Transcranial Magnetic Stimulation (TMS) Glenn Mason-Riseborough (31/8/1998) Functional imaging techniques provide powerful evidence for the link between the brain and behaviour. These techniques enable us to pinpoint the areas of the brain that are used in carrying out certain tasks. This essay will focus on one particular imaging technique that can be used for this purpose – transcranial magnetic stimulation (TMS). TMS is a new technique that, while not directly able to measure brain function, can be used to stimulate various areas of the brain to indirectly infer functionality of the area affected. The initial task of this essay will be to describe the principle of operation and instrumentation of TMS. This will involve a brief discussion of the electric fields within the brain and how TMS induces an electrical current within the neurons. In addition a brief section on some of the safety issues of TMS will be included, documenting some of the various side effects that have been observed. Finally, we will discuss a few of the various practical applications of TMS in research. A number of recent experiments will be discussed, which show the extent to which TMS has been used in various areas of research in cognitive neuroscience. TMS: How it works In brief, electrical currents are used within the brain to process and transmit data (Pinel, 1993). The details of the particular ions involved in this process and how they interact are unimportant in the context of this essay. In essence, during the resting state there is an electrical potential difference between the intercellular and extracellular space of approximately –70mV. An electrical current is produced within the cell if the cell membrane is depolarised sufficiently (approximately –65mV). This results in an electrochemical signal being transmitted through the neuron and across the synapse. We can manufacture an electric current within a specified area of the brain by applying an electrical field around the excitable tissue and depolarising the cell membrane sufficiently. Previous attempts at altering the electrical fields within the brain have required high voltages and consequently have been unable to achieve the desired levels of fine control and focus (Kirkcaldie, 1998). A relatively easy way to alter electrical fields is by induction, using a magnetic field. This is because this particular method of creating an electrical field is non-invasive (it does not require surgery or the injection of radioactive materials) and relatively straightforward. Magnetic fields pass easily through electrically insulating materials such as the skull and thus does not require the skull to be physically penetrated, or relative measuring (such as with scalp EEG) to be used. This is contrasted with electrical fields that require high levels of conductivity through the particular medium. Changing the magnetic field over time alters the electrical current within the brain. However, the technology to do this has only been around for about 10 years because it requires a large magnetic force to be changed extremely quickly (Kirkcaldie, 1998). Thus, the power of TMS is its ability to activate specific areas of the brain by inducing an electrical field in that area from a magnetic field produced non-intrusively. The TMS device simply needs to be held next to the skull, the magnetic field penetrates into the brain and activates the specified area of neurons. As stated above, unlike other functional imaging techniques TMS does not directly measure brain function. Instead it is used within an experimental situation to activate or temporarily lesion specific areas of the brain. The behaviour of the subject is observed in the context of specific tasks to determine the extent of the induced deficits or behavioural changes. From this, a functional map of the brain can be built up. TMS instrumentation The actual instrumentation used to produce the magnetic field is relatively straightforward (see Fig. 1). The magnetic field is produced by passing a current through the conducting coil, L. When the coil is held next to the skull it induces the electrical current by the method stated in the previous section. The shape of the coil determines the size and properties of the field. Repetitive TMS (rTMS) is the term used for the new technique of delivering the magnetic stimulation at regular intervals. This allows the neurons to be stimulated during their refractory period. High frequency rTMS refers to the alternation of magnetic fields at physiologically interesting rates (up to 25 Hz). This is a major improvement, as the first TMS machines could only deliver a pulse every three seconds (Kirkcaldie, 1998). Kirkcaldie (1998) states that currently machines are available that can create pulses of up to 50 Hz. TMS has been used since 1985 and approximately 3000 stimulators were in use as of February 1998 (Ruohonen, 1998). Safety Because TMS is still a relatively new technique, the long-term effects of its usage