Zhen Ni: Transcranial Magnetic Stimulation: Cortical Anatomy and Clinical Neurophysiology

Transcript

Zhen Ni: So, my name is Zhen Ni. I am a Senior Research Fellow working in NINDS.   So, today I will talk about the Cortical Anatomy and the Clinical Neurophysiology for the TMS Introduction.   As we know, TMS, the Transcranial Magnetic Stimulation, is a powerful but non-invasive technique to stimulate the human brain. And the -- it's a very good technique to study the human brain function.

So, as we can see from this slide that if we give a stimulation to the human brain, it produces a descending volley in the spinal cord. And then, you can activate the spinal motor neuron pool. In transmission, you can activate to the target muscle then we can record the response in the target muscle. So, in this talk, I want to focus on four different topics. The first one, how can we record the response from the -- from the stimulation of TMS? Second, how can we test the spinal cord activity? The third one, how do we do the motor cortical stimulation with TMS?   And what is the descending volley of the TMS? And the fourth one, I want to focus on the stimulation outside of motor cortex.

So, let's go to the first part.   How do we record the response of TMS?   There are -- usually, there are two different techniques. One is electroencephalography, EEG, and there's another technique named electromyography, EMG. EEG is a very good technique to record the activity of the brain. So, it's usually recorded using a system named the 10-20 EEG System. Here, 10-20 refers to the factor that the actual distance between the adjacent electrodes is either 10 percent or 20 percent of the total front to back, or left to right, distance of the skull.

Here, we measure the distance between the left ear and to the right ear. Also, we measure the distance from Nasion point to the Inion point as the total difference. We can mount many electrodes on the scalp. Here, we use the abbreviation of F as the frontal area. And the temporal area can be shortened by the T. Parietal area is P, and the occipital area is O, and the central area is C.

So, there are many different techniques to record the EEG. We can use a cap, for example, like showing in this slide. We use a 64-channel cap to do the EEG recording. So, there is a very important step to record the EEG.   That's the preparation of the cap or electrode in other techniques. The preparation -- the purpose of the preparation of the cap is to reduce the impedance of the electrodes. And in this slide, the red color means it's a very high impedance.   And the green color means low -- lower impedance, which we can use it for the next step for the recordings.

So, like in this slide, it's a new cap; it's named active cap. On the left side, it's a cap before the -- before the preparation.   And we can see the technician is using the gel to prepare for the cap. And on the right side, almost all lights turn to green. That means the cap is ready for the recording. And in the middle, that means we are doing the preparation.

There's another technique named the electromyography, EMG. This can also be used to record the response to TMS. And the mechanism behind the EMG is a size principle. The size principle means there are many motor neurons in the spinal cord. And these neurons can be recruited in order of -- from the smallest to the largest of size when the muscle is doing contraction, and the contraction is an increase little by little. So EMG, with different techniques, can record the activity of muscle fibers.   And the EMG recorder can reflect the excitability of the neurons connecting to the muscle fibers.

In this slide, we show the recording of a single motor unit. Here is a very important concept named the single motor unit. That means a single motor unit includes an alpha motor neuron and all the corresponding muscle fibers it innervates. That means all the fibers which connect to the motor -- connect to the single motor unit -- have the same firing property. But when we use a needle to insert into the muscle, and the tip of the needle is close to the muscle fibers, we want to record.   At that moment, we can get to the discharge of the muscle fibers. And this firing property of the muscle fiber can reflect the firing property of the motor neuron, which it -- which is connected to all these muscle fibers.

So, on the right side, we can see an example recorded of the single motor unit recorded in the -- in the first dorsal interosseous muscle. So, there is a very clear limitation of single motor unit recording. At first, of course, it's invasive and painful. And another important limitation is that it's almost impossible to record all the muscle fibers in the muscle with the single motor unit recording.

