Effect of Transcranial Magnetic Stimulation(TMS) on Visual Search Task

INTERNATIONAL JOURNAL OF APPLIED BIOMEDICAL ENGINEERING VOL.2, NO.2 2009 1 Effect of Transcranial Magnetic Stimulation(TMS) on Visual Search Task K. Iramina, Guest member ABSTRACT Transcranial magnetic stimulation (TMS) has been applied as an important method to investigate human cognitive process. In this study, we applied TMS to investigate temporal aspect of the functional processing of the visual search in the brain. Subjects were required to respond as quickly and accurately as possible by pressing a mouse button to indicate the presence or absence of the target, and the reaction times were measured. Subjects received four trials which the TMS stimulus onset asynchronies (SOA) were set as 100, 150, 200 and 250 ms after visual stimulus presentation for easy feature, hard feature and conjunction task, respectively. It was found that there was a significant elevation in target-present response time when the TMS pulses were applied 150 ms after visual stimulus presentation. However for the other SOA cases there was no significant difference between no-tms and TMS conditions. Therefore, we considered that the right posterior parietal cortex was involved in visual search at about 150 ms after visual stimulus presentation. When the TMS applied to the primary visual area on occipital area 50 ms after visual stimulus presentation, there was a significant decrease in response time. However, there was no difference at 150 ms SOA. Keywords: Transcranial Magnetic Stimulation (TMS), visual search task, visual perception, posterior parietal cortex(ppc) 1. INTRODUCTION Transcranial magnetic stimulation (TMS) is the application of a brief magnetic pulse or a train of pulses to the skull, which results in an induction of local electric current in the underlying surface of the brain, thereby producing a localized axonal depolarization. TMS has become an important tool for the study of the functional organization of the human brain [1]. Earier studies using transcranial magnetic stimulation were related to the mapping of the cerebral cortex. Mapping studies were carried out by a method of localized and vectorial magnetic stimulation using a figure eight coil [2]. The basic principle is to concen-trate induced eddy currents locally Manuscript received on December 16, 2009., K. Iramina, Kyushu University, 819-0395 Fukuoka, Japan Telephone & Fax: +81-92-802-3581 E-mail addresses: iramina@inf.kyushu-u.ac.jp near a target by a pair of opposing pulsed magnetic fields produced by a figure-eight coil. This method facilitates stimulation of the motor cortex of the human brain within a 5 mm resolution [3][4]. As a noninvasive and effective method to make reversible lesions in the human brain, TMS has a long and successful history. Now it has become a major tool of cognitive neuroscience and a treatment method for various neurobehavioral disorders. TMS can be used to stimulate the cortex to produce visual percepts[5] or movements[6]. It is more suitable to provide reversible disruption of activity in the cortex with millisecond accuracy. Because TMS has high temporal and spatial resolutions, it can investigate not only the spatial localization but also the time course of mental processes. TMS is a noninvasive and effective method to making reversible lesions in the human brain. The application of TMS in the investigation of neurological deficits provides an important method for investigating human cognitive processes. Visual search, as a traditionally visual neglect sensitive measure, was studied by many researchers. Selective spatial attention [7], memory for the target [8], object-based atten-tion and identification of the target are all required in visual search. Much is already known about the involvement of the large areas of the visual field [9] [10], the right parietal cortex [11], right superior temporal gyrus [12] and right posterior parietal cortex [12] [13]. In contrast to the knowledge of the location of particular cortex areas involved in the visual search, the study of temporal aspect of cortex areas is not sufficient. Ashbridge et al. [14] applied TMS over the subjects right parietal visual cortex while they were performing feature and conjunction visual search tasks. The same authors found that TMS had no detrimental effect on the performance of feature search, but significantly increased the response time in conjunction search when TMS was applied over the right parietal cortex 100 ms after the visual stimuli presentation. However, in that study, the temporal aspect of the posterior parietal cortex (PPC) in visual search was not discussed. In Ellison et al. s repetitive TMS (rtms) study [12], they found that TMS over the right PPC caused a significant increase in response time in the landmark task and hard conjunction search task. However, in their study, since the rtms was applied before the visual search stimuli presentation, the involvement of the PPC in visual search was confirmed but the time course was not in-

