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

A cannabigerol-rich Cannabis sativa extract, devoid of ∆9-tetrahydrocannabinol, elicits hyperphagia in rats

Objective: Non-psychoactive phytocannabinoids (pCBs) from Cannabis sativa may represent novel therapeutic options for cachexia due to their pleiotropic pharmacological activities, including appetite stimulation. We have recently shown that purified cannabigerol (CBG) is a novel appetite stimulant in rats. As standardised extracts from Cannabis chemotypes dominant in one pCB (botanical drug substances (BDS)) often show greater efficacy and/or potency than purified pCBs, we investigated the effects of a CBG-rich BDS, devoid of psychoactive ∆9-THC, on feeding behaviour. Methods: Following a 2 hour pre-feed satiation procedure, 16 male Lister-hooded rats were administered CBG-BDS (at 30-240 mg/kg) or vehicle. Food intake, meal pattern microstructure and locomotor activity were recorded over 2 hours. Results: Total food intake was increased by 120 and 240mg/kg CBG-BDS vs vehicle (1.53g and 1.36g, respectively, vs 0.56g; p<0.05 and p<0.01). Latency to feeding onset was dose-dependently decreased by all doses (p<0.05-0.01), and 120 and 240mg/kg doses increased both the number of meals consumed (p<0.01) and cumulative size of the first 2 meals (p<0.05 and p<.0.01). No significant effect was observed on ambulatory activity or rearing behaviour. Conclusions: CBG-BDS is a novel appetite stimulant, which may have greater potency than purified CBG, despite the absence of ∆9-THC in the extract

Childhood IQ and marriage by mid-life: the Scottish Mental Survey 1932 and the Midspan Studies

The study examined the influence of IQ at age 11 years on marital status by mid-adulthood. The combined databases of the Scottish Mental Survey 1932 and the Midspan studies provided data from 883 subjects. With regard to IQ at age 11, there was an interaction between sex and marital status by mid-adulthood (p &#61; 0.0001). Women who had ever-married achieved mean lower childhood IQ scores than women who had never-married (p &#60; 0.001). Conversely, there was a trend for men who had ever-married to achieve higher childhood IQ scores than men who had never-married (p &#61; 0.07). In men, the odds ratio of ever marrying was 1.35 (95&#37; CI 0.98–1.86&#59; p &#61; 0.07) for each standard deviation increase in childhood IQ. Among women, the odds ratio of ever marrying by mid-life was 0.42 (95&#37; CI 0.27–0.64; p &#61; 0.0001) for each standard deviation increase in childhood IQ. Mid-life social class had a similar association with marriage, with women in more professional jobs and men in more manual jobs being less likely to have ever-married by mid-life. Adjustment for the effects of mid-life social class and height on the association between childhood IQ and later marriage, and vice versa, attenuated the effects somewhat, but suggested that IQ, height and social class acted partly independently

“I can’t skip it”: does free report improve accuracy in false memories?

Strategic monitoring of recognition memory by children and adults was examined using a semantic DRM procedure. Children (7- and 10-year-olds) and adults (overall N?=?393) studied lists of semantically related words either incidentally or intentionally and were tested with old items, new items and critical lures to judge as old or new. Participants either made a decision about every item they saw (forced report), or they had the opportunity to withhold answers they were uncertain about (free report). Children were less likely to withhold an answer than adults. However, 7-year-olds were more able to resist false memories when given the opportunity to withhold an answer compared to 10-year-olds or adults. In contrast, adults were unable to improve false memory accuracy. These data suggest that once semantically induced false memories have been encoded they are amenable to strategic monitoring at retrieval in children but not adults

Cannabidiol (CBD) improves survival and behavioural comorbidities of Dravet syndrome in mice

Background and Purpose Dravet syndrome is a severe, genetic form of paediatric epilepsy associated with premature mortality and comorbidities such as anxiety, depression, autism, motor dysfunction, and memory deficits. Cannabidiol is an approved anticonvulsive drug in USA and Europe for seizures associated with Dravet syndrome therapy in patients 2 years of age and older; we investigated its potential to prevent premature mortality and improve associated comorbidities. Experimental Approach The efficacy of sub-chronic cannabidiol administration in two mouse models which reproduce characteristics of Dravet syndrome was investigated. The effect of cannabidiol on neonatal welfare and survival was studied using Scn1a-/- mice. We then used a hybrid, heterozygote Scn1a+/- mouse model to study the effect of cannabidiol on survival and behavioural comorbidities; motor deficits (rotarod and static-beam test), gait abnormality (gait test), social anxiety (social interaction test), anxiety-like (elevated plus maze) and depressive-like behaviours (sucrose preference test) and cognitive impairment (radial arm maze test). Key Results In Scn1a-/- mice, cannabidiol increased survival and delayed worsening of neonatal welfare. In Scn1a+/- mice chronic cannabidiol administration did not show any adverse effect on motor function and gait, reduced premature mortality, improved social behaviour and memory function, and reduced anxiety-like and depressive-like behaviours. Conclusion and Implications We are the first to demonstrate a potential disease-modifying effect of cannabidiol in animal models of Dravet syndrome. cannabidiol treatment reduced premature mortality and improved several behavioural comorbidities in Dravet syndrome mice. These crucial findings may be translated into human therapy to address behavioural comorbidities associated with Dravet syndrome

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

Introductory programming: a systematic literature review

As computing becomes a mainstream discipline embedded in the school curriculum and acts as an enabler for an increasing range of academic disciplines in higher education, the literature on introductory programming is growing. Although there have been several reviews that focus on specific aspects of introductory programming, there has been no broad overview of the literature exploring recent trends across the breadth of introductory programming. This paper is the report of an ITiCSE working group that conducted a systematic review in order to gain an overview of the introductory programming literature. Partitioning the literature into papers addressing the student, teaching, the curriculum, and assessment, we explore trends, highlight advances in knowledge over the past 15 years, and indicate possible directions for future research

The neurogenesis of P1 and N1: a concurrent EEG/LFP study

It is generally recognised that event related potentials (ERPs) of electroencephalogram (EEG) primarily reflect summed post-synaptic activity of the local pyramidal neural population(s). However, it is still not understood how the positive and negative deflections (e.g. P1, N1 etc) observed in ERP recordings are related to the underlying excitatory and inhibitory post-synaptic activity. We investigated the neurogenesis of P1 and N1 in ERPs by pharmacologically manipulating inhibitory post-synaptic activity in the somatosensory cortex of rodent, and concurrently recording EEG and local field potentials (LFPs). We found that the P1 wave in the ERP and LFP of the supragranular layers is determined solely by the excitatory post-synaptic activity of the local pyramidal neural population, as is the initial segment of the N1 wave across cortical depth. The later part of the N1 wave was modulated by inhibitory post-synaptic activity, with its peak and the pulse width increasing as inhibition was reduced. These findings suggest that the temporal delay of inhibition with respect to excitation observed in intracellular recordings is also reflected in extracellular field potentials (FPs), resulting in a temporal window during which only excitatory post-synaptic activity and leak channel activity are recorded in the ERP and evoked LFP time series. Based on these findings, we provide clarification on the interpretation of P1 and N1 in terms of the excitatory and inhibitory post-synaptic activities of the local pyramidal neural population(s)

Childhood socioeconomic position and objectively measured physical capability levels in adulthood: a systematic review and meta-analysis

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and Findings:&lt;/b&gt; Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.&lt;/p&gt