Local Activity Patterns Research Articles

Differential JAK-STAT Pathway Activation in Primary Mediastinal Large B-Cell Lymphoma: Two Subgroups with Differential Cytokine Activation Patterns and Predicted Responses to Kinase Inhibitors.

Abstract 968 Background:Primary mediastinal large B-cell lymphoma (PMBCL) is a specialized type of diffuse large B-cell lymphoma which shows diagnostic and pathogenetic overlap with mediastinal classical Hodgkin lymphoma. Approximately 60% of patients with PMBCL have good response to conventional chemoradiotherapy with the rest often showing distant relapses. Microarray studies of PMBCL have revealed overexpression of components and targets of the JAK-STAT signaling pathways including upregulation of IL13 receptor and STAT1; a subset of PMBCL have genome amplification of JAK2 or deletion of the JAK suppressor SOCS1. Given this complexity, we examined the most common mechanism and effects of JAK-STAT dysregulation in a series of newly diagnosed and recurrent PMBCL. Methods:Fifty-three biopsies from 23 patients with PMBCL were assessed and correlated with outcome. JAK2 and SOCS1 copy number status were determined by quantitative PCR on genomic DNA. JAK-STAT pathway activation was probed using reverse transcription quantitative (RQ)-PCR for JAK2, JAK3, and a panel of IL-4 and IL-13 transcriptional targets. JAK-STAT activation was assessed in tissue arrays using antisera against phospho-activation epitopes of STAT1, STAT3, STAT5, and STAT6 using immunohistochemistry (IHC). Activation patterns were modeled in the PMBCL cell line Karpas (K)1106P at baseline and following IL-4 and IL-13 stimulation with or without a range of small molecule inhibitors and blocking antibodies. Growth parameters were measured by MTT and protein levels by flow cytometry, Western blot, RQ-PCR and kinase profiling. Results:JAK2 genomic amplification was present in 40% of PMBCL and SOCS1 deletion in 10% as well as in the K1106P line. By phospho-activation IHC, tumors in 20/23 (87%) patients showed STAT activation, mostly due to STAT1 (60.8%) followed by STAT3 (26.1%), with 6 cases showing mixed patterns. In different tumors, localized and uniform STAT activation patterns were seen. Constitutive STAT activation was correlated with high expression of IL-4 transcription targets including CCL17 and IL13RA as well as JAK2 autophosphorylation and inferior outcome (p = .007). Tumors with more localized foci of activation were associated with alternate transcription patterns. In the K1106P cell line, IL-4 but not IL-13 treatment led to inducible STAT1 activation whereas baseline STAT3/6 activation was highly regulated by cytokine exposure. The JAK2 inhibitor JSI124 blocked IL-4 induced STAT1 activation whereas the JAK inhibitors AG-490, NSC7908 and WHI-P154 did not but did block IL-4/IL-13-induced STAT3 activation. The JAK3 inhibitor ZM39923 was most effective in blocking cell growth but did not block STAT1 activation. Conclusions:JAK2-STAT pathway activation characterizes nearly all cases of PMBCL but genetic mechanisms are distinct leading to distinct patterns of STAT1 activation (driven predominantly through the type I IL-4 receptor) and STAT3/6 activation (driven predominantly through the type II IL13RA/IL4RA) with differential effects on growth parameters and gene regulation. The patterns of STAT activation and target gene expression in primary tumors comprising these two groups mirrored the response to small molecule inhibitors following cytokine exposure in vitro in the K1106P line and highlights differences between IL-4 and IL-13 signaling in PMBCL. Profiling of PMBCL biopsies with phosphoactivation IHC for STAT isoforms may be useful to subcategorize cases and select the optimal JAK-STAT pathway inhibitors for adjuvant therapy. Disclosures:No relevant conflicts of interest to declare.