So, over to -- to overcome this limitation, we can use the surface EMG. So, see surface EMG is used to monitor the general picture of the muscle activity. So, the surface EMG can superimpose the activation potential of the muscle fibers under the electrode we use. So, here we used an electrode attached to the surface of the muscle. So, here is the concept named the compound muscle action potential, C-M-A-P, CMAP. It's a very useful measurement. And it can be recorded with surface EMG. And the CMAP represents the summation of almost simultaneous action potential from many muscle fibers in the same area. And usually, CMAP can be -- can be evoked by stimulation of the motor nerve.

So, with this surface or the single motor unit recording, we can test the spinal cord activity. The next part I will talk about, the test of spinal activity. So, in the clinical neurophysiology, a stimulation is often used to demonstrate whether the stimulated structure. For example, brain, spinal cord, this structure is involved in the -- in the special movement task. And we can analyze the response to the stimulation to look at the effect. So, spinal activity can be tested by stimulation on the afferent pathway of spinal motoneurons.

Here, we should say the basic mechanism, which underlining this test, is that the corticospinal neurons from the brain in the motor cortex send their fairly long axons down to the spinal cord and the synapse on these spinal alpha motoneurons. And the alpha motoneurons send the fibers, which can synapse on the muscle fibers. And this is the physiology called -- or -- and the anatomical mechanism for testing the spinal cord activity.

In this slide, we introduce the monosynaptic reflex in -- where -- which is related to the spinal cord activity.   The very classical monosynaptic reflex is a stretch reflex. So, we can see on -- in the picture when the doctor taps the tendon of the muscle, the muscle spindle can be activated. And this will induce monosynaptic reflex, and we call them tendon reflex.

On the right side is the pathway for the tendon reflex. We can see the muscle spindle can be activated by the stimulation through a 1a afferent. It goes up to the alpha motoneuron with a transfer in the alpha motoneuron it goes -- it sends the pulse to the muscle through the efferent nerve, which is the motor nerve. On the physiological level, we can do a technique named the Hoffmann reflex, H-reflex.   And the H-reflex is the analog to the tendon reflex.

On the left side, I show the example recordings for the H-reflex. I should mention here that when we do H-reflex, at the same time, we can record the muscle wave, M-wave. And this M-wave is similar to the CMAP, which I showed in the previous slides.   So, in the recordings from bottom to the top means an increase of intensity. At the very bottom, when we use various low intensity, no response can be recorded. When we increase the intensity, H-reflex appeared first. When the intensity was increased again, the H-reflex become larger. And, at the same, M-wave appears.

And when the intensity becomes very high, the H-reflex becomes smaller and smaller while the M-wave becomes bigger and bigger. When the stimulus intensity reached a very high level, H-reflex disappeared while M-wave reaches its maximum. So, the mechanism behind the -- this H-reflex that the stimulus comes -- the stimulation, the electrical stimulation, given to the nerve can go both to the afferent -- go to the afferent and the efferent fibers in both directions.

So, in the -- in this slide, I show the H-reflex mechanism. On the left side is results. The group analysis results for the recordings shown in the previous video.   So, the X-axis means the stimulus intensity, and Y-axis means the amplitude of H-reflex and the M-wave. We can see that the H-reflex has lower firing -- a lower threshold. And when the stimulus intensity increases, it reached to the maximum. And then, the decrease is the increase of the stimulus intensity.

On the other hand, the M-wave has lower -- has a higher threshold, and the increase almost linearly with the increment of stimulus intensity, and then finally reach the maximum.   On the right side, is the mechanism behind the H-reflex and M-wave. We can see the red line means -- red arrow means the stimulus given to the motor nerve, and the blue arrow means stimulus given to the sensory nerve. With the single stimulation, the inputs can go both ways. The antidromic nerve way and the orthodramic way on both sensory and the motor nerve.  

