Theta burst TMS increases cerebral blood flow in the primary motor cortex during motor performance as assessed by arterial spin labeling (ASL)

Theta burst stimulation (TBS) is a novel variant of repetitive transcranial magnetic stimulation (rTMS), which induces changes in neuronal excitability persisting up to 1h. When elicited in the primary motor cortex, such physiological modulations might also have an impact on motor behavior. In the present study, we applied TBS in combination with pseudo continuous arterial spin labeling (pCASL) in order to address the question of whether TBS effects are measurable by means of changes in physiological parameters such as cerebral blood flow (CBF) and if TBS-induced plasticity can modify motor behavior. Twelve right-handed healthy subjects were stimulated using an inhibitory TBS protocol at subthreshold stimulation intensity targeted over the right motor cortex. The control condition consisted of within-subject Sham treatment in a crossover design. PCASL was performed before (pre TBS/pre Sham) and immediately after treatment (post TBS/post Sham). During the pCASL runs, the subjects performed a sequential fingertapping task with the left hand at individual maximum speed. There was a significant increase of CBF in the primary motor cortex after TBS, but not after Sham. It is assumed that inhibitory TBS induced a "local virtual lesion" which leads to the mobilization of more neuronal resources. There was no TBS-specific modulation in motor behavior, which might indicate that acute changes in brain plasticity caused by TBS are immediately compensated. This compensatory reaction seems to be observable at the metabolic, but not at the behavioral level.

Repetitive TMS over the human oculomotor cortex: comparison of 1-Hz and theta burst stimulation

The aim of the study was to compare the effect duration of two different protocols of repetitive transcranial magnetic stimulation (rTMS) on saccade triggering. In four experiments, two regions (right frontal eye field (FEF) and vertex) were stimulated using a 1-Hz and a theta burst protocol (three 30Hz pulses repeated at intervals of 100ms). The same number of TMS pulses (600 pulses) was applied with stimulation strength of 80% of the resting motor threshold for hand muscles. Following stimulation the subjects repeatedly performed an oculomotor task using a modified overlap paradigm, and saccade latencies were measured over a period of 60min. The results show that both 1-Hz and theta burst stimulation had inhibitory effects on saccade triggering when applied over the FEF, but not over the vertex. One-hertz rTMS significantly increased saccade latencies over a period of about 8min. After theta burst rTMS, this effect lasted up to 30min. Furthermore, the decay of rTMS effects was protocol-specific: After 1-Hz stimulation, saccade latencies returned to a baseline level much faster than after theta burst stimulation. We speculate that these time course differences represent distinct physiological mechanisms of how TMS interacts with brain function.

Information processing in long delay memory-guided saccades: further insights from TMS

The performance of memory-guided saccades with two different delays (3 s and 30 s of memorisation) was studied in eight subjects. Single pulse transcranial magnetic stimulation (TMS) was applied simultaneously over the left and right dorsolateral prefrontal cortex (DLPFC) 1 s after target presentation. In both delays, stimulation significantly increased the percentage of error in amplitude of memory-guided saccades. Furthermore, the interfering effect of TMS was significantly higher in the short delay compared to that of the long delay paradigm. The results are discussed in the context of a mixed model of spatial working memory control including two components: First, serial information processing with a predominant role of the DLPFC during the early period of memorisation and, second, parallel information processing, which is independent from the DLPFC, operating during longer delays.

Visual vector inversion during memory antisaccades--a TMS study

In the memory antisaccade task, subjects are instructed to look at an imaginary point precisely at the opposite side of a peripheral visual stimulus presented short time previously. To perform this task accurately, the visual vector, i.e., the distance between a central fixation point and the peripheral stimulus, must be inverted from one visual hemifield to the other. Recent data in humans and monkeys suggest that the posterior parietal cortex (PPC) might be critically involved in the process of visual vector inversion. In the present study, we investigated the temporal dynamics of visual vector inversion in the human PPC by using transcranial magnetic stimulation (TMS). In six healthy subjects, single pulse TMS was applied over the right PPC during a memory antisaccade task at four different time intervals: 100 ms, 217 ms, 333 ms, or 450 ms after target onset. The results indicate that for rightward antisaccades, i.e., when the visual target was presented in the left screen-half, TMS had a significant effect on saccade gain when applied 100 ms after target onset, but not later. For leftward antisaccades, i.e., when the visual target was presented in the right screen-half, a significant TMS effect on gain was found for the 333 ms and 450 ms conditions, but not for the earlier ones. This double dissociation of saccade gain suggests that the initial process of vector inversion can be disrupted 100 ms after onset of the visual stimulus and that TMS interfered with motor saccade planning based on an inversed vector signal at 333 ms and 450 ms after stimulus onset.

