Changes In Response Properties Research Articles

Extracting Material Properties from Relaxation Experiments

Redox active oxides, with mixed ionic and electronic conductivity (MIEC), are critical components in a wide range of energy technologies, serving as electrodes in fuel cells and batteries, and as reactive substrates in solar-driven thermochemical reactors. Accurate knowledge of the surface reaction rate constant, k S, is essential for both optimal design of components using existing materials and rational discovery of new materials with enhanced catalytic activity. A variety of relaxation methods have been used extensively to determine k S. Such approaches rely on the change in some measurable property, most commonly conductivity, upon application of a step change in gas-phase oxygen partial pressure. Under the appropriate experimental conditions, the rate at which the property changes in response to the change in gas-phase oxygen chemical potential provides a direct measure of the material kinetic parameters. Here, we present several considerations relevant to accurate extraction of these parameters, with particular focus on identifying relaxation occurring due to thermodynamic rather than material kinetic reasons. Furthermore, while the electrical conductivity relaxation (ECR) method is one of the most widely employed relaxation techniques because of the ease with which high precision conductivity measurements can be made using samples of almost arbitrary dimensions, ECR is impractical for the evaluation of a material in which the change in conductivity in response to change in oxygen partial pressure is extremely small. For such materials mass relaxation emerges as a viable alternative measurement approach. To this end, we describe a high temperature mass relaxation apparatus based on a gallium phosphate piezocrystal microbalance that enables measurements at temperatures as high 700 °C.

Relations among Auditory Brainstem and Middle Latency Response Measures, Categorical Loudness Judgments, and Their Associated Physical Intensities.

This study characterizes changes in response properties of toneburst-evoked auditory brainstem responses (ABRs) and/or middle latency responses (MLRs) as a function of perceived loudness and physical intensity of these stimuli and delineates the range of levels corresponding to categorical loudness judgments for these stimuli. ABRs/MLRs were recorded simultaneously to 500- and 2,000-Hz tonebursts in 10 normal-hearing adults at levels corresponding to each listener's loudness judgments for four categories on Contour Test of Loudness. Group mean ABR wave V and MLR wave Pa latency values increased significantly as loudness judgments decreased. Group mean amplitude values for ABR wave V-V' and MLR wave Na-Pa increased as the listeners' categorical judgments increased. Listeners assigned a broad range (30 to 40 dB) of stimulus intensities when judging loudness of these stimuli within a specific loudness category. This was true for all four loudness categories and both frequencies. Thus, it appears that tone-evoked ABR/MLR response measures reflect, in part, the listener's perception of loudness. Response latencies are a more sensitive indicator of listener's loudness percept than corresponding response amplitudes. An appreciable range of signal levels was judged to be categorically equivalent across listeners. Thus, limiting how loudness judgments can be applied to prescriptive hearing aid fittings in individuals who cannot provide accurate loudness judgments.

Changes in response properties of periodontal mechanoreceptors during tooth movement in rats.

Using an in vitro model, we investigated the chronological effects of orthodontic force on the response properties of periodontal mechanoreceptors (PMRs) in the rat mandibular first molar (M1). Experimental tooth movement was obtained by attaching a super-elastic titanium-nickel (Ti-Ni) alloy closed coil spring from the mandibular incisors to the right M1. On 1, 2, 3, 4, 7 and 14 days after the appliances were set, three right mandibular molars were extracted and direct stimulation with von Frey hairs was applied to the PMRs remaining in the tooth sockets of right M1. Single unit discharges were recorded from the inferior alveolar nerve. Following results were obtained; (1) in the 1-, 2- and 3-day groups, the mechanical thresholds were significantly lower than those in the control group. In the 4-day group, the mechanical threshold was significantly higher than that of the 3-day group. (2) In the 3-, 4-, 7- and 14-day groups, the conduction velocities of A(beta) units were lower than those in the control group. These results imply that orthodontic force applied to M1 induced functional changes in the PMRs within a few days, suggesting that the PMR seems to respond to orthodontic force at early stage of tooth movement.

Exploring the basic science of prolapse meshes.

