For research use only, this application is not FDA-cleared nor CE-marked

TMS-EEG

TMS-EEG-evoked potential at Brain Stimulation Conference 2021 in Charleston South Carolina.
TMS-EEG-evoked potential at Brain Stimulation Conference 2021 in Charleston South Carolina.

Navigated TMS offers scientists the ability to non-invasively probe the brain with unparalleled accuracy.

Integrating TMS and EEG

Together with TMS, EEG can be used in several ways. In TMS-EEG, EEG is used simultaneously during TMS to measure TMS-evoked cortical reactivity and connectivity. In brain state-dependent (sometimes also called "closed-loop TMS") TMS, TMS is externally triggered based on on-going cortical activity recorded and monitored via EEG. In some TMS practices, EEG is also used as a standalone imaging modality to quantify cortical changes following TMS, and to monitor spontaneous and evoked brain activity in patients prone to epileptic seizures as an add-on safety procedure.

TMS-EEG-evoked potential at Brain Stimulation Conference 2021 in Charleston, South Carolina.

TMS-EEG Methods

The importance of neuronavigation - repeatability, precision and accuracy

Comparison of no navigation, line-navigation and E-field navigated TMS
Comparison of no navigation, line-navigation and E-field navigated TMS

 

As opposed to standard TMS, where TMS is used without navigation or by simply navigating the coil location, Nexstim integrates advanced real-time electric-field (e-field) modelling to allow the user to visualize the TMS stimulating field with unparalleled accuracy and ease of use. 

TMS-evoked EEG responses are sensitive to even the smallest shifts in stimulation location.1 While enabling highly location-specific data to be gathered, this also makes a reliable, precise and accurate navigation solution imperative for TMS-EEG measurements and even more so when studies require repeatability and reproducibility.1,2

As summarized by leading scientists in the field 5:

  • Neuronavigation ensures reproducibility of TMS-EEG within and across measurements.
  • Neuronavigation with real-time EEG visualization maximizes the TMS cortical impact.
  • Neuronavigation is key for reproducible and reliable TMS-EEG cortical mapping.
  • Neuronavigation may titrate TMS parameters for TMS-EEG biomarkers and therapies.
  • Neuronavigation can guide TMS-EEG by integrating other neuroimaging information.

The importance of the stimulation angle

TMS-EEG potentials at different coil orientations (Image courtesy of Silvia Casarotto / Milan University).
TMS-EEG potentials at different coil orientations (Image courtesy of Silvia Casarotto / Milan University).

 

Since the actual impact of TMS on cortical neurons also depends on the orientation of the induced E-field, this figure shows that it is possible to elicit larger early (0-50 ms) EEG responses to TMS by changing the coil orientation while keeping the same target location as well as stimulation intensity. The complete study can be accessed at Casarotto et al. The rt-TEP tool: real-time visualization of TMS-Evoked Potentials to maximize cortical activation and minimize artifacts. J Neurosci Methods. 2022 Mar 15;370:109486.

 

The importance of auditory masking

Auditory- and TMS-evoked potential (Image courtesy of Silvia Casarotto / Milan University).
Auditory- and TMS-evoked potential (Image courtesy of Silvia Casarotto / Milan University).

 

Panel 2 shows 20-trial average EEG responses to TMS (zoom on frontal channels) when stimulating the left premotor cortex (black cross) at 46% of the maximum stimulator output (MSO). Early (0-50 ms) EEG potentials are low in amplitude (< 4µV) and do not show a clear asymmetry between the two hemispheres. In addition, larger negative-positive deflections are elicited between 100 and 200 ms, with a central distribution. Panel 3 shows how EEG responses to TMS change after increasing stimulation intensity at 55% and after adjusting the noise masking until the subject does not report any auditory perception of the coil's click. In this case, early components (0-50 ms) show larger amplitude (> 10µV), especially in the channels closest to the stimulation target and in the stimulated hemisphere compared to the contralateral one. In addition, slow components with central distribution occurring at latencies between 100 and 200 ms are obliterated. The complete study can be accessed at Casarotto et al. The rt-TEP tool: real-time visualization of TMS-Evoked Potentials to maximize cortical activation and minimize artifacts. J Neurosci Methods. 2022 Mar 15;370:109486.

 

 

 

Dr. Silvia Casarotto, PhD

How to collect and distinguish genuine EEG responses to nTMS

Dr. Silvia Casarotto, PhD, tells in this webinar about how to collect and distinguish genuine EEG responses to nTMS.

