TMS_Basics_Presentation_at_BangorUniversity

Editor's Notes

• #6: The physical principle of MRI were discovered by this Guy who seem is holding a cigar. He had very little formal education (according to Wikipedia) but his contribution to phisics and chemistry were enoromous. One of the things he discovered was Electro-magnetic induction: BASICALLY HE FOUND OUT THE PHYSICAL PRINCIPLE OF TMS -> he found out that electric current passed onto a magnet generates a magnetic field. In turn such magnetic field CAN DETERMINE the induction of a secondary current in a nearby conductor, which, guess what, is the brain!! Some people started to try that pretty early on with the idea that a magnetic coil over the head
• #7: It is only in the 80s that barker et al., developed the first well-functioning, focal enough, transcranial magnetic stimulator in Sheffield, UK. Also you can see below he was the first who demonstrated scientifically the possibility to induce activity on the motor cortex. To work well:
• #8: Magnetic field has to change rapidly (2.5 Tesla). And this change has to be generated in a very short time < 1 ms An electrical current of up to 8 kA is generated by a capacitor (a) and discharged into a circular, or figure-of-eight shaped, coil which in turn produces a magnetic pulse of up to 2 T (b). The pulse has a rise time of about 200 μs and a duration of 1 ms and owing to its intensity and brevity changes at a rapid rate (c). The changing magnetic field generates an electric field (d) resulting in neural activity or changes in resting potentials (e). The net change in charge density in the cortex is zero. The pulse shown here is monophasic, but in studies that require repetitive pulse TMS (rTMS), the waveform will be a train of biphasic pulses which allow repeated stimulation. For an introduction to the details, see Ref. 52. (Figure adapted from Ref. 95; images of equipment kindly supplied by The Magstim Co. Ltd.)
• #10: Control group had to tactily identify roman letters How TMS can be useful for research, As in the title of this lecture TMS can directly prove links between Brain activity and behavior. Do I need this region to perform well in the task? There is evidence using fMRI that congenitally blind people use the Visual cortex to do braille reading./
• #11: TMS can be used to investigate WHEN a certain region is involved in a specific task, You remember the task I just explained. In a
• #12: You can also study the connectivity among regions using 2 coils on the head. Paired pulse TMS on V1 conditioning pulse (subthreshold) and on V5 test stim. V5 to V1 (v1 subthreshold v5 test) reduced the amount of phosphenes reported demonstrating that this connection is important for conscious perception.
• #13: TMS can be used to prove cortical excitability (how susceptible to be activated a region is? Fadiga, L., Fogassi, L., Pavesi, G., & Rizzolatti, G. (1995). Motor facilitation during action observation: a magnetic stimulation study. Journal of neurophysiology, 73(6), 2608-2611. Have you ever heard of embodied theories of cognition? The idea is based in part on the discovery of mirror neurons and on the fact that we understand stuff through sensorily experiencing it. We see an hand moving, the same cells that perform this movement will also activate when they observe it. So TMS allows to detect this thing happening. They recorded the MEP the Motor evoked potential evoked from TMS on M1 then recorded with EMG on one muscle.
• #15: Not a lot of consensus there still very debated a certain line of research says that at least for the motor cortex the action is driven by an effect on axons’s interneurons of motor cortex. How do you find out? You give mechanisms with specific mechanisms of action: seems that motor cortex depends on the effect of cortico-cortical axons so axons that are within the cortex and that in turn regulate cortico-spinal neurons. The stimulation blocks sodium channels…… From pharmacolocial studies with healthy volunteers, TMS measures used to estimate motor cortical and corticospinal excitability such as MT and MEP are assumed to rely on different physiological mechanisms. Thus, the MT, which depends on excitability of cortico-cortical axons and their excitatory contacts to corticospinal neurons, is influenced by agents blocking voltage-gated sodium channels that are crucial in regulating axon excitability [11] and by agents acting on ionotropic non-N-methyl-D-aspartate (non-NMDA) glutamate receptors such as ketamine that are responsible for fast excitatory synaptic transmission in the cortex [12]. In contrast, other neurotransmitters and neuromodulator systems such as GABA, dopamine, norepinephrine, serotonin or acetylcholine have no effect on MT. As for MT, the MEP can be depressed by agents that inactivate sodium channels such as volatile anesthetics [13]. MEP reduction is hypothesized to result from reduced excitability of I-waves due to sodium-channel inactivation, which leads to decreased action potential firing and in turn reduces calcium entry at the presynaptic terminal and finally synaptic transmission [14]. Moreover, MEP amplitude was found to vary after the application of modulators of inhibitory and excitatory transmission in neuronal networks. For instance, MEP is depressed by modulators of GABAA receptors or increased by dopamine agonists and various norepinephrine agonists. Of note, changes in MEP amplitude can occur without significant changes in MT, which supports the notion of a fundamental difference in physiology between the 2 measures [15]. But is still debated.
