Local Network Level Research Articles

State‐Dependent Modulation of Cortical Synchrony by Vagus Nerve Stimulation in Adult Rats

SUMMARYVagus nerve stimulation (VNS) is a palliative treatment for intractable epilepsy. Therapeutic mechanisms of VNS have not been elucidated. In this study, we measured the local field potential (LFP) with high‐spatial resolution using a microelectrode array in adult rats, and analyzed VNS‐induced phase modulation at a local network level. Eight adult Wistar rats (270–330 g) were used. Each rat underwent implantation of a VNS system under 1.5% isoflurane anesthesia. One week after implantation, right temporal craniotomy was performed under the same anesthesia as previously. Subsequently, a microelectrode array was placed in the temporal lobe cortex, and the LFP was recorded with a sampling rate of 1000 Hz. Phase‐locking values (PLV) between all pairs of electrodes in varied frequency bands were calculated in order to evaluate the effect of VNS in terms of synchrony of neuronal activities. The PLV was calculated both in a normal state and in an epileptic state induced by kainic acid. VNS increased the PLV in a normal state, particularly in the high‐γ band. In an epileptic state, on the other hand, VNS increased the PLV in the high‐γ band and decreased the PLV in the δ and low‐β bands. These results suggest that VNS modulates neural activities in a band‐specific and state‐dependent manner so as to keep cortical synchrony within the optimal state.

Vagus Nerve Stimulation‐Induced Synchrony Modulation of Local Field Potential in the Rat Cerebral Cortex

SUMMARYVagus nerve stimulation (VNS) is a surgical treatment for intractable epilepsy. Although VNS has been used to treat more than 60,000 patients, the precise therapeutic mechanism of action has not been elucidated. Here, we hypothesize that VNS modulates the local synchronization of cortical activities and thus inhibits seizures. In order to verify this hypothesis, we mapped local field potentials (LFPs) with high‐spatial resolution using a microelectrode array from the temporal cortices of adult rats and analyzed VNS‐induced phase modulation at the local network level. VNS significantly increased the phase locking value (PLV), an index of synchronization, specifically at the gamma band. The optimal stimulation pulse of VNS was 0.5 mA delivered at 10 Hz. This PLV modulation was most effective when the interelectrode distance was about 1.6 mm. Gamma‐band PLVs within the auditory cortex increased more significantly than those between the auditory and nonauditory cortices, while alpha‐ and low‐beta PLV exhibited more synchronization between the auditory and nonauditory cortices. These results demonstrate that VNS modulates cortical synchronization in a band specific manner, and has some implications for the mechanism of action of VNS.

Local sleep spindle modulations in relation to specific memory cues

Sleep spindles have been connected to memory processes in various ways. In addition, spindles appear to be modulated at the local cortical network level. We investigated whether cueing specific memories during sleep leads to localized spindle modulations in humans. During learning of word–location associations, words presented in the left and right visual hemifields were paired with different odors. By presenting a single odor during a subsequent nap, we aimed to selectively reactivate a subset of the studied material in sleeping subjects. During sleep, we observed topographically restricted spindle responses to memory cues, suggesting successful reactivation of specific memory traces. In particular, we found higher amplitude and greater incidence of fast spindles over posterior brain areas involved in visuospatial processing, contralateral to the visual field being cued. These results suggest that sleep spindles in different cortical areas reflect the reprocessing of specific memory traces.

State-dependent Modulation of Cortical Synchrony by Vagus Nerve Stimulation in Adult Rats

SUMMARY Vagus nerve stimulation (VNS) is a palliative treatment for intractable epilepsy. Therapeutic mechanisms of VNS have not been elucidated. In this study, we measured the local field potential (LFP) with high-spatial resolution using a microelectrode array in adult rats, and analyzed VNS-induced phase modulation at a local network level. Eight adult Wistar rats (270–330 g) were used. Each rat underwent implantation of a VNS system under 1.5% isoflurane anesthesia. One week after implantation, right temporal craniotomy was performed under the same anesthesia as previously. Subsequently, a microelectrode array was placed in the temporal lobe cortex, and the LFP was recorded with a sampling rate of 1000 Hz. Phase-locking values (PLV) between all pairs of electrodes in varied frequency bands were calculated in order to evaluate the effect of VNS in terms of synchrony of neuronal activities. The PLV was calculated both in a normal state and in an epileptic state induced by kainic acid. VNS increased the PLV in a normal state, particularly in the high-γ band. In an epileptic state, on the other hand, VNS increased the PLV in the high-γ band and decreased the PLV in the δ and low-β bands. These results suggest that VNS modulates neural activities in a band-specific and state-dependent manner so as to keep cortical synchrony within the optimal state.