2 K. Iramina: Effect of Transcranial Magnetic Stimulation(TMS) on Visual Search Task (1-8) vestigated. Fuggetta et al. s study [15] reported a significant increase in response time for conjunction task when a single-pulse TMS applied over right PPC 100 ms after the visual stimuli presentation. Ellison et al. [16] applied 5 pulse 100 ms apart TMS over right PPC, they found PPC plays significant effect in conjunction visual search proc-essing. In this study, to investigate the temporal aspect of the posterior parietal cortex involved in the visual search, we used different TMS stimulus onset asynchronies (SOA) and measured the visual search response times. The relationship between the SOA and the response time was investigated. We also investigated the effect of TMS on primary visual area V1 on visual search task. slash (/). In the hard feature task the target was a 90 counterclockwise rotated L shape among L shape. These two tasks which have only one different feature between the target and distractor are called pop-out tasks. On the other hand, the task which has more than two different features is called conjunction task. In this study, the target was a red backslash among red and green slash. All items were subtended in 4.7 4.7 visual angle on the screen. Subjects were required to respond as quickly and as accurately as possible by pressing a mouse button to indicate the presence or absence of the target. The target was present on 50% of the trials and there was never more than one target. Each trial was preceded by a central fixation cross for 1500 ms, followed immediately by the stimuli array which was presented for 1500 ms. 2. 2 Magnetic stimulation The TMS stimulator was a MagStim Super Rapid Stimulator. Stimulus strength was set as the subjects individual resting motor threshold which required to produce MEPs of >50 µv peak-to-peak amplitude in at least 6 of 10 successive trials. A figure-of-eight 70mm coil was used. The double coil windings in the figure-of-eight coil carry two currents in opposite directions. At the central point of the coil, the two loops meet and generate a localized summation of current. The localized electric current induced by the pulse has low attenuation and high spatial resolution. When the TMS coil is discharged, a loud click sound will be produced and this makes the interpretation of TMS-evoked activity difficult. To investigate the TMS effect without including auditory artifact, a control study, no-tms conditions were applied in this study. No- TMS condition used two coils. One is a dummy coil which does not produce the magnetic field and another coil which are located vertically to the scalp produces the click sound as shown in Fig.2. Fig.1: Examples of visual search stimuli (Top: easy feature, Middle: hard feature, Bottom: conjunction, Left: target-absent stimulus, Right: target present stimulus) 2. MATERIALS 2. 1 Visual search task Three visual search tasks were carried out (see Fig. 1). There were eight items in each array. In the easy feature task the target was a backslash (\) among 2. 3 Subjects Eight subjects (one female, seven males, and aged 21-31 years) participated in all the experiments of the present study, who were experienced psychophysical observers but ignored the purpose of the experiment. All were right handed, had normal or corrected-tonormal visual acuity. All the subjects had previous practice before the experiment in order to be familiar with visual search and to make stable response, and reported a complete absence of epilepsy, or any other neurological condition in themselves and their known family history. 3. EXPERIMENTAL PRCEDURE The time sequence of experiment is shown in Fig.3. Each trial was preceded by a central fixation cross for 1500 ms, followed immediately by a visual search

INTERNATIONAL JOURNAL OF APPLIED BIOMEDICAL ENGINEERING VOL.2, NO.2 2009 3 Fig.2: TMs coil was applied over the right posterior parietal cortex. (a) TMS condition (b) No-TMS condition stimulus, which would be presented for another 1500 ms. Subjects were required to respond as quickly and as accurately as possible by clicking a mouse button to indicate the presence or absence of the target (left button for target present and right button for target absent). The time from the visual search stimuli presentation till the button click was recorded as the response time. Transcranial magnetic stimulations were applied over the right PPC of the subject at different time intervals after the visual search stimuli presentation. These time intervals were called as TMS stimulus onset asynchronies (SOA). Fig.3: No-TMS condition In the TMS condition, since paired-pulse TMS can produce larger and longer effects on cortical activity than single-pulse, paired-pulse TMS was used in the present study. The highest frequency of TMS device is 50 Hz, thus, we set inter-stimulus interval=20 ms. Paired-pulse TMS were applied over the right PPC of subject. The coil was placed tangential to the surface of the skull and the centre of the coil was positioned over electrode site P4 of the international 10-20 system. The induced current in the brain was parallel to the Oz-Pz midline, flowed from the occipital to the frontal cortex. While in the no-tms condition, an open circuit coil was put over the subject s right PPC just like the TMS condition, while a figureof-eight coil discharged paired-pulse near to, but directed away from the subject s skull. The application sequences of TMS and no-tms conditions were randomized across subjects. Each subject received 60 trials for two times under TMS and no-tms conditions as one test. Subjects received four tests with the TMS stimulus onset asynchronies (SOA) were set as 100, 150, 200 and 250 ms after the visual search stimuli presentation. Subjects received these four tests for the easy feature and hard feature search tasks, respectively. Consequently, subjects received a total of eight tests in this study. The stimulation protocol was in accordance with published safety recommendations. In considering of the safety of TMS, only one test was performed within one day for each subject. 