European Journal of Neuroscience, Vol. 17, pp. 1129±1133, 2003
`
`ß Federation of European Neuroscience Societies
`
`SHORT COMMUNICATION
`Enhancing cognitive performance with repetitive transcranial
`magnetic stimulation at human individual alpha frequency
`
`Wolfgang Klimesch,1 Paul Sauseng1 and Christian Gerloff2
`1Department of Physiological Psychology, Institute of Psychology, University of Salzburg, Hellbrunnerstr. 34, A-5020 Salzburg,
`Austria
`2Department of Neurology, Cortical Physiology Research Group, University of Tuebingen Medical School, Hoppe-Seyler-Str. 3,
`72076 Tuebingen, Germany
`
`Keywords: alpha, EEG, mental rotation, oscillations, rTMS
`
`Abstract
`
`We applied rapid-rate repetitive transcranial magnetic stimulation (rTMS) at individual alpha frequency (IAF) to improve cognitive
`performance by in¯uencing the dynamics of alpha desynchronization. Previous research indicates that a large upper alpha power in a
`reference interval preceding a task is related to both large suppression of upper alpha power during the task and good performance.
`Here, we tested the hypothesis that rTMS at individual upper alpha frequency (IAF ‡ 1 Hz) can enhance alpha power in the reference
`interval, and can thus improve task performance. Repetitive TMS was delivered to the mesial frontal (Fz) and right parietal (P6) cortex,
`and as sham condition with 908-tilted coil (P6 position). The behavioural effect was assessed in a mental rotation task. Further control
`conditions were rTMS at a lower IAF (IAF 3 Hz) and at 20 Hz. The results indicate that rTMS at IAF ‡ 1 Hz can enhance task
`performance and, concomitantly, the extent of task-related alpha desynchronization. This provides further evidence for the functional
`relevance of oscillatory neuronal activity in the alpha band for the implementation of cognitive performance.
`
`Introduction
`
`Associations between cognitive performance and endogenous mod-
`ulations of oscillatory neuronal activity in the individual alpha fre-
`quency (IAF) range have been established in a number of studies (see
`Klimesch, 1999). If these associations are functionally relevant (rather
`than mere epiphenomena), then it should be possible to in¯uence cor-
`tical oscillations and thereby modulate behavioural performance. Here
`we tested the hypothesis that repetitive transcranial magnetic stimu-
`lation (rTMS) can induce predictable changes in oscillatory cortical
`activity and improve performance in a mental rotation task.
`Transcranial magnetic stimulation (TMS) has been used in various
`ways to interfere with cortical function. It has the potential to disrupt
`cortical functions in a target region of interest (for a recent review see
`Hallet, 2000). This ability to create a temporary `virtual brain lesion'
`allows to study the causal role of the affected region for complex motor
`(Gerloff et al., 1997) and cognitive processes (for a review see
`Jahanshahi & Rothwell, 2000). As an example, TMS applied over
`V5 can interfere selectively with the perception of motion of a stimulus
`without impairing its recognition (for a review see, e.g. Walsh &
`Cowey, 1998).
`Transcranial magnetic stimulation has also been used to improve
`brain function (for a recent review see Triggs & Kirshner, 2001). There-
`by, one important parameter is the frequency of repeatedly delivered
`single TMS pulses (rTMS). At frequencies of 5 Hz and higher, rTMS
`transiently enhances cortical excitability (Pascual-Leone et al., 1994),
`
`Correspondence: Dr Wolfgang Klimesch, as above.
`E-mail: wolfgang.klimesch@sbg.ac.at
`
`Received 16 September 2002, revised 17 December 2002, accepted 20 December 2002
`
`doi:10.1046/j.1460-9568.2003.02517.x
`
`whereas slow rTMS at a frequency of about 1 Hz induces a transient
`suppression of excitability (Chen et al., 1997a). Another important
`factor is the temporal relationship between task performance and
`magnetic stimulation. Application of fast rTMS (at a frequency of
`5 Hz or higher) during task performance (or the presentation of the task
`relevant stimulus) usually has detrimental effects on cognitive pro-
`cesses (Grafman et al., 1994; Wassermann et al., 1999). If, however,
`fast rTMS is delivered in a period preceding a task (Hamilton &
`Pascual-Leone, 1998; Mottaghy et al., 1999; Triggs et al., 1999; Evers
`et al., 2001; Sparing et al., 2001) or in short periods during processing
`of a task (Boroojerdi et al., 2001), enhanced performance can be
`observed. Facilitating effects have also been reported when single
`pulse TMS is used with a long interstimulus interval (500 ms or more)
`before task onset (ToÈpper et al., 1998).
