The effect of electrical stimulation on corticospinal excitability is dependent on application duration: a same subject pre-post test design

Background: In humans, corticospinal excitability is known to increase following motor electrical stimulation (ES) designed to mimic a voluntary contraction. However, whether the effect is equivalent with different application durations and whether similar effects are apparent for short and long applications is unknown. The aim of this study was to investigate whether the duration of peripheral motor ES influenced its effect on corticospinal excitability

Day differences in the cortisol awakening response predict day differences in synaptic plasticity in the brain

The cortisol awakening response (CAR) is the most prominent, dynamic and variable part of the circadian pattern of cortisol secretion. Despite this its precise purpose is unknown. Aberrant patterns of the CAR are associated with impaired physical and mental health and reduced cognitive function, suggesting that it may have a pervasive role or roles. It has been suggested that the CAR primes the brain for the expected demands of the day but the mechanisms underlying this process are unknown. We examined temporal covariation of the CAR and rapid transcranial magnetic stimulation (rTMS)-induced long term depression (LTD)-like responses in the motor cortex. Plasticity was evaluated across 180 measures from 5 time points on 4 sessions across 9 researcher participants, mean age 25 ± 2.5 years. Plasticity estimates were obtained in the afternoon after measurement of the CAR on 4 days, at least 3 days apart. As both CAR magnitude and rTMS-induced responses are variable across days we hypothesised that days with larger than individual average CARs would be associated with a greater than individual average plasticity response. This was confirmed by mixed regression modelling where variation in the CAR predicted variation in rTMS-induced responses (Df: 1, 148.24; F: 10.41; p=0.002). As the magnitude of the CAR is regulated by the ‘master’ circadian CLOCK, and synaptic plasticity is known to be modulated by peripheral ‘slave’ CLOCK genes, we suggest that the CAR may be a mediator between the master and peripheral circadian systems to entrain daily levels of synaptic plasticity

Human‐mediated dispersal and disturbance shape the metapopulation dynamics of a long‐lived herb

As anthropogenic impacts on the natural world escalate, there is increasing interest in the role of humans in dispersing seeds. But the consequences of this Human‐Mediated Dispersal (HMD) on plant spatial dynamics are little studied. In this paper, we ask how secondary dispersal by HMD affects the dynamics of a natural plant metapopulation. In addition to dispersal between patches, we suggest within‐patch processes can be critical. To address this, we assess how variation in local population dynamics, caused by small‐scale disturbances, affects metapopulation size. We created an empirically based model with stochastic population dynamics and dispersal among patches, which represented a real‐world, cliff‐top metapopulation of wild cabbage Brassica oleracea. We collected demographic data from multiple populations by tagging plants over eight years. We assessed seed survival, and establishment and survival of seedlings in intact vegetation vs. small disturbances. We modeled primary dispersal by wind using field data and used experimental data on secondary HMD by hikers. We monitored occupancy patterns over a 14‐yr period in the real metapopulation. Disturbance had large effects on local population growth rates, by increasing seedling establishment and survival. This meant that the modeled metapopulation grew in size only when the area disturbed in each patch was above 35%. In these growing metapopulations, although only 0.2% of seeds underwent HMD, this greatly enhanced metapopulation growth rates. Similarly, HMD allowed more colonizations in declining metapopulations under low disturbance, and this slowed the rate of decline. The real metapopulation showed patterns of varying patch occupancy over the survey years, which were related to habitat quality, but also positively to human activity along the cliffs, hinting at beneficial effects of humans. These findings illustrate that realistic changes to dispersal or demography, specifically by humans, can have fundamental effects on the viability of a species at the landscape scale

Historical data reveal contrasting habitat amount relationships with plant biodiversity