4. RESULTS 4. 1 Visual search task stimulating on the right PPC For the easy feature search task, hard feature task and conjunction task, the target-present response times at each SOA for each subject are shown in the Table 1. Obviously, the individual differences among subjects were large. Moreover, there were differences in response times between SOA cases even for the same subject. Since subjects participated all the 4 tests in different days, the mental condition, concentration and relaxation degrees were different even for the same subject. This logically led to difference in the response time. Therefore, it is not appropriate to use the average of response time of each subject as the typical value of the experimental data. In the present study, in order to remove the individual difference and the difference of experimental conditions, we used the average of normalized response time as the typical value of the experimental data. Thus, for each subject, the average of target-present response time in the TMS condition was normalized to the no-tms condition (set as the baseline=1). The difference between the average of normalized response time of all the subjects and the baseline was taken to demonstrate the TMS effect. Fig.4 shows the target-present response times and normalized response time at each SOA cases. In order to investigate the influence of TMS effects, paired t-test was used to analyze the difference between the TMS and no-tms conditions.

4 K. Iramina: Effect of Transcranial Magnetic Stimulation(TMS) on Visual Search Task (1-8) Table 1: Respose times at each SOA for the easy feature task, hard feature task and conjunction tasks of each subjects We found that, when SOA=150 ms, compared to the no-tms condition, there was a significant elevation in response time when the TMS pulses were applied. However, for the other SOA cases, there was no significant difference between the TMS and no-tms conditions. For the hard feature search task, the targetpresent response times and the difference between the average of normalized target-present response time of all the subjects is shown in Fig.5. Based on the paired t-test analysis results, we found that, when SOA=150 ms, compared to the no-tms condition, there was a significant elevation in response time when the TMS pulses were applied. However, for the other SOA cases, there was no significant difference between the TMS and no-tms conditions. For the conjunction task, the target-present response times and the difference between the average of norma-lized targetpresent response time of all the subjects and is shown in Fig.6. When SOA=150 ms, compared to the no- TMS condition, there was an elevation in response time when the TMS pulses were applied. For the target-absent condition, there was no significant difference between the TMS and no-tms conditions for all three visual search task and the SOA cases. Fig.4: (a) Target-present response times (b) Normalized target-present response times at each SOA for the easy feature visual search task when the right PPC was stimulated. 4. 2 Visual search task stimulating on the right V1 In order to investigate the difference between the role of right PPC and the primary visual cortex V1, TMS was applied to the right V1 at 50ms SOA, 100ms SOA and 150ms SOA. For the hard feature search task, the tar-get-present response times and the difference between the normalization of response time ratio TMS to no-tms condition is shown in Fig.7. When the TMS applied to the right V1 after visual stimulus presentation at 50 ms SOA, there was a significant decrease in response time. However, there was no difference at 150 ms SOA. 4. 3 Simple reaction task In this experiment, we investigated the simple reaction time. No-targeted hard feature visual search task was used in this experiment. The subjects re-

INTERNATIONAL JOURNAL OF APPLIED BIOMEDICAL ENGINEERING VOL.2, NO.2 2009 5 Fig.5: (a) Target-present response times (b) Normalized target-present response times at each SOA for the hard feature visual search task when the right PPC was stimulated. Fig.7: (a) Target-present response times (b) Normalized target-present response times at each SOA for the hard feature visual search task when the right V1 area was stimulated. Fig.6: (a) Target-present response times (b) Normalized target-present response times at each SOA for the conjuncion visual search task when the right PPC was stimulated. Fig.8: (a) Response times (b) Normalized response times at each SOA for the simple reaction task when the right V1 area was stimulated.