`In the present study, we applied rTMS at IAF to enhance cognitive
`performance. The rationale of the experimental procedure is derived
`from three basic ®ndings about the human electroencephalogram
`(EEG) alpha rhythm (for an extensive review of the following ®ndings
`cf. Klimesch, 1999). First, interindividual differences in mean or peak
`alpha frequency are large (7±13 Hz; mean for young adults is about
`10 Hz) and are related to memory performance and the speed of informa-
`tion processes. Second, the extent of alpha reactivity [as measured, e.g.
`by event-related desynchronization (ERD); cf. ref. Pfurtscheller &
`Aranibar, 1977] depends on the amplitude of alpha oscillations during
`a resting or reference period that precedes task performance. In a series
`of studies, we have shown that cognitive performance is related to the
`extent of ERD, which in turn depends on the extent of power in a
`resting or test interval. Subjects with large alpha power tend to exhibit
`a pronounced ERD and both measures are associated with good
`
`PeakLogic, Inc. Ex. 1005
`PeakLogic, Inc. v. Wave Neuroscience, Inc., Case No. TBD
`
`

`

`1130 W. Klimesch et al.
`
`cognitive performance in a variety of different tasks (Neubauer et al.,
`1995). Thus, large resting (or reference) alpha power and a large ERD
`are associated with good cognitive performance. Third, these ®ndings
`are frequency sensitive. They can be observed in a narrow upper alpha
`band (width of 2 Hz) but only if frequency boundaries are adjusted to
`IAF (e.g. for a subject with fast IAF of 12 Hz, the upper alpha band is
`12±14 Hz).
`On the basis of these ®ndings, our conclusion was that a period of
`pronounced (upper) alpha activity preceding task performance is
`associated both with a large ERD (alpha suppression or reactivity) and
`good performance. Thus, the logic underlying the present experiment
`was to apply rTMS at individual upper alpha frequency (IAF‡ 1 Hz)
`in a period preceding task performance. Because the human alpha
`rhythm (as measured by scalp EEG) shows a clear association with
`visual information processing demands, we used a mental rotation task
`and applied rTMS at IAF ‡ 1 Hz over a right parietal (P6) and a frontal
`site (Fz). These sites were selected because functional magnetic
`resonance imaging studies have shown repeatedly that the superior-
`parietal lobule (BA 7) particularly in the right hemisphere plays a
`signi®cant role in mental rotation (e.g. Richter et al., 2000; Thomsen
`et al., 2000). There is also evidence that the lateral premotor and sup-
`plementary motor area (lateral and medial BA 6) is involved (Richter
`et al., 2000). Control conditions were rTMS at IAF 3 Hz (lower
`alpha, individually adjusted) and at 20 Hz (beta frequency, not adjusted
`individually). We expected that compared with the control conditions,
`subjects would show improved mental rotation performance, increased
`upper alpha power during a reference period (preceding the task) and
`increased ERD (larger suppression) during task performance in the exp-
`erimental condition (rTMS at IAF‡ 1 over the right parietal cortex).
`It is interesting to note that almost all studies reporting facilitating
`effects (ignoring those exploiting the potential of disinhibition) applied
`rTMS at a frequency that either equals mean alpha frequency (which is
`about 10 Hz) (Hamilton & Pascual-Leone, 1998; Wassermann et al.,
`1999), harmonics of alpha at 20 Hz (Mottaghy et al., 1999; Triggs et al.,
`1999; Sparing et al., 2001) or subharmonics like 5 Hz (Boroojerdi et al.,
`2001). Thus, the facilitating effects of these studies may have been
`already been, at least in part, because of the in¯uence of IAF.