So, the orthodramic impasse on the motor pathway can produce an M-wave. And the antidromic pathway -- antidromic impasse on the sensory pathway can produce an H-reflex. At the same time, the antidromic impasse on the motor nerve can cancel the H-reflex.   So, that's why we can get to the experiment results, which I discussed previously.

So, with all these slides, we can know the H-reflex is analog to the stretch reflex in the physiological lab.   And the H-reflex is often used to test the spinal activity in motor physiology. That means if we use a TMS to stimulate the brain and get a response in the muscle if the -- we ask the subject to do two different tasks and we found a different response. At the same time, we must think about the spinal cord activity as the spinal cord is on the pathway of -- from the motor cortex to the -- to the muscle, which we want to record.

So, there's a limitation for H-reflex. That is, the H-reflex is sometimes very difficult to be recorded from hand muscles.   So, as a replacement, we can do an F-wave experiment. The mechanism behind the F-wave is that when we use very, very high stimulus intensity, the H-reflex can completely be blocked by the antidromic current, as we discussed before. At that time, no H-reflex can be recorded.

But, at the same time, the antidromic current on the motor fibers is this; we call it super maximum intensity. Such very high stimulus intensity can activate the motor neuron directly, and they induce a wave. This is named the F-wave. So, there is an implication for F-wave. We also can use it -- use F-wave to test for the spinal cord activity. So, there's very clear limitation for F-wave that the F-wave only reflects the excitability of motor neurons with very high firing threshold.

There's an immediate and very important implication for the F-wave recording. This is named the central motor conduction time, CMCT. So, when we give a stimulation to the cortex we can get, we call them motor evoked potential, MEP, in the muscle. When we measure the MEP, we can get to the latency of this MEP.   So, the MEP latency included two parts; one uses a central motor conduction time, another is a peripheral nerve conduction time.

Let's go back to the previous study, use F-wave. When we give electrical stimulation to the motor nerve, it goes up to the spinal cord and then goes -- then comes down to the muscle. This produces latency. If we add a slight latency with the M-wave latency, we can get two times of the peripheral nerve. So, at this time, we should consider a synaptic delay on the transfer from the motor nerve to the spinal cord and then come down to the muscle. So, in the form -- in the formula, we should subtract one synaptic delay, which is a one millisecond.

So, finally, the formula comes up like the central conduction time equals to the MEP latency minus F-wave latency plus M-wave latency minus one divided by two. So, the central conduction time can also be measured with TMS alone. In this figure, we can see when we measure the conduction time in the hand muscle, APB muscle on the thumb, we can give a stimulation to C3; that's close to the motor cortex, and it produces MEP.

And if we give the stimulation to the cervical level, it produced MEP with shorter latency. If we get to the difference between two -- between two MEP at a different side we can get -- finally get to the central conduction -- central motor conduction time. A very similar technique can be used to measure the conduction time in the leg muscle, tibialis anterior.

Then, we come to the next question. How can we do a motor cortical stimulation with TMS? This slide shows the primary motor cortex. The primary motor cortex is identified by Brodmann area 4. So, the primary motor cortex contains very large pyramidal cells, which is a cortical spinal neuron. These neurons send a very long axons down to the spinal cord and the synapses motoneuron pool. And the important primary motor cortex is a target for many TMS studies.

The physiological and the anatomical mechanism behind the TMS targeting motor cortex is showing in -- is shown in this slide. It's named the cortical homunculus. The cortical homunculus was founded by a Canadian neuron -- neurosurgeon named Penfield. And Dr. Penfield used a needle -- used a needle stimulation when he did neurosurgery, and he stimulated the motor cortex and created a map, which is shown in this slide.

So, what we can see is that the presentation of different muscles in the -- in the primary motor cortex are highly disproportionate, and this is named the cortical homunculus.   With this mechanism, we -- that's why we do many TMS studies using muscle -- we use very small hand muscles, as the small hand muscles have a large cortical presentation and can be easily recorded with surface EMG.  

