Abstract

Although some brain areas preferentially process information from a particular sensory modality, these areas can also respond to other modalities. Here we used fMRI to show that such responsiveness to tactile stimuli depends on the temporal frequency of stimulation. Participants performed a tactile threshold-tracking task where the tip of either their left or right middle finger was stimulated at 3, 20, or 100 Hz. Whole-brain analysis revealed an effect of stimulus frequency in two regions: the auditory cortex and the visual cortex. The BOLD response in the auditory cortex was stronger during stimulation at hearable frequencies (20 and 100 Hz) whereas the response in the visual cortex was suppressed at infrasonic frequencies (3 Hz). Regardless of which hand was stimulated, the frequency-dependent effects were lateralized to the left auditory cortex and the right visual cortex. Furthermore, the frequency-dependent effects in both areas were abolished when the participants performed a visual task while receiving identical tactile stimulation as in the tactile threshold-tracking task. We interpret these findings in the context of the metamodal theory of brain function, which posits that brain areas contribute to sensory processing by performing specific computations regardless of input modality.

INTRODUCTION

The traditional view is that sensory perception relies on brain areas specialized to process specific sensory modalities. However, recent studies indicate that stimuli in one sensory modality can engage brain areas that primarily process information originating in other modalities (Merabet & Pascual-Leone, 2010; Ghazanfar & Schroeder, 2006; Macaluso & Driver, 2005). For example, many studies have demonstrated that tactile stimuli can influence activity in the auditory cortex (Bolognini, Papagno, Moroni, & Maravita, 2010; Lemus, Hernández, Luna, Zainos, & Romo, 2010; Kayser, Petkov, & Logothetis, 2009; Lakatos, Chen, O'Connell, Mills, & Schroeder, 2007; Li Hegner et al., 2007; Caetano & Jousmäki, 2006; Schürmann, Caetano, Hlushchuk, Jousmäki, & Hari, 2006; Kayser, Petkov, Augath, & Logothetis, 2005; Fu et al., 2003; Foxe et al., 2002; Lütkenhöner, Lammertmann, Simões, & Hari, 2002; Schroeder et al., 2001) and visual cortex (Summers, Francis, Bowtell, McGlone, & Clemence, 2009; Beauchamp, Yasar, Kishan, & Ro, 2007; Blake, Sobel, & James, 2004; Merabet et al., 2004; Hagen et al., 2002; Sathian & Zangaladze, 2002; Amedi, Malach, Hendler, Peled, & Zohary, 2001).

The above observations are consistent with the metamodal theory of brain function, which posits that brain areas contribute to sensory processing by performing specific computations regardless of input modality (Pascual-Leone & Hamilton, 2001). However, it remains unknown whether different brain areas are engaged when changing the frequency of tactile stimulation. On the basis of the metamodal theory, we hypothesized that tactile stimulation at hearable frequencies (>∼12 Hz; Olson, 1967) would engage auditory areas because of their known computational specialization for detecting temporal features encoded in periodic mechanoreceptive afferent signals. We further hypothesized that visual areas may be engaged for infrasonic frequencies at which humans visually perceive object motion (<∼12 Hz; Nakayama & Tyler, 1981). Lastly, we expected that the frequency of tactile stimulation would differentially engage parts of somatosensory cortical areas (Friedman, Chen, & Roe, 2004; Harrington & Hunter Downs, 2001; Francis et al., 2000; Tommerdahl, Whitsel, Favorov, Metz, & O'Quinn, 1999; Fisher, Freeman, & Rowe, 1983).

We used fMRI to identify brain areas differentially involved in the processing of tactile information depending on temporal frequency when oscillatory skin displacements were delivered to the tip of either the left or the right middle finger. We contrasted cerebral BOLD signals recorded from the whole brain while the participants performed a tactile detection task at 3-, 20-, and 100-Hz stimulation frequencies. We chose these frequencies because they represent both infrasonic (3 Hz) and hearable (20 and 100 Hz) frequencies and because tactile detection at these frequencies is largely based on inputs from three different types of cutaneous mechanoreceptors in the glabrous skin of the hand (Löfvenberg & Johansson, 1984; Freeman & Johnson, 1982; Johansson, Landström, & Lundström, 1982; Talbot, Darian-Smith, Kornhuber, & Mountcastle, 1968). Indeed, these frequencies evoke different perceptions such that stimulation at 3 Hz is often described in visual terms, such as a gradual position change of an object stimulating the skin (Löfvenberg & Johansson, 1984), and stimulation at higher frequencies are described in auditory terms (20 Hz: wobble or flutter, 100 Hz: diffuse vibration; Talbot et al., 1968).

The detection task performed by the participants was based on a variant of the von Bekesy's threshold-tracking method (von Bekesy, 1947). The rationale for employing the threshold-tracking task was threefold: First, threshold tracking kept the subjects actively engaged in the task because they had to continuously use the tactile information. Second, threshold tracking ensured that the effective stimulus intensity was similar across the different frequencies. Since the sensitivity to tactile stimuli varies with frequency (Löfvenberg & Johansson, 1984; Talbot et al., 1968) and the effective stimulus intensity can influence the BOLD activity (Siedentopf et al., 2008; Nelson, Staines, Graham, & McIlroy, 2004; Arthurs & Boniface, 2002), normalizing the stimulus amplitude to perceptual threshold ensured that any observed effects were related to differences in stimulus frequency rather than intensity. And third, by keeping the signals near perceptual threshold, we could minimize both central and peripheral adaption to maintained tactile stimulation (Leung, Bensmaïa, Hsiao, & Johnson, 2005; Tommerdahl et al., 2005; Lundström & Johansson, 1986).

We present our results in four main sections. First, we analyze subject behavior while they performed the tactile threshold-tracking task in the scanner. Second, we identify brain areas that are differentially involved in the processing of tactile information depending on stimulation frequency (3, 20, and 100 Hz) in the tactile threshold-tracking task. On the basis of a factorial random-effect ANOVA, we analyze frequency-effects on BOLD signals recorded from the whole brain. In addition to frequency, we include the stimulated hand as a fixed effect to resolve whether lateralized frequency effects depend on stimulated hand. Note that this ANOVA only considers functional images from the tactile threshold-tracking task. Third, we test whether the frequency effects observed in particular brain areas during tactile threshold-tracking trials are task dependent. We analyze the BOLD activity in these particular areas in trials where participants received identical tactile stimuli as in the tactile threshold-tracking task but performed a visual threshold-tracking task where the tactile stimulation was not relevant to task performance. Finally, after dealing with our specific hypothesis, we briefly describe global brain activity associated with performing the tactile threshold-tracking task.

METHODS

Participants, General Experimental Procedure

Sixteen right-handed healthy individuals (eight women and eight men, aged 19–28 years) participated after providing written informed consent in accordance with the Declaration of Helsinki. The ethics committee of Umeå University approved the study.

