Induction of long-term potentiation-like plasticity in the primary motor cortex with repeated anodal transcranial direct current stimulation - better effects with intensified protocols?

Background: A single session of anodal tDCS induces LTP-like plasticity which lasts for about 1 h, while repetition of stimulation within a time interval of 30 min results in late-phase effects lasting for at least 24 h with standard stimulation protocols. Objective: In this pilot study, we explored if the after-effects of a recently developed intensified single session stimulation protocol are relevantly prolonged in the motor cortex by repetition of this intervention. Methods: 16 healthy right-handed subjects participated in this study. The effects of an intensified (3 mA-20min) and a standard anodal tDCS protocol (1 mA-15min) with short (20 min) and long (3 h) repetition intervals were compared with the effects of respective single session tDCS protocols (3 mA-20min, 1 mA-15min, and Sham). Cortical excitability alterations were monitored by single-pulse TMS-elicited MEPs. Results: Compared to sham, both single session tDCS protocols (1 mA-15min, and 3 mA-20min) resulted in cortical excitability enhancements lasting for about 30 min after stimulation. The short repetition interval (20 min) resulted in a prolongation of after-effects for the standard protocol, which lasted for more than 24 h after stimulation. For the intensified protocol, the prolongation of after-effects was limited to 120 min after stimulation. The long repetition interval (3 h) resulted in no excitabilityenhancing after-effects for the intensified, and only minor excitability enhancement within the first 30 min after the intervention for the standard protocol. Conclusion: These results suggest a non-linearity of late-phase LTP-like plasticity induction, which was dependent not only on the interval of intervention repetition, but also on other protocol characteristics, including intensity, and duration of tDCS. Further studies in larger samples are needed to confirm these results

Semi-automated motor hotspot search (SAMHS): a framework toward an optimised approach for motor hotspot identification

BackgroundMotor hotspot identification represents the first step in the determination of the motor threshold and is the basis for the specification of stimulation intensity used for various Transcranial Magnetic Stimulation (TMS) applications. The level of experimenters’ experience and the methodology of motor hotspot identification differ between laboratories. The need for an optimized and time-efficient technique for motor hotspot identification is therefore substantial.ObjectiveWith the current work, we present a framework for an optimized and time-efficient semi-automated motor hotspot search (SAMHS) technique utilizing a neuronavigated robot-assisted TMS system (TMS-cobot). Furthermore, we aim to test its practicality and accuracy by a comparison with a manual motor hotspot identification method.MethodA total of 32 participants took part in this dual-center study. At both study centers, participants underwent manual hotspot search (MHS) with an experienced TMS researcher, and the novel SAMHS procedure with a TMS-cobot (hereafter, called cobot hotspot search, CHS) in a randomized order. Resting motor threshold (RMT), and stimulus intensity to produce 1 mV (SI1mV) peak-to-peak of motor-evoked potential (MEP), as well as MEPs with 120% RMT and SI1mV were recorded as outcome measures for comparison.ResultsCompared to the MHS method, the CHS produced lower RMT, lower SI1mV and a trend-wise higher peak-to-peak MEP amplitude in stimulations with SI1mV. The duration of the CHS procedure was longer than that of the MHS (15.60 vs. 2.43 min on average). However, accuracy of the hotspot was higher for the CHS compared to the MHS.ConclusionsThe SAMHS procedure introduces an optimized motor hotspot determination system that is easy to use, and strikes a fairly good balance between accuracy and speed. This new procedure can thus be deplored by experienced as well as beginner-level TMS researchers

