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Knösche, T. R.

Publications and source records attributed to Knösche, T. R..

6 recordsLinked to original sources

Real-time posterior probabilistic TMS motor mapping with robust individualized stopping criteria

Background. Electric-field-informed regression provides high-resolution transcranial magnetic stimulation (TMS) motor maps, but conventional nonlinear fitting is too slow to update the map during acquisition, so sessions rely on predefined stimulation budgets, despite substantial inter-individual variability in the data required for stable localization. Objective. To develop a real-time analysis updating a posterior probability map between pulses and compare its hotspots with finger-tapping functional MRI (fMRI). Methods. We analyzed two independent cohorts (12 and 13 participants, one newly collected), analyzing each hand muscle independently. We replaced the conventional per-element sigmoid fit with Spearman's rank correlation coefficient and transformed the resulting score map into a posterior probability map using marginal-likelihood evidence. Acquisition stopped once posterior mass within 5 mm of the hotspot passed a preset confidence level. Results. The Spearman and linear scores updated the region of interest within milliseconds, versus tens of seconds for sigmoid fitting. Spearman more closely matched the full-data sigmoid hotspot in recorded sessions and converged faster and more precisely to the true source in virtual subjects. Across both fast scores, at a confidence level of 0.85, the stopping criterion was met after a median of 74-159 pulses, with 26-454 across individual problems. FDI hotspots lay 8.3 {+/-} 4.3 mm from the fMRI center of gravity, in the precentral hand region. Conclusions. Rank correlation reduces computation time without loss of accuracy relative to sigmoid fitting. The resulting posterior probability map provides a session-specific stopping criterion in place of a fixed pulse budget.

neuroscience↗

Spinal Recurrent Inhibition Shapes the Dynamics of TMS-induced Motor-Evoked Potentials: A Computational Modeling Study

Motor-evoked potentials (MEPs) recorded via surface electromyography (EMG) from peripheral muscles following transcranial magnetic stimulation (TMS) of the motor cortex reflect the integrity of the entire corticospinal pathway and are widely used in both basic neuroscience and clinical practice. However, the relative contributions of spinal and peripheral mechanisms to the observed MEP waveform remain poorly understood, partly because computational models that capture individual MEP characteristics are lacking. Here, we present a biologically plausible and computationally efficient model of the descending motor pathway, spanning the spinal cord and hand muscles, that can be fitted to individual MEP waveforms across a range of TMS intensities. The model successfully reproduces individual MEP waveforms, accounting for approximately 90% of the observed variance in waveforms across 10 healthy participants. Crucially, we demonstrate that recurrent inhibition of Renshaw cells in the spinal cord is indispensable for reproducing the fine temporal structure of MEP waveforms, even when input-output curve fitting appears adequate without it. Beyond waveform reproduction, the fitted model provides interpretable estimates of latent neural dynamics and subject-specific pathway parameters, including motor neuron size distribution, synaptic receptor balance, axonal conduction delay, and hand muscle refractoriness, that are consistent with known biological ranges. These results suggest that individual MEP waveforms, when analyzed using a biologically grounded model, carry substantially more information about spinal and peripheral motor pathway integrity than conventional amplitude-based measures alone.

neuroscience↗

Adaptive Bayesian localization of motor representation areas

Transcranial magnetic stimulation (TMS) enables non-invasive localization of cortical motor representations, with important clinical applications in presurgical planning. Existing methods either disregard spatial information about the TMS-induced electric field (E-field) or use acquisition schemes that do not leverage previously elicited motor responses to guide subsequent stimulation. We present an adaptive Bayesian localization method that combines real-time E-field optimization with per-trial probabilistic inference. The cortical origin of the motor responses is represented as a spatial probability distribution that is updated after each stimulus. Subsequent stimuli are then optimized to maximize the expected localization improvement given previous responses. We validated the method experimentally, using multi-locus TMS for adaptive localization and single-coil TMS as a non-adaptive reference with randomized coil placements. Across eight subjects, the adaptive protocol at least halved the number of stimuli required for stable localization compared to the randomized protocol, converging in 60 stimuli on average, with 95% highest-density regions often below 10 mm2 by 150 stimuli.

neuroscience↗

A Coupling Model of Transcranial Magnetic Stimulation Induced Electric Fields to Neural State Variables