`
`Materials and methods
`
`Subjects
`
`Experiments were carried out at the Department of Neurology, Uni-
`versity of TuÈbingen Medical School. They were performed in accor-
`dance to standard safety guidelines (Chen et al., 1997b) and the Code
`of Ethics of the World Medical Association and were approved by the
`Institutional Review Board of the University of Tuebingen. In Experi-
`ment 1, a sample of 16 subjects (six healthy males with a mean age of
`26.7 years, range 22±29 years and ten females with a mean age of
`23.1 years, range 18±30 years) was used. Because one female subject
`did not tolerate rTMS, 15 subjects remained for data analysis. In
`Experiment 2, a different sample of six subjects (three healthy males
`with a mean age of 27.3 years, range 24±29 years and three females
`with a mean age of 24.7 years, range 20±30 years) was used. All
`subjects were right handed, had normal or corrected to normal vision
`and were paid for participation. They participated after giving written
`informed consent.
`
`Stimulus presentation and cognitive tasks
`
`Stimuli were line drawings of cubes that were modi®ed versions of the
`subtest mental rotation of the IST-70 (a standard German intelligence
`test). The cubes had different symbols on each side. On each trial a set
`of six cubes (three in an upper and three in a lower row) were presented
`on a computer monitor. The target cube always appeared in the middle
`position of the ®rst row and was marked by a surrounding square.
`Subjects had to decide which of the other ®ve cubes matched the
`mentally rotated target. They were instructed to perform the task as fast
`and accurately as possible. The six cubes remained on the screen until
`the subject responded by pressing one of ®ve buttons. A single trial
`started with a warning signal (i.e. the visual presentation of the letters
``TMS') for 1000 ms. Then, the train of 24 TMS pulses was delivered
`starting at the offset of the warning signal. Immediately after the last
`TMS pulse, the cubes were presented. The next trial started 11 600 ms
`after the subject responded.
`The set of six cubes were presented in nine blocks, each consisting
`of eight trials. Analogous to the IST-70, the target cube differed for a
`series of sets (trials) whereas the ®ve test cubes remained the same. For
`construction of the trials, we used a sample of nine series with eight
`sets. In each of the eight sets the target cube was different, but the other
`®ve cubes remained the same. The sequence of blocks was randomized
`between subjects. Dependent variables were reaction time and per-
`centage correct answers calculated seperately for each block of trials.
`
`rTMS protocol
`
`A MagStim Rapid stimulator (MagStim, Whitland, UK) with a 70-mm
`®gure-8 coil was used. Locations for rTMS stimulation were deter-
`mined according to the international 10±20 system. In the experi-
`mental condition, rTMS was applied at P6 (above the intraparietal
`sulcus), at Fz and rotated by 908 over P6 for sham. This experimental
`manipulation is termed the stimulation condition. The output strength
`of the rTMS was set to 110% of the subjects' motor threshold, de®ned
`as the intensity needed for eliciting motor evoked potentials of at least
`50 mV recorded at the thumb of the left hand in 50% (5/10) of single
`pulses delivered to the contralateral motor cortex. The electromyo-
`gram was recorded from two bipolar Ag±AgCl electrodes over the left
`abductor pollicis brevis muscle (band pass, 5±200 Hz; sample rate,
`1000 Hz). Mean intensity for rTMS was 57.3% of maximal stimulator
`output. Sham served as the control condition in which the sensory
`effects of rTMS were simulated to some extent without interfering with
`cortical processes. Subjects could not be aware of whether a stimula-
`tion condition was real or not because conditions were applied in a
`randomized way, subjects could not see the coil and were not informed
`about the existence of placebo stimulation.
`In order to keep the total `energy' applied to the cortex by rTMS
`constant for the different frequencies (see below), a ®xed number of 24
`pulses was delivered in each condition. Thus, the duration of pulse
`trains varied between 1.2 to 4.8 s (depending on IAF and condition).
`No rTMS was given during execution of the task.
