Neural Spread Research Articles

Spectral Efficient Neural Network-Based M-ary Chirp Spread Spectrum Receivers for Underwater Acoustic Communication

Spectral Efficient Neural Network-Based M-ary Chirp Spread Spectrum Receivers for Underwater Acoustic Communication

Is the spread of excitation different between adults and children cochlear implants users?

While cochlea is adult size at birth, etiologies and bone density may differ between children and adults. Differences in neural response thresholds (tNRT) and the spread of excitation (SOE) width may impact the use of artificial intelligence algorithms in speech processor fitting. To identify whether neural response telemetry threshold and spread of excitation width are similar in adults and children. Retrospective cross-sectional study approved by the Ethical Board. Intraoperative tNRT and SOE recordings of consecutive cochlear implant surgeries in adults and children implanted with Cochlear devices (Cochlear™, Australia) were selected. SOE was recorded on electrode 11 (or adjacent, corresponding to the medial region of the cochlea) through the standard forward-masking technique in Custom Sound EP software, which provides SOE width in millimeters. Statistical comparison between adults and children was performed using the Mann-Whitney test (p ≤ 0.05). Of 1282 recordings of intraoperative evaluations, 414 measurements were selected from children and adults. Despite the tNRT being similar between adults and children, SOE width was significantly different, with lower values in children with perimodiolar arrays. Besides, it was observed that there is a difference in the electrode where the SOE function peak occurred, more frequently shifted to electrode 12 in adults implanted. In straight arrays, there was no difference in any of the parameters analyzed on electrode 11. Although eCAP thresholds are similar, SOE measurements differ between adults and children in perimodiolar electrodes.

A Precise and Intelligent Nanomedicine for Salivary Adenoid Cystic Carcinoma Treatment by Combining Antivascular Photodynamic Therapy and Neuroinhibitory Chemotherapy

AbstractSalivary adenoid cystic carcinoma (SACC) is one of the most common salivary gland malignancies. Current clinical therapies have limitations and cannot efficiently prevent the SACC development and metastasis. Hematogenous and neural spread are the two major routes of SACC metastasis. In this study, a precise and intelligent nanomedicine, RCDT, is designed to combine antivascular photodynamic therapy and neuroinhibitory chemotherapy against SACC. A tumor vessel‐targeted and reactive oxygen species (ROS)‐responsive photosensitizer (RC) is synthesized by linking cRGD to chlorin e6 (Ce6) via a bridge between the poly(ethylene glycol) and diselenide bonds. A neural‐targeted and pH‐responsive cytotoxic prodrug (DT) is synthesized by conjugating doxorubicin (DOX) with Tet1, a neural‐targeting peptide, via an acidic‐cleavable hydrazone bond. RC and DT are assembled to form RCDT via hydrophobic interactions, thereby shielding Tet1. Under the guidance of cRGD and the photodynamic action of Ce6, RCDT can precisely disrupt the tumor vasculature and simultaneously disintegrate to expose Tet1 by rupturing the diselenide bond. Guided by Tet1, disintegrated RCDT can be specifically internalized into neurons and release DOX to exert neuroinhibitory effects by cleaving the hydrazone bond. Using these stepwise dual‐targeting and dual‐responsive strategies, RCDT can efficiently suppress the growth and metastasis of SACC.

SpeedCAP: An Efficient Method for Estimating Neural Activation Patterns Using Electrically Evoked Compound Action-Potentials in Cochlear Implant Users.