This slide shows equipment for TMS -- for TMS study. In the TMS lab, there are several different devices that should be included. The first one, of course, is a stimulator of TMS.   And this stimulator can be connected to the -- a coil, and the coil delivers the stimulation to the brain.   And with this stimulation, we can record the -- from the small hand muscle. For example, the first dorsal interosseous muscle, the FDI muscle.

For many studies, we use different combinations. For example, we do a single pass; at that time, we only need one stimulator. And sometimes, we need two stimulators to do a paired-pulse protocol. At that time, we need a bistim to connect two different stimulators together.   This bistim will show on the top in the -- in the figure. And when we record the muscle response, we should use the amplifier, as the amplitude of the response is very small. The response, as shown on the right side, it's named the motor evoked potential, MEP.  

So, this slide shows the electrical mechanism of the transcranial magnetic stimulation. When we give this stimulation, it -- the stimulation produces a very large but brief current in the wire coil. And this brief but large current was produced by discharging of a bank of capacitors, which can be seen in the previous slide.   After -- when we give the stimulation to the brain, there's a secondary induced current in the brain. The current induced in the brain has the opposite direction to the -- to the current in the coil. Here we should mention that in the figure, this -- the magnetic field is produced by a round coil. There are many different coils with different shapes. And the round coil is not now -- not well used in many, many studies.

So, this slide shows the magnetic coil with different shapes. The first A coil is the same one showing in the -- in the previous slide.   It has a weak -- it produced a weak stimulation, which can -- we can see the electrical field on the right side.   Then, this idea to improve the coil shape with a different purpose. B coil and the C coil focus on the tip, the electrical field focus on the tip of the coil. And the D coil has a large coil with high stimulus intensity. And the E coil is small in size, which produced focal stimulation.

And the many studies use the figure of 8 coil, the F one. The figure of 8 coil used two coils, which produce this current with the same direction at the joint point of two coils. So, that means at the center of the -- of the figure 8 coil, the electrical field is the strongest. The figure of 8 coil is now well used, and the most used in many TMS studies.

This slide shows the example recording with a single stimulation to a single site, but with a recording in different muscles. On the top is an electrical stimulation, and the bottom is a magnetic stimulation.   In the early years, electrical stimulation was used to stimulate the brain. So, the disadvantage for the electrical stimulation is that when the current goes through the scalp, it activates the pain receptor in the scalp, and that's why the electrical stimulation is very painful, and that's why electrical stimulation cannot be widely used. And later, people developed the magnetic stimulation.

In this figure, we can focus on the motor evoked potential latency. What we can see is that with the stimulation -- with the single stimulation, the MEP latency is the shortest in the biceps muscle and they become longer in thrombus -- in the thumb, which is recorded in APB muscle.   And it's longest in the leg muscle, tibialis anterior. The latency becomes longer and longer from the upper limb to the low limb is consistent with the anatomic findings, anatomical location of different muscles.   The second evidence, which can be found in the figure, is that the magnetic stimulation produced MEP with a slightly longer latency than the electrical stimulation, which we will discuss later.  

And this slide shows the stimulation with different -- at different locations, but recording in different -- in the same muscle. The recording was made in the APB muscle. The top one shows a recording right hand, and the bottom one shows recording in the left hand. What we can see is that the first trial on the very top is recording from electrical stimulation at the wrist, which is similar to the M-wave we discussed before.  

The second trial is recording from TMS at the cervical level. It produced a little longer latencies than the M-wave. And the third line shows that MEP with TMS at the cortical level. It produced the longest MEP latency in three trials. This is also consistent with the anatomic locations of different stimulation. Here, we discuss the site of stimulation. The bottom one is the electrical stimulation to the motor cortex. Here, the cathode electrode is located in the center of the skull; we call it a vertex. And the anodal stimulation is located in the motor cortex, close to C3, C4.