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique used to modulate neural activity, with applications in clinical treatment, diagnostics, and neuroscientific research. TMS targeting the human primary motor cortex (M1) is well studied, aided by experimental readouts from the cerebral cortex, the spinal cord, and activated muscle targets. One key readout is a series of pulses that descend the spinal cord following TMS, called DI-waves. These reflect the output of M1 to the spinal cord and are influenced by TMS parameters such as orientation, strength, and waveform. Previous modeling studies have deployed numerous strategies to explain DI-wave generation, but generally approximate TMS inputs as semi-arbitrary current or synaptic inputs. A consistent missing piece to these models is a biophysically motivated coupling between TMS and the neural states of cells and cell populations. This study aims to leverage cable simulations of realistic neuron morphologies to couple TMS induced electric fields to average state variables of cortical cell populations. This coupling model quantifies the spatial-temporal activation function of directly stimulated axonal fibers and the average input current that downstream cells receive due to synaptic inputs from directly stimulated cells. An example M1 cortical circuit is studied, in which TMS stimulates layer 2/3 excitatory and inhibitory neurons that project synapses onto layer 5 corticospinal neurons. Results indicate that TMS induces unique directionally sensitive distributions of synaptic outputs in time and space for each cell type. Directional and dosage sensitivity carries forward to the dendritic current flowing into layer 5 cells. Ultimately, the coupling model provides a novel architecture to translate electric fields from TMS into activation functions that alter neural states and serve as inputs to cortical circuit modeling. The study of other brain regions is achievable through an alternate choice of cell morphologies, cell locations, and circuit design. Author summaryTranscranial magnetic stimulation is a powerful technique to interfere with the brains function in a non-invasive way. It does so by magnetically inducing an electric field in the brain that influences the state of neurons. It has widespread medical application for diagnostics and treatment of diseases, such as depression. Moreover, it is valuable for fundamental brain research as it allows stimulating the brain and then observing its response. In order to optimize its utility in medicine and drawing more well-founded conclusions from scientific experiments, it is important to precisely describe its working mechanisms. In this work, we introduce a computational technique to simulate a crucial ingredient of these mechanisms, namely the precise way the induced electric field excites populations of interconnected neurons. We exemplify the technique for the case of stimulating the motor areas of the cortex, causing muscle activity. However, it can be generalized to a wide variety of use cases, thus forming an important tool that helps researchers to devise accurate mechanistic links between transcranial magnetic stimulation and its observed effects. In consequence, it supports future research aiming at the development of better diagnostics and treatment of brain diseases, as well as better understanding of brain function.

neuroscience↗

Improved Source Localization of Auditory Evoked Fields using Reciprocal BEM-FMM

The precise localization of auditory evoked fields (AEFs) from magnetoencephalography (MEG) data is very important for the functional understanding of the auditory cortex in medicine and cognitive neuroscience. The numerical solution of the field equations in the human head using the boundary element method (BEM) is a powerful tool for achieving this. We hypothesized that the spatial resolution of the BEM is crucial for the achievable accuracy. However, in classical BEM (as implemented, e.g., in MNE-Python), very high resolutions are impractical due to the associated prohibitive computational effort. In contrast, our recently introduced reciprocal boundary element fast multipole method (reciprocal BEM-FMM) allows for hitherto unprecedented spatial resolution. In this work, we apply our reciprocal BEM-FMM technique for source estimation to localize AEFs, and we compare our results with the source estimates produced using a 3-layer BEM model (standard BEM) via MNE-Python. We first validate our methodology through comparison of source estimates of simulated N1m components of AEFs using a receiver operating characteristic (ROC) measure. While we obtain ROC measures of about 80% for the standard BEM, reciprocal BEM-FMM reaches about 90%, a significant statistical improvement. We then apply this methodology to analyze the source estimates of experimental data obtained from a cohort of 7 participants subjected to binaural auditory stimulation. Using a dispersion measurement to quantify the focality of localized sources, we find improvements upwards of 30% using reciprocal BEM-FMM over the standard BEM. Analyses from both simulated and experimental data show localization of AEFs using high-resolution reciprocal BEM-FMM is significantly better in terms of accuracy and focality than those estimates of the low-resolution standard BEM. We therefore recommend using the high-resolution reciprocal BEM-FMM to utilize high spatial anatomical precision for the modeling of neural activity.

neuroscience↗

Axon Diameter Measurements using Diffusion MRI are Infeasible

The feasibility of non-invasive axonal diameter quantification with diffusion MRI is a strongly debated topic due to the neuroscientific potential of such information and its relevance for the axonal signal transmission speed. It has been shown that under ideal conditions, the minimal diameter producing detectable signal decay is bigger than most human axons in the brain, even using the strongest currently available MRI systems. We show that resolving the simplest situations including multiple diameters is unfeasible even with diameters much bigger than the diameter limit. Additionally, the recently proposed effective diameter resulting from fitting a single value over a distribution is almost exclusively influenced by the biggest axons. We show how impractical this metric is for comparing different distributions. Overall, axon diameters currently cannot be quantified by diffusion MRI in any relevant way.

biophysics↗