Electrically evoked compound action-potentials (ECAPs) can be recorded using the electrodes in a cochlear implant (CI) and represent the synchronous responses of the electrically stimulated auditory nerve. ECAPs can be obtained using a forward-masking method that measures the neural response to a probe and masker electrode separately and in combination. The panoramic ECAP (PECAP) analyses measured ECAPs obtained using multiple combinations of masker and probe electrodes and uses a nonlinear optimization algorithm to estimate current spread from each electrode and neural health along the cochlea. However, the measurement of ECAPs from multiple combinations of electrodes is too time consuming for use in clinics. Here, we propose and evaluate SpeedCAP, a speedy method for obtaining the PECAP measurements that minimizes recording time by exploiting redundancies between multiple ECAP measures. In the first study, 11 users of Cochlear Ltd. CIs took part. ECAPs were recorded using the forward-masking artifact-cancelation technique at the most comfortable loudness level (MCL) for every combination of masker and probe electrodes for all active electrodes in the users' MAPs, as per the standard PECAP recording paradigm. The same current levels and recording parameters were then used to collect ECAPs in the same users with the SpeedCAP method. The ECAP amplitudes were then compared between the two conditions, as were the corresponding estimates of neural health and current spread calculated using the PECAP method previously described by Garcia et al. The second study measured SpeedCAP intraoperatively in 8 CI patients and with all maskers and probes presented at the same current level to assess feasibility. ECAPs for the subset of conditions where the masker and probe were presented on the same electrode were compared with those obtained using the slower approach leveraged by the standard clinical software. Data collection time was reduced from ≈45 to ≈8 minutes. There were no significant differences between normalized root mean squared error (RMSE) repeatability metrics for post-operative PECAP and SpeedCAP data, nor for the RMSEs calculated between PECAP and SpeedCAP data. The comparison achieved 80% power to detect effect sizes down to 8.2% RMSE. When between-participant differences were removed, both the neural-health (r = 0.73) and current-spread (r = 0.65) estimates were significantly correlated (p < 0.0001, df = 218) between SpeedCAP and PECAP conditions across all electrodes, and showed RMSE errors of 12.7 ± 4.7% and 16.8 ± 8.8%, respectively (with the ± margins representing 95% confidence intervals). Valid ECAPs were obtained in all patients in the second study, demonstrating intraoperative feasibility of SpeedCAP. No significant differences in RMSEs were detectable between post- and intra-operative ECAP measurements, with the comparison achieving 80% power to detect effect sizes down to 13.3% RMSE. The improved efficiency of SpeedCAP provides time savings facilitating multi-electrode ECAP recordings in routine clinical practice. SpeedCAP data collection is sufficiently quick to record intraoperatively, and adds no more than 8.2% error to the ECAP amplitudes. Such measurements could thereafter be submitted to models such as PECAP to provide patient-specific patterns of neural activation to inform programming of clinical MAPs and identify causes of poor performance at the electrode-nerve interface of CI users. The speed and accuracy of these measurements also opens up a wide range of additional research questions to be addressed.

Neural Reinstatement Tracks Spread of Attention between Object Features in Working Memory.

Attention can be allocated in working memory (WM) to select and privilege relevant content. It is unclear whether attention selects individual features or whole objects in WM. Here, we used behavioral measures, eye-tracking, and EEG to test the hypothesis that attention spreads between an object's features in WM. Twenty-six participants completed a WM task that asked them to recall the angle of one of two oriented, colored bars after a delay while EEG and eye-tracking data were collected. During the delay, an orthogonal "incidental task" cued the color of one item for a match/mismatch judgment. On congruent trials (50%), the cued item was probed for subsequent orientation recall; on incongruent trials (50%), the other memory item was probed. As predicted, selecting the color of an object in WM brought other features of the cued object into an attended state as revealed by EEG decoding, oscillatory α-power, gaze bias, and improved orientation recall performance. Together, the results show that attentional selection spreads between an object's features in WM, consistent with object-based attentional selection. Analyses of neural processing at recall revealed that the selected object was automatically compared with the probe, whether it was the target for recall or not. This provides a potential mechanism for the observed benefits of nonpredictive cueing in WM, where a selected item is prioritized for subsequent decision-making.