Reducing inter-subject anatomical variation: Effect of normalization method on sensitivity of functional magnetic resonance imaging data analysis in auditory cortex and the superior temporal region

Conventional group analysis of functional MRI (fMRI) data usually involves spatial alignment of anatomy across participants by registering every brain image to an anatomical reference image. Due to the high degree of inter-subject anatomical variability, a low-resolution average anatomical model is typically used as the target template, and/or smoothing kernels are applied to the fMRI data to increase the overlap among subjects' image data. However, such smoothing can make it difficult to resolve small regions such as subregions of auditory cortex when anatomical morphology varies among subjects. Here, we use data from an auditory fMRI study to show that using a high-dimensional registration technique (HAMMER) results in an enhanced functional signal-to-noise ratio (fSNR) for functional data analysis within auditory regions, with more localized activation patterns. The technique is validated against DARTEL, a high-dimensional diffeomorphic registration, as well as against commonly used low-dimensional normalization techniques such as the techniques provided with SPM2 (cosine basis functions) and SPM5 (unified segmentation) software packages. We also systematically examine how spatial resolution of the template image and spatial smoothing of the functional data affect the results. Only the high-dimensional technique (HAMMER) appears to be able to capitalize on the excellent anatomical resolution of a single-subject reference template, and, as expected, smoothing increased fSNR, but at the cost of spatial resolution. In general, results demonstrate significant improvement in fSNR using HAMMER compared to analysis after normalization using DARTEL, or conventional normalization such as cosine basis function and unified segmentation in SPM, with more precisely localized activation foci, at least for activation in the region of auditory cortex.

Persistent Neural States: Stationary Localized Activity Patterns in Nonlinear Continuous n-Population, q-Dimensional Neural Networks

Neural continuum networks are an important aspect of the modeling of macroscopic parts of the cortex. Two classes of such networks are considered: voltage and activity based. In both cases, our networks contain an arbitrary number, n, of interacting neuron populations. Spatial nonsymmetric connectivity functions represent cortico-cortical, local connections, and external inputs represent nonlocal connections. Sigmoidal nonlinearities model the relationship between (average) membrane potential and activity. Departing from most of the previous work in this area, we do not assume the nonlinearity to be singular, that is, represented by the discontinuous Heaviside function. Another important difference from previous work is that we relax the assumption that the domain of definition where we study these networks is infinite, that is, equal to [Formula: see text] or [Formula: see text]. We explicitly consider the biologically more relevant case of a bounded subset Ω of [Formula: see text], a better model of a piece of cortex. The time behavior of these networks is described by systems of integro-differential equations. Using methods of functional analysis, we study the existence and uniqueness of a stationary (i.e., time-independent) solution of these equations in the case of a stationary input. These solutions can be seen as ‘persistent’; they are also sometimes called bumps. We show that under very mild assumptions on the connectivity functions and because we do not use the Heaviside function for the nonlinearities, such solutions always exist. We also give sufficient conditions on the connectivity functions for the solution to be absolutely stable, that is, independent of the initial state of the network. We then study the sensitivity of the solutions to variations of such parameters as the connectivity functions, the sigmoids, the external inputs, and, last but not least, the shape of the domain of existence Ω of the neural continuum networks. These theoretical results are illustrated and corroborated by a large number of numerical experiments in most of the cases 2 ⩽ n ⩽ 3, 2 ⩽ q ⩽ 3.

Persistent Neural States: Stationary Localized Activity Patterns in Nonlinear Continuousn-Population,q-Dimensional Neural Networks

Neural continuum networks are an important aspect of the modeling of macroscopic parts of the cortex. Two classes of such networks are considered: voltage and activity based. In both cases, our networks contain an arbitrary number, n, of interacting neuron populations. Spatial nonsymmetric connectivity functions represent cortico-cortical, local connections, and external inputs represent nonlocal connections. Sigmoidal nonlinearities model the relationship between (average) membrane potential and activity. Departing from most of the previous work in this area, we do not assume the nonlinearity to be singular, that is, represented by the discontinuous Heaviside function. Another important difference from previous work is that we relax the assumption that the domain of definition where we study these networks is infinite, that is, equal to R or R2. We explicitly consider the biologically more relevant case of a bounded subset omega of Rq, q = 1, 2, 3, a better model of a piece of cortex. The time behavior of these networks is described by systems of integro-differential equations. Using methods of functional analysis, we study the existence and uniqueness of a stationary (i.e., time-independent) solution of these equations in the case of a stationary input. These solutions can be seen as 'persistent'; they are also sometimes called bumps. We show that under very mild assumptions on the connectivity functions and because we do not use the Heaviside function for the nonlinearities, such solutions always exist. We also give sufficient conditions on the connectivity functions for the solution to be absolutely stable, that is, independent of the initial state of the network. We then study the sensitivity of the solutions to variations of such parameters as the connectivity functions, the sigmoids, the external inputs, and, last but not least, the shape of the domain of existence omega of the neural continuum networks. These theoretical results are illustrated and corroborated by a large number of numerical experiments in most of the cases 2 < or = n < or = 3, 2 < or = q < or = 3.

