Long lasting modulation of cortical oscillations after continuous theta burst transcranial magnetic stimulation

Transcranial magnetic theta burst stimulation (TBS) differs from other high-frequency rTMS protocols because it induces plastic changes up to an hour despite lower stimulus intensity and shorter duration of stimulation. However, the effects of TBS on neuronal oscillations remain unclear. In this study, we used electroencephalography (EEG) to investigate changes of neuronal oscillations after continuous TBS (cTBS), the protocol that emulates long-term depression (LTD) form of synaptic plasticity. We randomly divided 26 healthy humans into two groups receiving either Active or Sham cTBS as control over the left primary motor cortex (M1). Post-cTBS aftereffects were assessed with behavioural measurements at rest using motor evoked potentials (MEPs) and at active state during the execution of a choice reaction time (RT) task in combination with continuous electrophysiological recordings. The cTBS-induced EEG oscillations were assessed using event-related power (ERPow), which reflected regional oscillatory activity of neural assemblies of θ (4-7.5 Hz), low α (8-9.5 Hz), μ (10-12.5 Hz), low β (13-19.5 Hz), and high β (20-30 Hz) brain rhythms. Results revealed 20-min suppression of MEPs and at least 30-min increase of ERPow modulation, suggesting that besides MEPs, EEG has the potential to provide an accurate cortical readout to assess cortical excitability and to investigate the interference of cortical oscillations in the human brain post-cTBS. We also observed a predominant modulation of β frequency band, supporting the hypothesis that cTBS acts more on cortical level. Theta oscillations were also modulated during rest implying the involvement of independent cortical theta generators over the motor network post cTBS. This work provided more insights into the underlying mechanisms of cTBS, providing a possible link between synchronised neural oscillations and LTD in humans.     

Human reaction time variability changes from low intensity 3-Hz and 10-Hz electric fields: Interactions with stimulus pattern,sex and field intensity

Eighty simple reaction times (RT) to the onset of a light stimulus during 40 min of 3 successive 10-min exposures to 3-Hz and 10-Hz electric field were measured for each of 70 human male and female subjects exposed to either 3 0 V/m, 0.3 V/m or sham field conditions. The electric fields were applied horizontally across the upper half of the subject who was seated in a Faraday cage during the experiment. Two methods of presenting the RT-stimulus (light onset) were used which incorporated rest or no rest periods. No significant differences in mean RT were noted between sexes, intensities or frequency changes. Significant sex, intensity and frequency interactions were found in the amount of RT variability as measured by the RT standard deviation of 20 trial blocks. However, the magnitude of the effects was quite small and may be of little practical importance.     

Effect of spike-timing-dependent plasticity on stochastic burst synchronization in a scale-free neuronal network

We consider an excitatory population of subthreshold Izhikevich neurons which cannot fire spontaneously without noise. As the coupling strength passes a threshold, individual neurons exhibit noise-induced burstings. This neuronal population has adaptive dynamic synaptic strengths governed by the spike-timing-dependent plasticity (STDP). However, STDP was not considered in previous works on stochastic burst synchronization (SBS) between noise-induced burstings of sub-threshold neurons. Here, we study the effect of additive STDP on SBS by varying the noise intensity D in the Barabási–Albert scale-free network (SFN). One of our main findings is a Matthew effect in synaptic plasticity which occurs due to a positive feedback process. Good burst synchronization (with higher bursting measure) gets better via long-term potentiation (LTP) of synaptic strengths, while bad burst synchronization (with lower bursting measure) gets worse via long-term depression (LTD). Consequently, a step-like rapid transition to SBS occurs by changing D, in contrast to a relatively smooth transition in the absence of STDP. We also investigate the effects of network architecture on SBS by varying the symmetric attachment degree \(l^*\) and the asymmetry parameter \(\Delta l\) in the SFN, and Matthew effects are also found to occur by varying \(l^*\) and \(\Delta l\). Furthermore, emergences of LTP and LTD of synaptic strengths are investigated in details via our own microscopic methods based on both the distributions of time delays between the burst onset times of the pre- and the post-synaptic neurons and the pair-correlations between the pre- and the post-synaptic instantaneous individual burst rates (IIBRs). Finally, a multiplicative STDP case (depending on states) with soft bounds is also investigated in comparison with the additive STDP case (independent of states) with hard bounds. Due to the soft bounds, a Matthew effect with some quantitative differences is also found to occur for the case of multiplicative STDP.     

