Retrieval-induced forgetting of spatial position depends on access to multiple shared features within categories.

Retrieval-induced forgetting (RIF) is typically observed in verbal memory tasks, although a few studies have observed RIF in visual spatial tasks. This leaves an open question as to whether RIF depends on semantic identity to link across semantic properties of objects, or whether RIF depends on access to the perceptual features of objects. To explore RIF of spatial positions, we report three experiments utilizing a continuous measure of the accessibility and precision for objects that were distinguished by their shape, color, and spatial region. After a study phase, half of the objects in a single-color category were selectively practiced for their spatial position, by requiring the object to be placed in the exact spatial position seen previously. Finally, all objects were probed for their spatial position at test. No RIF occurred for objects that shared only one color feature but were located within the same spatial region (in Experiment 1) or when objects shared the same color, but were located within different spatial regions (in Experiment 3). However, RIF did occur when objects shared the same spatial region and the same color (Experiment 2). Overall, the interim recall of the spatial positions of cue-objects impairs access to the position of other cue-objects within the same color category, but only when these groups had sufficient overlapping and competing features. The finding that RIF only occurs to the accessibility of spatial positions, not the precision of visual spatial memory, was interpreted as consistent with inhibitory theories of forgetting.

Errorful learning improves recognition memory for new vocabulary for people living with memory and dysexecutive impairment following brain injury.

A widely accepted view is that errorless learning is essential for supporting new learning in people with anterograde amnesia, but findings are mixed for those with a broader range of memory impairments. People at a chronic stage of recovery from brain injury (BI) with impaired memory and executive function (N = 26) were compared with adults in a comparison group without any known risks to brain function (N = 25). Learning techniques were compared using a "Generate-and-correct" and "Read-only" condition when learning novel word pairs. At test, both groups scored above chance and showed benefits of Generate-and-correct (errorful learning). Poor learners in the BI group were classified from "flat" learning slopes extracted from an independent word-pair learning task. Critically, poor learners showed no benefit, but also no decrement to learning, using the Generate-and-correct method. No group was harmed by errorful learning; all, except the poorest learners, benefitted from errorful learning. This study indicates, that in some rehabilitation settings, encouraging clients to guess the meaning of unfamiliar material (e.g., from cards, magazines, newspapers) and then correct their errors, could have benefits for recognition memory. Determining when and how errorful learning benefits learning is a key aim for future research.

Progressive retrieval practice leads to greater memory for image-word pairs than standard retrieval practice.

The benefits of retrieval practice on learning are robust and have transferred from laboratory findings to many real-world educational settings. We report two experiments that investigated a novel retrieval practice technique for remembering arbitrary associations (image-word pairs), with and without reward as a motivator. As well as typical retrieval practice and restudy conditions, we added a third condition of graded retrieval practice in which the image cue was partially released in a progressive process. Experiment 1 found significant benefits of retrieval practice over restudy, with an additional benefit of graded retrieval practice compared with standard retrieval practice after a 48-hour delay between study and retrieval. Experiment 2 included a reward manipulation by giving participants money based on their memory performance. The findings replicated the retrieval practice effects observed in Experiment 1, including a robust advantage for graded retrieval practice. Reward neither changed the additive advantage of graded recall nor the benefit of retrieval practice. The present study adds to the literature indicating that retrieval with progressive retrieval cues can boost the benefit of retrieval practice by generating repeated retrieval attempts. This benefit occurs most for items that are neither too easy nor too challenging to retrieve.

Sonic Hedgehog Guides Axons via Zipcode Binding Protein 1-Mediated Local Translation.

