Revealing ensemble state transition patterns in multi-electrode neuronal recordings using hidden Markov models

In order to harness the computational capacity of dissociated cultured neuronal networks, it is necessary to understand neuronal dynamics and connectivity on a mesoscopic scale. To this end, this paper uncovers dynamic spatiotemporal patterns emerging from electrically stimulated neuronal cultures using hidden Markov models (HMMs) to characterize multi-channel spike trains as a progression of patterns of underlying states of neuronal activity. However, experimentation aimed at optimal choice of parameters for such models is essential and results are reported in detail. Results derived from ensemble neuronal data revealed highly repeatable patterns of state transitions in the order of milliseconds in response to probing stimuli.

Experiments into biology-technology interaction

In this paper a look is taken at how the use of implant and electrode technology can be employed to create biological brains for robots, to enable human enhancement and to diminish the effects of certain neural illnesses. In all cases the end result is to increase the range of abilities of the recipients. An indication is given of a number of areas in which such technology has already had a profound effect, a key element being the need for a clear interface linking a biological brain directly with computer technology. The emphasis is placed on practical scientific studies that have been and are being undertaken and reported on. The area of focus is the use of electrode technology, where either a connection is made directly with the cerebral cortex and/or nervous system or where implants into the human body are involved. The paper also considers robots that have biological brains in which human neurons can be employed as the sole thinking machine for a real world robot body.

The future of human-machine interaction: implant technology

In this paper a look is taken at how the use of implant and electrode technology can be employed to create biological brains for robots, to enable human enhancement and to diminish the effects of certain neural illnesses. In all cases the end result is to increase the range of abilities of the recipients. An indication is given of a number of areas in which such technology has already had a profound effect, a key element being the need for a clear interface linking a biological brain directly with computer technology. The emphasis is placed on practical scientific studies that have been and are being undertaken and reported on. The area of focus is the use of electrode technology, where either a connection is made directly with the cerebral cortex and/or nervous system or where implants into the human body are involved. The paper also considers robots that have biological brains in which human neurons can be employed as the sole thinking machine for a real world robot body.

Hybrid Brains - Biology, Technology Merger

In this paper an attempt has been made to take a look at how the use of implant and electrode technology can now be employed to create biological brains for robots, to enable human enhancement and to diminish the effects of certain neural illnesses. In all cases the end result is to increase the range of abilities of the recipients. An indication is given of a number of areas in which such technology has already had a profound effect, a key element being the need for a clear interface linking the human brain directly with a computer. An overview of some of the latest developments in the field of Brain to Computer Interfacing is also given in order to assess advantages and disadvantages. The emphasis is clearly placed on practical studies that have been and are being undertaken and reported on, as opposed to those speculated, simulated or proposed as future projects. Related areas are discussed briefly only in the context of their contribution to the studies being undertaken. The area of focus is notably the use of invasive implant technology, where a connection is made directly with the cerebral cortex and/or nervous system. Tests and experimentation which do not involve human subjects are invariably carried out a priori to indicate the eventual possibilities before human subjects are themselves involved. Some of the more pertinent animal studies from this area are discussed including our own involving neural growth. The paper goes on to describe human experimentation, in which neural implants have linked the human nervous system bi-directionally with technology and the internet. A view is taken as to the prospects for the future for this implantable computing in terms of both therapy and enhancement.

Establishing a connection between knowledge transfer and innovation diffusion

Successful innovation diffusion process may well take the form of knowledge transfer process. Therefore, the primary objectives of this paper include: first, to evaluate the interrelations between transfer of knowledge and diffusion of innovation; and second to develop a model to establish a connection between the two. This has been achieved using a four-step approach. The first step of the approach is to assess and discuss the theories relating to knowledge transfer (KT) and innovation diffusion (ID). The second step focuses on developing basic models for KT and ID, based on the key theories surrounding these areas. A considerable amount of literature has been written on the association between knowledge management and innovation, the respective fields of KT and ID. The next step, therefore, explores the relationship between innovation and knowledge management in order to identify the connections between the latter, i.e. KT and ID. Finally, step four proposes and develops an integrated model for KT and ID. As the developed model suggests the sub-processes of knowledge transfer can be connected to the innovation diffusion process in several instances as discussed and illustrated in the paper.

On the connection between dissipation enhancement in the ocean surface layer and Langmuir circulations

A mechanism for the enhancement of the viscous dissipation rate of turbulent kinetic energy (TKE) in the oceanic boundary layer (OBL) is proposed, based on insights gained from rapid-distortion theory (RDT). In this mechanism, which complements mechanisms purely based on wave breaking, preexisting TKE is amplified and subsequently dissipated by the joint action of a mean Eulerian wind-induced shear current and the Stokes drift of surface waves, the same elements thought to be responsible for the generation of Langmuir circulations. Assuming that the TKE dissipation rate epsilon saturates to its equilibrium value over a time of the order one eddy turnover time of the turbulence, a new scaling expression, dependent on the turbulent Langmuir number, is derived for epsilon. For reasonable values of the input parameters, the new expression predicts an increase of the dissipation rate near the surface by orders of magnitude compared with usual surface-layer scaling estimates, consistent with available OBL data. These results establish on firmer grounds a suspected connection between two central OBL phenomena: dissipation enhancement and Langmuir circulations.

