Visual deviant stimuli produce mismatch responses in the amplitude dynamics of neuronal oscillations

Objectives: Auditory and visual deviant stimuli evoke mismatch negativity (MMN) responses, which can be recorded with electroencephalography (EEG) and magnetoencephalography (MEG). However, little is known about the role of neuronal oscillations in encoding of rare stimuli. We aimed at verifying the existence of a mechanism for the detection of deviant visual stimuli on the basis of oscillatory responses, so-called visual mismatch oscillatory response (vMOR). Methods: Peripheral visual stimuli in an oddball paradigm, standard vs. deviant (7: 1), were presented to twenty healthy subjects. The oscillatory responses to an infrequent change in the direction of moving peripheral stimuli were recorded with a 60-channel EEG system. In order to enhance the detection of oscillatory responses, we used the common spatial pattern (CSP) algorithm, designed for the optimal extraction of changes in the amplitude of oscillations. Results: Both standard and deviant visual stimuli produced Event-Related Desynchronization (ERD) and Synchronization (ERS) primarily in the occipito-parietal cortical areas. ERD and ERS had overlapping time-courses and peaked at about 500-730 ms. These oscillatory responses, however, were significantly stronger for the deviant than for the standard stimuli. A difference between the oscillatory responses to deviant and standard stimuli thus reflects the presence of vMOR. Conclusions: The present study shows that the detection of visual deviant stimuli can be reflected in both synchronization and desynchronization of neuronal oscillations. This broadens our knowledge about the brain mechanisms encoding deviant sensory stimuli. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

A New Paired Associative Stimulation Protocol with High-Frequency Peripheral Component and High-Intensity 20 Hz Repetitive Transcranial Magnetic Stimulation-A Pilot Study

Paired associative stimulation (PAS) is a stimulation technique combining transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) that can induce plastic changes in the human motor system. A PAS protocol consisting of a high-intensity single TMS pulse given at 100% of stimulator output (SO) and high-frequency 100-Hz PNS train, or "the high-PAS " was designed to promote corticomotoneuronal synapses. Such PAS, applied as a long-term intervention, has demonstrated therapeutic efficacy in spinal cord injury (SCI) patients. Adding a second TMS pulse, however, rendered this protocol inhibitory. The current study sought for more effective PAS parameters. Here, we added a third TMS pulse, i.e., a 20-Hz rTMS (three pulses at 96% SO) combined with high-frequency PNS (six pulses at 100 Hz). We examined the ability of the proposed stimulation paradigm to induce the potentiation of motor-evoked potentials (MEPs) in five human subjects and described the safety and tolerability of the new protocol in these subjects. In this study, rTMS alone was used as a control. In addition, we compared the efficacy of the new protocol in five subjects with two PAS protocols consisting of PNS trains of six pulses at 100 Hz combined with (a) single 100% SO TMS pulses (high-PAS) and (b) a 20-Hz rTMS at a lower intensity (three pulses at 120% RMT). The MEPs were measured immediately after, and 30 and 60 min after the stimulation. Although at 0 and 30 min there was no significant difference in the induced MEP potentiation between the new PAS protocol and the rTMS control, the MEP potentiation remained significantly higher at 60 min after the new PAS than after rTMS alone. At 60 min, the new protocol was also more effective than the two other PAS protocols. The new protocol caused strong involuntary twitches in three subjects and, therefore, its further characterization is needed before introducing it for clinical research. Additionally, its mechanism plausibly differs from PAS with high-frequency PNS that has been used in SCI patients.Peer reviewe

TMS with fast and accurate electronic control : Measuring the orientation sensitivity of corticomotor pathways

Background: Transcranial magnetic stimulation (TMS) coils allow only a slow, mechanical adjustment of the stimulating electric field (E-field) orientation in the cerebral tissue. Fast E-field control is needed to synchronize the stimulation with the ongoing brain activity. Also, empirical models that fully describe the relationship between evoked responses and the stimulus orientation and intensity are still missing. Objective: We aimed to (1) develop a TMS transducer for manipulating the E-field orientation electronically with high accuracy at the neuronally meaningful millisecond-level time scale and (2) devise and validate a physiologically based model describing the orientation selectivity of neuronal excitability. Methods: We designed and manufactured a two-coil TMS transducer. The coil windings were computed with a minimum-energy optimization procedure, and the transducer was controlled with our custommade electronics. The electronic E-field control was verified with a TMS characterizer. The motor evoked potential amplitude and latency of a hand muscle were mapped in 3 degrees steps of the stimulus orientation in 16 healthy subjects for three stimulation intensities. We fitted a logistic model to the motor response amplitude. Results: The two-coil TMS transducer allows one to manipulate the pulse orientation accurately without manual coil movement. The motor response amplitude followed a logistic function of the stimulus orientation; this dependency was strongly affected by the stimulus intensity. Conclusion: The developed electronic control of the E-field orientation allows exploring new stimulation paradigms and probing neuronal mechanisms. The presented model helps to disentangle the neuronal mechanisms of brain function and guide future non-invasive stimulation protocols. (C) 2022 The Authors. Published by Elsevier Inc.Peer reviewe