Neurophysiology and neuroanatomy of reflexive and volitional saccades as revealed by lesion studies with neurological patients and transcranial magnetic stimulation (TMS)

This review discusses the neurophysiology and neuroanatomy of the cortical control of reflexive and volitional saccades in humans. The main focus is on classical lesion studies and studies using the interference method of transcranial magnetic stimulation (TMS). To understand the behavioural function of a region, it is essential to assess oculomotor deficits after a focal lesion using a variety of oculomotor paradigms, and to study the oculomotor consequences of the lesion in the chronic phase. Saccades are controlled by different cortical regions, which could be partially specialised in the triggering of a specific type of saccade. The division of saccades into reflexive visually guided saccades and intentional or volitional saccades corresponds to distinct regions of the neuronal network, which are involved in the control of such saccades. TMS allows to specifically interfere with the functioning of a region within an intact oculomotor network. TMS provides advantages in terms of temporal resolution, allowing to interfere with brain functioning in the order of milliseconds, thereby allowing to define the time course of saccade planning and execution. In the first part of the paper, we present an overview of the cortical structures important for saccade control, and discuss the pro's and con's of the different methodological approaches to study the cortical oculomotor network. In the second part, the functional network involved in reflexive and volitional saccades is presented. Finally, studies concerning recovery mechanisms after a lesion of the oculomotor cortex are discussed.

In your eyes only: deficits in executive functioning after frontal TMS reflect in eye movements

This study investigated the roles of the right and left dorsolateral prefrontal (rDLPFC, lDLPFC) and the medial frontal cortex (MFC) in executive functioning using a theta burst transcranial magnetic stimulation (TMS) approach. Healthy subjects solved two visual search tasks: a number search task with low cognitive demands, and a number and letter search task with high cognitive demands. To observe how subjects solved the tasks, we assessed their behavior with and without TMS using eye movements when subjects were confronted with specific executive demands. To observe executive functions, we were particularly interested in TMS-induced changes in visual exploration strategies found to be associated with good or bad performance in a control condition without TMS stimulation. TMS left processing time unchanged in both tasks. Inhibition of the rDLPFC resulted in a decrease in anticipatory fixations in the number search task, i.e., a decrease in a good strategy in this low demand task. This was paired with a decrease in stimulus fixations. Together, these results point to a role of the rDLPFC in planning and response selection. Inhibition of the lDLPFC and the MFC resulted in an increase in anticipatory fixations in the number and letter search task, i.e., an increase in the application of a good strategy in this task. We interpret these results as a compensatory strategy to account for TMS-induced deficits in attentional switching when faced with high switching demands. After inhibition of the lDLPFC, an increase in regressive fixations was found in the number and letter search task. In the context of high working memory demands, this strategy appears to support TMS-induced working memory deficits. Combining an experimental TMS approach with the recording of eye movements proved sensitive to discrete decrements of executive functions and allows pinpointing the functional organization of the frontal lobes.

Transcranial magnetic stimulation (TMS) inhibits cortical dendrites

One of the leading approaches to non-invasively treat a variety of brain disorders is transcranial magnetic stimulation (TMS). However, despite its clinical prevalence, very little is known about the action of TMS at the cellular level let alone what effect it might have at the subcellular level (e.g. dendrites). Here, we examine the effect of single-pulse TMS on dendritic activity in layer 5 pyramidal neurons of the somatosensory cortex using an optical fiber imaging approach. We find that TMS causes GABAB-mediated inhibition of sensory-evoked dendritic Ca(2+) activity. We conclude that TMS directly activates fibers within the upper cortical layers that leads to the activation of dendrite-targeting inhibitory neurons which in turn suppress dendritic Ca(2+) activity. This result implies a specificity of TMS at the dendritic level that could in principle be exploited for investigating these structures non-invasively.

TMS- EEG Signatures of GABAergic Neurotransmission in the Human Cortex

Combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) constitutes a powerful tool to directly assess human cortical excitability and connectivity. TMS of the primary motor cortex elicits a sequence of TMS-evoked EEG potentials (TEPs). It is thought that inhibitory neurotransmission through GABA-A receptors (GABAAR) modulates early TEPs (<50 ms after TMS), whereas GABA-B receptors (GABABR) play a role for later TEPs (at ∼100 ms after TMS). However, the physiological underpinnings of TEPs have not been clearly elucidated yet. Here, we studied the role of GABAA/B-ergic neurotransmission for TEPs in healthy subjects using a pharmaco-TMS-EEG approach. In Experiment 1, we tested the effects of a single oral dose of alprazolam (a classical benzodiazepine acting as allosteric-positive modulator at α1, α2, α3, and α5 subunit-containing GABAARs) and zolpidem (a positive modulator mainly at the α1 GABAAR) in a double-blind, placebo-controlled, crossover study. In Experiment 2, we tested the influence of baclofen (a GABABR agonist) and diazepam (a classical benzodiazepine) versus placebo on TEPs. Alprazolam and diazepam increased the amplitude of the negative potential at 45 ms after stimulation (N45) and decreased the negative component at 100 ms (N100), whereas zolpidem increased the N45 only. In contrast, baclofen specifically increased the N100 amplitude. These results provide strong evidence that the N45 represents activity of α1-subunit-containing GABAARs, whereas the N100 represents activity of GABABRs. Findings open a novel window of opportunity to study alteration of GABAA-/GABAB-related inhibition in disorders, such as epilepsy or schizophrenia.