Polypropylene mesh has been widely used in the surgical repair of pelvic organ prolapse. However, low but persistent rates of complications related to mesh, most commonly mesh exposure and pain, have hampered its use. Complications are higher following transvaginal implantation prompting the Food and Drug Administration to release two public health notifications warning of complications associated with transvaginal mesh use (PHN 2008 and 2011) and to upclassify transvaginal prolapse meshes from Class II to Class III devices. Although there have been numerous studies to determine the incidence and management of mesh complications as well as impact on quality of life, few studies have focused on mechanisms. In this review, we summarize the current understanding of how mesh textile properties and mechanical behavior impact vaginal structure and function, as well as the local immune response. We also discuss how mesh properties change in response to loading. We highlight a few areas of current and future research to emphasize collaborative strategies that incorporate basic science research to improve patient outcomes.

Pattern Adaptation and Normalization Reweighting.

Adaptation to an oriented stimulus changes both the gain and preferred orientation of neural responses in V1. Neurons tuned near the adapted orientation are suppressed, and their preferred orientations shift away from the adapter. We propose a model in which weights of divisive normalization are dynamically adjusted to homeostatically maintain response products between pairs of neurons. We demonstrate that this adjustment can be performed by a very simple learning rule. Simulations of this model closely match existing data from visual adaptation experiments. We consider several alternative models, including variants based on homeostatic maintenance of response correlations or covariance, as well as feedforward gain-control models with multiple layers, and we demonstrate that homeostatic maintenance of response products provides the best account of the physiological data. Adaptation is a phenomenon throughout the nervous system in which neural tuning properties change in response to changes in environmental statistics. We developed a model of adaptation that combines normalization (in which a neuron's gain is reduced by the summed responses of its neighbors) and Hebbian learning (in which synaptic strength, in this case divisive normalization, is increased by correlated firing). The model is shown to account for several properties of adaptation in primary visual cortex in response to changes in the statistics of contour orientation.

Homeostatic Activity-Dependent Tuning of Recurrent Networks for Robust Propagation of Activity.

How are neural circuits organized and tuned to maintain stable function and produce robust output? This task is especially difficult during development, when circuit properties change in response to variable environments and internal states. Many developing circuits exhibit spontaneous activity, but its role in the synaptic organization of motor networks that produce rhythmic output is unknown. We studied a model motor network, that when appropriately tuned, generates propagating activity as during crawling inDrosophilalarvae. Based on experimental evidence of activity-dependent tuning of connectivity, we examined plausible mechanisms by which appropriate connectivity emerges. Our results suggest that activity-dependent homeostatic mechanisms are better suited than Hebbian mechanisms for organizing motor network connectivity, and highlight an important difference from sensory areas.

Acoustic Velocity and Attenuation in Magnetorhelogical fluids based on an effective density fluid model

Magnetrohelogical fluids (MRFs) represent a class of smart materials whose rheological properties change in response to the magnetic field, which resulting in the drastic change of the acoustic impedance. This paper presents an acoustic propagation model that approximates a fluid-saturated porous medium as a fluid with a bulk modulus and effective density (EDFM) to study the acoustic propagation in the MRF materials under magnetic field. The effective density fluid model derived from the Biot’s theory. Some minor changes to the theory had to be applied, modeling both fluid-like and solid-like state of the MRF material. The attenuation and velocity variation of the MRF are numerical calculated. The calculated results show that for the MRF material the attenuation and velocity predicted with this effective density fluid model are close agreement with the previous predictions by Biot’s theory. We demonstrate that for the MRF material acoustic prediction the effective density fluid model is an accurate alternative to full Biot’s theory and is much simpler to implement.

Responsive Polymer Photonics.

Responsive Polymer Photonics.

0247: Changes in blood pressure and arterial mechanical properties after antiangiogenic drugs: association with cancer progression and mortality

Hypertension is a frequent side effect of antiangiogenic drugs (AAD). Targeting VEGF pathway may also affect large and small artery properties, along with or independently of blood pressure changes. We hypothesized that large and small artery property changes in response to AAD reflect their effect on the microcirculation at the site of the tumor, and thus may be related to cancer progression and mortality. We included 60 patients [age 58 (15) years, mean SBP 127(21) mmHg] in whom treatment with AAD was indicated for various metastatic solid tumors. Noninvasive arterial investigation was performed before AAD (V0), 1 week later (V1) and then every two weeks for two months (V1 to V4): carotid-femoral pulse wave velocity (cfPWV), central SBP and augmentation index (cAIx) by applanation tonometry (SphygmoCor®), and carotid stiffness (CStiff) and internal diameter (CiD) by high resolution echotracking (Artlab®). Cancer progression and mortality were assessed at 6 months. 28(47%) patients developed hypertension during follow-up. bSBP significantly increased during follow-up (V0-V1: +9.3± 15.2mmHg, P<0.001; V0-V4: +6.0±17.8mmHg, P=0.03), as well as PWV, CStiff, and CiD. Baseline cAIx predicted cancer progression (RR=0.73 per 10%) and mortality (RR=0.73 per 10%, P<0.001) while SBP did not. The V0-V1 increase in CStiff predicted cancer progression (RR=1.37 per 1 m/s, P=0.02), independently of age and MBP. In conclusion, increased AIx and arterial stiffness, but not brachial or central SBP, were related with the effects of AAD on cancer progression and mortality.

