic maps using a model that balances constraints imposed by smoothness in the representation within an area and by congruence between areas. As in the primate cortex, this model usually leads to alternating mirror and nonmirror maps. However, we found that it can also produce a more complex type of map, consisting of sectors with opposing field sign within a single area. Using fully quantitative electrode array recordings, we then demonstrate that this type of inhomogeneous map exists in the controversial dorsomedial region of the primate extrastriate cortex.