`
`Experiments 1 and 2
`
`Both experiments started with the recording of the EEG to determine
`IAF. Experiment 1 served to assess cognitive performance and Experi-
`ment 2 to monitor changes in ERD and absolute band power (for the
`reference and test interval). In Experiment 1 the three stimulation
`
`Fig. 1. (A) Task performance increases after repetitive transcranial magnetic stimulation (rTMS) (A). The rTMS induced improvement of accuracy of mental rotation
`is signi®cant for individual alpha frequency (IAF)‡ 1 Hz only. The in¯uence of rTMS at individual upper alpha frequency (IAF ‡ 1 Hz) on the EEG is depicted in the
`lower panel. The results for the reference interval (a time period preceding rTMS), the test interval (time period during task performance) and event-related
`desynchronization (ERD) are shown in B, C and D, respectively. Note the rTMS-induced increase in power during reference and decrease during test.
`
`ß 2003 Federation of European Neuroscience Societies, European Journal of Neuroscience, 17, 1129±1133
`
`PeakLogic, Inc. Ex. 1005
`PeakLogic, Inc. v. Wave Neuroscience, Inc., Case No. TBD
`
`

`

`rTMS and individual alpha frequency 1131
`
`ß 2003 Federation of European Neuroscience Societies, European Journal of Neuroscience, 17, 1129±1133
`
`PeakLogic, Inc. Ex. 1005
`PeakLogic, Inc. v. Wave Neuroscience, Inc., Case No. TBD
`
`

`

`1132 W. Klimesch et al.
`
`conditions (Fz, P6, sham) were combined with three stimulation
`frequencies resulting in nine blocks of experimental conditions. Sti-
`mulation frequencies were IAF ‡ 1 Hz, IAF 3 Hz, and 20 Hz. The
`nine blocks of trials were assigned randomly to each of the nine
`experimental conditions. In order to increase the number of trials for
`the analysis of the EEG, only stimulation frequency at IAF ‡ 1 Hz was
`used, but three blocks of trials were presented under each of the three
`stimulation conditions in Experiment 2. In Experiment 1, the electro-
`des were removed before delivering rTMS. In Experiment 2, the
`electrodes remained on the subject's scalp throughout the entire
`session. The IAF was determined for right parietal sites on the basis
`of power spectra (obtained from a 3-min resting period with eyes
`closed, preceding the performance of the experiment) as the peak
`frequency within 7 and 14 Hz (IAF  SD, measured at rest was 9.7 
`1.57 Hz).
`
`EEG recording
`
`EEG signals were ampli®ed by a Neuroscan 32 channel ampli®er
`system (Neuroscan, El Paso, TX, USA). They were recorded referen-
`tially against a common linked earlobe reference (impedance <3 kO)
`from 21 Ag±AgCl electrodes according to the international 10±20
`system. Sampling rate was 250 Hz, upper frequency limit was 40 Hz.
`The electro-oculogram (EOG) was recorded from two additional
`electrodes. Data were converted to a digital format via a 32-channel
`A/D converter. Sampling rate was 250 Hz.
`
`EEG data analysis for Experiment 2
`
`Absolute band power (for the reference and test interval) and ERD
`were calculated in individually determined frequency bands. The
`reference interval consisted of a period of 3 s starting 5 s before the
`onset of the warning signal, and the test interval consisted of the ®rst 3 s
`following presentation onset of the cubes. In these time windows
`epochs of 1024 ms were used for averaging. Thus for each stimulation
`condition and subject 72 (3  24) epochs remained for analysis. All of
`the epochs in each condition were carefully checked individually for
`artifacts (eye blinks, horizontal and vertical eye movements, muscle
`artifacts, etc.) by visual inspection. Epochs that were associated even
`with small changes in the horizontal or vertical EOG-channel within
`the reference and test interval (see below) were rejected. The average
`number of artifact-free trials for the three stimulation conditions (Fz,
`Pz and sham) were 30.8, 30.4, and 35.1, respectively. During the rTMS
`train the EEG ampli®er was blocked.
`The ERD is the percentage change in test power with respect to a
`reference interval (Pfurtscheller & Aranibar, 1977):
`ERD ˆ 100  [(reference test power)/reference power]
`
`Frequency bands were determined individually for each subject i, by
`using individual alpha frequency IAF(i) as a cut-off point between the
`lower and upper alpha band. Four EEG frequency bands were analysed:
`Theta, IAF(i) 6Hz to IAF(i) 4Hz; lower-1 alpha, IAF(i) 4Hz to
`IAF(i) 2Hz; lower-2 alpha, IAF(i) 2Hz to IAF(i); and upper alpha,
`IAF(i) to IAF(i)‡ 2Hz. Mean alpha frequency at rest was 10.25 
`1.05 Hz).