Spontaneous and electrically modulated spatiotemporal dynamics of the neocortical slow oscillation and associated local fast activity

The neocortical slow oscillation (SO; ~1Hz) of non-REM sleep and anesthesia reflects synchronized network activity composed of alternating active and silent (ON/OFF) phases at the local network and cellular level. The SO itself shows self-organized spatiotemporal dynamics as it appears to originate at unique foci on each cycle and then propagates across the cortical surface. During sleep, this rhythm is relevant for neuroplastic processes mediating memory consolidation especially since its enhancement by slow, rhythmic electrical fields improves subsequent recall. However, the neurobiological mechanism by which spontaneous or enhanced SO activity might operate on memory traces is unknown. Here we show a series of original results, using cycle to cycle tracking across multiple neocortical sites in urethane anesthetized rats: The spontaneous spatiotemporal dynamics of the SO are complex, showing interfering propagation patterns in the anterior-to-posterior plane. These patterns compete for expression and tend to alternate following phase resets that take place during the silent OFF phase of the SO. Applying sinusoidal electrical field stimulation to the anterior pole of the cerebral cortex progressively entrained local field, gamma, and multi-unit activity at all sites, while disrupting the coordination of endogenous SO activity. Field stimulation also biased propagation in the anterior-to-posterior direction and more notably, enhanced the long-range gamma synchrony between cortical regions. These results are the first to show that changes to slow wave dynamics cause enhancements in high frequency cortico-cortical communication and provide mechanistic clues into how the SO is relevant for sleep-dependent memory consolidation.

Illumination Effects on the Capacitance Spectra and Signal Quality Factor of Al/InSe/C Microwave Sensors

Amorphous indium selenide thin films have been used in the design of a microwave-sensitive Schottky barrier. The illumination effects on the capacitance spectra, on the signal quality factor, and on the capacitance (C)–voltage (V) characteristics of the Al/InSe/C device are investigated. Particular shifts in the amplitude and in the resonance peaks of the capacitance spectra which were studied in the frequency range of 10.0 kHz to 3.0 GHz are observed. While the photoexcitation of these devices increased the capacity level by ∼1.6 times the original magnitude, the dark quality factor, which was 2.2 × 106 at 3.0 GHz, fell to 1.2 × 106 when subjected to luminance of 14.7 klux. Analysis of the C–V curves recorded at signal power ranging from wireless local area network (LAN) levels to the maximum output power of third generation (3G) mobiles reflected high tunability of capacitance upon increasing the voltage or power. The tunability of the biased capacitance was much more pronounced in the light than in the dark. The obtained characteristics of the Al/InSe/C sensors indicate their usability in radio and microwave technology.

Vagus Nerve Stimulation Induced Synchrony Modulation of Local Field Potential in the Rat Cerebral Cortex

SUMMARY Vagus nerve stimulation (VNS) is a surgical treatment for intractable epilepsy. Although VNS has been used to treat more than 60,000 patients, the precise therapeutic mechanism of action has not been elucidated. Here, we hypothesize that VNS modulates the local synchronization of cortical activities and thus inhibits seizures. In order to verify this hypothesis, we mapped local field potentials (LFPs) with high-spatial resolution using a microelectrode array from the temporal cortices of adult rats and analyzed VNS-induced phase modulation at the local network level. VNS significantly increased the phase locking value (PLV), an index of synchronization, specifically at the gamma band. The optimal stimulation pulse of VNS was 0.5 mA delivered at 10 Hz. This PLV modulation was most effective when the interelectrode distance was about 1.6 mm. Gamma-band PLVs within the auditory cortex increased more significantly than those between the auditory and nonauditory cortices, while alpha- and low-beta PLV exhibited more synchronization between the auditory and nonauditory cortices. These results demonstrate that VNS modulates cortical synchronization in a band specific manner, and has some implications for the mechanism of action of VNS.