  • See how to optimize TMS parameters, such as stimulation intensity, based on real-time EEG feedback and reduce signal artifacts.
  • Learn pre-processing and post-processing steps that may reduce pulse and muscle artifacts.
  • Get a sneak peek at an upcoming software tool developed by the speaker that offers a customized display of TMS-EEG data in real-time.

 

Silvia Casarotto, PhD / Sasha D'Ambrosio, PhD / Mario Rosanova, MD, PhD / Simone Russo, MD / Kevin Caulfield / Matteo Fecchio, PhD

TMS-EEG workshop (on-demand recording)

During this workshop, experienced researchers in the field perform a live measurement session with neuronavigated TMS-EEG. Their approach in this workshop represents a strategy for maximizing the impact of TMS on the cortex while minimizing the contribution of artifacts and confounding factors, thus ultimately facilitating the collection of reliable brain responses to direct and non-invasive perturbation of different cortical targets. 

  • See how to mask the coil's click with the help of a customized noise-masking generator (TAAC - TMS-Adaptable Auditory Control software tool) 
  • Learn how the quality of TMS-evoked EEG potentials can be effectively assessed during data collection through a dedicated real-time software tool (rt-TEP - real-time TMS-evoked EEG potential)

 

 

 

Essential publications

 

Casarotto, S. et al. EEG responses to TMS are sensitive to changes in the perturbation parameters and repeatable over time. PLoS One. 2010 Apr 22;5(4):e10281.

Lioumis, P. et al. Reproducibility of TMS-Evoked EEG responses. Hum Brain Mapp. 2009 Apr;30(4):1387-96.

Casarotto et al. The rt-TEP tool: real-time visualization of TMS-Evoked Potentials to maximize cortical activation and minimize artifacts. J Neurosci Methods. 2022 Mar 15;370:109486.

Ilmoniemi, R. & Kicic, D. Methodology for combined TMS and EEG. Brain Topogr. 2010 Jan; 22(4):233-48. 

 

Other interesting publications

 

Tervo, AE et al. Closed-loop optimization of transcranial magnetic stimulation with electroencephalography feedback. Brain Stimul. 2022 Mar-Apr;15(2):523-531.

Russo, S. et al. TAAC - TMS Adaptable Auditory Control: A universal tool to mask TMS clicks. Journal of Neuroscience Methods. 2022 Mar;15;370:109491.

Farzan, F. et al. Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography. Front Neural Circuits. 2016 Sep;10:73.

Salo et al. EEG Artifact Removal in TMS Studies of Cortical Speech Areas. Brain Topography. 2020 Jan 33(1):1-9.

Mutanen et al. Source-based artifact-rejection techniques available in TESA, an open-source TMS-EEG toolbox. Brain Stimulation. 2020 Jul;13(5):1349-1351.

Mutanen, T. et al. The effect of stimulus parameters on TMS-EEG muscle artifacts. Brain Stimul. 2013 May;6(3):371-6. 

Gosseries, O. et al. On the cerebral origin of EEG responses to TMS: insights from severe cortical lesions. Brain Stimul. 2015 Jan-Feb;8(1):142-9.

Julkunen, P. et al. TMS-EEG methods, data analysis and processing. J Neurosci Mthods. 2022. Access prior to publication. 

 

Disorders of Consciousness

Dr. Marcello Massimini, MD

How we can probe changes in cortical circuits with EnTMS-EEG

Dr. Marcello Massimini, MD, tells in this webinar about the use of E-field navigated TMS together with EEG to probe and examine changes in cortical circuits.

  • See how EnTMS-evoked EEG signals change characteristically under different states of vigilance and brain injury, including coma and stroke

  • Learn how EnTMS-EEG offers a reliable and repeatable brain-based index of consciousness, independent of sensory processing, executive and motor functions

  • Understand how EnTMS-EEG overcomes current challenges in assessing the level of consciousness in unresponsive patients and potentially offers a tool to predict functional outcomes and guide intervention

  • View videos demonstrating the set-up and implementation of EnTMS-EEG

 

 

 

 

Interesting publications

 

Rosanova, M. et al. Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients. Brain. 2012 Apr;135(Pt 4):1308-20.

Sinitsyn, D. et al. Detecting the Potential for Consciousness in Unresponsive Patients Using the Perturbational Complexity Index. Brain Sci. 2020 Nov;10(12):917. 