Elevated Correlations in Neuronal Ensembles of Mouse Auditory Cortex Following Parturition

The auditory cortex is malleable by experience. Previous studies of auditory plasticity have described experience-dependent changes in response profiles of single neurons or changes in global tonotopic organization. However, experience-dependent changes in the dynamics of local neural populations have remained unexplored. In this study, we examined the influence of a dramatic yet natural experience in the life of female mice, giving birth and becoming a mother on single neurons and neuronal ensembles in the primary auditory cortex (A1). Using in vivo two-photon calcium imaging and electrophysiological recordings from layer 2/3 in A1 of mothers and age-matched virgin mice, we monitored changes in the responses to a set of artificial and natural sounds. Population dynamics underwent large changes as measured by pairwise and higher-order correlations, with noise correlations increasing as much as twofold in lactating mothers. Concomitantly, changes in response properties of single neurons were modest and selective. Remarkably, despite the large changes in correlations, information about stimulus identity remained essentially the same in the two groups. Our results demonstrate changes in the correlation structure of neuronal activity as a result of a natural life event.

Advances and new directions in gas-sensing devices

Gas sensors are employed in many applications including detection of toxic and combustible gases, monitoring emissions from vehicles and other combustion processes, breath analysis for medical diagnosis, and quality control in the chemicals, food and cosmetics industries. Many of these applications employ miniaturized solid-state devices, whose electrical properties change in response to the introduction of chemical analytes into the surrounding gas phase. Key challenges remain as to how to optimize sensor sensitivity, selectivity, speed of response and stability. The principles of operation of such devices vary and a brief review of operating principles based on potentiometric/amperometric, chemisorptive, redox, field effect and nanobalance approaches is presented. Due to simplicity of design and ability to stand up to harsh environments, metal oxide-based chemoresistive devices are commonly selected for these purposes and are therefore the focus of this review. While many studies have been published on the operation of such devices, an understanding of the underlying physicochemical principles behind their operation have trailed behind their technological development. In this article, a detailed review is provided which serves to update progress made along these lines. The introduction of nanodimensioned materials has had a particularly striking impact on the field over the past decade. Advances in materials processing has enabled the fabrication of tailored structures and morphologies offering, at times, orders of magnitude improvements in sensitivity, while high-resolution analytical methods have enabled a much improved examination of the structure and chemistry of these materials. Selected examples, illustrating the type of nanostructured devices being fabricated and tested, are discussed. This review concludes by highlighting trends suggesting directions for future progress.

Changes in response properties of rostral ventromedial medulla neurons during prolonged inflammation: Modulation by neurokinin-1 receptors

Activation of neurokinin-1 (NK-1) receptors in the rostral ventromedial medulla (RVM) can facilitate pain transmission in conditions such as inflammation, and thereby contribute to hyperalgesia. Since blockade of NK-1 receptors in the RVM can attenuate hyperalgesia produced by prolonged inflammation, we examined the role of NK-1 receptors in changes of response properties of RVM neurons following four days of hind paw inflammation with complete Freund’s adjuvant. Recordings were made from functionally identified ON, OFF and NEUTRAL cells in the RVM. Spontaneous activity and responses evoked by a series of mechanical (10, 15, 26, 60, 100, and 180g) and heat (34–50°C) stimuli applied to the inflamed and non-inflamed hind paws were determined before and at 15 and 60min after injection of the NK-1-antagonist L-733,060 or vehicle into the RVM. Prolonged inflammation did not alter the proportions of functionally-identified ON, OFF and NEUTRAL cells. ON cells exhibited enhanced responses to mechanical (60–100g) and heat (48–50°C) stimuli applied to the inflamed paw, which were attenuated by L-733,060 but not by vehicle. Inhibitory responses of OFF cells evoked by mechanical stimuli applied to the inflamed paw were also inhibited by L-733,060, but responses evoked by stimulation of the contralateral paw were increased. Heat-evoked responses of OFF cells were not altered by L-733,060. Also, neither L-733,060 nor vehicle altered spontaneous ongoing discharge rate of RVM neurons. These data indicate that NK-1 receptors modulate excitability of ON cells which contribute to both mechanical and heat hyperalgesia, whereas NK-1 modulation of OFF cells contributes to mechanical hyperalgesia during prolonged inflammation.