Forecasting the number of intensive care beds occupied by COVID-19 patients through the use of Recurrent Neural Networks, mobility habits and epidemic spread data

Since 2019, the diffusion of COVID-19 all over the world has caused more than five millions deaths and the biggest economic disaster of last decades. A better prediction of the Intensive Care beds (ICUs) burden due to COVID-19 may optimize the public spending and beds occupancy, in the future. This can enable Public Institutions to apply control policies and a better regularization of regional mobility. In this work, we address the challenge of producing fully automated covid spread forecasting via Deep Learning algorithms. We developed our system by means of LSTM and Bidirectional LSTM models and new model regularization achievements such as “Inference Dropout”. Results highlight “state-of-art” accuracy in terms of ICUs prediction. We definitely believe that this breakthrough can become a valuable tool for policy makers in order to face with the problem of COVID-19 effects in the near future.

Single node deep learning frameworks: Comparative study and CPU/GPU performance analysis

AbstractDeep learning presents an efficient set of methods that allow learning from massive volumes of data using complex deep neural networks. To facilitate the design and implementation of algorithms, deep learning frameworks provide a high‐level programming interface. Based on these frameworks, new models, and applications are able to make better and better predictions. One type of deep learning application is the Internet of Things that can gather a continuous flow of data, which causes an explosion of the amount of data. Therefore, to handle this data management issue, computation technologies can offer new perspectives to analyze more data with more complex models. In this context, a cluster of computers can operate to quickly deliver a model or to enable the design of a complex neural network spread among computers. An alternative is to distribute a deep learning task with HPC cloud computing resources and to scale cluster in order to quickly and efficiently train a neural network. As a first step to design an infrastructure aware framework which is able to scale the computing nodes, this work aims to review and analyze the state‐of‐the‐art frameworks by collecting device utilization data during the training task. We gather information about the CPU, RAM and the GPU utilization on deep learning algorithms with and without multi‐threading. The behavior of each framework is discussed and analyzed in order to shed light on the strengths and weaknesses of the different deep learning frameworks.

Case report of restless anal syndrome as restless legs syndrome variant after COVID-19

BackgroundCoronavirus disease 2019 (COVID-19) has a broad spectrum from respiratory and nasopharyngeal symptoms, cerebrovascular diseases, impaired consciousness, and skeletal muscle injury. Emerging evidence has indicated the neural spread of this novel coronavirus. Restless legs syndrome (RLS) is a common neurological, sensorimotor disorder, but highly under diagnosis disorder. Restless anal syndrome as restless legs syndrome variant associated with COVID-19 has been previously not published. We report a case presenting with restless anal syndrome following COVID-19.Case presentationAlthough a 77-year-old male with COVID-19 improved to normal respiratory function 21 days after admission and treatment of favipiravir 200 mg per day for 14 days and dexamethasone 6.6 mg per day for 5 days, the insomnia and anxiety symptoms remained. Several weeks after discharge, he gradually began to experience restless, deep anal discomfort, approximately 10 cm from the perineal region. The following features were observed in the anal region; urge to move is essential, with worsening with rest, improvement with exercise, and worsening at evening. Colonoscopy revealed internal haemorrhoids without other rectal lesions. Neurological findings including deep tendon reflex, perineum loss of sensory and spinal cord injury, revealed no abnormalities. Diabetes militias, kidney dysfunction and iron deficiency status were not confirmed. Family history of RLS and periodic limb movements were not observed. Clonazepam at 1.5 mg per day resulted in the alleviation restless anal discomfort.ConclusionsWe reported a case presenting with restless anal syndrome following affection of COVID-19 as restless legs syndrome variant. This case fulfilled 4 essential features of RLS, urge to move, worsening with rest, improvement with exercise, and worsening at evening. To date, no case of restless anal syndrome associated with COVID-19 has been previously published. This case report may reflect the associative impacts of COVID-19 on the neuropsychiatric state. The long-term outcomes of neuropsychiatric conditions should continue to be monitored.

A novel mechanism for the formation and propagation of neural tumors and lesions through neural highways.

By recognizing anatomic and radiologic patterns of rare and often misdiagnosed peripheral nerve tumors/lesions, we have defined mechanisms for the propagation of neural diseases. The novel concept of the nervous system serving as a complex system of "highways" driving the neural and perineural spread of these lesions is described in three examples: Intraneural dissection of joint fluid in intraneural ganglion cysts, perineural spread of cancer cells, and dissemination of unknown concentrations of neurotrophic/inhibitory factors for growth in hamartomas/choristomas of nerve. Further mapping of these pathways to identify the natural history of diseases, the spectrum of disease evolution, the role of genetic mutations, and how these neural pathways interface with the lymphatic, vascular, and cerebrospinal systems may lead to advances in targeted treatments.