Effect of stimulus orientation and intensity on short-interval intracortical inhibition (SICI) and facilitation (SICF) : A multi-channel transcranial magnetic stimulation study

Publisher Copyright: © 2021 Tugin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Besides stimulus intensities and interstimulus intervals (ISI), the electric field (E-field) orientation is known to affect both short-interval intracortical inhibition (SICI) and facilitation (SICF) in paired-pulse transcranial magnetic stimulation (TMS). However, it has yet to be established how distinct orientations of the conditioning (CS) and test stimuli (TS) affect the SICI and SICF generation. With the use of a multi-channel TMS transducer that provides electronic control of the stimulus orientation and intensity, we aimed to investigate how changes in the CS and TS orientation affect the strength of SICI and SICF. We hypothesized that the CS orientation would play a major role for SICF than for SICI, whereas the CS intensity would be more critical for SICI than for SICF. In eight healthy subjects, we tested two ISIs (1.5 and 2.7 ms), two CS and TS orientations (anteromedial (AM) and posteromedial (PM)), and four CS intensities (50, 70, 90, and 110% of the resting motor threshold (RMT)). The TS intensity was fixed at 110% RMT. The intensities were adjusted to the corresponding RMT in the AM and PM orientations. SICI and SICF were observed in all tested CS and TS orientations. SICI depended on the CS intensity in a U-shaped manner in any combination of the CS and TS orientations. With 70% and 90% RMT CS intensities, stronger PM-oriented CS induced stronger inhibition than weaker AM-oriented CS. Similar SICF was observed for any CS orientation. Neither SICI nor SICF depended on the TS orientation. We demonstrated that SICI and SICF could be elicited by the CS perpendicular to the TS, which indicates that these stimuli affected either overlapping or strongly connected neuronal populations. We concluded that SICI is primarily sensitive to the CS intensity and that CS intensity adjustment resulted in similar SICF for different CS orientations.Peer reviewe

TMS and EEG in the study of human brain dynamics

Defence is held on 4.2.2022 12:00 – 16:00 (Zoom), https://aalto.zoom.us/j/68863302627The studies that comprise the basis of this Thesis intended to detect specific brain responses, known as event-related potentials (ERP), and changes in the cortical rhythms through the utilization of electroencephalography (EEG). In addition, transcranial magnetic stimulation (mTMS) was performed with a multichannel transducer to evaluate cortical excitability and connectivity for many locations and orientations. The results revealed novel aspects of the functioning network of the brain. Study I proves that detection of deviant visual stimuli is possible based on the amplitude modulation of the α-band oscillations. This was manifested in deviant stimuli inducing stronger synchronization and desynchronization of the α-rhythm, as compared to standard stimuli.Study II presents the principles of the electric field (E-field) electronic rotation using an mTMS transducer. The study quantifies the role of the E-field orientation for neuronal activation through the changes of amplitude and latencies in motor evoked potentials (MEP) recorded from hand muscles. The sensitivity of specific neuronal populations to the E-field orientation was demonstrated based on changes in inhibition and facilitation of the amplitude of MEP induced by different orientations of the stimulus during paired-pulse stimulation. Studies III and IV investigate the role of conditioning and test stimuli in short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and short-interval intracortical facilitation (SICF). The studies show that the sensitivity of these phenomena depends on mechanisms related to specific stimulus intensities, orientations, and interstimulus intervals. Finally, Study V explores the role of the E-field orientation in generating mismatch negativity (MMN)-like responses. Stimulation of the same area of the motor cortex with slightly differently oriented stimuli resulted in stronger brain responses induced by rare deviant stimulus than by standard stimulus. The presence of TMS-induced MMN suggests that the brain has the ability to automatically detect deviant stimuli. Due to technical limitations, Study V has not been published. This Thesis introduces novel methods and instrumentation for human brain investigation. The results demonstrate that these methods can elucidate new aspects of brain functioning, allowing for their further application in contemporary scientific research and clinical practice