are still unknown. However, its future is looking promising and there are no known harmful side effects of single-pulse TMS (Ruohonen, 1998). Research on both human and animal subjects has shown that there has been no detectable structural changes to brain tissue, and little effect on the body as a whole (Kirkcaldie, 1998). Having said that, the FDA is still investigating the safety of this procedure, and approval will probably not be for some time (Ruohonen, 1998). Ruohonen (1998) lists numerous side effects, in brief some of these are: ? It is possible to induce seizures with single-pulse TMS in patients, and both patients and normal subjects with rTMS. Kirkcaldie (1998) states that strict guidelines are available to minimise the possibility of these seizures. ? Subjects with either intracranial metallic pieces or pacemakers should be excluded from TMS usage. The magnetic fields of TMS will exert forces on any metallic object, either attracting or repelling it, and the magnetic field will disturb electronic devices such as a pacemaker. ? There may be hearing loss from repeated exposure to the device because there is a loud repeated clicking sound from the coil. The peak sound pressure is 120 – 130 dB, 10 cm from the coil. Most of the sound energy is between 2 and 7 kHz, this is the frequency range where the human ear is most sensitive. It is recommended that both the examiner and the subject wear hearing protection aids, although 1000 – 10000 pulses per day are within safety regulations. ? Subjects often complain of headaches. This is probably because of the activation of the scalp and neck muscles. ? Weak electromagnetic fields may be linked to cancer, however at this time there is insufficient information regarding pulsed fields. ? Brain heating is unlikely to be detrimental. The brain’s metabolic power is 13 W, while the theoretical power dissipation from TMS is a few milliwatts at 1 Hz. Ruohonen (1998) also mentions some possible equipment problems, such as scalp burns from EEG electrodes and safety considerations with regards to the high-voltage equipment. Where TMS is used Today, TMS has a wide range of uses in both the areas of medicine and cognitive neuroscience. Kircaldie (1998) states that rTMS may have applications as an antidepressant. In this respect it may replace ECT, which has many aversive side effects. As stated above, this essay will focus on the applications in cognitive neuroscience and not those in medicine. This section will briefly examine four recent journal articles, which document experiments that were conducted utilising TMS techniques. Freeman and Persinger (1996) This study examined the irritability levels of human subjects when a weak TMS field (1 microTesla) over the temporoparietal region was interrupted. It was hypothesised that subjects who had been receiving bilateral stimulation would react more aggressively than those who were receiving it unilaterally (either left or right hemisphere) or not at all. This was because it was thought that bilateral stimulation acted as a pleasant experience, and disrupting this experience would elicit irritability. The results indicated that there was statistical significance that subjects who had been subjected to bilateral stimulation experienced irritability, whereas those from the other three conditions did not. In addition, there were no sex differences. Thus, this study shows evidence that bilateral stimulation of the temoroparietal lobes by weak TMS can be considered pleasant, and that cessation of stimulation is unpleasant and thus induces irritability. Persinger (1996) Using a similar experimental design as Freeman and Persinger (1996), this experiment examined the feelings induced in subjects who were stimulated over either the left or right hemisphere by TMS. A complex weak magnetic field (1 to 5 microTesla) was aimed towards the hippocampal and amygdaloid regions. This field was intended to imitate the burst-firing of the neurons in those regions. The results of this experiment showed a statistically significant correlation between a belief in “reincarnation” and “exotic” experiences (such as feelings of the self detached from the body, displacement of consciousness to a different place, tingling, spinning, low frequency vibrations within the body, and odd tastes) induced by TMS. Those who did not have such beliefs did not have these experiences to the same degree as those who did hold those beliefs. This result was a confirmation of the hypothesis that there are neurocognitive processes that identify experiences as originating from the sense of self (defined by episodic memory) or non-self. The non-self is essentially an amalgamation of semantic memories that are outside the boundaries of normal episodic memories. Non-self memories should occur more frequently in subjects who are more imaginative or prone to dissociation. The use of TMS in this experiment showed that the stimulation of the medial temporal area induces these non-self experiences