The participants lay supine in the MR scanner with the head stabilized with sponges to the head coil. Cushions supported the arms down to the wrist. Mirrors attached to the head coil allowed the participant to view a computer screen located in the rostral end of the bore. Soundproof earphones combined with earplugs reduced scanner noise. As such, the tactile stimulator was inaudible at the stimulation amplitudes generated during the threshold-tracking tasks. Using a custom-made apparatus to deliver precise tactile stimuli in MR scanners, we measured cerebral BOLD signals when participants detected sinusoidal displacements at 3, 20, and 100 Hz of a thin ridge in contact with the tip of either the left or the right middle finger (Figure 1A). During the 20-sec trials, the participants continuously reported their awareness of ridge movements using a variant of the von Bekesy's threshold-tracking method (von Bekesy, 1947; Figure 1B, tactile threshold-tracking trial). The participants indicated that they felt the ridge moving by pressing a button, which caused the stimulus amplitude to decrease. When stimulation could no longer be felt they released the button, which caused the stimulus amplitude to increase.

Figure 1. 

Apparatus and threshold-tracking tasks in the MR scanner. (A) With either their left or right hand, the participants grasped a rectangular box anchored to a wooden frame extending above their hips. Perpendicular movements of a ridge protruding above the surface of the box stimulated the tip of the middle finger. The ridge extended over the entire area of contact between the fingertip and the box. (B) One of six consecutive blocks of trials delivered during a scanning session (top). Each block included one tactile threshold-tracking trial lasting for 20 sec with each of the three stimulation frequencies (3, 20, and 100 Hz) appearing in a random order across blocks. Each tactile trial was followed by a visual threshold-tracking trial in which the stimulus in the preceding tactile trial was replayed to the fingertip. During a 14-sec rest period between trials, the otherwise white screen displayed a solid black cross. The participant was cued about an upcoming tactile trial and its stimulation frequency 3–4.5 sec before trial start by a colored cross shown on the display; during the trial, the screen showed a black cross with thin lines. Before a visual trial, the display showed a filled circle (cue) of the same color as that of the cross in the preceding tactile trial and as that of the circular visual image to be detected. The participant pressed the button when perceiving the stimulus, which caused the intensity to decrease (arrows), and when the sensation vanished, the participant released the button, which caused the intensity to increase. (C) The participant could view a computer screen via mirrors and the big toe of the contralateral foot operated the push button.

Figure 1. 

Apparatus and threshold-tracking tasks in the MR scanner. (A) With either their left or right hand, the participants grasped a rectangular box anchored to a wooden frame extending above their hips. Perpendicular movements of a ridge protruding above the surface of the box stimulated the tip of the middle finger. The ridge extended over the entire area of contact between the fingertip and the box. (B) One of six consecutive blocks of trials delivered during a scanning session (top). Each block included one tactile threshold-tracking trial lasting for 20 sec with each of the three stimulation frequencies (3, 20, and 100 Hz) appearing in a random order across blocks. Each tactile trial was followed by a visual threshold-tracking trial in which the stimulus in the preceding tactile trial was replayed to the fingertip. During a 14-sec rest period between trials, the otherwise white screen displayed a solid black cross. The participant was cued about an upcoming tactile trial and its stimulation frequency 3–4.5 sec before trial start by a colored cross shown on the display; during the trial, the screen showed a black cross with thin lines. Before a visual trial, the display showed a filled circle (cue) of the same color as that of the cross in the preceding tactile trial and as that of the circular visual image to be detected. The participant pressed the button when perceiving the stimulus, which caused the intensity to decrease (arrows), and when the sensation vanished, the participant released the button, which caused the intensity to increase. (C) The participant could view a computer screen via mirrors and the big toe of the contralateral foot operated the push button.

The participants performed the tactile threshold-tracking tasks with both the left and right middle fingers (Figure 1A) because we wanted to resolve whether lateralized BOLD effects depended on which hand was stimulated. To address whether frequency-dependent effects were linked to the execution of the tactile threshold-tracking task, we investigated BOLD responses when participants performed visual threshold-tracking tasks while receiving the same tactile stimulation as experienced during tactile threshold-tracking trials (Figure 1B, visual threshold tracking). Visual trials were interleaved with tactile trials. During each tactile trial, the ridge movement was recorded and then replayed to the fingertip in the subsequent visual trial. In either task, the participants operated the response button with the big toe of the foot contralateral to the stimulated hand (Figure 1C), so that BOLD responses primarily related to the execution of the button presses and to the primary processing of tactile stimulation would show up in opposite hemispheres.

Apparatus

A rectangular box containing the custom-built tactile stimulator was anchored to a wooden frame that extended above the participant's hips in either of two positions, one suitable for a left-hand grasp and one for a right-hand grasp (Figure 1A and C). The participants grasped and held the box such that the fingertips of the stimulated hand contacted the vertical surface of one side of the box and the thumb contacted the opposing surface (width of the box = 4.9 cm). The stimuli were sinusoidal perpendicular movements of a 2-mm wide and 40-mm long ridge contacted by the tip of the middle finger (Figure 1A). The ridge protruded 1 mm above the flat surface of the box and extended in the proximal–distal direction of the fingertip. Thus, the ridge was in stable contact with the skin throughout the movement cycles. Bars parallel to the stimulating ridge guided the positioning of the middle finger so that it made appropriate contact with the stimulating ridge. The foot contralateral to the stimulated hand was strapped in a position that allowed the big toe to operate the push button by which the participant controlled the amplitude of the tactile and visual stimuli (Figure 1C; see further below).

Two coupled moving coils that generated a Lorentz force induced by the large static magnetic field of the MR scanner (Riener, Villgrattner, Kleiser, Nef, & Kollias, 2005; Graham, Staines, Nelson, Plewes, & McIlroy, 2001) moved the stimulation ridge. An 80-mm long lever transferred the torque generated by the rotating coils to the center of the ridge (maximum displacement: ±3 mm; frequency range: 0–100 Hz). The two matched coils were electrically and mechanically connected so that they rotated in opposite directions to counterbalance the induced voltages from the gradient coils. Current to the coils was provided by a battery-powered power amplifier (Class AB) located in a shielded box in the scanning room. To avoid interference from high-frequency MR pulses, a low pass pi-filter was located at the output of the amplifier. A stiff spring loaded the coils (4 N/mm ridge displacement) to prevent possible variations in viscoelastic properties between digits to significantly influence the relationship between the motor current and amplitude of the ridge movement. The ridge movements were calibrated by using a laser beam reflected by a mirror attached to the torque-transferring lever. The reflection was projected onto a scale on the wall of the scanning room which magnified the ridge movements (gain = 136; overall resolution ∼1 μm). Using this technique, we found that the amplitude of the attenuation when the skin loaded the stimulator was <10%, and we could not detect any influence of the MR equipment on the stimulator. Furthermore, we found no significant influence of the apparatus on images collected using an MR phantom. A microcomputer located outside the scanning room, connected via optical fibers to the power amplifier unit and to the push button in the scanning room, controlled the tactile and visual stimulus parameters, and administered the experimental protocol.