Out of the frying pan? Streamlining the ethics review process of multisite qualitative research projects

This paper describes the ethics approval processes for two multicentre, nationwide, qualitative health service research projects. The paper explains that the advent of the National Ethics Application Form has brought many improvements, but that attendant processes put in place at local health network and Human Research Ethics Committee levels may have become significantly more complicated, particularly for innovative qualitative research projects. The paper raises several questions based on its analysis of ethics application processes currently in place. WHAT IS KNOWN ABOUT THE TOPIC? The complexity of multicentre research ethics applications for research in health services has been addressed by the introduction of the National Ethics Application Form. Uptake of the form across the country's human research ethics committees has been uneven. WHAT DOES THIS PAPER ADD? This paper adds detailed insight into the ethics application process as it is currently enacted across the country. The paper details this process with reference to difficulties faced by multisite and qualitative studies in negotiating access to research sites, ethics committees' relative unfamiliarity with qualitative research , and apparent tensions between harmonisation and local sites' autonomy in approving research. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? Practitioners aiming to engage in research need to be aware that ethics approval takes place in an uneven procedural landscape, made up of variable levels of ethics approval harmonization and intricate governance or site-specific assessment processes.

Religion and Volunteering in Context

This study examines whether religion’s effect on volunteering spills over to nonreligious individuals through personal ties between religious and nonreligious individuals. We use three different analytic strategies that focus on national, local, and personal network level contexts to identify the network spillover effect of religion on volunteering. We find that if nonreligious people have close friends with religious affiliations, they are more likely to volunteer for religious and nonreligious causes. However, this network spillover effect cannot be inferred from the relationship between volunteering and national or local level religious context—a common approach in the literature. In fact, we find that the average level of local religious participation is negatively associated with volunteering among the nonreligious in the United States. This novel finding suggests that to fully understand religion’s civic role in the wider community, we need to consider how religion might influence the civic life of people outside religious communities, not just those within them. Our findings also suggest that in spite of methodological advances, studies that purport to test mechanisms at one level of analysis by using data at a larger level of aggregation run a high risk of committing an ecological fallacy.

The impact of patient and public involvement in the work of the Dementias & Neurodegenerative Diseases Research Network (DeNDRoN): case studies

(i) To describe patient and public involvement (PPI) in a network promoting research in dementia and neurodegenerative diseases, in terms of activity at the different stages of the research cycle and within the different levels of the research network. (ii) To use case studies to try and answer the question: what benefits (if any) does PPI in research bring to the research process? PPI in health research is a central part of government policy, but the evidence base underpinning it needs strengthening. PPI allows exploration of feasibility, acceptability and relevance of hypotheses, assists in the precise definition of research questions and increases accrual to studies. However, the measurement of outcomes is methodologically difficult, because the impact of lay researchers may occur through team interactions and be difficult to untangle from the efforts of professional researchers. Opportunities for PPI in rapidly progressive diseases may be limited, and involvement of people with marked cognitive impairment is particularly challenging. (i) Description of PPI within the DeNDRoN network. (ii) Case studies of three research projects which asked for extra help from centrally organized PPI. PPI in research projects on the DeNDRoN portfolio may function at different levels, occurring at project, local research network and national level. Case studies of three research projects show different roles for PPI in research and different functions for centrally organized PPI, including contribution to remedial action in studies that are not recruiting to target, solving problems because of the complexity and sensitivity of the research topic, and linking researchers to PPI resources. The case studies suggest that centrally organized PPI can have 'diagnostic' and remedial functions in studies that are struggling to recruit and serve as reinforcement for study-level PPI in the complex and sensitive research topics that are typical in neurodegenerative diseases research. PPI may be actively sought by researchers, but the infrastructure of PPI is not yet so widespread in the research community that lay researchers are easy to find; a centrally organized PPI resource can assist in this situation.