Assessing habitat loss effects on biodiversity is a major focus of ecological research. The relationship between habitat amount and biodiversity, postulated in the habitat amount hypothesis, is usually assessed at one point in time, which does not account for habitat loss as a temporal process. We examined habitat amount effects at two time periods, 1930s and 2010s, using plant data from three semi-natural habitats: calcareous grassland, heathland and broadleaved woodland, across Dorset, southern England. Woodlands, which changed little in area over the time period, showed minimal effects of habitat amount on species occurrence in both time periods. For grassland and heathland, which had undergone severe losses over the study period, we found the expected positive relationship in the 2010s, but the relationship was negative for these habitats in the 1930s. We explored possible reasons for this result. Total perimeter-to-area ratio (TPAR) showed positive effects in the 1930s for grassland and heathland, suggesting effects of habitat configuration, specifically edge. However, TPAR was highly correlated with habitat amount so this finding is speculative. One possible explanation for the relationships with habitat amount, and the change between the two periods could be the quality of the surrounding matrix. In the 1930s, the landscape was less intensified and was dominated by semi-natural habitats, whereas by the 2010s much had been converted to arable and intensive grasslands. We speculate that species could likely utilise the matrix to a greater degree in the 1930s compared with the 2010s when the matrix was more hostile, thereby decreasing the importance of habitat amount in the 1930s compared with the 2010s. These findings have important implications for conservation, as they show the importance of context (i.e. matrix quality) in determining the relationship between habitat amount and biodiversity

Historical data reveal contrasting habitat amount relationships with plant biodiversity

Assessing habitat loss effects on biodiversity is a major focus of ecological research. The relationship between habitat amount and biodiversity, postulated in the habitat amount hypothesis, is usually assessed at one point in time, which does not account for habitat loss as a temporal process. We examined habitat amount effects at two time periods, 1930s and 2010s, using plant data from three semi-natural habitats: calcareous grassland, heathland and broadleaved woodland, across Dorset, southern England. Woodlands, which changed little in area over the time period, showed minimal effects of habitat amount on species occurrence in both time periods. For grassland and heathland, which had undergone severe losses over the study period, we found the expected positive relationship in the 2010s, but the relationship was negative for these habitats in the 1930s. We explored possible reasons for this result. Total perimeter-to-area ratio (TPAR) showed positive effects in the 1930s for grassland and heathland, suggesting effects of habitat configuration, specifically edge. However, TPAR was highly correlated with habitat amount so this finding is speculative. One possible explanation for the relationships with habitat amount, and the change between the two periods could be the quality of the surrounding matrix. In the 1930s, the landscape was less intensified and was dominated by semi-natural habitats, whereas by the 2010s much had been converted to arable and intensive grasslands. We speculate that species could likely utilise the matrix to a greater degree in the 1930s compared with the 2010s when the matrix was more hostile, thereby decreasing the importance of habitat amount in the 1930s compared with the 2010s. These findings have important implications for conservation, as they show the importance of context (i.e. matrix quality) in determining the relationship between habitat amount and biodiversity

Plasticity and dystonia: a hypothesis shrouded in variability.

Studying plasticity mechanisms with Professor John Rothwell was a shared highlight of our careers. In this article, we discuss non-invasive brain stimulation techniques which aim to induce and quantify plasticity, the mechanisms and nature of their inherent variability and use such observations to review the idea that excessive and abnormal plasticity is a pathophysiological substrate of dystonia. We have tried to define the tone of our review by a couple of Professor John Rothwell's many inspiring characteristics; his endless curiosity to refine knowledge and disease models by scientific exploration and his wise yet humble readiness to revise scientific doctrines when the evidence is supportive. We conclude that high variability of response to non-invasive brain stimulation plasticity protocols significantly clouds the interpretation of historical findings in dystonia research. There is an opportunity to wipe the slate clean of assumptions and armed with an informative literature in health, re-evaluate whether excessive plasticity has a causal role in the pathophysiology of dystonia

Direct-current-dependent shift of theta-burst-induced plasticity in the human motor cortex