6 K. Iramina: Effect of Transcranial Magnetic Stimulation(TMS) on Visual Search Task (1-8) Fig.9: (a) Response times (b) Normalized response times at each SOA for the simple reaction task when the right PPC was stimulated. spond the visual stimulation sa soon as possible without judgement of the presenttation. Stimulus points of TMS were right PPC or right V1. Fig. 8 shows the normalization of response time ratio TMS to no- TMS condition of all the subject when the right V1 was stimulated at 50 ms or 100 ms SOA. Fig. 9 shows the normalization of response time ratio TMS to no- TMS condition of all the subjects when the right PPC was stimulated at 50 ms or 150 ms SOA. When the right V1 was stimulated at 50 ms SOA, there was a significant decrease in response time. However, SOA is 100 ms, there was no difference. When the right PPC was stimulated at 50 ms SOA, there was a significant decrease in response time. However, SOA is 100 ms, there was no difference. 5. DISCUSSION Two previous studies have investigated the involvement of the PPC in visual search task using TMS[12, 14]. However, the former used repetitive TMS (rtms) before visual search stimuli presentation. That study indicated that the PPC is involved in visual search, however the temporal aspect of the PPC involved in visual search was not discussed. The other one used single pulse TMS but reported TMS over the PPC had no detrimental effect on the performance of feature search. In the present study, to investigate the temporal aspect of the PPC involved in feature search, a paired-pulse TMS was applied over the right PPC, and the time intervals between visual search stimuli presentation and TMS stimuli were set as four types, i.e., SOA=100, 150, 200 and 250 ms. Several past TMS experiments on the PPC showed that TMS over the PPC does not induce eye movement [14, 17]. Furthermore, some past studies suggested that the PPC plays a role in the saccadic eye movement beyond 200 ms after target presentation[18]. In our study, we found a significant influence in response time when SOA=150 ms; Based on the above-mentioned studies, we considered that the saccadic eye movement was not bound at all at 150 ms after visual search task presentation. This lead to the conclusion that the disruption of eye movement, which is induced by the TMS, is not the key factor for the elevation in response time when SOA=150 ms. A common knowledge of TMS experiments is that TMS can either excite the cortex or disturb its function. The observed excitatory effects are normally muscle twitches or phosphenes, whereas in the lesion mode, TMS can transiently suppress perception or interfere with task performance. An appropriately applied TMS pulse delivered in time and space can transiently disrupt the function of a certain cortical area at a given time, creating a temporary and localized cortical virtual brain lesion. Thus, TMS can be used to disrupt the brain activation at a specified cortical area at a given time point. Therefore, TMS can be used to investigate not only the spatial but also the temporal characteristics of task performance. In the present study, compared to the sham TMS condition, since a significant elevation in response time was only observed when SOA=150 ms, we concluded that the feature search was probably processed in the PPC at about 150-170 ms after stimulus presentation. Based on the past conjunction search research[14] and present study, it seems reasonable to consider that the PPC plays a dominant role not only in the conjunction search but also in the feature search tasks. On the other hand, for the target-absent condition, it was found that there was no significant difference between TMS and sham TMS conditions for all the SOAsettings in both easy and hard feature search tasks. Based on the actual experimental experience, we considered that the response of target present or target absent is different to that of where is the target in the visual search task. i.e., detection of target and localization of target are two different processes. When the primary visual area V1 was stimulated in the hard feature task, response time shows the significant decreasing in the case of 50 ms SOA and 100 ms SOA. For the simple reaction experiment, when the primary visual area V1 was stimulated, response time shows the decreasing significantly in the case of 50 ms SOA. There is no difference in 100 ms SOA. When the right PPC was stimulated, There was no significant difference of response time in the case of 150 ms SOA. These results suggest that right