Processing of Facial Emotion in the Human Fusiform Gyrus

Electrophysiological and fMRI-based investigations of the ventral temporal cortex of primates provide strong support for regional specialization for the processing of faces. These responses are most frequently found in or near the fusiform gyrus, but there is substantial variability in their anatomical location and response properties. An outstanding question is the extent to which ventral temporal cortex participates in processing dynamic, expressive aspects of faces, a function usually attributed to regions near the superior temporal cortex. Here, we investigated these issues through intracranial recordings from eight human surgical patients. We compared several different aspects of face processing (static and dynamic faces; happy, neutral, and fearful expressions) with power in the high-gamma band (70-150 Hz) from a spectral analysis. Detailed mapping of the response characteristics as a function of anatomical location was conducted in relation to the gyral and sulcal pattern on each patient's brain. The results document responses with high responsiveness for static or dynamic faces, often showing abrupt changes in response properties between spatially close recording sites and idiosyncratic across different subjects. Notably, strong responses to dynamic facial expressions can be found in the fusiform gyrus, just as can responses to static faces. The findings suggest a more complex, fragmented architecture of ventral temporal cortex around the fusiform gyrus, one that includes focal regions of cortex that appear relatively specialized for either static or dynamic aspects of faces.

Stimuli responsive polymeric nanoparticles in regulated drug delivery for cancer

Stimuli responsive polymeric nanoparticles in regulated drug delivery for cancer Stimuli-responsive drug delivery system is a concept in which a drug is delivered at a suitable rate in response to stimuli. States of diseases may cause an alteration in some parameters of the body (e.g. in tumors) and the onset and offset of the drug delivery can be done by using this as a stimuli or a "trigger". Stimuli-responsive ("intellectual" or "sharp") resources and molecules show abrupt property changes in response to miniature changes in external stimuli such as pH, temperature etc. For regulated drug delivery, environmental stimuli such as pH and temperature, which undertake phase transition in polymer system, have been investigated. Thermally-responsive polymers can be tuned to a preferred temperature variety by copolymerization with a hydrophilic co-monomer or a hydrophobic co-monomer. Hydrophilic co-monomers increase the LCST while hydrophobic co-monomers decrease the LCST. The stimuli responsive polymer for regulated drug delivery can contain a polymer and copolymers having equilibrium of hydrophilic and hydrophobic groups. A number of these polymers have been investigated extensively and some success in drug delivery with them has been achieved, such as polymers and copolymers of N-isopropylacrylamide, PLGA, and PLA, HEMA etc. Thus this review is designed for stimuli pH and temperature responsive polymeric nanoparticles, which would be helpful to treat various cronic diseases such as cancer and others, for scientists in the field of the regulated drug delivery system.