Small scale activity patterns of Eptesicus nilssonii – an indication of habitat preference or interspecific processes

ABSTRACT Habitat use and interspecific processes are key factors shaping regional distribution as well as local activity patterns of mammals. To assess the importance of differential habitat use and interspecific processes for the distribution of local activity in Eptesicus nilssonii, a critically endangered bat species in Germany, a bat detector transect survey was conducted in central Germany. One transect end was close to a maternity roost of E. nilssonii. We compared the bats' use of habitat types and the use of distance zones centred around this maternity roost. We arranged the 11 bat species detected into four foraging categories, E. nilssonii, Pipistrellus pipistrellus, larger open-space bats (Vespertilio murinus, Nyctalus noctula, Eptesicus serotinus) and narrow-space bats (Myotis species). General bat activity was highest in lake and lowest in agricultural habitats. We found significant differences in the use of habitats and distance zones between the foraging categories. However, these differenc...

Selective Activation of Cat Primary Auditory Cortex by way of Direct Intraneural Auditory Nerve Stimulation

Although cochlear implants have been successfully used by many individuals with profound hearing impairment, limitations still remain with this approach to hearing restoration, including poor stimulation selectivity because of cross-talk between electrodes and poor low-frequency percepts. These limitations may be mitigated by direct intraneural stimulation of the auditory nerve by way of an array of penetrating microelectrodes. Such an approach should provide focal stimulation and selective activation of the nerve fibers, thereby minimizing cross-talk among implanted stimulating electrodes and evoking narrow-band frequency percepts. We investigated the activation of primary auditory cortex evoked by such direct intraneural electrical stimulation of the auditory nerve. We implanted 11 penetrating microelectrodes in the cat auditory nerve, simulated the nerve by way of these electrodes, and recorded the evoked neuronal activity patterns in cat primary auditory cortex. We compared these activation patterns with acoustically evoked cortical activity patterns obtained in a different animal. Our results showed that direct stimulation of the auditory nerve evoked localized activity patterns in primary auditory cortex similar in spatial extent to those evoked by acoustic stimulation and that the extent of cortical activation by both acoustic and electrical stimuli was graded with stimulus intensity. These results suggest that the implanted electrodes can excite independent and small populations of nerve fibers. This study demonstrates the functional feasibility of direct intraneural auditory nerve stimulation with an array of penetrating microelectrodes and that such an approach could form the foundation for an auditory prosthesis with improved frequency coding.

Overcoming Mismatch: Beyond Dispersal, Mobility, and Development Strategies

Since the 1960s, John Kain's theory of spatial mismatch has influenced policy responses to the poor employment prospects of low-income and minority residents of inner cities by aiming to connect them with suburban jobs. My literature review examines this policy legacy using what we now know about disadvantaged jobseekers' employment searches. Recent evaluations of poverty deconcentration and employment accessibility programs show that these programs have failed to improve employment outcomes significantly. However, using evidence from studies of job search and job training programs, I show that local activity patterns do shape employment chances. Planners trying to improve employment outcomes for the disadvantaged should focus on policies that will provide them with opportunities to interact with a diverse social network and meet workforce intermediaries capable of linking them with jobs.

The geometry of neuronal recruitment

We address the question of whether or not a periodic train of excitatory synaptic inputs recruits an excitable cell, such that it fires repeatedly, or does not recruit a cell, such that it fails to fire, possibly after some transient. In particular, we study the scenarios of one or two inputs per period; in the latter case, the degree of synchrony of the inputs is a crucial factor in recruitment. We establish rigorous geometric conditions that pinpoint the transition between recruitment and non-recruitment as the degree of synchrony between input pairs, or other input parameters, is varied. These conditions can be used to determine whether a particular temporal relation between periodic input pairs leads to recruitment or not and to prove, in certain parameter regimes, that recruitment can only occur when the inputs are sufficiently closely synchronized. The concepts in this paper are derived for both the integrate-and-fire neuron and the theta neuron models. In the former, the location in phase space of the unique fixed point of a relevant two-dimensional map determines firing, while in the latter, it is the existence or lack of existence of a fixed point of the map which does so. These results are discussed in the context of recruitment of cells into localized activity patterns.