So, the current produced by this electrical stimulation is a vertical current. It goes down from the surface of the cortex to the very deep area in layer -- in layer five, six where the large cortical spinal neuron is located. It is a little different for the magnetic stimulation on the top. The magnetic stimulation, which we discussed previously, it's parallel to the surface of the cortex. So, the stimulation only goes to -- only goes to the inter neurons in the layers two and the layer three. And with both stimulation, the stimulation -- with both stimulation of the electrical stimulation, and the magnetic stimulation the stimulation is given to the primary motor cortex, which can see from the right slide. The primary motor cortex is located at the anterior bank of the central gyrus or central sulcus.

So, we discussed that the magnetic stimulation and the electrical stimulation are different.   As the magnetic stimulation is a parallel to the motor cortex, which activated the layer two and the layer three neurons in the motor cortex. And the electrical stimulation can activate the pyramidal cells located in the layer five and layer six. This led to a very important concept in TMS, which is D and I-waves. D-wave, which is a direct wave, it shows a direct activation of the pyramidal neurons. And I-wave is an indirect wave. It's indirect wave reflect the indirect activation of the cortical spinal neuron through the synaptic mechanism.

In this figure, we show the cortical spinal wave, the descending wave recordings with implanted spinal cord electrodes. On the right side, is an x-ray photo for the electrode. We can see the electrode. The spinal electrode was implanted at the cervical level. There are four contacts, zero, one, two, three on the electrode. When we give stimulation to the motor cortex, the impasse goes down to the spinal cord.   Then, we can record a very tiny potential named the descending wave from contact to zero and the three.

These recordings are shown on the left side. And the -- on the middle is the MEP recording with EMG electrodes. There is a red line in each -- in each recording figure. For the cortical spinal wave recording, the red line means the D-wave latency. And then -- on the right side, for the MEP recording, the red line means the T -- the electrical stimulation induced the T -- the MEP latency.

There are different panels.   On the top panel, is the recording for electrical stimulation. What we can see is that with the electro stimulation, it produced a D-wave. And the second line is the TMS with a lateral, medial current. With this current direction, we also can produce D-wave. But following this D-wave, this -- the indirect wave, I-waves, the bottom electrodes are -- the recordings with posterior-anterior TMS stimulation. With this direct current stimulation, we can see there is no D-wave can be recorded.   The first wave appears as the I-wave, I1-wave. Then, there's a series of different waves we name it I1, I2, I3.

So, from this recording, we can get information that the lateral medial direct current first generated D-wave.   And the posterior-anterior current generates an I1-wave, and the more waves can be generated when stimulus intensity increases. So, different waves can also be recorded with current or with TMS with different currents. In this figure, at the top is the recording for TMS with latero-medial current. As we already discussed, a D-wave can be generated, followed by later I1, I2, I3 waves.

And in the middle is the stimulation with the posterior-anterior current, which can be -- which can be seen in most of TMS studies. With this current direction, no D-wave can be recorded. Only I1-wave can be recorded with low intensity by incrementing stimulus intensity produce more waves, including I2 and I3 waves. And at the bottom, the anterior-posterior current initially produced I3-wave with low stimulus intensity.   And with incrementing stimulus intensity, more waves, including I1-wave, can be seen.

And this slide shows the recording with a single motor unit. This -- the experiment was also done for recording different waves with different stimulus current. On the recording on the left side is the MEP recording. And there's a dashed line showing the latency with LM current direction.   On the right side, is the single motor unit recording with the analysis named the Peristimulus time histogram, PSTH, analysis.

So, on the top of each panel is the recording with the posterior-anterior current. What we can see is that the MEP latency is slightly longer than -- with slightly longer than the dashed line, which shows the MEP latency with the lateral, medial current. And with the single motor unit recording, we can see there are three different waves that can be recorded I1, I2, and I3 waves. On the other side, the anterior-posterior current, which is showing in the bottom, with this current MEP latency is longer than the posterior-anterior current. And with the single motor unit recording, we can see that only later I-waves, including I3-waves and the I4-waves, were recorded.