Evaluation of the returning traveler with fever and neurologic symptoms.

Exposure to infectious disease increases in tandem with international travel rates. Globally, up to 70% of travelers to developing countries report health problems while traveling, most being self-limiting. Few travelers are ill enough to seek medical care while abroad or upon returning home. Although fever is one of the more common symptoms in these travelers, little attention has been paid to those who return with fever and neurologic symptoms. This article describes conditions that can present with fever and neurologic changes and how to evaluate patients in a timely manner to prevent progression of neural dysfunction and spread of disease in local communities.

Neuropsychiatric manifestations of COVID-19 and possible pathogenic mechanisms: Insights from other coronaviruses.

Coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has emerged as a global public health threat. Though the fear, anxiety, and stress related to COVID-19 have been studied in depth, the direct effects of SARS-CoV-2 on the central nervous system (CNS) remain elusive. Research related to the earlier coronavirus (CoV) outbreaks (like Severe Acute Respiratory Syndrome, SARS and Middle East Respiratory Syndrome, MERS) shows the neurotropic nature of CoV and the plethora of neuropsychiatric effects that it can cause. Though the current health priorities in managing COVID-19 remain restricted to containment and targeting pulmonary symptoms, the potential acute and long-term neuropsychiatric sequelae of the infection can increase morbidity and worsen the quality of life. Emerging evidence shows neural spread of the novel coronavirus. Delirium, encephalopathy, olfactory disturbances, acute behavioral changes, headache and cerebrovascular accidents are its common neuropsychiatric complications. These are directly related to increase in peripheral immunological markers, severity of infection and case fatality rate. This narrative review synthesizes available evidence related to the neuropsychiatric manifestations of COVID-19. Also, as SARS-CoV-2 shares structural and functional similarities with its earlier congeners, this article proposes possible long-term neuropsychological sequelae and pathogenic mechanisms for the same, based on research in the other coronavirus outbreaks.

Contrast Medium Volume Needed to Reach Anterior Epidural Space via the Kambin Triangle or Subpedicular Approach for Transforaminal Epidural Injection

Transforaminal (TF) lumbar injection is a commonly used minimally invasive intervention for management of chronic low back pain. TF injection can be performed using various approaches to inject the drug to the anterior epidural space (AES). To identify the volumes of contrast medium needed to reach the AES and other landmarks in the Kambin triangle (KB) and subpedicular (SP) approach of TF injection in patients with lumbosacral radicular pain. Randomized controlled trial. Pain clinic and operating room of a tertiary care hospital. Seventy-five eligible patients were randomized to receive TF epidural injection either by SP (SP group; n = 38) or the KB (KB group; n = 37) approach under fluoroscopic guidance. After confirming the appropriate needle position, contrast medium was injected at 0.5 mL increments up to 2 mL under intermittent fluoroscopy. Contrast medium volumes needed to reach specific landmarks, that is, AES, medial to superior pedicle, medial to inferior pedicle, medial aspect of both the superior, and neural spread, were recorded. Following this, 4 mL of the drug (0.5% lidocaine 1 mL + methylprednisolone 80 mg + 1 mL normal saline solution) was injected. Patients were evaluated for Visual Analog Scale (VAS) and modified Oswestry Disability Questionnaire (MODQ) scores after epidural injections at 2 weeks, 1 month, and 2 months. Average volume of contrast medium needed to reach AES was 1.10 ± 0.46 mL in the KB approach and 1.10 ± 0.38 mL in the SP approach. Contrast medium volume needed to reach other landmarks showed comparable results in both groups. AES was seen in 27.02% (10/37) patients in the KB group and 23.6% (9/38) patients in the SP group with 0.5 mL of contrast medium. This increased to 56.76% (21/37) and 77.7% (28/38) with 1 mL of contrast medium (P = 0.03, chi-square test). No anterior spread was seen even after 2 mL of contrast medium in 4 patients in the KB group and 2 patients in the SP group. Neural spread was seen in 100% of patients in the KB group after 0.5 mL of contrast medium, but in 34 (89.4%) patients in the SP group (P = 0.03, chi-square test). We did not note any contralateral spread. Short-term effectiveness in pain relief in terms of VAS for back pain and functional improvement in terms of MODQ score over time showed similar results in both groups. Intravascular needle puncture and needle paresthesia was comparable in both groups. Small follow-up duration is one the limitations of this study. Future studies will be needed to assess any long-term differences in outcome between approach methods. Also, use of intermittent fluoroscopy might have limited detection of intravascular injections of the contrast medium in comparison to the continuous fluoroscopy. To conclude, our study revealed that average volume of contrast medium needed to reach AES and other landmarks were comparable with both approaches of TF injection. Transforaminal injection, subpedicular approach, Kambin triangle approach, contrast medium spread, anterior epidural spread.