`
`Statistical analysis
`
`We have focused on the comparison between stimulation at Fz, P6 and
`sham. One-way ANOVAs with the factor stimulation condition (Fz, Pz,
`sham) were used to analyse the behavioural data (percentage of correct
`responses and reaction time) of Experiment 1. Separate ANOVAs were
`carried out for each dependent variable and stimulation frequency.
`For Experiment 2, we performed two-way ANOVAs with the factors
`
`stimulation condition (Fz, Pz, sham) and recording site (the entire set
`of 21 electrode sites) to analyse ERD in the four EEG bands. The
`Greenhouse Geisser correction was applied. Signi®cance level was set
`at 5%. For Experiment 2, again separate ANOVAs were carried out for
`each dependent variable (ERD, reference and test power).
`
`Results
`
`Behavioural data
`
`Performance (percentage correct responses) increased signi®cantly
`only after rTMS at IAF ‡ 1 Hz as indicated by the signi®cant factor
`stimulation condition (F2,28 ˆ 8.86, P < 0.01; cf. Fig. 1). Post hoc
`Scheffe tests indicate signi®cant differences between stimulation at
`Fz and sham (P < 0.01) as well as P6 and sham (P < 0.01) but not
`between P6 and Fz. No signi®cant changes in performance were
`induced with stimulation frequencies at IAF 3 Hz, or 20 Hz. No
`signi®cant effects were found for reaction time in any condition.
`
`EEG data: ERD
`
`From the four EEG bands analysed, only the upper alpha and lower-2
`alpha band showed signi®cant results. Compared with sham, rTMS at
`IAF ‡1 Hz, induced a signi®cant increase in lower-2 and upper alpha
`desynchronization (ERD) during mental rotation. For the ERD in the
`lower-2 alpha band, the only signi®cant effect was found for factor
`stimulation condition (F2,10 ˆ 5.68, P < 0.05). Scheffe tests revealed a
`signi®cantly larger ERD only at P6 (P < 0.05) compared to sham. For
`the upper alpha band factor stimulation condition (F2,10 ˆ 8.82,
`P < 0.05) reached signi®cance. Again, no other variance sources were
`signi®cant. Scheffe tests show a signi®cant increase between rTMS at
`Fz and sham (P < 0.05) as well as P6 and sham (P < 0.01). No
`signi®cant difference was found between P6 and Fz. Figure 1D indi-
`cates that the increase in upper alpha ERD during rTMS stimulation is
`a result of both decreased poststimulus power (Fig. 1C) and increased
`reference power (Fig. 1B). For ERD/ERS in the remaining two EEG
`bands (lower-1 alpha and theta) none of the variance sources reached
`signi®cance.
`
`EEG data: band power in reference and test interval
`
`For band power values in the reference and test interval, only one
`signi®cant effect of factor stimulation condition was found (F2,10 ˆ
`5.44, P < 0.05). This was obtained for the lower-2 alpha band during
`the test interval. Scheffe tests revealed a signi®cantly lower band
`power after stimulation at P6 as compared with Fz (P < 0.05). Factor
`recording site reached signi®cance in all but two cases (lower-2 alpha,
`reference and upper alpha, test interval). In none of the cases did the
`interaction between the two factors reach signi®cance. Because factor
``recording site' re¯ects the usual pattern of topographical differences,
`these ®ndings will not be considered in the following.
`
`Discussion and conclusions
`
`As predicted, rTMS delivered at the subjects' IAF at Fz and P6 lead to a
`signi®cant improvement in mental rotation performance when com-
`pared with sham. This most likely because of the fact that both frontal
`and parietal sites play an important role in mental rotation (Richter
`et al., 2000; Thomsen et al., 2000).