Cross-approximate entropy of cortical local field potentials quantifies effects of anesthesia - a pilot study in rats

BackgroundAnesthetics dose-dependently shift electroencephalographic (EEG) activity towards high-amplitude, slow rhythms, indicative of a synchronization of neuronal activity in thalamocortical networks. Additionally, they uncouple brain areas in higher (gamma) frequency ranges possibly underlying conscious perception. It is currently thought that both effects may impair brain function by impeding proper information exchange between cortical areas. But what happens at the local network level? Local networks with strong excitatory interconnections may be more resilient towards global changes in brain rhythms, but depend heavily on locally projecting, inhibitory interneurons. As anesthetics bias cortical networks towards inhibition, we hypothesized that they may cause excessive synchrony and compromise information processing already on a small spatial scale. Using a recently introduced measure of signal independence, cross-approximate entropy (XApEn), we investigated to what degree anesthetics synchronized local cortical network activity. We recorded local field potentials (LFP) from the somatosensory cortex of three rats chronically implanted with multielectrode arrays and compared activity patterns under control (awake state) with those at increasing concentrations of isoflurane, enflurane and halothane.ResultsCortical LFP signals were more synchronous, as expressed by XApEn, in the presence of anesthetics. Specifically, XApEn was a monotonously declining function of anesthetic concentration. Isoflurane and enflurane were indistinguishable; at a concentration of 1 MAC (the minimum alveolar concentration required to suppress movement in response to noxious stimuli in 50% of subjects) both volatile agents reduced XApEn by about 70%, whereas halothane was less potent (50% reduction).ConclusionsThe results suggest that anesthetics strongly diminish the independence of operation of local cortical neuronal populations, and that the quantification of these effects in terms of XApEn has a similar discriminatory power as changes of spontaneous action potential rates. Thus, XApEn of field potentials recorded from local cortical networks provides valuable information on the anesthetic state of the brain.

Relationship between GABAergic interneurons migration and early neocortical network activity

Available evidence converges to suggest that during the early development of the cerebral cortex, the emergence of the spontaneous network activity chronologically overlap with the end of the cell migration period in the developing cortex. We approached the functional regulation of neuronal migration in a culture model of neocortical networks, using time lapses to detect migratory movements, calcium-imaging to assess the activity of migratory neurons, and immunocytochemical methods to identify the migratory cells retrospectively. In cell cultures, early physiological development and cell migration are reproduced at a local network level, thus allowing the study of the interrelationships between cell migration and network development independent of the topographical complexity. Neurons migrate at least until 12 days in vitro and GABAergic neurons migrate faster compared with non-GABAergic neurons. A decline of migratory activity was coincident with the development of spontaneous synchronous network activity. Migrating interneurons did not participate in synchronous network activity, but interneurons that ended cell migration during observation time frequently engaged in synchronous activity within less than an hour. Application of GABA(A) and ionotropic glutamate receptor antagonists significantly increased the number of migrating GABAergic neurons without changing the dynamics of the migratory movements. Thus, neurotransmitters released by early network activity might favor the termination of neuronal migration. These results reinforce the idea that network activity plays an important role in the development of late-born GABAergic cells.

Dual Time Scales for Categorical Decision Making in Auditory Cortex

Category formation allows us to group perceptual objects into meaningful classes and is fundamental to cognition. Categories can be derived from similarity relationships of object features by using prototypes or multiple exemplars, or from abstract relationships of features and rules . A variety of brain areas have been implicated in categorization processes, but mechanistic insights on the single-cell and local-network level are still rare and limited to the matching of individual objects to categories . For directional categorization of tone steps, as in melody recognition , abstract relationships between sequential events (higher or lower in frequency) have to be formed. To explore the neuronal mechanisms of this categorical identification of step direction, we trained monkeys for more than two years on a contour-discrimination task with multiple tone sequences. In the auditory cortex of these highly trained monkeys, we identified two interrelated types of neuronal firing: Increased phasic responses to tones categorically represented the reward-predicting downward frequency steps and not upward steps; subsequently, slow modulations of tonic firing predicted the behavioral decisions of the monkeys, including errors. Our results on neuronal mechanisms of categorical stimulus identification and of decision making attribute a cognitive role to auditory cortex, in addition to its role in signal processing.