Rhythm makes the world go round:an MEG-TMS study on the role of right TPJ theta oscillations in embodied perspective taking

While some aspects of social processing are shared between humans and other species, some aspects are not. The former seems to apply to merely tracking another's visual perspective in the world (i.e., what a conspecific can or cannot perceive), while the latter applies to perspective taking in form of mentally “embodying” another's viewpoint. Our previous behavioural research had indicated that only perspective taking, but not tracking, relies on simulating a body schema rotation into another's viewpoint. In the current study we employed Magnetoencephalography (MEG) and revealed that this mechanism of mental body schema rotation is primarily linked to theta oscillations in a wider brain network of body-schema, somatosensory and motor-related areas, with the right posterior temporo-parietal junction (pTPJ) at its core. The latter was reflected by a convergence of theta oscillatory power in right pTPJ obtained by overlapping the separately localised effects of rotation demands (angular disparity effect), cognitive embodiment (posture congruence effect), and basic body schema involvement (posture relevance effect) during perspective taking in contrast to perspective tracking. In a subsequent experiment we interfered with right pTPJ processing using dual pulse Transcranial Magnetic Stimulation (dpTMS) and observed a significant reduction of embodied processing. We conclude that right TPJ is the crucial network hub for transforming the embodied self into another's viewpoint, body and/or mind, thus, substantiating how conflicting representations between self and other may be resolved and potentially highlighting the embodied origins of high-level social cognition in general.

Tecniche di stimolazione transcranica: TMS e tDCS a confronto

Nel corso degli ultimi decenni si è assistito a un aumento di malattie e disturbi che colpiscono il sistema nervoso,specialmente il cervello. Si è dunque resa necessaria la ricerca e l'analisi di tecniche di stimolazione transcranica a fini sperimentali, clinici e di diagnosi. Tra queste spiccano per la loro versatilità la TMS e la tDCS, le quali hanno già trovato e possono ancora trovare la loro applicazione in numerosi ambiti anche molto differenti tra loro, tra cui quello motorio, verbale, della memoria o per disturbi neurodegenerativi. L'analisi approfondita delle loro applicazioni può non solo portare a meglio comprendere i limiti che le due tecniche hanno al giorno d'oggi e quindi portare a un miglioramento delle stesse, ma anche ad una comprensione più accurata del funzionamento del sistema nervoso, tutt'ora ancora alquanto oscuro nella sua complessità. Infine, confrontando le due tecniche si può meglio definire anche quali possano essere gli ambiti in cui l'una e l'altra sono più vantaggiose o possano dare contributi più incisivi.

Archival Collections and TMS at Reynolda House Museum of American Art

Presentation from the MARAC conference in Roanoke, VA on October 7–10, 2015. S8 - Minimal Processing and Preservation: Friends or Foes?

Predicting corticospinal excitability from pre-TMS EEG using convolutional neural networks

The amplitude of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) shows a large variability from trial to trial, although MEPs are evoked by the same repeated stimulus. A multitude of factors is believed to influence MEP amplitudes, such as cortical, spinal and motor excitability state. The goal of this work is to explore to which degree the variation in MEP amplitudes can be explained by the cortical state right before the stimulation. Specifically, we analyzed a dataset acquired on eleven healthy subjects comprising, for each subject, 840 single TMS pulses applied to the left M1 during acquisition of electroencephalography (EEG) and electromyography (EMG). An interpretable convolutional neural network, named SincEEGNet, was utilized to discriminate between low- and high-corticospinal excitability trials, defined according to the MEP amplitude, using in input the pre-TMS EEG. This data-driven approach enabled considering multiple brain locations and frequency bands without any a priori selection. Post-hoc interpretation techniques were adopted to enhance interpretation by identifying the more relevant EEG features for the classification. Results show that individualized classifiers successfully discriminated between low and high M1 excitability states in all participants. Outcomes of the interpretation methods suggest the importance of the electrodes situated over the TMS stimulation site, as well as the relevance of the temporal samples of the input EEG closer to the stimulation time. This novel decoding method allows causal investigation of the cortical excitability state, which may be relevant for personalizing and increasing the efficacy of therapeutic brain-state dependent brain stimulation (for example in patients affected by Parkinson’s disease).