A Synthetic Approach Toward a Self‐Regulated Insulin Delivery System

Stimuli-responsive “smart gels” that undergo physicochemical property changes in response to external stimuli can provide both a functional and structural basis for selfregulated materials and systems. Of particular interest are those materials sensitive to chemical stimuli, that is, the fluctuation in the concentration of specific biomolecules, that can mimic biofeedback systems, thus providing many attractive platforms for biomedical applications. Glucose has been a molecule of interest for decades owing to its relevance to the treatment of diabetes. Diabetes is not an infectious disease, but its rapidly increasing worldwide prevalence has been recognized as a pandemic, and thus diabetes poses a serious global health threat much like epidemics of truly infectious diseases, such as HIV/AIDS. Despite the necessity for the continuous and accurate glycemic control in the management of insulin-dependent diabetes mellitus (IDDM), the current palliative treatment relies almost solely on the patients self injection of insulin; this self injection not only impinges on the quality of life of the patient but also fails to precisely control the dose of insulin, where an overdose must be strictly avoided as it causes serious hypoglycemia. For the preparation of self-regulated insulin delivery systems, the following two approaches have historically prevailed. One is based on enzymatic reactions between glucose oxidase (GOD) and glucose, a similar rationale to those exploited in commercial glucose sensors. The other type utilizes carbohydrate-binding lectin proteins, such as concanavalin A (Con A), as a complementary binder to glucose. These protein-based materials eventually denature and lose activity, and thus are not practical for long-term use and storage. Another problem is the strong cytotoxicity of Con A; this cytotoxicity has, thus far, prevented any clinical applications of these materials. Herein we describe a totally synthetic alternative to these materials. Phenylboronic acid (PBA), a synthetic molecule capable of reversibly binding with 1,2or 1,3-cis-diols including glucose, is utilized as the molecular basis. Our previous studies have shown that the glucose-dependent shift in the equilibrium of PBA between the uncharged and anionically charged forms, when coupled with a properly amphiphilic three-dimensional backbone (or gel), could induce a reversible change in the volume of the gel. The resultant abrupt and rapid change in the hydration, under certain conditions, could cause a localized dehydration of the gel surface, that is, a so-called skin layer, thus offering a method to instantly control the permeation of gel-loaded insulin. This goal is a great challenge and relies on achieving sufficient glucose sensitivity under physiological pH and temperature, that is, pH 7.4 and 37 8C, while also fine tuning the system so it shows a gated response to the change in glucose concentration critically at the level of normoglycemia, i.e., ca. 1 gl . To achieve this goal, we have systemically explored the structure–property correlation by focusing on (meth)acrylamide-based hydrogels. The major efforts have been directed to controlling the apparent pKa of PBA; the pKa depends not only on chemical structure of PBA, but also on the state of hydration. To make the situation more complicated, in a hydrogel environment the degree of hydration is a function of (as well as temperature, ionic strength, pH, and sugar concentration) the hydrophilicity, rigidity, and density of the main chain components and the amount of PBA. Herein we describe a gel that meets all the above criteria; the chemical structure of this gel turned out to be a remarkably simple copolymer system. A smart gel has been shown to act as an artificial pancreas under conditions closely related to human glucose homeostasis. As illustrated in Figure 1a, PBA derivatives in water exist in equilibrium between uncharged (i) and anionically charged (ii) forms. Upon addition of glucose, only the charged PBA (ii) can form a stable complex with glucose (iii), and the formation of this complex results in an apparent decrease in the amount of anionically charged PBA (ii). On consumption of the phenylboronate (ii), the equilibrium between (i) and (ii) shifts toward the latter (ii). Since the complexed PBA (iii) is also anionically charged, further addition of glucose leads to a shift in the equilibrium (i + ii + iii) toward the phenylboronate anions (ii + iii), and a decrease in the amount of [*] Dr. A. Matsumoto, J. Nishida, Dr. H. Matsumoto, Dr. Y. Miyahara Institute of Biomaterials and Bioengineering Tokyo Medical and Dental University Kanda-surugadai 2-3-10, Chiyoda-ku, Tokyo 101-0062 (Japan) E-mail: miyahara.bsr@tmd.co.jp Dr. T. Ishii Department of Bioengineering, The University of Tokyo Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan)

Changes in response properties of nociceptors and dorsal horn neurons in a murine model of cancer pain

Changes in response properties of nociceptors and dorsal horn neurons in a murine model of cancer pain

Response properties of nociceptive neurons in the caudal ventrolateral medulla (CVLM) in monoarthritic and healthy control rats: Modulation of responses by the paraventricular nucleus of the hypothalamus (PVN)

We characterized response properties of neurons in the caudal ventrolateral medulla (CVLM), a structure involved in pain modulation. Electrophysiological recordings were performed in pentobarbitone-anesthetized control and monoarthritic rats. Noxious pinch, heat, cold and colorectal distension were used for peripheral test stimulation. To study central modulation of CVLM neurons and role in mediating descending pain regulation from the hypothalamus, glutamate was administered into the paraventricular nucleus of the hypothalamus (PVN). CVLM neurons gave excitatory, inhibitory or no response to noxious test stimulation. Response patterns for part of the neurons varied with submodality of test stimulation; e.g., a cell with an excitatory response to heat could give no or an inhibitory response to cold. Arthritis induced cell type-dependent changes in the spontaneous activity, most prominent of which was increased discharge rate of CVLM cells with an excitatory response to noxious stimulation. Significant arthritis-induced changes were also observed in the magnitudes of the nociceptive responses, among which was an increase in the pinch-induced excitatory response. Glutamate in the PVN of arthritic but not control animals suppressed the excitatory responses of CVLM cells, independent of the submodality of test stimulation and without influence on their spontaneous discharge rates. The results indicate that CVLM neurons give differential responses to noxious stimulation. Arthritis induces changes in response properties of CVLM neurons and in their central regulation by the PVN. These findings are in line with the evidence indicating that the CVLM plays a role in processing of nociceptive signals under inflammatory as well as control conditions.