`The in¯uence of rTMS at IAF on EEG parameters mimicked exactly
`that situation which we know is typical for good performance:
`increased reference power, decreased test power and, consequently,
`a large ERD. It is important to note that the in¯uence of rTMS was not
`restricted to the time period immediately following the delivery of
`pulses (i.e. to the test interval) but could be observed also in the
`
`ß 2003 Federation of European Neuroscience Societies, European Journal of Neuroscience, 17, 1129±1133
`
`PeakLogic, Inc. Ex. 1005
`PeakLogic, Inc. v. Wave Neuroscience, Inc., Case No. TBD
`
`

`

`reference interval that followed the last rTMS stimulation after an
`inter-trial interval of about 30 s (depending on the reaction time). Most
`interestingly, the direction of change in power is different in the
`reference and test interval. In the same way as we know from EEG
`studies, good performance was related to increased alpha band power
`in a reference, but decreased band power during a test period (for an
`extensive review see Klimesch, 1999). Thus, we conclude that rTMS at
`IAF improves performance by way of those factors that are known to
`be of importance under normal conditions.
`The physiological nature of those mechanisms underlying the
`rTMS-related improvements are not known. It could be assumed that
`during rTMS cortical networks are put in a state of `resonance', in a
`similar way as was observed for photic driving (Silberstein, 1995;
`Hermann, 2001). However, little is known about the dynamic changes
`in spontaneous electrocortical activity during and immediately after
`rTMS.
`The present ®ndings suggest that the relationship between the
`dynamics of alpha desynchronization and cognitive performance is
`not correlative but causal in nature. Consequently, rTMS at IAF might
`even be useful as a therapeutic tool for patients with cortical dysfunc-
`tions. The timing of the rTMS application relative to the task will be
`critical and future research is necessary to clarify this aspect.
`
`Acknowledgements
`
`This research was supported by the Austrian `Fonds zur FoÈrderung der
`wissenschaftlichen Forschung', Project P13047 to W.K. C.G. was supported
`by the Deutsche Forschungsgemeinschaft (grant SFB 550/C5).
`
`Abbreviations
`
`ANOVA, analysis of variance; EEG, electroencephalogram; EOG, electro-
`oculogram; ERD, event-related desynchronization;
`IAF, individual alpha
`frequency;
`rTMS, repetitive transcranial magnetic stimulation; TMS, tran-
`scranial magnetic stimulation.
`
`References
`
`Boroojerdi, B., Phipps, M., Kopylev, L., Wharton, C.M., Cohen, L.G. &
`Grafman, J. (2001) Enhancing analogic reasoning with rTMS over the left
`prefrontal cortex. Neurology, 56, 526±528.
`Chen, R., Classen, J., Gerloff, C., Celnik, P., Wassermann, E.M., Hallett, M. &
`Cohen, L.G. (1997a) Depression of motor cortex excitability by low fre-
`quency transcranial magnetic stimulation. Neurology, 48, 1398±1403.
`Chen, R., Gerloff, C., Classen, J., Wassermann, E.M., Hallett, M. & Cohen, L.G.
`(1997b) Safety of different inter-train intervals for repetitive transcranial
`magnetic stimulation and recommendations for safe ranges of stimulation
`parameters. Electroencephalogr. Clin. Neurophysiol., 105, 415±421.
`Evers, S., BoÈckermann, I. & Nyhuis, W. (2001) The inpact of transcranial
`magnetic stimulation on cognitive processing: an event-related potential
`study. Neuroreport, 12, 2915±2918.
`Gerloff, C., Corwell, B., Chen, R., Hallett, M. & Cohen, L.G. (1997) Stim-
`ulation over the human supplementary motor area interferes with the
`
`rTMS and individual alpha frequency 1133
`
`organization of future elements in complex motor sequences. Brain, 120,
`1587±1602.
`Grafman, J., Pascual-Leone, A., Alway, D., Nichelli, P., Gomez-Tortosa, E. &
`Hallett, M. (1994) Induction of a recall de®cit by rapid-rate transcranial
`magnetic stimulation. Neuroreport, 5, 1157±1160.
`Hallet, M. (2000) Transcranial magnetic stimulation and the human brain.
`Nature, 406, 147±150.
`Hamilton, R.H. & Pascual-Leone, A. (1998) Cortical Plasticity associated with
`Braille reading. Trends Cogn. Sci., 2, 168±174.
`Hermann, C.S. (2001) Human EEG responses to 1±100 HZ. Flicker: resonance
`phenomena in visual cortex and their potential correlation to cognitive
`phenomena. Exp. Brain Res., 137, 346±353.