Ruiz de Miras,J. et al. Fractal dimension analysis of states of consciousness and unconsciousness using transcranial magnetic stimulation. Comput Methods Programs Biomed. 2019 Jul;175:129-137.

Comolatti, R. et al. A fast and general method to empirically estimate the complexity of brain responses to transcranial and intracranial stimulations. Brain Stimul. 2019 Sep-Oct;12(5):1280-1289.

Bodart, O. et al. Global structural integrity and effective connectivity in patients with disorders of consciousness. Brain Stimul. 2018 Mar-Apr;11(2):358-365.

Bodart, O. et al. Measures of metabolism and complexity in the brain of patients with disorders of consciousness. Neuroimage Clin. 2017 Feb 6;14:354-362.

Casarotto, S. et al. Stratification of unresponsive patients by an independently validated index of brain complexity. Ann Neurol. 2016 Nov;80(5):718-729.

Rosanova, M. et al. Sleep-like cortical OFF-periods disrupt causality and complexity in the brain of unresponsive wakefulness syndrome patients. Nat Commun. 2018 Oct;9:4427.

Casali, AG. et al. A theoretically based index of consciousness independent of sensory processing and behavior. Sci Transl Med. 2013 Aug;5(198):198ra105.

Anesthesia

Mapping stimulus location and orientation

In this study by Sarasso et al. (2015), E-field navigated TMS enabled to map the optimum cortical stimulus location and E-field orientation, to get the strongest TMS-evoked responses. The navigation also allows for the same cortical location to be stimulated accurately, repeatedly for clinical diagnostics.3

Spatiotemporal Dynamics Induced by Propofol during TMS-EEG
Spatiotemporal Dynamics Induced by Propofol during TMS-EEG (Image courtesy of Silvia Casarotto / Milan University).

Interesting publications

Ferrarelli, F. et al. Breakdown in cortical effective connectivity during midazolam-induced loss of consciousness. Proc Natl Acad Sci U S A. 2010 Feb;107(6):2681-6.
 
Sarasso, S. et al. Consciousness and Complexity during Unresponsiveness Induced by Propofol, Xenon, and Ketamine. Current Biology. 2015 Dec;25(23):3099-3105.

Stroke

TMS reveals local, sleep-like slow waves associated with cortical OFF-periods over the affected hemisphere during TMS-EEG
TMS reveals local, sleep-like slow waves associated with cortical OFF-periods over the affected hemisphere during TMS-EEG (Image courtesy of Silvia Casarotto / Milan University).

Mapping stimulus location and orientation

In this study by Sarasso et al. (2019), E-field navigated TMS enabled to map the optimum cortical stimulus location and E-field orientation, to get the strongest TMS-evoked responses. The navigation also allows for the same cortical location to be stimulated accurately, repeatedly for clinical diagnostics.4

Interesting publications

Sarasso et al. Local sleep-like cortical reactivity in the awake brain after focal injury. Brain. 2019 Dec;143(12):3672-3684.

Tscherpel, C. et al. Brain responsivity provides an individual readout for motor recovery after stroke. Brain. 2020 Jun;143(6):1873-1888.

 

Alzheimer's

Parkinson's

Cortical excitability changes in the supplementary motor area

Cortical excitability changes in the supplementary motor area in Parkinson patients with and without medication during TMS-EEG as shown in Casarotto et al. 2019 (Image courtesy of Silvia Casarotto / Milan University).
Cortical excitability changes in the supplementary motor area in Parkinson patients with and without medication during TMS-EEG as shown in Casarotto et al. 2019 (Image courtesy of Silvia Casarotto / Milan University).

Interesting publications

Casarotto, S. et al. Excitability of the supplementary motor area in Parkinson's disease depends on subcortical damage. Brain Stimulation. 2019 Jan;12(1):152-160. 

Turco, F. et al. Cortical response to levodopa in Parkinson's disease patients with dyskinesias. Eur J Neurosci. 2018 Sep;48(6):2362-2373. 

 

 

Epilepsy

Psychiatry

Neuroscience

TMS in Neuroscience research

TMS induced widespread scalp EEG oscillations with a dominant frequency that was characteristic for the stimulated site as shown by Rosanova et al. in 2009.
TMS induced widespread scalp EEG oscillations with a dominant frequency that was characteristic for the stimulated site as shown by Rosanova et al. in 2009 (Image courtesy of Silvia Casarotto / Milan University).