Sonic hedgehog (Shh) attracts spinal cord commissural axons toward the floorplate. How Shh elicits changes in the growth cone cytoskeleton that drive growth cone turning is unknown. We find that the turning of rat commissural axons up a Shh gradient requires protein synthesis. In particular, Shh stimulation increases ß-actin protein at the growth cone even when the cell bodies have been removed. Therefore, Shh induces the local translation of ß-actin at the growth cone. We hypothesized that this requires zipcode binding protein 1 (ZBP1), an mRNA-binding protein that transports ß-actin mRNA and releases it for local translation upon phosphorylation. We found that Shh stimulation increases phospho-ZBP1 levels in the growth cone. Disruption of ZBP1 phosphorylation in vitro abolished the turning of commissural axons toward a Shh gradient. Disruption of ZBP1 function in vivo in mouse and chick resulted in commissural axon guidance errors. Therefore, ZBP1 is required for Shh to guide commissural axons. This identifies ZBP1 as a new mediator of noncanonical Shh signaling in axon guidance.SIGNIFICANCE STATEMENT Sonic hedgehog (Shh) guides axons via a noncanonical signaling pathway that is distinct from the canonical Hedgehog signaling pathway that specifies cell fate and morphogenesis. Axon guidance is driven by changes in the growth cone in response to gradients of guidance molecules. Little is known about the molecular mechanism of how Shh orchestrates changes in the growth cone cytoskeleton that are required for growth cone turning. Here, we show that the guidance of axons by Shh requires protein synthesis. Zipcode binding protein 1 (ZBP1) is an mRNA-binding protein that regulates the local translation of proteins, including actin, in the growth cone. We demonstrate that ZBP1 is required for Shh-mediated axon guidance, identifying a new member of the noncanonical Shh signaling pathway.

No evidence of binding items to spatial configuration representations in visual working memory.

When detecting changes in visual features (e.g., colour or shape), object locations, represented as points within a configuration, might also be automatically represented in working memory. If the configuration of a scene is represented automatically, the locations of individual items might form part of this representation, irrespective of their relevance to the task. Participants took part in a change-detection task in which they studied displays containing different sets of items (shapes, letters, objects), which varied in their task relevance. Specifically, they were asked to remember the features of two sets, and ignore the third set. During the retention interval, an audio cue indicated which of the to-be-remembered sets would become the target set (having a 50% probability of containing a new feature). At test, they were asked to indicate whether a new feature was present amongst the target set. We measured binding of individual items to the configuration by manipulating the locations of the different sets so that their position in the test display either matched or mismatched their original location in the study display. If items are automatically bound to the configuration, location changes should disrupt performance, even if they were explicitly instructed not to remember the features of that particular set of items. There was no effect on performance of changing the locations of any of the sets between study and test displays, indicating that the configural representation did not enter their decision stage, and therefore that individual item representations are not necessarily bound to the configuration.

Cue quality and criterion setting in recognition memory.

Previous studies on how people set and modify decision criteria in old-new recognition tasks (in which they have to decide whether or not a stimulus was seen in a study phase) have almost exclusively focused on properties of the study items, such as presentation frequency or study list length. In contrast, in the three studies reported here, we manipulated the quality of the test cues in a scene-recognition task, either by degrading through Gaussian blurring (Experiment 1) or by limiting presentation duration (Experiment 2 and 3). In Experiments 1 and 2, degradation of the test cue led to worse old-new discrimination. Most importantly, however, participants were more liberal in their responses to degraded cues (i.e., more likely to call the cue "old"), demonstrating strong within-list, item-by-item, criterion shifts. This liberal response bias toward degraded stimuli came at the cost of increasing the false alarm rate while maintaining a constant hit rate. Experiment 3 replicated Experiment 2 with additional stimulus types (words and faces) but did not provide accuracy feedback to participants. The criterion shifts in Experiment 3 were smaller in magnitude than Experiments 1 and 2 and varied in consistency across stimulus type, suggesting, in line with previous studies, that feedback is important for participants to shift their criteria.

No evidence for binding of items to task-irrelevant backgrounds in visual working memory.

When representing visual features such as color and shape in visual working memory (VWM), participants also represent the locations of those features as a spatial configuration of the locations of those features in the display. In everyday life, we encounter objects against some background, yet it is unclear whether the configural representation in memory obligatorily constitutes the entire display, including that (often task-irrelevant) background information. In three experiments, participants completed a change detection task on color and shape; the memoranda were presented in front of uniform gray backgrounds, a textured background (Exp. 1), or a background containing location placeholders (Exps. 2 and 3). When whole-display probes were presented, changes to the objects' locations or feature bindings impacted memory performance-implying that the spatial configuration of the probes influenced participants' change decisions. Furthermore, when only a single item was probed, the effect of changing its location or feature bindings was either diminished or completely extinguished, implying that single probes do not necessarily elicit the entire spatial configuration. Critically, when task-irrelevant backgrounds were also presented that may have provided a spatial configuration for the single probes, the effect of location or bindings was not moderated. These findings suggest that although the spatial configuration of a display guides VWM-based recognition, this information does not necessarily always influence the decision process during change detection.

What Adverse Events and Injuries Are Cited in Anesthesia Malpractice Claims for Nonspine Orthopaedic Surgery?