Local Morphology Predicts Functional Organization of the Dorsal Premotor Region in the Human Brain

A confusing picture of the functional organization of the dorsal premotor region of the human brain emerged when functional neuroimaging studies that either examined visuomotor hand conditional activity or attempted to localize the human frontal eye field reported activity increases at the same general location, namely the junction of the superior precentral sulcus with the superior frontal sulcus. The present functional magnetic resonance imaging study examined visuomotor hand conditional activity and the locus of the frontal eye field as defined by a standard task, on a subject-by-subject basis, to clarify their location and reveal relationships between the pattern of local morphology and functional activity. The results demonstrate that visuomotor hand conditional activity and the frontal eye field lie within distinct parts of the superior precentral sulcus, revealing an organization of the human premotor cortex consistent with that observed in experimental studies in the monkey.

High-density activation mapping of fractionated electrograms in the atria of patients with paroxysmal atrial fibrillation

Areas of complex fractionated atrial electrograms (CFAEs) have been implicated in the atrial substrate of atrial fibrillation (AF). The mechanisms underlying CFAE in humans are not well investigated. The purpose of this study was to investigate the regional activation pattern associated with CFAE using a high-density contact mapping catheter. Twenty patients with paroxysmal AF were mapped using a high-density multielectrode catheter. CFAE were mapped at 10 different sites (left atrium [LA]: inferior, posterior, roof, septum, anterior, lateral; right atrium [RA]: anterior, lateral, posterior, septum). Local atrial fibrillation cycle length (AFCL) was measured immediately before and after the occurrence of CFAE, and the longest electrogram duration (CFAEmax) was assessed. Longer electrogram durations were recorded in the LA compared with the RA (CFAEmax 118 +/- 21 ms vs 104 +/- 23 ms, P = .001). AFCL significantly shortened before the occurrence of CFAEmax compared with baseline (LA: 174 +/- 32 ms vs 186 +/- 32 ms, P = .0001; RA: 177 +/- 31 ms vs 188 +/- 31 ms, P = .0001) and returned to baseline afterwards. AFCL shortened by >or=10 ms in 91% of mapped sites. Two different local activation patterns were associated with occurrence of CFAEmax: a nearly simultaneous activation in all spines in 84% indicating passive activation, and a nonsimultaneous activation sequence suggesting local complex activation or reentry. Fractionated atrial electrograms during AF demonstrate dynamic changes that are dependent on regional AFCL. Shortening of AFCL precedes the development of CFAE; thus, cycle length is a major determinant of fractionation during AF. High-density mapping in AF may help to differentiate passive activation of CFAE from CFAE associated with an active component of the AF process.

Daily Patterns of Locomotion Expressed by American Lobsters (Homarus Americanus) in Their Natural Habitat

The local movements and activity patterns of American lobsters, Homarus americanus, were monitored inside a 50 m by 50 m underwater enclosure (mesocosm) using ultrasonic telemetry. Forty-four lobsters of both sexes, ranging in size from 62 to 93 mm in carapace length, were continuously tracked for 2-10 days in 2002 and 2003. As a population, the movement rate of lobsters depended on time of day, as defined by dawn, day, dusk or night. Lobster movement rates were significantly higher during night and dawn than day and dusk hours. Movement rates did not differ by lobster sex, size or between years of the study. The effect of time of day differed between lobsters, and there was considerable variability in the time of day when individual lobsters were most active. Thirty lobsters moved significantly more during the night, five moved significantly more during the day, and nine did not move significantly more during the day or night. Therefore, while there was a general tendency for lobsters in this study to be more active at night, certain factors in their natural habitat modulated this nocturnal bias, which led to a tremendous amount of variability in their daily patterns of behavior.

New multichannel near infrared spectrophotometry system for functional studies of the brain in adults and neonates

We have designed a versatile, multi-channel near-infrared spectrophotometry (NIRS) instrument for the purpose of mapping neuronal activation in the neonatal and adult brain in response to motor, tactile, and visual stimulation. The optical linearity, stability, and high signal to noise ratio (>70 dB) of the instrument were demonstrated using an in vitro validation procedure. In vivo measurements on the adult forearm were also performed. Changes in oxygenation, induced by arterial occlusion of the forearm, were recorded and were shown to compare well with measurements acquired using a conventional NIRS instrument. To demonstrate the capabilities of the instrument, functional measurements in adults and neonates were performed. The instrument exhibited the capability to differentiate with a spatial resolution in the order of cm, local activation patterns associated with a finger tapping sequence.