Threshold-tracking Trials

During the tactile threshold-tracking trials, each lasting for 20 sec, the participants' task was to press the button as soon as they could feel the stimulus and to release the button when the sensation disappeared. For each participant, stimulation frequency and hand stimulated, we computed one median value of the amplitudes recorded at all button presses (upper threshold limen) and one at all button releases (lower threshold limen). We then defined the detection threshold as the midpoint between the two median values. To prevent participants from simply controlling the stimulus amplitude around some arbitrary value by rhythmically pressing the button, we varied the rate of change of the amplitude during the trials in a manner unpredictable to the participants. Furthermore, to normalize the number of button presses across trials to around five per trial, we used an adaptive algorithm to tune the rate of amplitude change. To meet these conditions, first, the change of amplitude between button actions occurred at three different rates (uniform random distribution) that in the first trial with each stimulation frequency corresponded to a doubling/halving of the amplitude during 0.8, 1.1, and 1.6 sec, respectively. Second, while keeping the same ratio between the rates, in the subsequent trials with the same stimulation frequency, the doubling/halving time of the amplitude was adjusted by a coefficient computed as 5 divided by the number of button presses in the previous trial multiplied by the coefficient used in the previous trial. Averaged across participants, this algorithm rendered 4.7 ± 0.6 button presses per tactile trial (mean ± SD of median values computed for each participant, data pooled across stimulation frequencies and hands). The variation in the number of button presses between trials within participants corresponded, on average, to a standard deviation of 0.4 (range of 0.1–0.7 across participants). There was no effect of stimulation frequency.

During the visual threshold-tracking trials, also lasting for 20 sec each, the participants' task was to detect a colored circular image displayed in the center of the computer screen against a white background. The rate of change of the color saturation and the frequency of button presses was controlled using the same algorithm as for the changes of the amplitude of the bar movement in the tactile trials. That is, the color saturation (red, green, or blue) decreased and increased when the participants pressed and released the push button, respectively. Red visual tracking was always accompanied by 3-Hz tactile stimuli, blue with 20-Hz and green with 100-Hz. Averaged across participants, the number of button presses per tactile trial was 4.8 ± 0.1 (mean ± SD of median values computed for each participant, data pooled across stimulation frequencies and hands). The variation in the number of button actions within participants corresponded to an SD of 0.4 for data pooled across all trials (range of 0.1–0.7). The image corresponded to a right circular cone with a diameter of 2° visual angle that was oriented in the plane of the screen. That is, the color was most saturated in the center of the image (corresponding to the apex of the cone) and declined linearly towards its perimeter where it was zero. A given color was obtained by subtraction of the other two colors with equal amount. For example, a reddish cone was obtained by attenuating the intensity of the green and blue colors.

Experimental Protocol

Counterbalanced across participants, each participant was engaged in two scanning sessions, one in which the left hand was stimulated and one in which the right hand was stimulated. A session included 18 tactile and 18 visual trials and lasted for ∼23 min. It contained six consecutive blocks, each of which included one tactile trial with 3-, 20-, and 100-Hz stimulation paired with the corresponding visual threshold-tracking trial. The order by which the stimulation frequencies occurred was counterbalanced across the six blocks.

Before the first trial and after each tactile and visual trial, there was a 14-sec period of rest during which a solid black cross (1.0° visual angle) was displayed in the center of the white screen. Before each tactile trial, the participants were alerted about the upcoming task and stimulation frequency by the cross changing from black to a color that depended on the frequency (see “Cue” in Figure 1B: 3 Hz, red; 20 Hz, green; 100 Hz, blue) for 3–4.5 sec. During the tactile trials, the screen showed a black cross with thin lines. When the tactile trial ended, the lines of the cross switched from thin to solid, which indicated the commencement of the rest period. Cues were also provided before the start of the visual trials. Instead of a cross, the screen showed a filled circle (∼1.0° visual angle) whose color was the same as the color of the cross in the previous tactile trial and as the upcoming visual image.

The day before the participants were scanned, they practiced the protocol in a replica of the apparatus. The participants were instructed to press the button as soon as they detected the relevant stimulus and to release the button as soon as the stimulus disappeared. Furthermore, the participants were asked to look at the display throughout the scanning session and to keep the fingers in contact with the tactile stimulator. These instructions were repeated before the scanning started on Day 2.

MRI Parameters and Data Analysis

Functional and structural brain scans were acquired on a 3-T MR scanner (Achieva 3.0, Phillips Medical Systems, Eindhoven, The Netherlands) using an eight-channel SENSE head coil. The following parameters were used for the functional scanning: repetition time = 1.5 sec (31 slices acquired), echo time = 30 msec, flip angle = 70 degrees, field of view = 22 × 22 cm. The in-plane resolution was 3.44 × 3.44 mm2 (64 × 64 matrix) and the slice thickness was 4.65 mm with no interslice gaps. Ten surplus scans were collected before each scanning session. The structural high-resolution T1 images were based on 170 sagittal 1-mm thick slices with an in plane resolution of 0.71 × 0.71 mm2 (field of view = 24 × 24 cm2).

The BOLD signals provided by the scanner were analyzed with SPM5 (The Wellcome Department of Cognitive Neurology, London, UK; www.fil.ion.ucl.ac.uk/spm). Slice timing correction to the first slice was performed using SPM5's Fourier phase shift interpolation. The obtained volumes were realigned to the first volume and unwarped to correct for head movements, and then normalized to the standard Montreal Neurological Institute (MNI) EPI template to allow group analysis (2 × 2 × 2 mm3 voxel size) after smoothing with an isotropic Gaussian kernel of 6 mm (FWHM). High-pass filtering (128-sec period) reduced participant-specific drifts in the BOLD signal and proportional grand mean scaling applied over each scanning session reduced effects of slow global changes in BOLD activity.

For data obtained during each scanning session, we used 12 “boxcar” regressors to model the various functional states of the participants during the scanning sessions. Six regressors (20 sec) represented the different types of trials (tactile and visual trials with three different tactile stimulation frequencies) and six regressors (3.0–4.5 sec) represented the matching cue periods. In addition, to capture residual movement-related artifacts, the model included six covariates corresponding to the spatial realignment parameters. After convolving the boxcar regressors with the standard canonical hemodynamic response function provided by SPM5, we fit a general linear model to the BOLD activity recorded in each experimental session.

In our main analysis, the single-subject images representing the tactile threshold-tracking trials were entered into a random effects group analysis. For each voxel, we conducted a 3 × 2 factorial ANOVA on the BOLD responses and used F tests to test for main effects and interactions of stimulation frequency and stimulated hand. To protect against false positives while at the same time retaining the power to detect reliable effects, we subjected the statistical images of the group analyses to a double-threshold approach, in which we combined a voxel-based threshold with a minimum cluster size (Forman et al., 1995). With our brain volume and an individual voxel threshold of Z > 3.09, we used a cluster size corresponding to p < .01 at the cluster level. This cluster threshold, corrected for multiple comparisons across the whole brain, was determined based on random field theory (Worsley et al., 2002; Cao, 1999; Worsley, Andermann, Koulis, MacDonald, & Evans, 1999) and implemented with the stat_threshold function of fmristat (www.math.mcgill.ca/keith/fmristat). For areas with significant frequency effects, we used Bonferroni corrected paired t tests to examine how stimulation frequency affected the BOLD activity. For these areas, we also analyzed effects of task (tactile vs. visual threshold tracking) using repeated measures ANOVAs. Both analyses were based on the average BOLD effect sizes (β values) measured in each participant. Corresponding analyses were also performed for the cue period.

In addition to our main analysis, we performed two conjunction analyses (Nichols, Brett, Andersson, Wager, & Poline, 2005). In one, we assessed brain regions jointly activated by all the experimental conditions of the tactile task, and in the other, we assessed brain regions jointly activated during the tactile and the visual tasks (for details, see Results). On the basis of functional images for the each relevant condition and participant, we obtained the comparisons in the conjunction analyses by means of multiple-regression in SPM5. Finally, to determine the general effects of task (tactile vs. visual threshold tracking) on BOLD activity in the whole brain, we performed a random-effects group analysis (ANOVA) with task and stimulated hand as fixed effects using images based on data pooled across stimulation frequencies. In these additional analyses, the statistical images of the group analyses were subjected to the same double-threshold approach as described above.