BACKGROUND: Malpractice claims that arise during the perioperative care of patients receiving orthopaedic procedures will frequently involve both orthopaedic surgeons and anesthesiologists. The Anesthesia Closed Claims database contains anesthesia malpractice claim data that can be used to investigate patient safety events arising during the care of orthopaedic patients and can provide insight into the medicolegal liability shared by the two specialties. QUESTIONS/PURPOSES: (1) How do orthopaedic anesthetic malpractice claims differ from other anesthesia claims with regard to patient and case characteristics, common events and injuries, and liability profile? (2) What are the characteristics of patients who had neuraxial hematomas after spinal and epidural anesthesia for orthopaedic procedures? (3) What are the characteristics of patients who had orthopaedic anesthesia malpractice claims for central ischemic neurologic injury occurring during shoulder surgery in the beach chair position? (4) What are the characteristics of patients who had malpractice claims for respiratory depression and respiratory arrests in the postoperative period? METHODS: The Anesthesia Closed Claims Project database was the source of data for this study. This national database derives data from a panel of liability companies (national and regional) and includes closed malpractice claims against anesthesiologists representing > 30% of practicing anesthesiologists in the United States from all types of practice settings (hospital, surgery centers, and offices). Claims for damage to teeth or dentures are not included in the database. Patient characteristics, type of anesthesia, damaging events, outcomes, and liability characteristics of anesthesia malpractice claims for events occurring in the years 2000 to 2013 related to nonspine orthopaedic surgery (n = 475) were compared with claims related to other procedures (n = 1592) with p < 0.05 as the criterion for statistical significance and two-tailed tests. Odds ratios and their 95% confidence intervals were calculated for all comparisons. Three types of claims involving high-impact injuries in patients undergoing nonspine orthopaedic surgery were identified through database query for in-depth descriptive review: neuraxial hematoma (n = 10), central ischemic neurologic injury in the beach chair position (n = 9), and injuries caused by postoperative respiratory depression (n = 23). RESULTS: Nonspine orthopaedic anesthesia malpractice claims were more frequently associated with nerve injuries (125 of 475 [26%], odds ratio [OR] 2.12 [1.66-2.71]) and events arising from the use of regional anesthesia (125 of 475 [26%], OR 6.18 (4.59-8.32) than in malpractice claims in other areas of anesthesia malpractice (230 of 1592 [14%] and 87 of 1592 [6%], respectively, p < 0.001 for both comparisons). Ninety percent (nine of 10) of patients with claims for neuraxial hematomas were receiving anticoagulant medication and all had severe long-term injuries, most with a history of significant delay in diagnosis and treatment after first appearance of signs and symptoms. Central ischemic injuries occurring during orthopaedic surgery in the beach chair position did not occur solely in patients who would have been considered at high risk for ischemic stroke. Patients with malpractice claims for injuries resulting from postoperative respiratory depression events had undergone lower extremity procedures (20 of 23 [87%]) and most events (22 of 23 [96%]) occurred on the day of surgery or the first postoperative day. CONCLUSIONS: Nonspine orthopaedic anesthesia malpractice claims more frequently cited nerve injury and events arising from the use of regional anesthesia than other surgical anesthesia malpractice claims. This may reflect the frequency of regional anesthesia in orthopaedic cases rather than increased risk of injury associated with regional techniques. When neuraxial procedures and anticoagulation regimens are used concurrently, care pathways should emphasize clear lines of responsibility for coordination of care and early investigation of any unusual neurologic findings that might indicate neuraxial hematoma. We do not have a good understanding of the factors that render some patients vulnerable to the rare occurrence of intraoperative central ischemic injury in the beach chair position, but providers should carefully calculate cerebral perfusion pressure relative to measured blood pressure for patients in the upright position. Postoperative use of multiple opioids by different concurrent modes of administration warrant special precautions with consideration given to the provision of care in settings with enhanced respiratory monitoring. The limitations of retrospective closed claims database review prevent conclusions regarding causation. Nonetheless, the collection of relatively rare events with substantial clinical detail provides valuable data to generate hypotheses about causation with potential for future study to improve patient safety. LEVEL OF EVIDENCE: Level III, therapeutic study.

Towards sensory substitution and augmentation: Mapping visual distance to audio and tactile frequency.

