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.

Neural field theory of synaptic metaplasticity with applications to theta burst stimulation.

Transcranial magnetic stimulation (TMS) is characterized by strong nonlinear plasticity effects. Experimental results that highlight such nonlinearity include continuous and intermittent theta-burst stimulations (cTBS and iTBS, respectively), where depression is induced in the continuous case, but insertion of an off period of around 8s for every 2s of stimulation changes the induced plasticity to potentiation in the intermittent case. Another nonlinearity is that cTBS and iTBS exhibit dosage dependency, where doubling of the stimulation duration changes the direction of induced plasticity. Guided by previous experimental results, this study postulates on the characteristics of metaplasticity and formulates a physiological system-level plasticity theory to predict TMS experiments. In this theory, plasticity signaling induces plasticity in NMDA receptors to modulate further plasticity signals, and is followed by a signal transduction delayed plasticity expression. Since this plasticity in NMDA receptor affects subsequent plasticity induction, it is a form of metaplasticity. Incorporating this metaplasticity into a recent neural field theory of calcium dependent plasticity gives a physiological basis for the theory of Bienenstock, Cooper, Munro (1982), where postsynaptic intracellular calcium level becomes the measure of temporal averaged postsynaptic activity, and converges to the plasticity threshold to give homeostatic effects. Simulations of TMS protocol responses show that intracellular calcium oscillations around the threshold predicts the aforementioned nonlinearities in TMS-induced plasticity, as well as the interpersonal TBS response polarity found experimentally, where the same protocol may induce opposite plasticity effect for different subjects. Thereby, recommendations for future experiments and TMS protocol optimizations are made. Input selectivity via spatially extended, mean field neural dynamics is also explored.

Neural field theory of calcium dependent plasticity with applications to transcranial magnetic stimulation.

Calcium dependent plasticity (CaDP), a physiologically realistic plasticity mechanism in the microscopic regime, is incorporated into a neural field theory to explore system-level plasticity. This system-level plasticity model is capable of reproducing the characteristic plasticity window of spike-timing dependent plasticity (STDP) in paired associative stimulation (PAS), where a peripheral electric pulse stimulation is paired to transcranial magnetic stimulation (TMS) in the cortex, and rTMS frequency dependent plasticity, where low and high frequency rTMS trains induce depression and potentiation, respectively. These thus reproduce experimental results for system-level plasticity for the first time. This also bridges the gap between microscopic plasticity theory and system-level plasticity observed experimentally, and addresses long standing problems of stability and adaptability by predicting stable plasticity, a possible seizure state where neurons fire at a high rate, and spike-rate adaptation.

Neural field theory of plasticity in the cerebral cortex.

A generalized timing-dependent plasticity rule is incorporated into a recent neural field theory to explore synaptic plasticity in the cerebral cortex, with both excitatory and inhibitory populations included. Analysis in the time and frequency domains reveals that cortical network behavior gives rise to a saddle-node bifurcation and resonant frequencies, including a gamma-band resonance. These system resonances constrain cortical synaptic dynamics and divide it into four classes, which depend on the type of synaptic plasticity window. Depending on the dynamical class, synaptic strengths can either have a stable fixed point, or can diverge in the absence of a separate saturation mechanism. Parameter exploration shows that time-asymmetric plasticity windows, which are signatures of spike-timing dependent plasticity, enable the richest variety of synaptic dynamics to occur. In particular, we predict a zone in parameter space which may allow brains to attain the marginal stability phenomena observed experimentally, although additional regulatory mechanisms may be required to maintain these parameters.

Acute gastroenteritis in Hong Kong: a population-based telephone survey.

A population-based telephone survey of acute gastroenteritis (AG) was conducted in Hong Kong from August 2006 to July 2007. Study subjects were recruited through random digit-dialing with recruitments evenly distributed weekly over the 1-year period. In total, 3743 completed questionnaires were obtained. An AG episode is defined as diarrhoea >or=3 times or any vomiting in a 24-h period during the 4 weeks prior to interview, in the absence of known non-infectious causes. The prevalence of AG reporting was 7%. An overall rate of 0.91 (95% CI 0.81-1.01) episodes per person-year was observed with women having a slightly higher rate (0.94, 95% CI 0.79-1.08) than men (0.88, 95% CI 0.73-1.04). The mean duration of illness was 3.6 days (S.D.=5.52). Thirty-nine percent consulted a physician, 1.9% submitted a stool sample for testing, and 2.6% were admitted to hospital. Of the subjects aged >or=15 years, significantly more of those with AG reported eating raw oysters (OR 2.4, 95% CI 1.3-4.4), buffet meals (OR 1.8, 95% CI 1.3-2.5), and partially cooked beef (OR 1.8, 95% CI 1.2-2.7) in the previous 4 weeks compared to the subjects who did not report AG. AG subjects were also more likely to have had hot pot, salad, partially cooked or raw egg or fish, sushi, sashimi, and 'snacks bought at roadside' in the previous 4 weeks. This first population-based study on the disease burden of AG in Asia showed that the prevalence of AG in Hong Kong is comparable to that experienced in the West. The study also revealed some 'risky' eating practices that are more prevalent in those affected with AG.