To assess the anatomical localization of detected clusters and their local maxima, we superposed the SPM{Z} maps on the group mean anatomical T1 images calculated after each individual's MRI had been stereotactically transformed into the MNI stereotaxic space. In addition, to help identify the major sulci and gyri, we used the Automated Anatomical Labeling software (Tzourio-Mazoyer et al., 2002) and the stereotactic atlas of Talairach and Tournoux (1988). Local maxima located within <10 mm of statistically more significant local maxima were ignored.

RESULTS

Subject Performance during the Tactile Task

The thresholds we measured during tactile threshold-tracking task performed in the scanner were similar to those previously reported for oscillatory displacements of the skin of the fingertips (e.g., Löfvenberg & Johansson, 1984; Talbot et al., 1968). That is, the frequency of the stimulation markedly affected the amplitude threshold, F(2, 30) = 148.8; p < .0001. For each participant (n = 16), the threshold measured was highest at 3 Hz, intermediate at 20 Hz, and lowest at 100 Hz (Figure 2). We also noted that the detection threshold differed between the hands, F(1, 15) = 7.1; p < .02, with the right hand showing modestly higher thresholds than the left at all test frequencies (Figure 2). This observation is also in agreement with previous results (Rhodes & Schwartz, 1981; Weinstein, 1962). There was no interaction between hand and stimulation frequency, F(2, 30) = 1.54; p > .23. Taken together, the participants' performance in the tactile threshold-tracking task indicates that they complied with the task instructions and were monitoring and using tactile afferent input irrespective tactile stimulation frequency. Thus, any effect of stimulation frequency on BOLD responses during the tactile trials should depend on frequency-specific engagement of brain areas rather than on the intensity of the stimulation or lack of concentration on the task.

Figure 2. 

Detection thresholds during the tactile trials shown for each stimulus frequency and stimulated hand. Heights of columns give mean values computed across participants, and error bars indicate 1 SEM (n = 16).

Figure 2. 

Detection thresholds during the tactile trials shown for each stimulus frequency and stimulated hand. Heights of columns give mean values computed across participants, and error bars indicate 1 SEM (n = 16).

Effects of Stimulation Frequency on BOLD Signals during the Tactile Task

We performed a factorial random-effects ANOVA with Frequency and Hand as fixed effects using functional images from the tactile threshold-tracking task (see Methods). This analysis revealed a main effect of Stimulus Frequency in only two regions, a 2.5 cm3 volume of the left auditory cortex (Figure 3A) and a 0.9 cm3 volume of the right visual cortex (Figure 3C). There was no significant effect of Stimulated Hand in either of these areas (main effect or interactions). For the auditory cortex, the effect extended along the caudomedial part of the Heschl's gyrus on the superior surface of the temporal lobe and apparently involved the left primary auditory cortex (Rademacher et al., 2001; Liegeois-Chauvel, Musolino, & Chauvel, 1991; Figure 3A). Examination of the BOLD effect sizes (β values), averaged over all voxels (Figure 3B), indicated that the activity during the 3-Hz stimulus differed from that during the 20- and 100-Hz stimuli [t(15) = 5.4; pcorrected < .0005 and t(15) = 6.5; pcorrected < .0001, respectively], whereas the activity did not differ for the 20- and 100-Hz stimuli [t(15) = 1.0; p = .33]. Notably, the BOLD effect indicated a significant change from rest for the 20- and 100-Hz [t(15) = 4.9; pcorrected < .001, t(15) = 3.7; pcorrected < .01, respectively] stimuli but not for the 3-Hz stimulus [t(15) = 1.6; p = .13], indicating that auditory cortex was most responsive to the 20- and 100-Hz stimuli.

Figure 3. 

Effect of stimulus frequency on BOLD activity during the tactile threshold-tracking task. (A) Main effect of Stimulus Frequency in the left superior temporal gyrus rendered on the smooth average brain surface template in SPM5 and shown on sagittal and transversal slices of the averaged brain calculated across the participant-specific T1-weighted images (n = 16) after being normalized to the MNI brain template. The detected area comprised 314 contiguous voxels (voxel size = 2 × 2 × 2 mm3) and showed two local maxima (x, y, z = −46, −20, −6; Ze = 4.7; −40, −30, 0, Ze = 4.9; BA 41/42/22). A, anterior; P, posterior; L, left. (B) For each stimulus frequency and stimulated hand, histograms show BOLD effect sizes (β values) averaged over all voxels of the cluster in A given in percentage relative to mean BOLD signal level during the session; dotted lines show the corresponding activity in the same area during the visual threshold-tracking task. Height of columns gives mean values across participants, and vertical lines represent unilaterally 1 SEM (n = 16). (C) Main effect of Stimulus Frequency in the right lingual gyrus rendered on the posterior aspect of the smooth average brain surface template in SPM5 and shown on a sagittal slice of the obtained as described in A. The area comprised 112 voxels and had a single local maximum (X, Y, Z = 4, −84, −4; Ze = 4.5, BA 18). (D) Histograms indicate BOLD effect sizes for the cluster in C represented as in B.

Figure 3. 

Effect of stimulus frequency on BOLD activity during the tactile threshold-tracking task. (A) Main effect of Stimulus Frequency in the left superior temporal gyrus rendered on the smooth average brain surface template in SPM5 and shown on sagittal and transversal slices of the averaged brain calculated across the participant-specific T1-weighted images (n = 16) after being normalized to the MNI brain template. The detected area comprised 314 contiguous voxels (voxel size = 2 × 2 × 2 mm3) and showed two local maxima (x, y, z = −46, −20, −6; Ze = 4.7; −40, −30, 0, Ze = 4.9; BA 41/42/22). A, anterior; P, posterior; L, left. (B) For each stimulus frequency and stimulated hand, histograms show BOLD effect sizes (β values) averaged over all voxels of the cluster in A given in percentage relative to mean BOLD signal level during the session; dotted lines show the corresponding activity in the same area during the visual threshold-tracking task. Height of columns gives mean values across participants, and vertical lines represent unilaterally 1 SEM (n = 16). (C) Main effect of Stimulus Frequency in the right lingual gyrus rendered on the posterior aspect of the smooth average brain surface template in SPM5 and shown on a sagittal slice of the obtained as described in A. The area comprised 112 voxels and had a single local maximum (X, Y, Z = 4, −84, −4; Ze = 4.5, BA 18). (D) Histograms indicate BOLD effect sizes for the cluster in C represented as in B.

For the visual cortex, the effect involved an area in the right lingual gyrus likely involving both the primary and secondary visual cortex (Figure 3C). Similar to our findings in the auditory cortex, the BOLD response was different during the 3-Hz stimulus compared with the 20- and 100-Hz stimuli [t(15) = 3.7; pcorrected < .01 and t(15) = 4.3; pcorrected < .002, respectively], for which the activity did not differ [t(15) = 0.05; p = .96; Figure 3D]. However, for the lingual gyrus, significant changes from rest were found for the 3-Hz stimulus [t(15) = 5.1; pcorrected < .0005] but not for the 20- or 100-Hz stimuli [t(15) = 1.4; p = .18 and t(15) = 1.1; p = .29, respectively]. Furthermore, in contrast to the response recorded in the Heschl's gyrus to the 20- and 100-Hz trials, which was expressed as an increase in the BOLD signal, the response in the lingual gyrus to the 3-Hz trials was a decrease in the BOLD signal level.