Model of corporate bond spread based on improved neural network

The reasons for credit spreads can be divided into enterprise-specific non-systematic risks and widespread macroeconomic systemic risks. The previous traditional research mainly focused on the perspective of unsystematic risk. However, at present, more and more scholars are beginning to focus on systemic risks. Based on the neural network algorithm, this paper constructs an improved neural network-based corporate bond spread model to explore the impact of macro systemic risks on credit spreads. Based on the multi-factor no-arbitrage model, the linear relationship between the credit spread and the risk premium of each factor is obtained. At the same time, based on previous research results and observations of the current market reality, this paper identifies five important macroeconomic factors: actual economic output factors, inflation factors, stock market volatility factors, stock market return factors and inter-bank funding factors. The research results show that the model constructed in this paper has excellent performance.

Creating virtual electrodes with 2D current steering

Objective. Current steering techniques have shown promise in retinal prostheses as a way to increase the number of distinct percepts elicitable without increasing the number of implanted electrodes. Previously, it has been shown that ‘virtual’ electrodes can be created between simultaneously stimulated electrode pairs, producing unique cortical response patterns. This study investigated whether virtual electrodes could be created using 2D current steering, and whether these virtual electrodes can produce cortical responses with predictable spatial characteristics. Approach. Normally-sighted eyes of seven adult anaesthetised cats were implanted with a 42-channel electrode array in the suprachoroidal space and multi-unit neural activity was recorded from the visual cortex. Stimuli were delivered to individual physical electrodes, or electrodes grouped into triangular, rectangular, and hexagonal arrangements. Varying proportions of charge were applied to each electrode in a group to ‘steer’ current and create virtual electrodes. The centroids of cortical responses to stimulation of virtual electrodes were compared to those evoked by stimulation of single physical electrodes. Main results. Responses to stimulation of groups of up to six electrodes with equal ratios of charge on each electrode resulted in cortical activation patterns that were similar to those elicited by the central physical electrode (centroids: RM ANOVA on ranks, p > 0.05; neural spread: one-way ANOVA on Ranks, p > 0.05). We were also able to steer the centroid of activation towards the direction of any of the electrodes of the group by applying a greater charge to that electrode, but the movement in the centroid was not found to be significant. Significance. The results suggest that current steering is possible in two dimensions between up to at least six electrodes, indicating it may be possible to increase the number of percepts in patients without increasing the number of physical electrodes. Being able to reproduce spatial characteristics of responses to individual physical electrodes suggests that this technique could also be used to compensate for faulty electrodes.

Upregulation of RET induces perineurial invasion of pancreatic adenocarcinoma.