Thermally responsive polymer–nanoparticle composites for biomedical applications

Thermally responsive polymer-metal nanoparticle composites couple the ability of certain metal nanoparticles to convert external stimuli to heat with polymers that display sharp property changes in response to temperature changes, allowing for external control over polymer properties. These systems have been investigated for a variety of biomedical applications, including drug delivery, microfluidic valve control, and cancer therapy. This article focuses on three different size scales of this system: bulk systems (>1mm), nano- or microscale systems, and individual particle coatings. These composite systems will continue to be widely researched in the future for their vast potential in various biomedical applications.

Arc/Arg3.1 mRNA expression reveals a subcellular trace of prior sound exposure in adult primary auditory cortex

Acquiring the behavioral significance of sound has repeatedly been shown to correlate with long term changes in response properties of neurons in the adult primary auditory cortex. However, the molecular and cellular basis for such changes is still poorly understood. To address this, we have begun examining the auditory cortical expression of an activity-dependent effector immediate early gene (IEG) with documented roles in synaptic plasticity and memory consolidation in the hippocampus: Arc/Arg3.1. For initial characterization, we applied a repeated 10 min (24 h separation) sound exposure paradigm to determine the strength and consistency of sound-evoked Arc/Arg3.1 mRNA expression in the absence of explicit behavioral contingencies for the sound. We used 3D surface reconstruction methods in conjunction with fluorescent in situ hybridization (FISH) to assess the layer-specific subcellular compartmental expression of Arc/Arg3.1 mRNA. We unexpectedly found that both the intranuclear and cytoplasmic patterns of expression depended on the prior history of sound stimulation. Specifically, the percentage of neurons with expression only in the cytoplasm increased for repeated versus singular sound exposure, while intranuclear expression decreased. In contrast, the total cellular expression did not differ, consistent with prior IEG studies of primary auditory cortex. Our results were specific for cortical layers 3–6, as there was virtually no sound driven Arc/Arg3.1 mRNA in layers 1–2 immediately after stimulation. Our results are consistent with the kinetics and/or detectability of cortical subcellular Arc/Arg3.1 mRNA expression being altered by the initial exposure to the sound, suggesting exposure-induced modifications in the cytoplasmic Arc/Arg3.1 mRNA pool.

Severe and extensive neonatal hearing loss in cats results in auditory cortex plasticity that differentiates into two regions

We examined the response characteristics of primary auditory cortex (A1) neurons in adult cats partially but extensively deafened by ototoxic drugs 2-8 days after birth. The damage evoked extensive A1 topographic map reorganization as also found by others, but a novel finding was that in the majority of cats with low-frequency edges to the cochlear lesion, the area of reorganization segregated into two areas expressing the same novel frequency inputs but differentiated by neuronal sensitivity and responsiveness. Immediately adjacent to normal A1 is an approximately 1.2-mm-wide area of reorganization in which sensitivity and responsiveness to sound are similar to that in normal A1 in the same animals and in unlesioned adult animals. Extending further into deprived A1 is a more extensive area of reorganization where neurons have poorer sensitivity and responsiveness to new inputs. These two areas did not differ in response-area bandwidth and response latency. We interpret these novel changes as the cortical consequences of severe receptor organ lesions extending to low-frequency cochlear regions. We speculate that the two areas of A1 reorganization may reflect differences in the transcortical spatial distribution of thalamo-cortical and horizontal intracortical connections. Qualitatively similar changes in response properties have been seen after retinal lesions producing large areas of visual cortical reorganization, suggesting they might be a general consequence of receptor lesions that deprive large regions of cortex of normal input. These effects may have perceptual implications for the use of cochlear implants in patients with residual low-frequency hearing.