Before each tactile trial, the participants were alerted to the upcoming stimulation frequency (Figure 1B, cue period). A factorial random-effects ANOVA with frequency and hand as fixed effects using functional images from the cue period of the tactile threshold-tracking task did not reveal any brain area with a main effect of stimulation frequency. Furthermore, examination of the average BOLD signals (β values) in those areas identified above failed to show a significant effect of stimulation frequency during the cue period (Heschl's gyrus: F(2, 30) = 2.3, p = .11; lingual gyrus: F(2, 30) = 0.14, p = .87).

Effects of Stimulated Hand on BOLD Signals during the Tactile Task

As indicated above, there was no effect of stimulated hand in the auditory and visual cortex during the tactile threshold-tracking task. However, stimulated hand (left vs. right) affected the BOLD activity in the hand areas of the postcentral gyri (Figure 4). As expected, the activity in each hemisphere was stronger when the contralateral hand was stimulated than when the ipsilateral hand was stimulated. For the left hemisphere, the effect was restricted to a 0.8 cm3 zone centered in the posterior bank of the postcentral gyrus likely involving BA 1 and BA 2 (blue area in Figure 4A; Table 1) whereas the more widespread activation in the right hemisphere (4.2 cm3) extended into the central sulcus with an inlet into the precentral gyrus and thus also involved BA 3 and BA 4 (red area in Figure 4A; Table 1). For these areas, the stimulation frequency did not affect the BOLD signal and there was no interaction between stimulation frequency and stimulated hand. For the cue period, we observed a similar pattern of effects of stimulated hand on BOLD signals in hand areas of the postcentral gyri.

Figure 4. 

Effect of stimulated hand on BOLD activity during the tactile threshold-tracking task. (A) Areas with main effect of stimulated hand (left vs. right) rendered on the smooth average brain surface template in SPM5. Filled areas represent primary somatosensory hand areas and outlined areas foot sensorimotor areas. Red and blue colors indicate stronger BOLD activity when the left and right hand received the stimuli, respectively. A, anterior; P, posterior; R, right; L, left. (B) Histograms show, for each stimulus frequency and stimulated hand, the percent BOLD signal change (β values) in the left and the right primary somatosensory hand area as percentage relative to mean BOLD signal level during the session. Height of columns gives mean values across participants and vertical lines represent unilaterally 1 SEM.

Figure 4. 

Effect of stimulated hand on BOLD activity during the tactile threshold-tracking task. (A) Areas with main effect of stimulated hand (left vs. right) rendered on the smooth average brain surface template in SPM5. Filled areas represent primary somatosensory hand areas and outlined areas foot sensorimotor areas. Red and blue colors indicate stronger BOLD activity when the left and right hand received the stimuli, respectively. A, anterior; P, posterior; R, right; L, left. (B) Histograms show, for each stimulus frequency and stimulated hand, the percent BOLD signal change (β values) in the left and the right primary somatosensory hand area as percentage relative to mean BOLD signal level during the session. Height of columns gives mean values across participants and vertical lines represent unilaterally 1 SEM.

Table 1. 

Main Effect of Hand Stimulated (Left vs. Right) during the Tactile Threshold-tracking Task

Voxels
Region
X
Y
Z
Ze
L > R Hand 
1355 L Paracentral lobule (BA 4) −6 −30 70 8.1 
−8 −14 72 7.7 
L Postcentral gyrus (BA 3) −26 −28 68 4.4 
544 R Cerebellum (Lobule III) 16 −36 −32 8.1 
R Cerebellum (Vermis IV) −50 −14 3.9 
529 R Postcentral (BA 2) 52 −24 54 6.0 
R Central sulcus (BA 3/4) 46 −14 58 4.4 
R Postcentral (BA 1/2) 58 −16 46 4.3 
 
R > L Hand 
933 R Paracentral lobule (BA 4) −26 74 8.1 
R Paracentral lobule (BA 6) −12 70 7.3 
R Postcentral gyrus (BA 2/6) 16 −46 72 4.9 
791 L Cerebellum (Lobule IV) −16 −38 −28 8.1 
177 R Putamen 32 −8 6.3 
94 L Postcentral (BA1/2) −50 −30 56 4.0 
Voxels
Region
X
Y
Z
Ze
L > R Hand 
1355 L Paracentral lobule (BA 4) −6 −30 70 8.1 
−8 −14 72 7.7 
L Postcentral gyrus (BA 3) −26 −28 68 4.4 
544 R Cerebellum (Lobule III) 16 −36 −32 8.1 
R Cerebellum (Vermis IV) −50 −14 3.9 
529 R Postcentral (BA 2) 52 −24 54 6.0 
R Central sulcus (BA 3/4) 46 −14 58 4.4 
R Postcentral (BA 1/2) 58 −16 46 4.3 
 
R > L Hand 
933 R Paracentral lobule (BA 4) −26 74 8.1 
R Paracentral lobule (BA 6) −12 70 7.3 
R Postcentral gyrus (BA 2/6) 16 −46 72 4.9 
791 L Cerebellum (Lobule IV) −16 −38 −28 8.1 
177 R Putamen 32 −8 6.3 
94 L Postcentral (BA1/2) −50 −30 56 4.0 

Number of voxels is given for each identified cluster (F test; voxel-based threshold of Ze > 3.09 with an extent threshold of 71 voxels, corresponding to p < .01, corrected for the whole brain, random-effects group analysis). Hemisphere (L, left; R, right), brain region, and Brodmann area refer to coordinates (X, Y, Z; provided in MNI stereotaxic space) of peak Z equivalent (Ze) values located within each cluster. Voxel size = 2 × 2 × 2 mm3. By comparing the sign of the BOLD signal changes obtained with either hand stimulated, we assessed brain areas that showed stronger activation with the left versus right-hand stimulated (L > R hand) and vice versa (R > L hand).

As expected from the fact that the participants operated the push button with the foot contralateral to the simulated hand, a main effect related to stimulated hand was present bilaterally in the primary sensorimotor and premotor areas of the feet and in the anterior foot areas of the cerebellum (Figure 4; Table 1). When the left hand received the stimuli and the right foot operated the button, the left sensorimotor cortex and the right cerebellum showed stronger BOLD activity than when the right hand was stimulated and the left foot operated the button (Figure 4A, areas outlined in red). Conversely, the right sensorimotor cortex and the left cerebellum showed stronger activity when the left foot was used to press the button (Figure 4A, areas outlined in blue).