in people who have a greater tendency to have these beliefs. Ashbridge, Walsh and Cowey (1997) This experiment looked at the effect of TMS on visual search tasks. A monophasic pulse of 1.6 Tesla was used to stimulate a small area (approximately of radius 1 cm) of the parietal visual area in order to disrupt the activity in that region. The subjects were required to watch a monitor and respond as fast as possible to whether or not a target was observed in a grid containing eight distractors. The target was present 50% of the time, and two types of arrays were used – pop-out and conjunction. The results showed that there was a significant increase in the reaction times when TMS was applied to the right parietal visual area during the conjunction task. Reaction times were slowed when stimulation was applied 100 ms after the onset of the visual display when the target was present. They were also slowed when stimulation was applied 160 ms after the onset of the visual display when the target was absent. TMS did not significantly alter performance during the pop-out search, nor did it effect the number of errors made for either search task. The theory is that when the target is present, TMS in this area disrupts the focusing of attention in spatial processing. When the target is absent, TMS in this area disrupts a frontal signal to the parietal cortex to terminate the search. Triggs, Calvanio and Levine (1997) The aim of this experiment was to examine hemispheric asymmetries in the context of motor performance of left-handed and right-handed subjects (based on writing preference). The subjects’ hand preference was recorded along with their wrist- finger speed, finger dexterity, and static strength for each hand. In addition, a TMS motor threshold was obtained for each subject. This was achieved by measuring the threshold for eliciting a motor evoked potential (MEP) in each subject’s left and right abductor pollicis brevis (APB). This threshold reflected the excitability of both the cortical and spinal motorneurons. The results then showed a statistically significant correlation between the hand-differences in TMS thresholds and the hand-difference in manual performance of the subjects. The highest correlation was between the TMS threshold scores and wrist-finger speed scores, followed by finger dexterity scores, and finally static strength scores. Thus, in this experiment TMS was used as a technique to indicate hand-difference in subjects by stimulating cortical and spinal motorneurons. Conclusions Transcranial magnetic stimulation is a relatively new technique that has proven to have significant potential in the area of cognitive neuroscience (and also to the field of medicine). TMS operates by magnetically stimulating areas of the brain to induce an electrical current. Depending on the shape of the coil, the size of magnetic field produced, and the area of stimulation, the electrical current may either be excitatory or inhibitory. The functionality of the area of the brain stimulated can then be inferred by observing the subject’s performance during specific tasks. Because it is such a new technique, the relative safety of TMS is still being examined. As yet, no harmful long-term side effects have been documented, but formal approval is still forthcoming. TMS has already found a useful place in cognitive neuroscience research, and numerous experiments have incorporated this technique to make invaluable discoveries. This essay focused on four such experiments, showing the wide range of uses that have been found for TMS. References: Ashbridge, E., Walsh, V., & Cowey, A. (1997). Temporal aspects of visual search studied by transcranial magnetic stimulation. Neuropsychologia, 35, 8, 1121-1131. Freeman, J., & Persinger, M. A. (1996). Repeated verbal interruptions during exposure to complex transcerebral magnetic fields elicit irritability: Implications for opiate effects. Perceptual and Motor Skills, 82, 639-642. Kirkcaldie, M. (1998). Transcranial magnetic stimulation (TMS). Retrieved 24 August 1998 from the World Wide Web: http://pni.unibe.ch/TMS.htm http://www.musc.edu/tmsmirror/intro/layintro.html http://www.musc.edu/tmsmirror/intro.html Persinger, M. A. (1996). Feelings of past lives as expected perturbations within the neurocognitive process that generate the sense of self: Contributions from limbic lability and vectorial hemisphericity. Perceptual and Motor Skills, 83, 1107-1121. Pinel, J. P. J. (1993). Biopsychology (2nd ed.). Boston: Allyn and Bacon. Ruohonen, J. (1997). Basic principles. Retrieved 24 August 1998 from the World Wide Web: http://www.biomag.helsinki.fi/tms/basic.html Ruohonen, J. (1998). Safety of TMS. Retrieved 25 August 1998 from the World Wide Web: http://www.biomag.helsinki.fi/tms/safety.html Triggs, W. J., Calvanio, R., & Levine, M. (1997). Transcranial magnetic stimulation reveals a hemispheric asymmetry correlate of intermanual differences in motor performance. Neuropsychologia, 35, 10, 1355-1363.