Infants’ cortical responses to audiovisual looming studied with high-density EEG

Infants’ cortical electrical activity as a function of audiovisual looming perception was investigated using high-density electroencephalogram (EEG). Fourteen infants between the ages of 3 and 4 months participated in the study. The aim was to study how audiovisual looming is processed by the infant brain and what timing strategies infants used to time their brain responses to the approaching audiovisual loom. Analysis was performed on all EEG trials in which a looming-related VEP or AEP peak was detected. Results indicated that infants significantly showed earlier looming-related brain responses to the auditory loom than to the visual loom. The results further showed infants used the less sophisticated visual angle/pitch and velocity timing strategies in timing their looming-related brain responses. Using these strategies resulted in errors in judging the loom’s time-to-collision as they are dependent on the approach velocity of the loom. Three infants, however, had developed a more advanced strategy which was based on timing responses to the time-to-collision of the approaching audiovisual loom, but only when timing the collision of the visual loom and not the auditory loom. Furthermore, infants significantly showed looming-related brain responses closer to contact for the faster looms, but no differences in the duration of looming-related VEP and AEP peak responses were detected. When the looming-related peaks at channels Oz (vision) and Cz (audition) were compared, peaks at occipital channel Oz were significantly higher in amplitude for all three loom speeds. In conclusion, it was suggested that audiovisual integration was heavily influenced by infants’ spatial attention captured by the visual loom which resulted in looming-related VEPs that occurred relatively late in the looming sequence. Infants’ response asymmetry was also suggested to represent an evolutionary bias for survival which prioritizes an early auditory response over that of the visual in audiovisual looming perception. The use of less sophisticated timing strategies showed infants’ levels of neural maturity and locomotion experience, two very important factors needed for accurate timing of looming

A systematic evaluation of stimulation-specific parameters of anodal transcranial direct current stimulation for inducing LTP-like plasticity in the primary motor cortex

Der physiologische Einfluss von tDCS-induzierten Nacheffekten ist teilweise nicht-linear mit Stimulationsparametern verbunden. Um die Wirksamkeit der tDCS zu verbessern, ist es wichtig, den Parameterraum zu erweitern, um systematische Informationen zu optimal geeigneten Protokollen für die Induktion einer lang anhaltenden Neuroplastizität zu sammeln. In dieser Arbeit wurden zwei Experimente durchgeführt. Für jedes der beiden Experimente wurde eine Stichprobe von 16 jungen gesunden Teilnehmern rekrutiert. In Experiment 1 wurden für alle drei Stromintensitäten und -dauern keine signifikanten Unterschiede hinsichtlich der Erhöhung der kortikalen Erregbarkeit beobachtet. In Experiment 2 wurde die kortikale Erregbarkeit basierend auf dem Wiederholungsintervall verbessert oder verringert. Diese Ergebnisse legen nahe, dass anodale tDCS im untersuchten Intensitäts- und Stimulationsdauerbereich relativ robust gegenüber graduellen Änderungen der Stimulationsparameter ist

Probing the relevance of repeated cathodal transcranial direct current stimulation over the primary motor cortex for prolongation of after‐effects

Transcranial direct current stimulation (tDCS) has shown promising results in pilot studies as a therapeutic intervention in disorders of the central nervous system, but more sustained effects are required for clinical application. To address this issue, one possible solution is the use of repeated stimulation protocols. Previous studies indicated the possibility of extending the after‐effects of single intervention cathodal tDCS by repeating the tDCS, with relatively short intervals between repetitions being most effective. In this study, we thus investigated the effects of repeated stimulation protocols at short and long intervals, for a conventional tDCS protocol (1 mA for 15 min) and a newly developed optimized protocol (3 mA for 20 min). In 16 healthy participants, we compared single interventions of conventional and optimized protocols, repeated application of these protocols at intervals of 20 min and 24 h, and a sham tDCS session. tDCS‐induced neuroplastic after‐effects were then monitored with transcranial magnetic stimulation (TMS)‐induced motor evoked potentials (MEPs) until the following evening after stimulation. The results revealed that the duration of the after‐effects of repeated conventional and optimized protocols with short intervals remained nearly unchanged compared to the respective single intervention protocols. For the long‐interval (24 h) protocol, stimulation with the conventional protocol did not significantly alter respective after‐effects, while it reduced the efficacy of the optimized protocol, compared with respective single interventions. Thus late‐phase plasticity could not be induced by a single repetition of stimulation in this study, but repetition reduced the efficacy of stimulation protocols with higher intensities. This study provides further insights into the dependency of tDCS‐induced neuroplasticity on stimulation parameters, and therefore delivers crucial information for future tDCS applications

Expanding the parameter space of anodal transcranial direct current stimulation of the primary motor cortex