Task Dependency of the Frequency Effects Observed in the Auditory and Visual Cortex

To address whether frequency dependent effects were linked to the execution of the tactile threshold-tracking task, we investigated BOLD responses when participants performed a visual threshold-tracking task. During the visual threshold-tracking trials, the participants received a playback of the tactile stimulus experienced in the previous tactile trial (Figure 1B). In the visual trials, participants reported their perception of an image appearing in the center of the computer screen against white background (see Figure 1B). Just like the intensity of the tactile stimuli was controlled in the tactile trials, the intensity (color saturation) of the image changed depending on the state of the button operated by the big toe contralateral to the hand receiving the tactile stimulation (see Methods). Our results indicate that when the participant performed the visual threshold-tracking task, the frequency of the tactile stimulation did not significantly affect the BOLD signal in Heschl's gyrus, F(2, 30) = 0.96; p = .39 (Figure 3B), and the overall activity did not differ from rest, F(1, 15) = 0.00; p = .98. For the lingual gyrus, there was also no significant effect of stimulation frequency, F(2, 30) = 1.14; p = .33 (Figure 3D). In fact, a factorial random-effects ANOVA with frequency and hand as fixed effects using functional images from the visual threshold-tracking task revealed no areas with a significant frequency effect. However, the overall activity in the lingual gyrus was significantly higher than in the rest condition, F(1, 15) = 7.91; p < .02, which likely reflects the visual nature of this task. As such, the overall stronger BOLD activity is consistent with previous findings that selective attention to a particular sensory modality increases the activity in regions primarily devoted to that modality and decreases activity in regions primarily devoted to other “unattended” modalities (Kawashima, O'Sullivan, & Roland, 1995; Haxby et al., 1994).

General Observations on BOLD Activity

In addition to addressing our principle hypothesis, we identified brain regions with increased BOLD activity relative to rest during the tactile threshold-tracking task irrespective of stimulated hand and stimulation frequency (Figure 5A, orange areas; Table 2). As expected, we found bilateral activation in the perisylvian cortex including the secondary somatosensory cortex, the superior temporal cortex, inferior parietal lobule, supramarginal gyrus and insula (e.g., Dijkerman & de Haan, 2007; Eickhoff, Grefkes, Zilles, & Fink, 2007; Hinkley, Krubitzer, Nagarajan, & Disbrow, 2007; Li Hegner et al., 2007; Disbrow, Roberts, & Krubitzer, 2000). We also found bilateral activation in the mesial frontal cortex (including pre-SMA), the rostral anterior cingulate cortex, and in the putamen and palladium of basal ganglia. One belt of prefrontal activity, which was particularly extensive for the right hemisphere, engaged the precentral gyrus and extended laterally to the posterior part of the ventrolateral prefrontal cortex and insula. A separate prominent cluster engaged the right dorsolateral prefrontal cortex. Most of the activated regions in prefrontal cortex and basal ganglia have been implicated in cognitive functions such as attention, decision-making and response selection (see, e.g., Hernández et al., 2010; Heekeren, Marrett, & Ungerleider, 2008; Seeley et al., 2007; Bunge, 2004; Picard & Strick, 2001), which are components of both the tactile and visual threshold-tracking tasks. Indeed, a conjunction of images obtained in the tactile and the visual tasks revealed substantial overlap of activation in these prefrontal regions (Figure 5A, yellow zones). Interestingly, we also observed a corresponding overlap of activation in a part of the left lateral cerebellum that are functionally connected via ventral thalamus to the regions we identified in right prefrontal cortex (Habas et al., 2009).

Figure 5. 

Cortical areas engaged during the threshold-tracking tasks rendered on the smooth average brain surface template in SPM5. (A) Filled areas (orange and yellow) represent common activations in all types of trials (all frequencies, both hands) of the tactile threshold-tracking task averaged across participants. The yellow zones indicate areas jointly activated in the tactile and visual threshold-tracking tasks. (B) Areas with main effect of task (tactile vs. visual threshold tracking). Orange zones indicate areas with stronger BOLD activity during the tactile threshold tracking and dark green zones indicate areas with stronger activity during visual threshold tracking. Transparent yellow zones indicate areas with an interaction between task and stimulated hand. (A and B) Render depth, 20 mm; L, left; R, right; A, anterior; P, posterior.

Figure 5. 

Cortical areas engaged during the threshold-tracking tasks rendered on the smooth average brain surface template in SPM5. (A) Filled areas (orange and yellow) represent common activations in all types of trials (all frequencies, both hands) of the tactile threshold-tracking task averaged across participants. The yellow zones indicate areas jointly activated in the tactile and visual threshold-tracking tasks. (B) Areas with main effect of task (tactile vs. visual threshold tracking). Orange zones indicate areas with stronger BOLD activity during the tactile threshold tracking and dark green zones indicate areas with stronger activity during visual threshold tracking. Transparent yellow zones indicate areas with an interaction between task and stimulated hand. (A and B) Render depth, 20 mm; L, left; R, right; A, anterior; P, posterior.

Table 2. 

Brain Regions Jointly Activated by All the Experimental Conditions of the Tactile Task (See Methods)