Endogenous cholinergic tone modulates spontaneous network level neuronal activity in primary cortical cultures grown on multi-electrode arrays

Background Cortical cultures grown long-term on multi-electrode arrays (MEAs) are frequently and extensively used as models of cortical networks in studies of neuronal firing activity, neuropharmacology, toxicology and mechanisms underlying synaptic plasticity. However, in contrast to the predominantly asynchronous neuronal firing activity exhibited by intact cortex, electrophysiological activity of mature cortical cultures is dominated by spontaneous epileptiform-like global burst events which hinders their effective use in network-level studies, particularly for neurally-controlled animat (‘artificial animal’) applications. Thus, the identification of culture features that can be exploited to produce neuronal activity more representative of that seen in vivo could increase the utility and relevance of studies that employ these preparations. Acetylcholine has a recognised neuromodulatory role affecting excitability, rhythmicity, plasticity and information flow in vivo although its endogenous production by cortical cultures and subsequent functional influence upon neuronal excitability remains unknown. Results Consequently, using MEA electrophysiological recording supported by immunohistochemical and RT-qPCR methods, we demonstrate for the first time, the presence of intrinsic cholinergic neurons and significant, endogenous cholinergic tone in cortical cultures with a characterisation of the muscarinic and nicotinic components that underlie modulation of spontaneous neuronal activity. We found that tonic muscarinic ACh receptor (mAChR) activation affects global excitability and burst event regularity in a culture age-dependent manner whilst, in contrast, tonic nicotinic ACh receptor (nAChR) activation can modulate burst duration and the proportion of spikes occurring within bursts in a spatio-temporal fashion. Conclusions We suggest that the presence of significant endogenous cholinergic tone in cortical cultures and the comparability of its modulatory effects to those seen in intact brain tissues support emerging, exploitable commonalities between in vivo and in vitro preparations. We conclude that experimental manipulation of endogenous cholinergic tone could offer a novel opportunity to improve the use of cortical cultures for studies of network-level mechanisms in a manner that remains largely consistent with its functional role.

Connection between Caspian sea level variability and ENSO

The problem of the world greatest lake, the Caspian Sea, level changes attracts the increased attention due to its environmental consequences and unique natural characteristics. Despite the huge number of studies aimed to explain the reasons of the sea level variations the underlying mechanism has not yet been clarified. The important question is to what extent the CSL variability is linked to changes in the global climate system and to what extent it can be explained by internal natural variations in the Caspian regional hydrological system. In this study an evidence of a link between the El Niño/Southern Oscillation phenomenon and changes of the Caspian Sea level is presented. This link was also found to be dominating in numerical experiments with the ECHAM4 atmospheric general circulation model on the 20th century climate.

On the connection between the 1984 Atlantic warm event and the 1982-1983 ENSO

The warm event which spread in the tropical Atlantic during Spring-Summer 1984 is assumed to be partially initiated by atmospheric disturbances, themselves related to the major 1982–1983 El-Niño which occurred 1 year earlier in the Pacific. This paper tests such an hypothesis. For that purpose, an atmospheric general circulation model (AGCM) is forced by different conditions of climatic and observed sea surface temperature and an Atlantic ocean general circulation model (OGCM) is subsequently forced by the outputs of the AGCM. It is firstly shown that both the AGCM and the OGCM correctly behave when globally observed SST are used: the strengthening of the trades over the tropical Atlantic during 1983 and their subsequent weakening at the beginning of 1984 are well captured by the AGCM, and so is the Spring 1984 deepening of the thermocline in the eastern equatorial Atlantic, simulated by the OGCM. As assumed, the SST anomalies located in the El-Niño Pacific area are partly responsible for wind signal anomaly in the tropical Atlantic. Though this remotely forced atmospheric signal has a small amplitude, it can generate, in the OGCM run, an anomalous sub-surface signal leading to a flattening of the thermocline in the equatorial Atlantic. This forced oceanic experiment cannot explain the amplitude and phase of the observed sub-surface oceanic anomaly: part of the Atlantic ocean response, due to local interaction between ocean and atmosphere, requires a coupled approach. Nevertheless this experiment showed that anomalous conditions in the Pacific during 82–83 created favorable conditions for anomaly development in the Atlantic.