Size and duration of the neuroplastic effects of tDCS depend on stimulation parameters, including stimulation duration and intensity of current. The impact of stimulation parameters on physiological effects is partially non-linear. To improve the utility of this intervention, it is critical to gather information about the impact of stimulation duration and intensity on neuroplasticity, while expanding the parameter space to improve efficacy. Anodal tDCS of 1–3 mA current intensity was applied for 15–30 minutes to study motor cortex plasticity. Sixteen healthy right-handed non-smoking volunteers participated in 10 sessions (intensity-duration pairs) of stimulation in a randomized cross-over design. Transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEP) were recorded as outcome measures of tDCS effects until next evening after tDCS. All active stimulation conditions enhanced motor cortex excitability within the first 2 hours after stimulation. We observed no significant differences between the three stimulation intensities and durations on cortical excitability. A trend for larger cortical excitability enhancements was however observed for higher current intensities (1 vs 3 mA). These results add information about intensified tDCS protocols and suggest that the impact of anodal tDCS on neuroplasticity is relatively robust with respect to gradual alterations of stimulation intensity, and duration

Transferability of cathodal tDCS effects from the primary motor to the prefrontal cortex: A multimodal TMS-EEG study

Neurophysiological effects of transcranial direct current stimulation (tDCS) have been extensively studied over the primary motor cortex (M1). Much less is however known about its effects over non-motor areas, such as the prefrontal cortex (PFC), which is the neuronal foundation for many high-level cognitive functions and involved in neuropsychiatric disorders. In this study, we, therefore, explored the transferability of cathodal tDCS effects over M1 to the PFC. Eighteen healthy human participants (11 males and 8 females) were involved in eight randomized sessions per participant, in which four cathodal tDCS dosages, low, medium, and high, as well as sham stimulation, were applied over the left M1 and left PFC. After-effects of tDCS were evaluated via transcranial magnetic stimulation (TMS)-electroencephalography (EEG), and TMS-elicited motor evoked potentials (MEP), for the outcome parameters TMS-evoked potentials (TEP), TMS-evoked oscillations, and MEP amplitude alterations. TEPs were studied both at the regional and global scalp levels. The results indicate a regional dosage-dependent nonlinear neurophysiological effect of M1 tDCS, which is not one-to-one transferable to PFC tDCS. Low and high dosages of M1 tDCS reduced early positive TEP peaks (P30, P60), and MEP amplitudes, while an enhancement was observed for medium dosage M1 tDCS (P30). In contrast, prefrontal low, medium and high dosage tDCS uniformly reduced the early positive TEP peak amplitudes. Furthermore, for both cortical areas, regional tDCS-induced modulatory effects were not observed for late TEP peaks, nor TMS-evoked oscillations. However, at the global scalp level, widespread effects of tDCS were observed for both, TMS-evoked potentials and oscillations. This study provides the first direct physiological comparison of tDCS effects applied over different brain areas and therefore delivers crucial information for future tDCS applications

Monitoring Changes in TMS-Evoked EEG and EMG Activity During 1 Hz rTMS of the Healthy Motor Cortex

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique capable of inducing neuroplasticity as measured by changes in peripheral muscle electromyography (EMG) or electroencephalography (EEG) from pre-to-post stimulation. However, temporal courses of neuromodulation during ongoing rTMS are unclear. Monitoring cortical dynamics via TMS-evoked responses using EMG (motor-evoked potentials; MEPs) and EEG (transcranial-evoked potentials; TEPs) during rTMS might provide further essential insights into its mode of action – temporal course of potential modulations. The objective of this study was to first evaluate the validity of online rTMS-EEG and rTMS-EMG analyses, and second to scrutinize the temporal changes of TEPs and MEPs during rTMS. As rTMS is subject to high inter-individual effect variability, we aimed for single-subject analyses of EEG changes during rTMS. Ten healthy human participants were stimulated with 1,000 pulses of 1 Hz rTMS over the motor cortex, while EEG and EMG were recorded continuously. Validity of MEPs and TEPs measured during rTMS was assessed in sensor and source space. Electrophysiological changes during rTMS were evaluated with model fitting approaches on a group- and single-subject level. TEPs and MEPs appearance during rTMS was consistent with past findings of single pulse experiments. Heterogeneous temporal progressions, fluctuations or saturation effects of brain activity were observed during rTMS depending on the TEP component. Overall, global brain activity increased over the course of stimulation. Single-subject analysis revealed inter-individual temporal courses of global brain activity. The present findings are in favor of dose-response considerations and attempts in personalization of rTMS protocols