Voxels
Region
X
Y
Z
Ze
1487 L Inferior parietal lobule (BA 40) −52 −28 18 5.1 
−60 −20 20 4.9 
−52 −34 32 4.0 
−54 −36 50 3.6 
−52 −44 24 3.3 
L Superior temporal gyrus (BA 22/41) −58 −14 4.2 
−44 −26 12 4.0 
−50 −28 3.7 
L Supramarginal gyrus (BA 40) −64 −32 30 3.9 
2508 R Inferior parietal lobule (BA 40) 56 −38 52 5.0 
60 −40 28 4.9 
52 −24 20 4.5 
44 −44 42 4.4 
R Middle temporal gyrus (BA 21) 58 −52 3.4 
R Postcentral gyrus (BA 2) 66 −18 16 4.5 
52 −24 38 3.6 
R Superior temporal gyrus (BA 22) 50 −42 10 4.5 
64 −42 4.2 
62 −36 14 3.3 
R Supramarginal gyrus (BA 40) 56 −42 38 4.4 
164 R Middle temporal gyrus (BA 21) 58 −22 −12 4.0 
2937 L Cingulate gyrus (BA 24/32) −6 18 38 4.6 
−8 20 28 3.8 
L Paracentral lobule (BA 6) −2 −12 70 3.9 
L Superior frontal gyrus (pre-SMA, BA 6) −8 48 5.0 
−10 68 4.4 
−10 58 4.0 
R Cingulate gyrus (BA 32) 20 42 4.8 
R Medial frontal gyrus (BA 6) 18 12 68 4.7 
32 42 4.0 
R Paracentral lobule (BA 6) −24 70 3.5 
R Superior frontal gyrus (pre-SMA, BA 6/8) 20 52 5.2 
56 5.0 
66 4.9 
2544 L Anterior Insula −30 16 −4 5.1 
L Caudate nucleus −10 10 −12 3.3 
L Insula −38 4.2 
L Pallidum −20 −2 4.3 
L Precentral (BA 6) −56 24 4.3 
L Putamen −16 −2 4.6 
−20 14 4.1 
−26 −6 3.8 
L Superior temporal gyrus (BA 22) −52 −6 4.9 
4151 R Anterior Insula 36 20 4.8 
R Inferior frontal gyrus (BA 44) 50 14 −8 5.3 
56 18 22 5.2 
50 20 5.2 
62 4.3 
R Insula 40 −6 4.4 
38 3.9 
R Middle frontal gyrus (BA 6) 46 52 4.3 
R Precentral gyrus (BA 6/44) 52 4.6 
40 38 4.4 
R Putamen 22 5.1 
28 10 4.9 
20 −8 4.8 
561 R Inferior frontal gyrus (BA 46) 34 38 20 3.6 
R Middle frontal gyrus (BA 10) 42 46 3.8 
44 44 22 3.7 
40 54 14 3.6 
358 L Cerebelum (Crus 1) −38 −56 −38 5.3 
−26 −70 −30 4.3 
Voxels
Region
X
Y
Z
Ze
1487 L Inferior parietal lobule (BA 40) −52 −28 18 5.1 
−60 −20 20 4.9 
−52 −34 32 4.0 
−54 −36 50 3.6 
−52 −44 24 3.3 
L Superior temporal gyrus (BA 22/41) −58 −14 4.2 
−44 −26 12 4.0 
−50 −28 3.7 
L Supramarginal gyrus (BA 40) −64 −32 30 3.9 
2508 R Inferior parietal lobule (BA 40) 56 −38 52 5.0 
60 −40 28 4.9 
52 −24 20 4.5 
44 −44 42 4.4 
R Middle temporal gyrus (BA 21) 58 −52 3.4 
R Postcentral gyrus (BA 2) 66 −18 16 4.5 
52 −24 38 3.6 
R Superior temporal gyrus (BA 22) 50 −42 10 4.5 
64 −42 4.2 
62 −36 14 3.3 
R Supramarginal gyrus (BA 40) 56 −42 38 4.4 
164 R Middle temporal gyrus (BA 21) 58 −22 −12 4.0 
2937 L Cingulate gyrus (BA 24/32) −6 18 38 4.6 
−8 20 28 3.8 
L Paracentral lobule (BA 6) −2 −12 70 3.9 
L Superior frontal gyrus (pre-SMA, BA 6) −8 48 5.0 
−10 68 4.4 
−10 58 4.0 
R Cingulate gyrus (BA 32) 20 42 4.8 
R Medial frontal gyrus (BA 6) 18 12 68 4.7 
32 42 4.0 
R Paracentral lobule (BA 6) −24 70 3.5 
R Superior frontal gyrus (pre-SMA, BA 6/8) 20 52 5.2 
56 5.0 
66 4.9 
2544 L Anterior Insula −30 16 −4 5.1 
L Caudate nucleus −10 10 −12 3.3 
L Insula −38 4.2 
L Pallidum −20 −2 4.3 
L Precentral (BA 6) −56 24 4.3 
L Putamen −16 −2 4.6 
−20 14 4.1 
−26 −6 3.8 
L Superior temporal gyrus (BA 22) −52 −6 4.9 
4151 R Anterior Insula 36 20 4.8 
R Inferior frontal gyrus (BA 44) 50 14 −8 5.3 
56 18 22 5.2 
50 20 5.2 
62 4.3 
R Insula 40 −6 4.4 
38 3.9 
R Middle frontal gyrus (BA 6) 46 52 4.3 
R Precentral gyrus (BA 6/44) 52 4.6 
40 38 4.4 
R Putamen 22 5.1 
28 10 4.9 
20 −8 4.8 
561 R Inferior frontal gyrus (BA 46) 34 38 20 3.6 
R Middle frontal gyrus (BA 10) 42 46 3.8 
44 44 22 3.7 
40 54 14 3.6 
358 L Cerebelum (Crus 1) −38 −56 −38 5.3 
−26 −70 −30 4.3 

Number of voxels is given for each identified cluster. Hemisphere (L, left; R, right), brain region, and Brodmann's area refer to coordinates (X, Y, Z; provided in MNI stereotaxic space) of peak Z equivalent (Ze) values located within each cluster.

Finally, we looked for general effects of task (tactile vs. visual threshold tracking) on BOLD activity in the whole brain based on an ANOVA with Task and Stimulated Hand as fixed effects. As expected, we found that Task had widespread effects on BOLD activity. Stronger BOLD activity during the tactile task was present bilaterally in a belt of cortical tissue extending from the hand area of the postcentral gyrus down into the perisylvian region and further into the anterior insula of the frontal lobe (Figure 5B, orange areas). In contrast, the visual task was associated with stronger BOLD activity bilaterally in large areas of the occipital lobe extending into the neighboring temporal gyrus and also engaging the fusiform and parahippocampal areas (Figure 5B, green areas). Consistent with our findings based on the tactile task, we found a main effect of Hand in foot areas of the sensorimotor cortex and cerebellum (see Figure 4). We also found an interaction between Task and Stimulated Hand bilaterally in the primary sensorimotor cortex and adjacent dorsolateral premotor areas and in the hand areas of the cerebellum (Figure 5B, yellowish areas). Compared with the BOLD activity in the tactile task, the activity in the visual task was markedly suppressed in the sensorimotor cortex contralateral to the stimulated hand and largely unchanged in the ipsilateral sensorimotor cortex. Similarly, cerebellar activity ipsilateral to the stimulated hand was suppressed and contralateral activity was largely unchanged.

DISCUSSION

Our analysis of BOLD responses recorded from the whole brain during the tactile threshold-tracking task performed at 3-, 20-, and 100-Hz stimulation revealed an effect of Stimulus Frequency in only two regions, the left auditory cortex and the right lingual gyrus of the visual cortex. The BOLD response in the auditory cortex was stronger during the detection of oscillatory tactile stimulation at hearable frequencies (20 and 100 Hz) than at infrasonic frequencies (3 Hz). For the visual cortex, we observed a suppression of the BOLD signal level during detection of infrasonic stimulation frequencies (3 Hz) compared with stimulation in the flutter (20 Hz) and vibration (100 Hz) ranges. Thus, changing a single parameter, that is, stimulation frequency, in the context of the same tactile task caused a significant change in the neural activity of two traditionally unimodal brain areas, neither of which is primarily associated with processing tactile information. The absence of a detectable frequency effect during the cue period suggests that frequency-dependent BOLD responses during the tactile trials required the presence of tactile stimuli rather than just focused attention on detecting them.

Numerous studies have demonstrated functional interactions between the tactile and the auditory modality and between the tactile and the visual modality (for reviews, see Macaluso & Maravita, 2010; Soto-Faraco & Deco, 2009). Overall, these studies suggest that correlated tactile and auditory inputs, as well as correlated tactile and visual inputs, can improve performance in perceptual tasks by yielding a joint estimate of an external event that can both reinforce unisensory processing and support a veridical representation of the outside world (Driver & Noesselt, 2008; Stein & Stanford, 2008). It is important to emphasize that the effect of the stimulus frequency we report for the tactile threshold-tracking task cannot reflect this kind of multisensory integration because we confined the task-relevant sensory input to a single (tactile) modality.

Rather, our findings relate to the metamodal theory of brain function, which posits that brain areas, including primary sensory areas, can contribute to sensory perception by performing specific computations regardless of input modality (Pascual-Leone & Hamilton, 2001). The most striking evidence supporting this theory comes from pathological conditions of sensory deprivation (Merabet & Pascual-Leone, 2010). For example, visual cortex can support certain kinds of tactile or auditory processing in the congenital or early blind (Gougoux, Zatorre, Lassonde, Voss, & Lepore, 2005; Pascual-Leone & Hamilton, 2001; Sadato et al., 1996) and auditory cortex visual processing in the deaf (Lomber, Meredith, & Kral, 2010; Levänen, Jousmäki, & Hari, 1998). There is also evidence that this theory applies to healthy individuals especially regarding involvement of visual cortical areas during tactile tasks requiring discrimination of an objects' geometric features (Merabet et al., 2004; Sathian & Zangaladze, 2002; Amedi et al., 2001) and motion (Blake et al., 2004; Hagen et al., 2002). Our findings advance the metamodal theory by showing that changing input to a single sensory modality in the context of the same task can affect BOLD activity in two unimodal cortical areas primarily associated with processing other sensory modalities.