Probing the orientation specificity of excitatory and inhibitory circuitries in the primary motor cortex with multi-channel TMS

Background The electric field orientation is a crucial parameter for optimizing the excitation of neuronal tissue in transcranial magnetic stimulation (TMS). Yet, the effects of stimulus orientation on the short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) paradigms are poorly known, mainly due to significant technical challenges in manipulating the TMS-induced stimulus orientation within milliseconds.Objective Our aim is to assess the effect of the TMS-induced stimulus orientation on the SICI and ICF paradigms and search for the optimal orientations to maximize the facilitation and suppression of the motor evoked potentials (MEP).Methods We applied paired-pulse multi-channel TMS in healthy subjects to generate SICI and ICF with conditioning and test pulses in the same, opposite, and perpendicular orientations to each other. The conditioning- and test-stimulus intensities were 80% and 110% of the resting motor threshold, respectively.Results Both SICI and ICF were significantly affected by the conditioning- and test-stimulus orientation. MEP suppression and facilitation were strongest with both pulses delivered in the same direction. SICI with a 2.5-ms and ICF with a 6.0-ms interstimulus interval (ISI) were more sensitive to changes in stimulus orientation compared with SICI at 0.5- and ICF at 8.0-ms ISIs, respectively.Conclusion Our findings provide evidence that SICI and ICF at specific ISIs are mediated by distinct mechanisms. Such mechanisms exhibit a preferential orientation depending on the anatomical and morphological arrangement of inhibitory and excitatory neuronal populations. We also demonstrate that the SICI and ICF can be maximized by adjusting the TMS-induced electric field orientation

Stability of transcranial magnetic stimulation electroencephalogram evoked potentials in pediatric epilepsy

Abstract Transcranial magnetic stimulation paired with electroencephalography (TMS–EEG) can measure local excitability and functional connectivity. To address trial-to-trial variability, responses to multiple TMS pulses are recorded to obtain an average TMS evoked potential (TEP). Balancing adequate data acquisition to establish stable TEPs with feasible experimental duration is critical when applying TMS–EEG to clinical populations. Here we aim to investigate the minimum number of pulses (MNP) required to achieve stable TEPs in children with epilepsy. Eighteen children with Self-Limited Epilepsy with Centrotemporal Spikes, a common epilepsy arising from the motor cortices, underwent multiple 100-pulse blocks of TMS to both motor cortices over two days. TMS was applied at 120% of resting motor threshold (rMT) up to a maximum of 100% maximum stimulator output. The average of all 100 pulses was used as a “gold-standard” TEP to which we compared “candidate” TEPs obtained by averaging subsets of pulses. We defined TEP stability as the MNP needed to achieve a concordance correlation coefficient of 80% between the candidate and “gold-standard” TEP. We additionally assessed whether experimental or clinical factors affected TEP stability. Results show that stable TEPs can be derived from fewer than 100 pulses, a number typically used for designing TMS-EEG experiments. The early segment (15–80 ms) of the TEP was less stable than the later segment (80–350 ms). Global mean field amplitude derived from all channels was less stable than local TEP derived from channels overlying the stimulated site. TEP stability did not differ depending on stimulated hemisphere, block order, or antiseizure medication use, but was greater in older children. Stimulation administered with an intensity above the rMT yielded more stable local TEPs. Studies of TMS-EEG in pediatrics have been limited by the complexity of experimental set-up and time course. This study serves as a critical starting point, demonstrating the feasibility of designing efficient TMS–EEG studies that use a relatively small number of pulses to study pediatric epilepsy and potentially other pediatric groups

DELMEP: a deep learning algorithm for automated annotation of motor evoked potential latencies

Abstract The analysis of motor evoked potentials (MEPs) generated by transcranial magnetic stimulation (TMS) is crucial in research and clinical medical practice. MEPs are characterized by their latency and the treatment of a single patient may require the characterization of thousands of MEPs. Given the difficulty of developing reliable and accurate algorithms, currently the assessment of MEPs is performed with visual inspection and manual annotation by a medical expert; making it a time-consuming, inaccurate, and error-prone process. In this study, we developed DELMEP, a deep learning-based algorithm to automate the estimation of MEP latency. Our algorithm resulted in a mean absolute error of about 0.5 ms and an accuracy that was practically independent of the MEP amplitude. The low computational cost of the DELMEP algorithm allows employing it in on-the-fly characterization of MEPs for brain-state-dependent and closed-loop brain stimulation protocols. Moreover, its learning ability makes it a particularly promising option for artificial-intelligence-based personalized clinical applications