Localized activity patterns in two-population neuronal networks

We investigate a two-population neuronal network model of the Wilson–Cowan type with respect to existence of localized stationary solutions (“bumps”) and focus on the situation where two separate bump solutions (one narrow pair and one broad pair) exist. The stability of the bumps is investigated by means of two different approaches: The first generalizes the Amari approach, while the second is based on a direct linearization procedure. A classification scheme for the stability problem is formulated, and it is shown that the two approaches yield the same predictions, except for one notable exception. The narrow pair is generically unstable, while the broad pair is stable for small and moderate values of the relative inhibition time. At a critical relative inhibition time the broad pair is typically converted to stable breathers through a Hopf bifurcation. In our numerical example the broad pulse pair remains stable even when the inhibition time constant is three times longer than the excitation time constant. Thus, our model results do not support the claim that slow excitation mediated by, e.g., NMDA-receptors is needed to allow stable bumps.

From single fine roots to a black alder forest ecosystem: How system behaviour emerges from single component activities

Based on empirical findings in a natural black alder ecosystem in Northern Germany we developed an individual based model that integrates components of a black alder ecosystem interacting on different levels of organisation. The factors determining seasonal fine root biomass development of forest ecosystems are not yet fully understood. We used an object oriented model approach to investigate this complex matter for black alder trees. Processes like growth, storage, respiration, transport, nutrient mineralisation and uptake as well as interactions among these factors are described on the level of functionally differentiated plant organs (fine roots, coarse roots, stem, branches, leaves) and soil units. The object structure of the model is determined by spatial relations between plant modules as well as between plant modules and their local environment modules. As results of model application we found that (i) on the organ level, spatio-temporal plasticity of (root) growth allocation is related to spatio-temporal variation of resource availability, (ii) on the plant level, balanced root:shoot growth appears in response to variation of available resources light and nutrients, (iii) on the population level, tree stand development (population structure, self-thinning) resulted from coexistence and competition between plant individuals. For the understanding of the root compartment it seems relevant that the model implementation of local scale fine root dynamics is consistent with a self-organised large scale spatial heterogeneity of fine root activity pattern. On the other hand, fine-root dynamics cannot be explained as a result of autonomous dynamics. A reference to above-ground processes is a necessary condition and the overall plant seems to act as an integrator providing boundary conditions for local activity pattern. At the same time fine-root characteristics are of some importance for properties on hierarchically higher levels, e.g. co-existence in a tree population or element cycling in the ecosystem. As a conclusion, modelling of the spatio-temporal dynamics of tree root systems appears as a paradigmatic example of scale and organisation level integrating processes.

Development of Indicators to Assess Economic Vulnerabilities to Changes in Ecosystem Services: Case Study of Counties in Maryland, USA

We develop indicators showing the relative environmental burdens that human activities place on locales for a given level of economic benefits. The main purpose is to develop tools that allow us to examine the potential vulnerabilities within economies to changes in resource conditions. The indicators of pollution emission or resource consumption per job can be used to identify potential challenges to resource and industry managers and to compare areas in terms of their ability to adapt to change. For example, if a large number of area jobs are dependent on abundant water, this indicates a vulnerability to a reduction in water availability for industrial use. We develop a case study for 23 counties and 1 city in Maryland to examine the usefulness and limitations of the indicators. Our case study demonstrates that the indicators provide an informative view into patterns of local economic activity and use of an area's environmental goods and services. In contrast to patterns for total environmental burdens (e.g., total SO2 emissions) that are typically reported, the rates of environmental burden per job are not simply correlated with high or low economic output. Thus, the indicators represent distinct patterns of environmental burdens per job that reflect reliance on environmental services. The indicators have some limitations when used at this fine scale because they can misrepresent conditions in counties in which economic sectors are dominated by one or a few businesses. For this reason, the indicators are best used as a regional screening tool.

Localized activity patterns in excitatory neuronal networks

The existence of localized activity patterns, or bumps, has been investigated in a variety of spatially distributed neuronal network models that contain both excitatory and inhibitory coupling between cells. Here we show that a neuronal network with purely excitatory synaptic coupling can exhibit localized activity. Bump formation ensues from an initial transient synchrony of a localized group of cells, followed by the emergence of desynchronized activity within the group. Transient synchrony is shown to promote recruitment of cells into the bump, while desynchrony is shown to be good for curtailing recruitment and sustaining oscillations of those cells already within the bump. These arguments are based on the geometric structure of the phase space in which solutions of the model equations evolve. We explain why bump formation and bump size are very sensitive to initial conditions and changes in parameters in this type of purely excitatory network, and we examine how short-term synaptic depression influences the characteristics of bump formation.