Tumor spread along nerves, a phenomenon known as perineurial invasion, is common in various cancers including pancreatic ductal adenocarcinoma (PDAC). Neural invasion is associated with poor outcome, yet its mechanism remains unclear. Using the transgenic Pdx-1-Cre/KrasG12D /p53R172H (KPC) mouse model, we investigated the mechanism of neural invasion in PDAC. To detect tissue-specific factors that influence neural invasion by cancer cells, we characterized the perineurial microenvironment using a series of bone marrow transplantation (BMT) experiments in transgenic mice expressing single mutations in the Cx3cr1, GDNF and CCR2 genes. Immunolabeling of tumors in KPC mice of different ages and analysis of human cancer specimens revealed that RET expression is upregulated during PDAC tumorigenesis. BMT experiments revealed that BM-derived macrophages expressing the RET ligand GDNF are highly abundant around nerves invaded by cancer. Inhibition of perineurial macrophage recruitment, using the CSF-1R antagonist GW2580 or BMT from CCR2-deficient donors, reduced perineurial invasion. Deletion of GDNF expression by perineurial macrophages, or inhibition of RET with shRNA or a small-molecule inhibitor, reduced perineurial invasion in KPC mice with PDAC. Taken together, our findings show that RET is upregulated during pancreas tumorigenesis and its activation induces cancer perineurial invasion. Trafficking of BM-derived macrophages to the perineurial microenvironment and secretion of GDNF are essential for pancreatic cancer neural spread.

Laminin-5 and insulin-like growth factor-II mRNA binding protein-3 (IMP3) expression in preoperative biopsy specimens from oral cancer patients: Their role in neural spread risk and survival stratification.

Perineural invasion (PNI) hinders the ability to establish local control of oral squamous cell carcinoma (OSCC). To date, PNI can be evaluated only in surgical specimens and not in preoperative biopsy material, rendering timely therapeutic planning impossible. Insulin-like growth factor-II mRNA binding protein-3 (IMP3) expression appears to be of diagnostic and prognostic utility for many solid tumours, and laminin-5 expression in surgical specimens has been identified as a valid predictor of neural spread of head-and-neck neoplasms. The ability to use preoperative biopsy material to identify patients exhibiting PNI is fundamental for good management of OSCC. We examined a series of 64 consecutive patients treated (primarily via surgery) for OSCC between 2009 and 2014 at the Maxillofacial Surgery Unit, University of Bologna. We evaluated IMP3 and laminin-5 expression in preoperative biopsy material using immunohistochemistry and quantitative reverse transcription polymerase chain reaction. We sought to correlate expression of IMP3 and laminin-5 with PNI evident in surgical specimens. Expression of IMP3 and laminin-5 in preoperative biopsy material appeared to be predictive of PNI in patients with OSCC (P<0.001). Additionally, the results of multivariate analyses showed that IMP3 status was an independent predictor of death of patients with OSCC (P=0.001). The present study demonstrates that IMP3 and laminin-5 expression in preoperative biopsy material correlate well with PNI status and may allow accurate preoperative risk stratification of patients with OSCC.

Exploring the Source of Neural Responses of Different Latencies Obtained from Different Recording Electrodes in Cochlear Implant Users

In this study we measured the electrically evoked compound action potential (ECAP) from different recording electrodes in the cochlea. Under the assumption that different response latencies may be the result of differences in the neural population contributing to the response, we assessed the relationship between neural response latency and spread of excitation. First, we evaluated changes in N1 latency when the recording electrode site was varied. Second, we recorded channel interaction functions using a forward masking technique but with recording electrodes at different intracochlear locations. For most individuals, N1 latency was similar across recording electrodes. However, reduced N1 latencies were observed in 21% of cochlear implant users when ECAPs were recorded using a remote recording electrode. We hypothesized that if recordings from different electrodes represented contributions from different populations of neurons, then one might expect that channel interaction functions would be different. However, we did not observe consistent differences in channel interaction functions (neither peak location nor breadth of the functions), and further, any variation in channel interaction functions was not correlated with ECAP latency. These results suggest that ECAPs from different recording electrodes with different latencies originate from similar neural populations.

Perineural Spread in Noncutaneous Head and Neck Cancer: New Insights into an Old Problem.