Multimodal perception is the predominant means by which individuals experience and interact with the world. However, sensory dysfunction or loss can significantly impede this process. In such cases, cross-modality research offers valuable insight into how we can compensate for these sensory deficits through sensory substitution. Although sight and hearing are both used to estimate the distance to an object (e.g., by visual size and sound volume) and the perception of distance is an important element in navigation and guidance, it is not widely studied in cross-modal research. We investigate the relationship between audio and vibrotactile frequencies (in the ranges 47-2,764 Hz and 10-99 Hz, respectively) and distances uniformly distributed in the range 1-12 m. In our experiments participants mapped the distance (represented by an image of a model at that distance) to a frequency via adjusting a virtual tuning knob. The results revealed that the majority (more than 76%) of participants demonstrated a strong negative monotonic relationship between frequency and distance, across both vibrotactile (represented by a natural log function) and auditory domains (represented by an exponential function). However, a subgroup of participants showed the opposite positive linear relationship between frequency and distance. The strong cross-modal sensory correlation could contribute to the development of assistive robotic technologies and devices to augment human perception. This work provides the fundamental foundation for future assisted HRI applications where a mapping between distance and frequency is needed, for example for people with vision or hearing loss, drivers with loss of focus or response delay, doctors undertaking teleoperation surgery, and users in augmented reality (AR) or virtual reality (VR) environments.

Vertebral Subluxation and Systems Biology: An Integrative Review Exploring the Salutogenic Influence of Chiropractic Care on the Neuroendocrine-Immune System.

In this paper we synthesize an expansive body of literature examining the multifaceted influence of chiropractic care on processes within and modulators of the neuroendocrine-immune (NEI) system, for the purpose of generating an inductive hypothesis regarding the potential impacts of chiropractic care on integrated physiology. Taking a broad, interdisciplinary, and integrative view of two decades of research-documented outcomes of chiropractic care, inclusive of reports ranging from systematic and meta-analysis and randomized and observational trials to case and cohort studies, this review encapsulates a rigorous analysis of research and suggests the appropriateness of a more integrative perspective on the impact of chiropractic care on systemic physiology. A novel perspective on the salutogenic, health-promoting effects of chiropractic adjustment is presented, focused on the improvement of physical indicators of well-being and adaptability such as blood pressure, heart rate variability, and sleep, potential benefits that may be facilitated through multiple neurologically mediated pathways. Our findings support the biological plausibility of complex benefits from chiropractic intervention that is not limited to simple neuromusculoskeletal outcomes and open new avenues for future research, specifically the exploration and mapping of the precise neural pathways and networks influenced by chiropractic adjustment.

Assessment of intraoperative awareness with explicit recall: a comparison of 2 methods.

BACKGROUND: Superiority of the modified Brice interview over quality assurance techniques in detecting intraoperative awareness with explicit recall has not been demonstrated definitively. METHODS: We studied a single patient cohort to compare the detection of definite awareness using a single modified Brice interview (postoperative day 28-30) versus quality assurance data (postoperative day 1). RESULTS: The incidence of awareness based on the modified Brice interview was 19 per 18,847 or 0.1%. Fewer awareness cases (incidence 0.02%) were detected by the quality assurance approach (P < 0.0001). CONCLUSION: The modified Brice interview is the preferred modality for assessing intraoperative awareness with explicit recall.

Graded prioritisation of targets in search: reward diminishes the low prevalence effect.

In many real-life contexts, observers are required to search for targets that are rarely present (e.g. tumours in X-rays; dangerous items in airport security screenings). Despite the rarity of these items, they are of enormous importance for the health and safety of the public, yet they are easily missed during visual search. This is referred to as the prevalence effect. In the current series of experiments, we investigate whether unequal reward can modulate the prevalence effect, in a multiple target search task. Having first established the impact of prevalence (Experiment 1) and reward (Experiment 2) on how efficiently participants can find one of several targets in the current paradigm, we then combined the two forms of priority to investigate their interaction. An unequal reward distribution (where lower prevalence items are more rewarded; Experiment 3) was found to diminish the effect of prevalence, compared to an equal reward distribution (Experiment 4) as indicated by faster response times and fewer misses. These findings suggest that when combined with an unequal reward distribution, the low prevalence effect can be diminished.

Subsecond lung cancer detection within a heterogeneous background of normal and benign tissue using single-point Raman spectroscopy.