• #16: Some TMS frequencies would have inhibitory effects in a task
• #17: P
• #18: Guess which coil we prefer?
• #22: Pretty good, for one pulse the pulse will decline within 1 ms. On behavior the duration depends on a lot of things : are we on the right spot in the right time or not/ There might be a peak of the TMS effect but you want to be careful about carry over effects! And these are largely dependent on the protocol that we use. pulse is greatest close to the time of onset and then declines within one millisecond. The effect this has on behaviour is a function of the intensity of the physiological effects of TMS and the probability that the neurons stimulated are critical to the task. a | The pulse here would not have a behavioural effect because it is applied too early. b | The pulse here would interfere with behaviour because an early (that is, high) phase of the TMS noise is applied even though the probability of the area's involvement is low. c,d | Similarly, the pulses here would have a behavioural effect because of the high probability of the area's involvement at the time of the pulse. c,e | Although the pulses applied here arrive at similar parts of the probability curve, the neural noise at e is higher because there is no recovery time. So the product of neural noise and neural necessity would be higher at e than at c. The time course of TMS effects in this framework shows that the temporal resolution of TMS is limited by two factors: duration of TMS pulse effects and duration of an area's involvement in the task. The figure also illustrates why the effect of TMS need not necessarily correspond to the timing of the event-related potentials or magnetoencephalographic signals. The appropriate application of TMS may have effects at times well before b and c or well after e, the reported peak.
• #23: Explain here the different protocols and the HUGE difference between online and offline. How do you get rid of confounds of less precision in time? Timing control, Control regions Control tasks!!!
• #24: Read the abstract. Highlight the hypothesis, show the imaging study where this hypothesis comes from.
• #25: You see how many subquestion from a simple experimental question? Welcome to science the art of making problems just for the sake of solving them
• #28: Which one do you think it’s best?
• #39: As previously reported, tES (tDCS, tACS, and tRNS) is a non-invasive method of cortical stimulation in which weak direct currents are used to polarise target brain regions. The most used and best known method is tDCS, as all considerations for the use of tDCS have been extended to the other tES methods. The hypotheses concerning the application of tDCS in cognition are very similar to those of TMS, with the exception that tDCS was never considered a virtual lesion method. It has been suggested that, depending on the polarity of the stimulation, tDCS can increase or decrease cortical excitability in the stimulated brain regions and facilitate or inhibit behaviour accordingly, thereby enabling the investigation of the causal relationships between brain activity and behaviour by means of neural modulation. As previously mentioned tES does not induce action potentials but instead modulates the neuronal response threshold so that it can be defined as subthreshold stimulation. tDCS induces membrane depolarisation (anodal stimulation) and hyperpolarisation (cathodal stimulation) (Liebetanz et al., 2002, Nitsche et al., 2003a, Nitsche et al., 2003b, Nitsche et al., 2004, Nitsche et al., 2005). From a methodological perspective, most of the general concerns for TMS are valid for tDCS, with some exceptions: tDCS does not induce depolarisation and therefore will only induce the firing of neurons that are near threshold, which means that neurons not influenced by the task are less likely to discharge. From a cognitive neuroscience standpoint, the effect of applying anodal tDCS during task execution is considered to induce facilitation, while cathodal tDCS should induce inhibition of task performance. In this sense, it is believed that tDCS primes the behavioural system by increasing/decreasing cortical excitability and producing corresponding effects in the cognitive system. Therefore, tDCS-induced effects are more likely to be sensitive to the state of the network that is active at that moment. Thus, the polarisation of neurons in combination with ongoing synaptic input can be contextualised in a framework of synaptic co-activation. This is evocative of Hebbian-like plasticity mechanisms as the combination of tDCS with task execution is like the co-activation of a specific network. The spatial and temporal resolution of the tDCS effects are somewhat reduced compared with those of TMS, but this drawback may be overcome by considering the state of the system, as previously described. tACS allows the brain to be stimulated at specific frequencies: like rTMS, it has been suggested that tACS can modulate ongoing neuronal activity (Zaehle et al., 2010) and related behaviour (Kanai et al., 2008) by inducing specific brain oscillations. We can theoretically predict that this mechanism will produce a frequency ‘entrainment’ in the stimulated cortical region or in the connected areas during a prolonged stimulation. Using tACS (as for rTMS), an oscillatory current can be delivered to the cortex to induce it to oscillate at that particular frequency, which is area-dependent (Kanai et al., 2008). An advantage of tACS is that there are fewer safety concerns for this method than for rTMS (Rossi et al., 2009), and therefore there are no restrictions on the frequency that can be used. The idea is that, like for TMS, the so-called ‘rhythmic approach’ (Miniussi et al., 2012a, Thut and Miniussi, 2009) refers to the possibility of investigating how tACS interacts with oscillatory brain activity in order to establish a causal relationship between brain oscillations and cognition.