The GABAA receptor-mediated recurrent inhibition in ventral compared with dorsal CA1 hippocampal region is weaker, decays faster and lasts less

Hippocampal functions appear to be segregated along the dorso-ventral axis of the structure. Differences at the cellular and local neuronal network level may be involved in this functional segregation. In this study the characteristics of CA1 recurrent inhibition (RI) were measured and compared between dorsal (DH, n = 95) and ventral (VH, n = 60) hippocampal slices, using recordings of suprathreshold field potentials. RI strength was estimated as the percentile decrease of the population spike (PS) amplitude evoked with an orthodromic stimulus (at the Schaffer collaterals) when preceded by an antidromic stimulus (at the alveus). Varying the interpulse interval (IPI) between the two stimuli, we estimated RI duration. Alvear stimulation produced significant PS suppression in both VH and DH at every IPI tested, from 10 to 270 ms. Moreover, gradually more oblique DH (but not VH) slices displayed increasing RI, which at IPIs < or = 125 ms was reversibly abolished by the GABAA receptor antagonist picrotoxin (10 microM). The GABAA-mediated RI, measured under the blockade of GABAB receptors, was weaker, decayed faster and lasted less in VH compared to DH slices, regardless of the slice orientation. Specifically, in VH compared to DH, the PS suppression at 20 ms was 34.4 +/- 4.5% versus 69.9 +/- 6.5% (P < 0.001), the time constant of RI decay was 29 +/- 2.4 versus 87.5 +/- 13.6 ms (P < 0.01) and the duration was 50 versus 125 ms (P < 0.001). Thus, GABAA-mediated RI may control the CA1 excitatory output less effectively in VH compared to DH. The observed dorso-ventral differences in RI contribute to the longitudinal diversification of the structure and may underlie to some extent the region-specificity of hippocampal functions.

Improving Prediction Accuracy in Mechanistic-Empirical Pavement Design Guide

Model calibration plays a fundamental role in the implementation of the mechanistic-empirical pavement design guide. The data used in the default calibration effort, which were afforded by the Long Term Pavement Performance (LTPP) database, have a network-level inference space. As implementation proceeds, state highway agencies may be inclined to calibrate at a local network level. However, with a focus on the calibration data set to local project-level conditions, model prediction error can be reduced further. Under this study, Nebraska Department of Roads Pavement Management System data were used to calibrate two design guide smoothness models at the local project level. The focused data set was categorized by annual daily truck traffic and surface layer thickness. Results showed that project-level calibrations reduced default model prediction error by nearly twice that of network-level calibration. This study offers a window into the accuracy that can be achieved with local focus calibrations of design...

Improving Prediction Accuracy in Mechanistic–Empirical Pavement Design Guide

Model calibration plays a fundamental role in the implementation of the mechanistic–empirical pavement design guide. The data used in the default calibration effort, which were afforded by the Long Term Pavement Performance (LTPP) database, have a network-level inference space. As implementation proceeds, state highway agencies may be inclined to calibrate at a local network level. However, with a focus on the calibration data set to local project-level conditions, model prediction error can be reduced further. Under this study, Nebraska Department of Roads Pavement Management System data were used to calibrate two design guide smoothness models at the local project level. The focused data set was categorized by annual daily truck traffic and surface layer thickness. Results showed that project-level calibrations reduced default model prediction error by nearly twice that of network-level calibration. This study offers a window into the accuracy that can be achieved with local focus calibrations of design guide prediction models.

Integrated imaging for neurosurgery

The authors address using the concept of multimodal bioimage integration at the local area network level, using 3D MRI and PET data of the human head. Here, integration is intended between structural and functional multidimensional images of the same body area of a patient. They analyze the role of present technology and standards (such as the X Window protocol) in providing the physician with a better understanding of the structure-to-function relationships of a given biological organ. They analyze the concept of integration intended as a tool to extract the significative information content from bioimages, i.e. to perform image analysis. The fusion of visual eidetic and linguistic knowledge, which plays an important role in medical diagnosis formation, is seen as a significant step towards obtaining quantitative evaluation of the relevant information content of bioimages. >