Toward establishing a therapeutic window for rTMS by theta burst stimulation

In this issue of Neuron, Huang et al. show that a version of the classic theta burst stimulation protocol used to induce LTP/LTD in brain slices can be adapted to a transcranial magnetic stimulation (TMS) protocol to rapidly produce long lasting (up to an hour), reversible effects on motor cortex physiology and behavior. These results may have important implications for the development of clinical applications of rTMS in the treatment of depression, epilepsy, Parkinson's, and other diseases.     

Muscle metabolic status and acid-base balance during 10-s work:5-s recovery intermittent and continuous exercise

Gastrocnemius muscle phosphocreatine ([PCr]) and hydrogen ion ([H(+)]) were measured using (31)P-magnetic resonance spectroscopy during repeated bouts of 10-s heavy-intensity (HI) exercise and 5-s rest compared with continuous (CONT) HI exercise. Recreationally active male subjects (n = 7; 28 yr ± 9 yr) performed on separate occasions 12 min of isotonic plantar flexion (0.75 Hz) CONT and intermittent (INT; 10-s exercise, 5-s rest) exercise. The HI power output in both CONT and INT was set at 50% of the difference between the power output associated with the onset of intracellular acidosis and peak exercise determined from a prior incremental plantar flexion protocol. Intracellular concentrations of [PCr] and [H(+)] were calculated at 4 s and 9 s of the work period and at 4 s of the rest period in INT and during CONT exercise. [PCr] and [H(+)] (mean ± SE) were greater at 4 s of the rest periods vs. 9 s of exercise over the course of the INT exercise bout: [PCr] (20.7 mM ± 0.6 vs. 18.7 mM ± 0.5; P < 0.01); [H(+)] (370 nM ± 13.50 vs. 284 nM ± 13.6; P < 0.05). Average [H(+)] was similar for CONT vs. INT. We therefore suggest that there is a glycolytic contribution to ATP recovery during the very short rest period (<5 s) of INT and that the greater average power output of CONT did not manifest in greater [H(+)] and greater glycolytic contribution compared with INT exercise.     

Multigeneration reproductive toxicity assessment of 60-Hz magnetic fields using a continuous breeding protocol in rats

Male and female reproductive functions have been proposed as possibly sensitive targets for the biological effects of 60-Hz (power frequency) magnetic fields (MF). However, experimental data relevant to this hypothesized association are very limited. In the present study, the "reproductive assessment by continuous breeding" design was used to identify possible effects of MF exposure on reproductive performance, fetal development, and early postnatal growth in rats. Groups of age-matched Sprague-Dawley rats (40 breeding pairs/group) were exposed continuously (18.5 hr per day) to linearly polarized, transient-free 60-Hz MF at field strengths of 0 Gauss (G; sham control), 0.02 G, 2.0 G, or 10.0 G. An additional group of 40 breeding pairs received intermittent (1 hr on/1 hr off) exposure to 10.0 G fields. F0 breeding pairs were exposed to MF or sham fields for 1 week prior to mating, during a 14-week period of cohabitation, and during a 3-week holding period after cohabitation. The duration of the cohabitation period was selected to be sufficient for the delivery of five litters in the sham control group. Pups from the final F1 litter from each breeding pair were exposed to MF or sham fields until sexual maturity, were cohabitated in MF or sham fields for 7 days with nonsiblings from the same exposure group, and were held in the MF or sham fields for 22 days to permit delivery of F2 pups for evaluation. No evidence of exposure-related toxicity was identified in any rat in the F0, F1, or F2 generations. Fetal viability and body weights in all litters of groups exposed to MF were comparable to those of sham controls. No significant differences between sham controls and MF-exposed groups were seen in any measure of reproductive performance (litters/breeding pair, percent fertile pairs, latency to parturition, litter size, or sex ratio) in either the F0 or F1 generation. Exposure of Sprague-Dawley rats to 60-Hz MF strengths of up to 10.0 G either during their peak reproductive period (F0) or during gestation and throughout their life span (F1) has no biologically significant effects on reproductive performance. These results do not support the hypothesis that exposure to pure, linearly polarized 60-Hz MF is a significant reproductive or developmental toxicant.     