Interesting publications

Massimini, M. et al. Breakdown of cortical effective connectivity during sleep. Science. 2005 Sep;309(5744):2228-32.

Esser, SK. et al. A direct demonstration of cortical LTP in humans: a combined TMS/EEG study. Brain Res Bull. 2006 Mar 15;69(1):86-94.

Chang, JY et al. Assessing recurrent interactions in cortical networks: Modeling EEG response to transcranial magnetic stimulation. J Neurosci Methods. 2019 Jan 15;312:93-104.

Fecchio, M. The spectral features of EEG responses to transcranial magnetic stimulation of the primary motor cortex depend on the amplitude of the motor evoked potentials. PLoS One. 2017 Sep 14;12(9):e0184910.

Amico, E. et al. Tracking Dynamic Interactions Between Structural and Functional Connectivity: A TMS/EEG-dMRI Study. Brain Connect. 2017 Mar;7(2):84-97.

Rosanova, M. et al. Natural frequencies of human corticothalamic circuits. J Neurosci. 2009 Jun 17;29(24):7679-85.

Massimini, M. et al. Slow waves, synaptic plasticity and information processing: insights from transcranial magnetic stimulation and high-density EEG experiments. Eur J Neurosci. 2009 May;29(9):1761-70.

Chellappa, SL. et al. Circadian dynamics in measures of cortical excitation and inhibition balance. Sci Rep. 2016 Sep 21;6:33661.

Pigorini et al. Time-frequency spectral analysis of TMS-evoked EEG oscillations by means of Hilbert-Huang transform. J Neurosci Methods. 2011 Jun 15;198(2):236-45. 

Casali, AG. et al. General indices to characterize the electrical response of the cerebral cortex to TMS. Neuroimage. 2010 Jan 15;49(2):1459-68.

Romero Lauro, LJ. et al. TDCS increases cortical excitability: direct evidence from TMS-EEG. Cortex. 2014 Sep;58:99-111.

Pisoni, A. et al. Cognitive Enhancement Induced by Anodal tDCS Drives Circuit-Specific Cortical Plasticity. Cereb Cortex. 2018 Apr;28(4):1132-1140. 
 

 

Stay up-to-date on nTMS-EEG

If you leave us your contact details, we are happy to let you know about any upcoming workshops, webinars or events in your region or educational resources on neuronavigated TMS-EEG or nTMS in general (depending on how you select your interests). You can unsubscribe from notifications at any time. 

Interested in doing neuronavigated TMS-EEG experiments yourself?

Interested in a live demo of nTMS?

Our team of physicians, researchers, and engineers is prepared to answer your questions. If you would like to learn more or set up a virtual demonstration for your team, please contact us at info@nexstim.com

References

1 Casarotto, S. et al. EEG responses to TMS are sensitive to changes in the perturbation parameters and repeatable over time. PLoS One. 2010 Apr 22;5(4):e10281.
2 Lioumis, P. et al. Reproducibility of TMS-Evoked EEG responses. Hum Brain Mapp. 2009 Apr;30(4):1387-96.
3 Sarasso, S. et al. Consciousness and Complexity during Unresponsiveness Induced by Propofol, Xenon, and Ketamine. Current Biology. 2015 Dec;25(23):3099-3105.
4 Sarasso et al. Local sleep-like cortical reactivity in the awake brain after focal injury. Brain. 2019 Dec;143(12):3672-3684.
5 Lioumis, P. and Rosanova, M. The role of neuronavigation in TMS–EEG studies: Current applications and future perspectives. J of Neuroscience Methods. 2022 Oct;1;380.

Indications for use

The Nexstim Navigated Brain Stimulation (NBS) System 5 is indicated for non-invasive mapping of the primary motor cortex of the brain to its cortical gyrus. The Nexstim NBS System 5 provides information that may be used in the assessment of the primary motor cortex for pre-procedural planning.

Nexstim NexSpeech®, when used together with the NBS System 5, is indicated for non-invasive localization of cortical areas that do not contain essential speech function. NexSpeech® provides information that may be used in pre-surgical planning in patients undergoing brain surgery. Intra-operatively, the localization information provided by NexSpeech® is intended to be verified by direct cortical stimulation.

The Nexstim NBS System 5 and NBS System 5 with NexSpeech® are not intended to be used during a surgical procedure.

The Nexstim NBS System 5 and NBS System 5 with NexSpeech® are intended to be used by trained clinical professionals.