INTERNATIONAL JOURNAL OF APPLIED BIOMEDICAL ENGINEERING VOL.2, NO.2 2009 7 PPC plays a dominant role in spatial processing during visual search. This TMS study opens up a new possibility for understanding not only the physiological role of the PPC in the visual search but also the temporal aspect of the PPC involved in the visual search. We expect that this study will contribute to the theories about the visual search dynamics. 6. CONCLUSION We concluded that it is most difficult to find the target in the conjunction task. Furthermore, compared with easy feature task, we found that it is more difficult to find the target in the hard feature task. In easy and hard feature tasks, when SOA=150 ms, compared to no-tms condition the response time of the TMS condition were increased. Especially in the hard feature task, there is a significant difference between TMS and no-tms conditions. However, in the other SOA cases of all tasks, we could not found such TMS effect. Paired t-test was used to examine whether there is a significant difference between TMS and no-tms conditions or not. There was a significant difference between TMS and no-tms conditions when SOA=150 ms in easy feature tasks, hard feature tasks (p<0.01 for easy feature task, p 0.05 for hard feature, respectively.). However, there was no significant difference for the other SOA cases. It means that TMS created an obstacle in visual search task while SOA=150 ms at the right posterior parietal cortex. 7. ACKNOWEDGMENT This work was supported in part by a Grant-in Aid for Scientific Research, Education, Science, Sports, Culture and Technology, Japan (No. 21300168) References [1] AT. Barke, R. Jalinous and IL. Freeston, Noninvasive magnetic stimulation of human motor cortex. The Lancet, 1, 1106-1107 (1985) [2] S. Ueno, T. Tashiro and K. Harada, Localized stimulation of neural tissues in the brain by means of paired configuration of time-varying magnetic fields. J. Appl. Phys., 64, 5862-5864 (1988) [3] S. Ueno, T. Matsuda, M. Fujiki and S. Hori, Localized stimulation of the human motor cortex by means of a pair of opposing magnetic field. Digest of IEEE Intermag. Conf, GD-10, Washington DC, (1989) [4] S. Ueno, T. Matsuda and M. Fujiki, Vectorial and focal magnetic stimulation of the brain for the understanding of the functional organization of the brain. IEEE Trans Magn, 26, 1539-1544 (1990) [5] V.E. Amassian, P.J. Maccabee, R.Q. Cracco, J.B. Cracco, A.P. Rudell and L. Eberle, Measurement of information processing delays in human visual cortex with repetitive magnetic coil stimulation. Brain Research, 605, 317-321 (1993) [6] M.C. Day: Visual search by children, the effect of background variation and the use of visual cues. Journal of experimental Child Psychology, 25, 1-16 (1978) [7] M.I. Posner, Orienting of attention. Quarterly Journal of Experimental. Psychology, 32, 3-25 (1980) [8] L. Chelazzi, E. K. Miller, J. Duncan and R. Desimon, A neural basis for visual search in inferior temporal cortex, Nature, 363, pp.345-347 (1993) [9] J. Moran and R. Desimone, Selective attention gates visual processing in the extrastriate cortex. Science, 229, 782-784 (1985) [10] B. C. Motter, Neural correlates of feature selective memory and pop-out in extrastriate area V4. Journal of Neuroscience 14, 2190-2199 (1994) [11] V. Walsh, E. Ashbridge and a. Cowey, Cortial plasticity in perceptual learning demonstrated by transcranial magnetic stimulation. Neuropsychologia, 36, 1, 45-49 (1998) [12] A. Ellison, I.Schindler, Lara L. Pattison and A. David milner, An exploration of the role of the superior temporal gyrus in visual search and spatial perception using TMS. Brain. Vol. 127, No.10, 2307-2315 (2004) [13] A.C. Nobre, J.T. Coull, V. Walsh and C.D. Frith, Brain activa-tions during visual search: contributins of search efficiency versus feature binding. Neuroimage, 18, 91-103 (2003) [14] E. Ashbridge, V. Walsh and A. Cowey, Temporal aspects of visual search studied by transcranial magnetic stimulation, Neuropsychologia, 35, 1221-1131 (1997) [15] G. Fuggetta, E.F. Pavone, V. Walsh, M. Kiss, M. Eimer, Cortico-Cortical interactions in spatial attention: a combined ERP/TMS study. Journal of Neurophysiology, 95 (5). 3277-3280 (2006) [16] A. Ellison, A. R. Lane, and T. Schenk, The Interaction of Brain Regions during Visual Search Processing as Revealed by Transcranial Magnetic Stimulation, Cereb Cortex Advance Access published January 11 (2007) [17] D.M. Beck, N. Muggleton, V. Walsh, N. Lavie, Right parietal cortex plays a critical role in change blindness. Cerebral Cortex, 16(5), 712-717 (2006) [18] R.M. Muri, A.I. Vermersch, S. Rivaud, B. Gaymard and C. Pierrot-Deseilligny, Effects of single-pulse transcranial magnetic stimulation over the prefrontal and posterior parietal cortices during memory-guided saccades in humans. Journal of Neurophysiology, 76, 2102-2106 (1996)

8 K. Iramina: Effect of Transcranial Magnetic Stimulation(TMS) on Visual Search Task (1-8) K. Iramina received his Ph.D degree in Engineering from Kyushu University, Japan, in 1991. From 1991 to 1995, he worked at the Department of Electronics, Kyushu University. In 1996, he moved to the University of Tokyo, Japan and he has been an associate professor of Institute of Biomedical Engineering, the University of Tokyo. In 2005, he moved o Kyushu University as a professor of Graduate School of Information Science an Electrical Engineering. He has been also a professor of Graduate School of Systems Life Sciences in Kyushu University.