Classification of cortical microcircuits based on micro-electrode-array data from slices of rat barrel cortex

The bewildering complexity of cortical microcircuits at the single cell level gives rise to surprisingly robust emergent activity patterns at the level of laminar and columnar local field potentials (LFPs) in response to targeted local stimuli. Here we report the results of our multivariate data-analytic approach based on simultaneous multi-site recordings using micro-electrode-array chips for investigation of the microcircuitary of rat somatosensory (barrel) cortex. We find high repeatability of stimulus-induced responses, and typical spatial distributions of LFP responses to stimuli in supragranular, granular, and infragranular layers, where the last form a particularly distinct class. Population spikes appear to travel with about 33 cm/s from granular to infragranular layers. Responses within barrel related columns have different profiles than those in neighbouring columns to the left or interchangeably to the right. Variations between slices occur, but can be minimized by strictly obeying controlled experimental protocols. Cluster analysis on normalized recordings indicates specific spatial distributions of time series reflecting the location of sources and sinks independent of the stimulus layer. Although the precise correspondences between single cell activity and LFPs are still far from clear, a sophisticated neuroinformatics approach in combination with multi-site LFP recordings in the standardized slice preparation is suitable for comparing normal conditions to genetically or pharmacologically altered situations based on real cortical microcircuitry.

Concurrent recordings of bladder afferents from multiple nerves using a microfabricated PDMS microchannel electrode array

In this paper we present a compliant neural interface designed to record bladder afferent activity. We developed the implant's microfabrication process using multiple layers of silicone rubber and thin metal so that a gold microelectrode array is embedded within four parallel polydimethylsiloxane (PDMS) microchannels (5 mm long, 100 μm wide, 100 μm deep). Electrode impedance at 1 kHz was optimized using a reactive ion etching (RIE) step, which increased the porosity of the electrode surface. The electrodes did not deteriorate after a 3 month immersion in phosphate buffered saline (PBS) at 37 °C. Due to the unique microscopic topography of the metal film on PDMS, the electrodes are extremely compliant and can withstand handling during implantation (twisting and bending) without electrical failure. The device was transplanted acutely to anaesthetized rats, and strands of the dorsal branch of roots L6 and S1 were surgically teased and inserted in three microchannels under saline immersion to allow for simultaneous in vivo recordings in an acute setting. We utilized a tripole electrode configuration to maintain background noise low and improve the signal to noise ratio. The device could distinguish two types of afferent nerve activity related to increasing bladder filling and contraction. To our knowledge, this is the first report of multichannel recordings of bladder afferent activity.

Microchannel electrode interfaces to assess bladder afferent activity

By placing axons into polymeric micro-channels hosting embedded electrodes the extracellular amplitude of action potentials is greatly increased, allowing for robust recording and noise suppression. We are developing such an electrode interface to record electrical activity from bladder afferents to restore bladder control in patients suffering from spinal cord injury. Here we describe our microchannel electrode interface in terms of design, microfabrication and electrode characteristics and report on in vivo bladder function after implantation of teased dorsal rootlets within microchannels.

Compliant Multi-electrode Micro-channel Array for Recording Afferent Nerve Activity

We have fabricated a compliant neural interface to record afferent nerve activity. Stretchable gold electrodes were evaporated on a polydimethylsiloxane (PDMS) substrate and were encapsulated using photo-patternable PDMS. The built-in microstructure of the gold film on PDMS allows the electrodes to twist and flex repeatedly, without loss of electrical conductivity. PDMS microchannels (5mm long, 100μm wide, 100μm deep) were then plasma bonded irreversibly on top of the electrode array to define five parallel-conduit implants. The soft gold microelectrodes have a low impedance of ~200kΩ at the 1kHz frequency range. Teased nerves from the L6 dorsal root of an anaesthetized Sprague Dawley rat were threaded through the microchannels. Acute tripolar recordings of cutaneous activity are demonstrated, from multiple nerve rootlets simultaneously. Confinement of the axons within narrow microchannels allows for reliable recordings of low amplitude afferents. This electrode technology promises exciting applications in neuroprosthetic devices including bladder fullness monitors and peripheral nervous system implants.

The history curriculum and its personal connection to students from minority ethnic backgrounds

Whereas history is seen by some as crucial in developing a sense of identity and fostering social cohesion, it is however, often based around narrowly nationalistic views of the past, and yet little is known about how students relate to the past they are taught. Thus, this paper focuses on the history curriculum and the ways in which students aged 12-14, from different ethnic backgrounds, relate to it. Moreover, the small-scale study which enabled this paper, focused, in particular, on whether students enjoyed and valued history and whether they felt any sense of personal connection to the topics studied. Drawing on survey data collected from 102 students and focus group discussions with 42 students, from two high schools, the findings indicate that although many students enjoy history, they fail to fully understand its value. Additionally most students, especially those from minority ethnic backgrounds, feel a lack of personal connection to the past, as they do not see themselves in the history they are taught.