Rising to the challenge: a study of patient and public involvement in four primary care trusts

As new organizations with responsibility for the health and health care of their local populations, primary care trusts (PCTs) need to engage with patients and the wider public. This paper identi. es the challenges faced by PCTs in implementing patient and public involvement and reports on a qualitative study of four PCTs in one health district. Findings from two pieces of data collection are reported on: an audit of community involvement activity and 16 semi-structured interviews with individuals working in the PCTs. The findings show that organizational capacity for undertaking patient and public involvement activities increased considerably over an 18 month period. The PCTs were found to be engaging with individuals and groups from the community and voluntary sector through a range of different structures and processes. Considerable commitment to patient and public involvement was reported but there were concerns over implementation. A number of influencing factors were identified including national policy, organizational factors, leadership, workload, access to experienced involvement workers and the pattern of local community activity. The paper discusses the implications for the development of patient and public involvement in PCTs including the importance of cultural change and the need for organizational development. The potential for PCTs to be involved in a range of participatory activities and to work with other partner organizations in localities is also discussed. The paper concludes that, despite challenges, progress can be made in implementing patient and public involvement as a mainstream activity in PCTs.

Imaging cortical correlates of illusion in early visual cortex

Exploring visual illusions reveals fundamental principles of cortical processing. Illusory motion perception of non-moving stimuli was described almost a century ago by Gestalt psychologists. However, the underlying neuronal mechanisms remain unknown. To explore cortical mechanisms underlying the 'line-motion' illusion, we used real-time optical imaging, which is highly sensitive to subthreshold activity. We examined, in the visual cortex of the anaesthetized cat, responses to five stimuli: a stationary small square and a long bar; a moving square; a drawn-out bar; and the well-known line-motion illusion, a stationary square briefly preceding a long stationary bar presentation. Whereas flashing the bar alone evoked the expected localized, short latency and high amplitude activity patterns, presenting a square 60-100 ms before a bar induced the dynamic activity patterns resembling that of fast movement. The preceding square, even though physically non-moving, created gradually propagating subthreshold cortical activity that must contribute to illusory motion, because it was indistinguishable from cortical representations of real motion in this area. These findings demonstrate the effect of spatio-temporal patterns of subthreshold synaptic potentials on cortical processing and the shaping of perception.

Localized activity patterns in excitatory neuronal networks

The existence of localized activity patterns, or bumps, has been investigated in a variety of spatially distributed neuronal network models that contain both excitatory and inhibitory coupling between cells. Here we show that a neuronal network with purely excitatory synaptic coupling can exhibit localized activity. Bump formation ensues from an initial transient synchrony of a localized group of cells, followed by the emergence of desynchronized activity within the group. Transient synchrony is shown to promote recruitment of cells into the bump, while desynchrony is shown to be good for curtailing recruitment and sustaining oscillations of those cells already within the bump. These arguments are based on the geometric structure of the phase space in which solutions of the model equations evolve. We explain why bump formation and bump size are very sensitive to initial conditions and changes in parameters in this type of purely excitatory network, and we examine how short-term synaptic depression influences the characteristics of bump formation.

Sustained Spatial Patterns of Activity in Neuronal Populations without Recurrent Excitation

Spatial patterns of neuronal activity arise in a variety of experimental studies. Previous theoretical work has demonstrated that a synaptic architecture featuring recurrent excitation and long-range inhibition can support sustained, spatially patterned solutions in integrodifferential equation models for activity in neuronal populations. However, this architecture is absent in some areas of the brain where persistent activity patterns are observed. Here we show that sustained, spatially localized activity patterns, or bumps, can exist and be linearly stable in neuronal population models without recurrent excitation. These models support at most one bump for each background input level, in contrast to the pairs of bumps found with recurrent excitation. We explore the shape of this bump as well as the mechanisms by which this bump is born and destroyed as background input level changes. Further, we introduce spatial inhomogeneity in coupling and show that this induces bump pinning: for a given starting position, bumps can exist only for a small, discrete set of background input levels, each with a unique corresponding bump width.