This slide shows animal studies, which discusses the mechanism of later I-waves. On the left side is the stimulation to the motor cortex.   And the recording is also the spinal cord recording in a monkey. With the motor cortical stimulation, we can see a series of I-waves can be recorded.   At the bottom, with a stimulation to the pre-motor cortex, no I-waves can be recorded except for the stimulation with very high intensity.

So, on the right side showing the two stimulation was -- were given along -- were given together.   What we can see is that when we give pre-motor stimulation with the motor cortical stimulation, the later I-waves were facilitated large -- were largely facilitated in both monkeys, CS-14 and the CS-17. That means the pre-motor cortex is not directly producing the later I-waves, but is involved in the production of later I-waves.

This figure shows the leading hypothesis in the field, which can explain the production of cortical spinal waves. With a single stimulation of TMS, many neurons can be activated in the primary motor cortex; these neurons, including the larger cortical spinal neurons in layer five, we call them P5. At the same time, the facilitatory inter neurons in layer two and the layer three, we call them P2 P3, can be activated. Also, there are inhibitory inter neurons in the motor cortex. Some of them are mediated by GABA transmitter, which is shown in the black square.

So, with a single stimulation, all these neurons can be activated. The activation of the axon of P5 can produce the D-wave. And the activation of the P2 and the P3 neuron can produce the I1-wave.   So, when the stimulation activated the GABA neurons, it can eliminate the activation of I1-wave. This is the inhibitory phase of the I1-wave after the activation of I1-wave.

So, when the P2 and the P3 are activated again, and the GABA neuron stops firing it -- the later I-waves are produced. When we use a different current direction, for example, the anterior-posterior current direction, we may activate all these neurons. And the -- these -- all these neurons can be influenced by the inputs from the pre-motor cortex. And this is shown in the larger circle around all these areas. So, this figure shows the leading hypothesis in the field. But there are many other models that can explain the mechanism behind the very complex cortical spinal descending volley. And all these models and the hypothesis should be tested in further experiments.

So, let's move to the fourth part of the talk. TMS can also be applied to different cortical areas outside of the motor cortex.   This one is showing an important TMS technique named the TMS Mapping. The coil of -- the TMS coil is moved in a different direction. On the X-axis, it's moved from the medial to the lateral side. And the Y-axis showing the coil moving from the posterior to the anterior locations.   At the center of this figure, showing the location which produced the largest MEP amplitude, we call it the center of gravity. And when TMS coil is moving around this -- around this point of the center of gravity, the MEP size becomes smaller.  

And finally, we can get an MEP map from this technique. This technique has many different but very important implications. For example, in the patient with amputation, the recording on the intact side was shown on the left, and the amputated side was shown on the right side. And the recording was made from biceps -- and the biceps muscle. And the patient has upper limb amputation, but the biceps muscle has remained. What we can see is that the amputated side has a much larger activation area than the intact side, which reflects the more activated state after the amputation.  

The MEP mapping technique can also be used for the motor learning experiment. In this experiment, the subject does a serial reaction time task. That means the people -- the subject used four fingers from the index, middle finger, ring finger, to the small finger, the little finger, which we’re referring to as one, two, three, four. And the subject was asked to do a serial reaction time task with a different sequence, which can be shown on the screen. And this did a very long time to learn for the subject. And the learning of the course can be recorded.   And the performance during the learning as shown on the right side, we can see both the reaction time and the performance become better after many, many blocks.

On the left side is the brain mapping, the MEP mapping, for each different block. We can see, before the training, the stimulation didn't cause any activation of the corresponding muscles. But with the stimulation -- with -- when the training course is going on, the activation of the involved muscles become larger and larger. And finally, at the block nine, the TMS map become the largest. So, that means the cortical areas for muscle involved in the task increased after the motor learning process.