Calcium dependent plasticity applied to repetitive transcranial magnetic stimulation with a neural field model

The calcium dependent plasticity (CaDP) approach to the modeling of synaptic weight change is applied using a neural field approach to realistic repetitive transcranial magnetic stimulation (rTMS) protocols. A spatially-symmetric nonlinear neural field model consisting of populations of excitatory and inhibitory neurons is used. The plasticity between excitatory cell populations is then evaluated using a CaDP approach that incorporates metaplasticity. The direction and size of the plasticity (potentiation or depression) depends on both the amplitude of stimulation and duration of the protocol. The breaks in the inhibitory theta-burst stimulation protocol are crucial to ensuring that the stimulation bursts are potentiating in nature. Tuning the parameters of a spike-timing dependent plasticity (STDP) window with a Monte Carlo approach to maximize agreement between STDP predictions and the CaDP results reproduces a realistically-shaped window with two regions of depression in agreement with the existing literature. Developing understanding of how TMS interacts with cells at a network level may be important for future investigation.     

Theta burst stimulation of the human motor cortex

It has been 30 years since the discovery that repeated electrical stimulation of neural pathways can lead to long-term potentiation in hippocampal slices. With its relevance to processes such as learning and memory, the technique has produced a vast literature on mechanisms of synaptic plasticity in animal models. To date, the most promising method for transferring these methods to humans is repetitive transcranial magnetic stimulation (rTMS), a noninvasive method of stimulating neural pathways in the brain of conscious subjects through the intact scalp. However, effects on synaptic plasticity reported are often weak, highly variable between individuals, and rarely last longer than 30 min. Here we describe a very rapid method of conditioning the human motor cortex using rTMS that produces a controllable, consistent, long-lasting, and powerful effect on motor cortex physiology and behavior after an application period of only 20-190 s.     

Stochastic theory of early viral infection: continuous versus burst production of virions

Viral production from infected cells can occur continuously or in a burst that generally kills the cell. For HIV infection, both modes of production have been suggested. Standard viral dynamic models formulated as sets of ordinary differential equations can not distinguish between these two modes of viral production, as the predicted dynamics is identical as long as infected cells produce the same total number of virions over their lifespan. Here we show that in stochastic models of viral infection the two modes of viral production yield different early term dynamics. Further, we analytically determine the probability that infections initiated with any number of virions and infected cells reach extinction, the state when both the population of virions and infected cells vanish, and show this too has different solutions for continuous and burst production. We also compute the distributions of times to establish infection as well as the distribution of times to extinction starting from both a single virion as well as from a single infected cell for both modes of virion production.     

Muscle development in dendrobranchiate shrimp, with comparison with Artemia

The muscle pattern of malacostracan and entomostracan crustacean nauplius larvae was compared using fluorescent phallotoxins. In the dendrobranchiate malacostracan Sicyonia ingentis, F-actin staining was first detected in limb setae at 12 h, likely within sensory nerves. Staining of F-actin was detected in the trunk at 15 h and grew into the naupliar limbs. Sarcomeres were detected at 19 h, identifying the structures as extrinsic limb muscles. The extrinsic limb muscles enlarged but retained their general pattern during the later nauplius stages. Longitudinal trunk muscles and circumferential visceral muscle (VM) developed in the post-naupliar region during nauplius instars 4 and 5, at the time when the gut also formed. In the anostracan branchiopod Artemia salina, the newly hatched nauplius contained an extensive system of extrinsic and intrinsic limb muscles. The gut was almost complete at hatching, along with its associated circumferential VM. Muscles similar in position and structure could be identified in nauplii from the two taxa, but different anatomical origins of extrinsic muscles were evident. Whether the naupliar limb muscles are homologous in malacostracans and branchiopods remains an open question. The strong musculature of the dendrobranchiate naupliar limbs correlates with the use of all three pairs of limbs for swimming.     