`Jahanshahi, M. & Rothwell, J. (2000) Transcranial magnetic stimulation studies
`of cognition: an emerging ®eld. Exp. Brain Res., 131, 1±9.
`Klimesch, W. (1999) EEG alpha and theta oscillations re¯ect cognitive and
`memory performance: a review and analysis. Brain Res. Brain Res. Rev., 29,
`169±195.
`Mottaghy, F.M., Hungs, M., BruÈgmann, M., Sparing, R., Boroojerdi, B., Foltys,
`H., Huber, W. & ToÈpper, R. (1999) Facilitation of picture naming after
`repetitive transcranial magnetic stimulation. Neurology, 53, 1806±1812.
`Neubauer, A., Freudenthaler, H.H. & Pfurtscheller, G. (1995) Intelligence and
`spatiotemporal patterns of event-related desynchronization (ERD). Intelli-
`gence, 20, 249±266.
`Pascual-Leone, A., Valls-Sole, J. & Wassermann, E.M. (1994) Responses to
`rapid-rate transcranial magnetic stimulation of the human motor cortex.
`Brain, 117, 847±858.
`Pfurtscheller, G. & Aranibar, A. (1977) Event-related cortical desynchroniza-
`tion detected by power measurements of the scalp EEG. Electroencephalogr.
`Clin. Neurophysiol., 42, 817±826.
`Richter, W., Somorjai, R., Summers, R., Jarmasz, M., Menon, R.S., Gati, J.S.,
`Georgopoulos, A.P., Tegeler, C., Urgubil, K. & Kim, S.G. (2000) Motor area
`activity during mental rotation studied by time-resolved single-trial fMRI. J.
`Cogn. Neurosci., 12, 310±320.
`Silberstein, R.B. (1995) Steady state visually evoked potentials, brain reso-
`nances and cognitive processes. In Nunez, P.L. (ed.), Neocortical Dynamics
`and Human EEG Rhythms. Oxford University Press, New York, pp.
`272±303.
`Sparing, R., Mottaghy, F.M., Hungs, M., BruÈgmann, M., Foltys, H., Huber, W.
`& ToÈpper, R. (2001) Repetitive transcranial magnetic stimulation effects on
`language function depend on the stimulation parameters. J. Clin. Neurophy-
`siol., 18, 326±330.
`Thomsen, T., Hugdahl, K., Erslang, L., Barndon, R., Lundervold, A., Smievoll,
`A.I., Roscher, B.E. & Sundberg, H. (2000) Functional magnetic resonance
`imaging (fMRI) study of sex differences in a mental rotation task. Med. Sci.
`Monit., 6, 1186±1196.
`ToÈpper, R., Mottaghy, F.M., BruÈgmann, M., Noth, J. & Huber, W. (1998)
`Facilitation of picture naming by focal transcranial magnetic stimulation of
`Wernicke's area. Exp. Brain Res., 121, 371±378.
`Triggs, W.J. & Kirshner, H.S. (2001) Improving brain function with transcranial
`magnetic stimulation?. Neurology, 56, 429±430.
`Triggs, W.J., McCoy, K.J.M., Greer, R., Rossi, F., Bowers, D., Kortenkamp, S.,
`Nadeau, S., Heilman, K. & Goodman, W.K. (1999) Effects of left frontal
`transcranial magnetic stimulation on depressed mood, cognition and corti-
`comotor threshold. Biol. Psychiatry, 45, 1440±1446.
`Walsh, V. & Cowey, A. (1998) Magnetic stimulation studies of visual cognition.
`Trends Cogn. Sci., 2, 103±110.
`Wassermann, E.M., Blaxton, T.A., Hoffman, E.A., Berry, C.D., Oletsky, H.,
`Pascual-Leone, A. & Theodrone, W.H. (1999) Repetitive transcranial mag-
`netic stimulation of the dominant hemisphere can disrupt visual naming in
`temporal lobe epilepsy patients. Neuropsychologia, 37, 537±544.
`
`ß 2003 Federation of European Neuroscience Societies, European Journal of Neuroscience, 17, 1129±1133
`
`PeakLogic, Inc. Ex. 1005
`PeakLogic, Inc. v. Wave Neuroscience, Inc., Case No. TBD
`
`