Head and neck malignancies have the propensity to invade nerves. Perineural tumor invasion is common, with some series reporting rates of 30 to 100%. Squamous cell carcinoma and adenoid cystic carcinoma are the most commonly involved tumors. The most commonly involved nerves are the trigeminal (cranial nerve [CN] V) and facial (CN VII) and their branches. Neural spread away from a tumor is encountered less often and usually causes specific symptoms such as pain, muscle weakness, and atrophy, depending on the involved nerves. While clinical symptoms and physical examination may suggest the presence of neural invasion, specific imaging modalities such as fat-suppressed T1-weighted magnetic resonance images, should be utilized to identify perineural tumor spread in its early phases. Perineural tumor spread should be considered and addressed in the treatment planning of patients with head and neck or skull base cancers as it can influence the extent of surgery, and the dosage and fields of radiation therapy. In the current review, we discuss the clinical course of perineural tumor spread and its therapeutic implications.

Neural coding of passive lump detection in compliant artificial tissue.

Here, we investigate the neural mechanisms of detecting lumps embedded in artificial compliant tissues. We performed a combined psychophysical study of humans performing a passive lump detection task with a neurophysiological study in nonhuman primates (Macaca mulatta) where we recorded the responses of peripheral mechanoreceptive afferents to lumps embedded at various depths in intermediates (rubbers) of varying compliance. The psychophysical results reveal that human lump detection is greatly degraded by both lump depth and decreased compliance of the intermediate. The neurophysiology results reveal that only the slowly adapting type 1 (SA1) afferents provide a clear spatial representation of lumps at all depths and that the representation is affected by lump size, depth, and compliance of the intermediate. The rapidly adapting afferents are considerably less sensitive to the lump. We defined eight neural response measures that we hypothesized could explain the psychophysical behavior, including peak firing rate, spatial spread of neural activity, and additional parameters derived from these measures. We find that peak firing rate encodes the depth of the lump, and the neural spatial spread of the SA1 response encodes for lump size but not lump shape. We also find that the perception of lump size may be affected by the compliance of the intermediate. The results show that lump detection is based on a spatial population code of the SA1 afferents, which is distorted by the depth of the lump and compliance of the tissue.

Glycosylphosphatidylinositol Anchoring Directs the Assembly of Sup35NM Protein into Non-fibrillar, Membrane-bound Aggregates

In prion-infected hosts, PrPSc usually accumulates as non-fibrillar, membrane-bound aggregates. Glycosylphosphatidylinositol (GPI) anchor-directed membrane association appears to be an important factor controlling the biophysical properties of PrPSc aggregates. To determine whether GPI anchoring can similarly modulate the assembly of other amyloid-forming proteins, neuronal cell lines were generated that expressed a GPI-anchored form of a model amyloidogenic protein, the NM domain of the yeast prion protein Sup35 (Sup35(GPI)). We recently reported that GPI anchoring facilitated the induction of Sup35(GPI) prions in this system. Here, we report the ultrastructural characterization of self-propagating Sup35(GPI) aggregates of either spontaneous or induced origin. Like membrane-bound PrPSc, Sup35(GPI) aggregates resisted release from cells treated with phosphatidylinositol-specific phospholipase C. Sup35(GPI) aggregates of spontaneous origin were detergent-insoluble, protease-resistant, and self-propagating, in a manner similar to that reported for recombinant Sup35NM amyloid fibrils and induced Sup35(GPI) aggregates. However, GPI-anchored Sup35 aggregates were not stained with amyloid-binding dyes, such as Thioflavin T. This was consistent with ultrastructural analyses, which showed that the aggregates corresponded to dense cell surface accumulations of membrane vesicle-like structures and were not fibrillar. Together, these results showed that GPI anchoring directs the assembly of Sup35NM into non-fibrillar, membrane-bound aggregates that resemble PrPSc, raising the possibility that GPI anchor-dependent modulation of protein aggregation might occur with other amyloidogenic proteins. This may contribute to differences in pathogenesis and pathology between prion diseases, which uniquely involve aggregation of a GPI-anchored protein, versus other protein misfolding diseases.