Animal studies using polarising currents have shown that induction of synaptic long-term potentiation (LTP) and long-term depression (LTD) by bursts of patterned stimulation is affected by the membrane potential of the postsynaptic neurone. The aim of the present experiments was to test whether it is possible to observe similar phenomena in humans with the aim of improving present protocols of inducing synaptic plasticity for therapeutic purposes. We tested whether the LTP/LTD-like after effects of transcranial theta-burst stimulation (TBS) of human motor cortex, an analogue of patterned electrical stimulation in animals, were affected by simultaneous transcranial direct-current stimulation (tDCS), a non-invasive method of polarising cortical neurones in humans. Nine healthy volunteers were investigated in a single-blind, balanced cross-over study; continuous TBS (cTBS) was used to introduce LTD-like after effects, whereas intermittent TBS (iTBS) produced LTP-like effects. Each pattern was coupled with concurrent application of tDCS (<200 s, anodal, cathodal, sham). Cathodal tDCS increased the response to iTBS and abolished the effects of cTBS. Anodal tDCS changed the effects of cTBS towards facilitation, but had no impact on iTBS. Cortical motor thresholds and intracortical inhibitory/facilitatory networks were not altered by any of the stimulation protocols. We conclude that the after effects of TBS can be modulated by concurrent tDCS. We hypothesise that tDCS changes the membrane potential of the apical dendrites of cortical pyramidal neurones and that this changes the response to patterned synaptic input evoked by TBS. The data show that it may be possible to enhance LTP-like plasticity after TBS in the human cortex

Does agricultural intensification cause tipping points in ecosystem services?

Context: Agricultural intensification is being widely pursued as a policy option to improve food security and human development. Yet, there is a need to understand the impact of agricultural intensification on the provision of multiple ecosystem services, and to evaluate the possible occurrence of tipping points. Objectives: I.To quantify and assess the long-term spatial dynamics of ecosystem service (ES) provision in a landscape undergoing agricultural intensification at four time points 1930, 1950, 1980 and 2015.II.Determine if thresholds or tipping points in ES provision may have occurred and if there are any detectable impacts on economic development and employment. Methods: We used the InVEST suite of software models together with a time series of historical land cover maps and an Input–Output model to evaluate these dynamics over an 85-year period in the county of Dorset, southern England. Results: Results indicated that trends in ES were often non-linear, highlighting the potential for abrupt changes in ES provision to occur in response to slight changes in underlying drivers. Despite the fluctuations in provision of different ES, overall economic activity increased almost linearly during the study interval, in line with the increase in agricultural productivity. Conclusions: Such non-linear thresholds in ES will need to be avoided in the future by approaches aiming to deliver sustainable agricultural intensification. A number of positive feedback mechanisms are identified that suggest these thresholds could be considered as tipping points. However, further research into these feedbacks is required to fully determine the occurrence of tipping points in agricultural systems

How to transition to reduced-meat diets that benefit people and the planet

Initiation Grant of IIT Kanpur, India (project number 2018386); Wellcome Trust, Our Planet Our Health (Livestock, Environment and People - LEAP), award number 205212/Z/16/Z. L.E.R.; research program NE/N018125/1 LTS-M ASSIST -Achieving Sustainable Agricultural Systems, funded by NERC and BBSRC

Area 5 Influences Excitability within the Primary Motor Cortex in Humans

In non-human primates, Brodmann's area 5 (BA 5) has direct connectivity with primary motor cortex (M1), is largely dedicated to the representation of the hand and may have evolved with the ability to perform skilled hand movement. Less is known about human BA 5 and its interaction with M1 neural circuits related to hand control. The present study examines the influence of BA 5 on excitatory and inhibitory neural circuitry within M1 bilaterally before and after continuous (cTBS), intermittent (iTBS), and sham theta-burst stimulation (sham TBS) over left hemisphere BA 5. Using single and paired-pulse TMS, measurements of motor evoked potentials (MEPs), short interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were quantified for the representation of the first dorsal interosseous muscle. Results indicate that cTBS over BA 5 influences M1 excitability such that MEP amplitudes are increased bilaterally for up to one hour. ITBS over BA 5 results in an increase in MEP amplitude contralateral to stimulation with a delayed onset that persists up to one hour. SICI and ICF were unaltered following TBS over BA 5. Similarly, F-wave amplitude and latency were unaltered following cTBS over BA 5. The data suggest that BA 5 alters M1 output directed to the hand by influencing corticospinal neurons and not interneurons that mediate SICI or ICF circuitry. Targeting BA 5 via cTBS and iTBS is a novel mechanism to powerfully modulate activity within M1 and may provide an avenue for investigating hand control in healthy populations and modifying impaired hand function in clinical populations