Background: Neurons demonstrate very distinct nonlinear activation dynamics, influenced by the neuron type, morphology, ion channel expression, and various other factors. The measurement of the activation dynamics can...
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Background: Neurons demonstrate very distinct nonlinear activation dynamics, influenced by the neuron type, morphology, ion channel expression, and various other factors. The measurement of the activation dynamics can identify the neural target of stimulation and detect deviations, e.g., for diagnosis. This paper describes a tool for closed-loop sequential parameter estimation (SPE) of the activation dynamics through transcranial magnetic stimulation (tms). The proposed SPE method operates in real time, selects ideal stimulus parameters, detects and processes the response, and concurrently estimates the input-output (IO) curve and the first-order approximation of the activated neural target. Objective: To develop a method for concurrent SPE of the first-order activation dynamics and IO curve with closed-loop tms. Method: First, identifiability of an integrated model of the first-order neural activation dynamics and IO curve is assessed, demonstrating that at least two IO curves need to be acquired with different pulse widths. Then, a two-stage SPE method is proposed. It estimates the IO curve by using Fisher information matrix (FIM) optimization in the first stage and subsequently estimates the membrane time constant as well as the coupling gain in the second stage. The procedure continues in a sequential manner until a stopping rule is satisfied. Results: The results of 73 simulation cases confirm the satisfactory estimation of the membrane time constant and coupling gain with average absolute relative errors (AREs) of 6.2% and 5.3%, respectively, with an average of 344 pulses (172 pulses for each IO curve or pulse width). The method estimates the IO curves' lower and upper plateaus, mid-point, and slope with average AREs of 0.2%, 0.7%, 0.9%, and 14.5%, respectively. The conventional time constant estimation method based on the strength-duration (S-D) curve leads to 33.3% ARE, which is 27.0% larger than 6.2% ARE obtained through the proposed real-time FIM-based SPE
Objective. To obtain a formalism for real-time concurrent sequential estimation of neural membrane time constant and input-output (IO) curve with transcranial magnetic stimulation (tms). Approach. First, the neural me...
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Objective. To obtain a formalism for real-time concurrent sequential estimation of neural membrane time constant and input-output (IO) curve with transcranial magnetic stimulation (tms). Approach. First, the neural membrane response and depolarization factor, which leads to motor evoked potentials with tms are analytically computed and discussed. Then, an integrated model is developed which combines the neural membrane time constant and IO curve. Identifiability of the proposed integrated model is discussed. A condition is derived, which assures estimation of the proposed integrated model. Finally, sequential parameter estimation (SPE) of the neural membrane time constant and IO curve is described through closed-loop optimal sampling and open-loop uniform sampling tms. Without loss of generality, this paper focuses on a specific case of commercialized tms pulse shapes. The proposed formalism and SPE method are directly applicable to other pulse shapes. Main results. The results confirm satisfactory estimation of the membrane time constant and IO curve parameters. By defining a stopping rule based on five times consecutive convergence of the estimation parameters with a tolerances of 0.01, the membrane time constant and IO curve parameters are estimated with 82 tms pulses with absolute relative estimation errors (AREs) of less than 4% with the optimal sampling SPE method. At this point, the uniform sampling SPE method leads to AREs up to 16%. The uniform sampling method does not satisfy the stopping rule due to the large estimation variations. Significance. This paper provides a tool for real-time closed-loop SPE of the neural time constant and IO curve, which can contribute novel insights in tms studies. SPE of the membrane time constant enables selective stimulation, which can be used for advanced brain research, precision medicine and personalized medicine.
Transcranial magnetic stimulation (tms) protocols often include a manual search of an optimal location and orientation of the coil or peak stimulating electric field to elicit motor responses in a target muscle. This ...
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Transcranial magnetic stimulation (tms) protocols often include a manual search of an optimal location and orientation of the coil or peak stimulating electric field to elicit motor responses in a target muscle. This target search is laborious, and the result is user-dependent. Here, we present a closed-loop search method that utilizes automatic electronic adjustment of the stimulation based on the previous responses. The electronic adjustment is achieved by multi-locus tms, and the adaptive guiding of the stimulation is based on the principles of Bayesian optimization to minimize the number of stimuli (and time) needed in the search. We compared our target-search method with other methods, such as systematic sampling in a predefined cortical grid. Validation experiments on five healthy volunteers and further offline simulations showed that our adaptively guided search method needs only a relatively small number of stimuli to provide outcomes with good accuracy and precision. The automated method enables fast and user-independent optimization of stimulation parameters in research and clinical applications of tms.
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