Significance: Lung cancer is the most frequently diagnosed cancer overall and the deadliest cancer in North America. Early diagnosis through current bronchoscopy techniques is limited by poor diagnostic yield and low specificity, especially for lesions located in peripheral pulmonary locations. Even with the emergence of robotic-assisted platforms, bronchoscopy diagnostic yields remain below 80%. Aim: The aim of this study was to determine whether in situ single-point fingerprint (800 to 1700 cm-1) Raman spectroscopy coupled with machine learning could detect lung cancer within an otherwise heterogenous background composed of normal tissue and tissue associated with benign conditions, including emphysema and bronchiolitis. Approach: A Raman spectroscopy probe was used to measure the spectral fingerprint of normal, benign, and cancer lung tissue in 10 patients. Each interrogated specimen was characterized by histology to determine cancer type, i.e., small cell carcinoma or non-small cell carcinoma (adenocarcinoma and squamous cell carcinoma). Biomolecular information was extracted from the fingerprint spectra to identify biomolecular features that can be used for cancer detection. Results: Supervised machine learning models were trained using leave-one-patient-out cross-validation, showing lung cancer could be detected with a sensitivity of 94% and a specificity of 80%. Conclusions: This proof of concept demonstrates fingerprint Raman spectroscopy is a promising tool for the detection of lung cancer during diagnostic procedures and can capture biomolecular changes associated with the presence of cancer among a complex heterogeneous background within less than 1 s.

Intraoperative neuromuscular monitoring site and residual paralysis.

BACKGROUND: Residual paralysis is common after general anesthesia involving administration of neuromuscular blocking drugs (NMBDs). Management of NMBDs and reversal is frequently guided by train-of-four (TOF) monitoring. We hypothesized that monitoring of eye muscles is associated with more frequent residual paralysis than monitoring at the adductor pollicis. METHODS: This prospective cohort study enrolled 180 patients scheduled for elective surgery with anticipated use of NMBDs. Collected variables included monitoring site, age, gender, weight, body mass index, American Society of Anesthesiologists physical status class, type and duration of surgery, type of NMBDs, last and total dose administered, TOF count at time of reversal, dose of neostigmine, and time interval between last dose of NMBDs to quantitative measurement. Upon postanesthesia care unit admission, we measured TOF ratios by acceleromyography at the adductor pollicis. Residual paralysis was defined as a TOF ratio less than 90%. Multivariable logistic regression was used to account for unbalances between the two groups and to adjust for covariates. RESULTS: 150 patients received NMBDs and were included in the analysis. Patients with intraoperative TOF monitoring of eye muscles had significantly greater incidence of residual paralysis than patients monitored at the adductor pollicis (P < 0.01). Residual paralysis was observed in 51/99 (52%) and 11/51 (22%) of patients, respectively. The crude odds ratio was 3.9 (95% CI: 1.8-8.4), and the adjusted odds ratio was 5.5 (95% CI: 2.1-14.5). CONCLUSIONS: Patients having qualitative TOF monitoring of eye muscles had a greater than 5-fold higher risk of postoperative residual paralysis than those monitored at the adductor pollicis.

Distractors slow information accumulation in simple feature search.

M. Carrasco and B. McElree (2001) presented a speed-accuracy trade-off experiment, investigating covert attention in visual search. One of the conclusions from Carrasco and McElree was that adding distractors to a single feature search does not decrease the speed with which information is accumulated about target identity. We present a reanalysis of the relevant data from Carrasco and McElree in which we demonstrate that their conclusion was incomplete and we demonstrate a processing speed advantage for single feature search displays with no distractors compared with displays with distractors. This finding is confirmed in a new speed-accuracy trade-off experiment presented here. Further, we demonstrate that increasing the display duration increases the processing speed of displays with distractors but not for displays without distractors. We discuss these results in relation to theories of visual attention and the debate between graded and fixed architecture accounts for attentional allocation.

Ambulatory surgery: is the liability risk lower?

PURPOSE OF REVIEW: To summarize the currently available data on malpractice claims related to ambulatory anesthesia and provide an insight into the emerging patterns of anesthesia liability in this practice setting. RECENT FINDINGS: At present, studies are mixed about how the continued growth of outpatient surgery will impact liability for anesthesiologists. Data derived from the ASA Closed Claims Project suggests that malpractice claims for major damaging events are less common in the outpatient settings than in inpatient settings. Correspondingly, the payment amounts for outpatient claims are significantly lower than those for inpatients. Nevertheless, nondisabling adverse events are common and involve respiratory, cardiac, equipment-related, and drug errors. In addition, the vast majority of injuries in outpatient claims was the result of substandard care and judged preventable by better monitoring. Although major incidents leading to malpractice suits are less, new liability exposure may be on the horizon, due to the changing landscape of ambulatory practice that permits care for sicker patients who require more complex surgeries. The areas of potential concern include postoperative discharge criteria, care for the obstructive sleep apnea patient, and the choice of anesthetic techniques such as neuraxial blocks and monitored anesthesia care. SUMMARY: With steady increase in outpatient surgery, anesthesiologists are confronted with new areas of liability. More data are needed to identify these risks and reduce exposure to malpractice claims.