TMS can also be given to other different cortical areas, as the -- there are very complex cortical networks in the brain. And the TMS can be used to test the connectivity between different cortical areas.   In this figure, we use the electroencephalography, the EEG, to record the effect of TMS. And if we analyze the different response, the different component, and the different location for the TMS induced effect, we can know TMS at one side can activate the -- which area and which component. TMS can also be given to a different cortical area.  

In this figure, we show the -- show the recording with electroencephalography after TMS on one side.   And with analysis with different components and at different locations, we can know the TMS on one side can activate the remote cortical areas. But with EEG recording, there's an important limitation to do the experiment. That is, the TMS evoked potential, we call it TEP, the TEP may be technically difficult for the very large artifact produced by TMS. So, one way to overcome this problem is to select the TMS compatible caps in the experiment. We can also use different software to remove the TMS artifact with such kind of experiment.   But with all these efforts, the TMS artifact is still a very big problem in the area of the TMS evoked potential.  

The TMS can also be given to the non-motor cortical areas. Sometimes this can lead to very high impact studies. For example, in this nature experiment, TMS was given to different cortical areas. On the left side, we can see the experiment was set up. In this experiment, the authors compare the effect of TMS in the very early blind subjects to the healthy controls. So, all the subjects performed a Braille -- a Braille reading task, which shows on the left side. At the beginning of the task, the subject moved their index finger to start the Braille reading task. When the finger moved to the left side, we can see there is a laser beam on that.   When the finger covered the laser beam, it triggered a TMS trait with three seconds at one -- at about 10 hertz.   With this train of stimulation, it produced a virtual lesion in the stimulated area. The results are on the right side.

For this braille-reading task, the subject should read out what the characters they have read during the stimulation. And what was measured is the error of the reading task. The interesting thing is that, in the healthy control subject, the stimulation on the sensory motor cortex produced a lot of error in the subject.   This is because the sensory inputs were impaired by the train of stimulation. Another very important result is that, in the blind subject, the sensory motor stimulation did not impair the results. But the middle occipital stimulation was -- which is targeted on the primary visual cortex impair the -- impair the task, and they impair the performance of the subject a lot. So, the results suggest that the visual cortex is involved in the cognitive task in the early blind subjects.

This is the follow-up study for the previous one. In this experiment, the stimulation -- the set up was changed a little bit. The motor task is that the subject was given -- was presented a word with auditory stimulation. For example, in this subject, the apple -- the word apple was presented to the subject. And with this auditory stimulation, the subject should respond with a logically correct word, for example, eat. But the subject cannot respond like a drink or other words.

At the same time, a train of stimulation at 10 hertz lasted for three seconds was given to different cortical areas. These areas, including the visual cortex, the prefrontal cortex, the somatosensory cortex, and the lateral occipital cortex. The interesting thing is that, in the site control, in the healthy control, the prefrontal cortex stimulation impaired the performance of the subject.   That means in healthy control, the prefrontal cortex is important for the cognitive tasks.  

But the result says different in the subject with early blind. Only visual cortex -- visual cortical stimulation produced the impairment of the motor performance. So, all these experiments show that the stimulation, the TMS stimulation, to different cortical areas can be important for the -- for the cognitive and the motor learning tasks.

Going to the summary of this lecture, at first, TMS is a powerful neurophysiological technique to study human brain functions. The effect of TMS can be recorded with electroencephalography and the electromyography. Spinal activity should be taken into consideration for a TMS study. Motor cortical stimulation activates the cortical spinal neurons, and it produces descending cortical spinal waves. The effect of TMS at other cortical areas are often complex, and they may interfere with motor learning and the cognitive process.

So, again, I am Dr. Zhen Ni.   I am working at the National Institute of Neurology Disorders and Stroke. I am a Senior Research Fellow. Thank you very much for watching this video. I hope this video can help you when you do TMS studies.   Thank you very much.

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