Traits correlate with invasive success more than plasticity: A comparison of three Centaurea congeners

The importance of phenotypic plasticity for successful invasion by exotic plant species has been well studied, but with contradictory and inconclusive results. However, many previous studies focused on comparisons of native and invasive species that co‐occur in a single invaded region, and thus on species with potentially very different evolutionary histories. We took a different approach by comparing three closely related Centaurea species: the highly invasive C. solstitialis, and the noninvasive but exotic C. calcitrapa and C. sulphurea. These species have overlapping distributions both in their native range of Spain and in their non‐native range of California. We collected seeds from 3 to 10 populations from each region and species and grew them in common garden greenhouse conditions to obtain an F1 generation in order to reduce maternal effects. Then, F1 seeds were grown subjected to simulated herbivory, variation in nutrient availability, and competition, to explore plasticity in the responses to these conditions. We found little variation in phenotypic plasticity among species and regions, but C. solstitialis plants from California produced more biomass in competition than their Spanish conspecifics. This species also had the highest relative growth rates when in competition and when grown under low nutrient availability. Noninvasive congeners produced intermediate or opposite patterns.     

Defenselike patterns of spinal sympathetic outflow involving the 10-Hz and cardiac-related rhythms

Frequency- and time-domain analyses were used to compare the effects of stimulation of the defense region of the midbrain periaqueductal gray (PAG) on the 10-Hz and cardiac-related discharges of sympathetic nerves with different cardiovascular targets. In baroreceptor-denervated cats anesthetized with urethan, PAG stimulation at frequencies equal to or higher (up to 25 Hz) than that of the free-running 10-Hz rhythm produced an immediate and sustained decrease in vertebral sympathetic nerve (VN) 10-Hz activity but increased the 10-Hz discharges of the inferior cardiac (CN) and renal (RN) nerves. In baroreceptor-innervated cats, VN cardiac-related activity was initially unchanged by high-frequency (25-Hz) PAG stimulation, or it increased along with that in the CN and RN. Later, during high-frequency PAG stimulation, when the rise in blood pressure approached its peak, VN cardiac-related activity usually was reduced below control level. At this time, the increases in CN and RN cardiac-related discharges were largely sustained. The cardiac-related discharges of the three nerves were unaffected by PAG stimulation at frequencies just below or just above that of the heartbeat. We conclude that the defenselike pattern of spinal sympathetic outflow involving the 10-Hz rhythm is different in mechanism and character from that involving the cardiac-related rhythm.     

Limited phenotypic plasticity in range-edge populations: a comparison of co-occurring populations of two Agrimonia species with different geographical distributions

Increased importance of genetic drift and selection for stress resistance have been predicted to lead to a reduction in the degree of phenotypic plasticity in populations at margins of a species' geographical range, relative to those in the centre. We examined the effect of population positioning within the species range on degree of active morphological plasticity to vegetation shade. Importantly, we discriminated between active, size-independent morphological adjustments in response to shade and passive changes in morphology caused by the dependence of morphological traits on plant size, as only the former are considered to be adaptive. Two closely related and ecologically similar Agrimonia species were examined in the same geographical location, where one species reaches the edge of its distribution (Agrimonia pilosa) and the other does not (A. eupatoria). Plasticity to light availability is likely to be advantageous for both species as they occupy habitats with variable light conditions. However, we hypothesised that high levels of environmental stress should lead to reduced active plasticity in marginal compared with more central populations. Agrimonia eupatoria exhibited active adjustments in leaf morphology in response to tree shade, and in elongation of stems and inflorescences in response to herbaceous shade. In contrast, A. pilosa exhibited very limited active plasticity. High active plasticity allowed A. eupatoria to retain constant shoot growth in a wide range of light conditions, while the lack of active plasticity in A. pilosa resulted in a strong dependence of shoot growth on light availability. We propose that high levels of environmental stress in marginal areas of a species' range may lead to a significant reduction in the degree of active plasticity. Our results clearly indicate that discrimination between active and passive plasticity is crucial for reaching valid conclusions about differences in adaptive plasticity between marginal and non-marginal populations.