Unequal allocation of overt and covert attention in Multiple Object Tracking.

In many real-life contexts, where objects are moving around, we are often required to allocate our attention unequally between targets or regions of different importance. However, typical multiple object tracking (MOT) tasks, primarily investigate equal attention allocation as the likelihood of each target being probed is the same. In two experiments, we investigated whether participants can allocate attention unequally across regions of the visual field, using a MOT task where two regions were probed with either a high and low or with equal priority. Experiment 1 showed that for high-priority regions, accuracy (for direction of heading judgments) improved, and participants had more frequent and longer fixations in that region compared with a low-priority region. Experiment 2 showed that eye movements were functional in that they slightly improved accuracy when participants could freely move their eyes compared with when they had to centrally fixate. Replicating Experiment 1, we found better tracking performance for high compared with low-priority regions, in both the free and fixed viewing conditions, but the benefit was greater for the free viewing condition. Although unequal attention allocation is possible without eye movements, eye movements seem to improve tracking ability, presumably by allowing participants to fixate more in the high-priority region and get a better, foveal view of the objects. These findings can help us better understand how observers in real-life settings (e.g., CCTV monitoring, driving) can use their limited attentional capacity to allocate their attention unequally in a demand-based manner across different tracking regions.

A calming hug: Design and validation of a tactile aid to ease anxiety.

Anxiety disorders affect approximately one third of people during their lifetimes and are the ninth leading cause of global disability. Current treatments focus on therapy and pharmacological interventions. However, therapy is costly and pharmacological interventions often have undesirable side-effects. Healthy people also regularly suffer periods of anxiety. Therefore, a non-pharmacological, intuitive, home intervention would be complementary to other treatments and beneficial for non-clinical groups. Existing at-home anxiety aids, such as guided meditations, typically employ visual and/or audio stimuli to guide the user into a calmer state. However, the tactile sense has the potential to be a more natural modality to target in an anxiety-calming device. The tactile domain is relatively under-explored, but we suggest that there are manifold physiological and affective qualities of touch that lend it to the task. In this study we demonstrate that haptic technology can offer an enjoyable, effective and widely accessible alternative for easing state anxiety. We describe a novel huggable haptic interface that pneumatically simulates slow breathing. We discuss the development of this interface through a focus group evaluating five prototypes with embedded behaviours ('breathing', 'purring', 'heartbeat' and 'illumination'). Ratings indicated that the 'breathing' prototype was most pleasant to interact with and participants described this prototype as 'calming' and 'soothing', reminding them of a person breathing. This prototype was developed into an ergonomic huggable cushion containing a pneumatic chamber powered by an external pump allowing the cushion to 'breathe'. A mixed-design experiment (n = 129) inducing anxiety through a group mathematics test found that the device was effective at reducing pre-test anxiety compared to a control (no intervention) condition and that this reduction in anxiety was indistinguishable from that of a guided meditation. Our findings highlight the efficacy of this interface, demonstrating that haptic technologies can be effective at easing anxiety. We suggest that the field should be explored in more depth to capture the nuances of different modalities in relation to specific situations and trait characteristics.

LGI1 is a Nogo receptor 1 ligand that antagonizes myelin-based growth inhibition.

Mutations in leucine-rich glioma inactivated (LGI1) are a genetic cause of autosomal dominant temporal lobe epilepsy with auditory features. LGI1 is a secreted protein that shares homology with members of the SLIT family, ligands that direct axonal repulsion and growth cone collapse, and we therefore considered the possibility that LGI1 may regulate neuronal process extension or growth cone collapse. Here we report that LGI1 does not affect growth directly but instead enhances neuronal growth on myelin-based inhibitory substrates and antagonizes myelin-induced growth cone collapse. We show that LGI1 mediates this effect by functioning as a specific Nogo receptor 1 (NgR1) ligand that antagonizes the action of myelin-based inhibitory cues. Finally, we demonstrate that NgR1 and ADAM22 physically associate to form a receptor complex in which NgR1 facilitates LGI1 binding to ADAM22.