Auditory Cortex

Our results indicate that the auditory cortex was engaged during our tactile threshold-tracking task at hearable frequencies. Presumably, the auditory cortex was recruited to take advantage of its specialization in detecting temporal features encoded in periodic mechanoreceptive afferent signals, whether originating from the mechanoreceptors in the cochlea or in the skin. The detection of oscillatory tactile stimuli at hearable frequencies below ∼50 Hz are based on impulses in one or a few Fast-adapting type I (FA-I) afferents that innervate Meissner corpuscles whereas stimuli at higher frequencies depend on signals in highly vibration-sensitive FA-II afferents that innervate Pacinian corpuscles (Löfvenberg & Johansson, 1984; Talbot et al., 1968). These afferents fire in a phase-locked manner to the frequency of the driving stimulus (Freeman & Johnson, 1982; Johansson et al., 1982; Talbot et al., 1968) and the periodic afferent inputs lead to perception of oscillatory tactile events with a discernable pitch (Vallbo, Olsson, Westberg, & Clark, 1984; Ochoa & Torebjörk, 1983). Engagement of the auditory cortex in the processing of such inputs might explain why people describe their perception of oscillatory tactile stimuli in hearable frequencies in auditory terms. That is, oscillatory stimuli that primarily excite FA-I afferents are typically felt as flutter of the skin, which can be accurately localized whereas stimuli primarily exciting FA-II afferents are felt as a “diffuse vibratory hum” (Löfvenberg & Johansson, 1984; Talbot et al., 1968).

The fact that our stimulation with either 20 or 100 Hz affected the left auditory cortex is consistent with the known lateralization of auditory processing. That is, the left auditory cortex is specialized for detecting fundamental frequencies and the right auditory cortex is more involved in spectral, timbre-related processing (Warrier et al., 2009; Schneider et al., 2005). It remains to be investigated whether the right auditory cortex would be recruited in the detection of spectrally more complex tactile stimuli.

The frequency-dependent responsiveness of the human auditory cortex to tactile inputs has escaped previous studies for various reasons. The most obvious reason is that no previous studies reporting effects of tactile stimulation in the auditory cortex have directly compared brain activity in response to tactile stimulation limited to low (infrasonic) frequencies, primarily exciting Slowly adapting type I afferents that innervate Merkel endings (Freeman & Johnson, 1982; Johansson et al., 1982), with stimulation in the flutter and vibration ranges. The tactile stimuli used in previous studies either contained frequency components in the flutter or vibratory range or both (Lemus et al., 2010; Caetano & Jousmäki, 2006; Schürmann et al., 2006; Kayser et al., 2005; Fu et al., 2003; Foxe et al., 2002; Lütkenhöner et al., 2002), and activation of afferents associated with both flutter (FA-I) and vibration (FA-II) perception would have occurred when electric peripheral nerve stimulation were used (Lakatos et al., 2007; Schroeder & Foxe, 2002; Schroeder et al., 2001; Foxe et al., 2000).

Visual Cortex

The effect of stimulation frequency during the tactile threshold-tracking task in the visual cortex consisted of a suppressed BOLD signal level in the right lingual gyrus, likely involving both the primary and secondary visual cortex, during the 3-Hz tactile stimulation when compared with both the 20- and 100-Hz stimulations and to rest. Human and animal studies have indicated an association between inhibition of neural activity and negative BOLD responses both in the visual (Shmuel, Augath, Oeltermann, & Logothetis, 2006; Shmuel et al., 2002) and in the somatosensory cortex (Devor et al., 2007). Accordingly, the suppression of the BOLD signal in the lingual gyrus specifically during the 3-Hz tactile detection task could represent decreased processing in that area, which would not directly agree with our hypothesis. Instead, suppressed activity in visual cortex to the 3-Hz tactile stimulus might reflect a mechanism that contributes to task performance by restricting the crossmodal responsiveness of this area to object motion. In the absence of concurrent visual information about the moving tactile stimuli, such suppression might help the brain avoid interference between the tactile and visual modality regarding perception of object motion, which would be especially important given that the participants were performing a tactile detection task that required maximal focus on the presence of weak tactile inputs. That said, the relationship between changes in BOLD signal levels and neural processes in a brain area is highly complex and largely unknown (Logothetis, 2008). Therefore, it remains possible that the right lingual gyrus supports detection of tactile afferent information at low stimulation frequencies by virtue of its engagement in processing animate object motion (Pelphrey, Morris, Michelich, Allison, & McCarthy, 2005; Servos, Osu, Santi, & Kawato, 2002), which is limited to infrasonic frequencies (Amaya, Bruderlin, & Calvert, 1996). More speculatively, the lateralized effect that we observed is consistent with previous suggestions that the right lingual gyrus is involved when processing global forms rather than local details (Fink et al., 1996) because low-frequency tactile stimulation generally evokes sensations of global object motion rather than events localized to the surface of the skin (Löfvenberg & Johansson, 1984).

Primary and Secondary Somatosensory Cortex

Our results did not reveal differences in the BOLD responses, in either the primary or secondary somatosensory cortex, to flutter (20 Hz) or vibration (100 Hz) stimulation primarily targeting FA-I and FA-II afferents although such effects have previously been suggested in earlier fMRI studies (Harrington & Hunter Downs, 2001; Francis et al., 2000). Methodological factors could explain this discrepancy. In contrast to these previous studies, our experimental design ensured that the effective stimulus intensity was matched across the different frequencies, which required the amplitude of vibration stimulation to be about 1 order of magnitude weaker than flutter stimulation (see Figure 2; Lundström & Johansson, 1986; Talbot et al., 1968). Without such matching, differences in effective stimulus intensity, rather than stimulation frequency, could have accounted for the reported effects on BOLD signals (Siedentopf et al., 2008; Nelson et al., 2004; Arthurs & Boniface, 2002). Second, our studies were based on a random effects analysis including 16 participants whereas the previous studies used fixed-effect analyses on four and eight participants, respectively. And our analysis was based on contrasting functional images obtained for the different frequencies (ANOVA) rather than making comparisons against a baseline. Third, the intensity of our tactile stimulation was much weaker than in the previous studies and our participants performed a task that ensured that they actively used the afferent information. Indeed, the finding that frequency effects were present only during the tactile task and not during the visual task emphasizes the task dependence of the neural processing of sensory information (Ghazanfar & Schroeder, 2006; Nelson et al., 2004; Porro, Lui, Facchin, Maieron, & Baraldi, 2004; Staines, Graham, Black, & McIlroy, 2002; Carlsson, Petrovic, Skare, Petersson, & Ingvar, 2000; Johansen-Berg & Lloyd, 2000; Drevets et al., 1995; Hyvärinen, Poranen, & Jokinen, 1980). Furthermore, the widespread effect we observed of task on BOLD activity in the brain (Figure 5B) suggests that the responsiveness of traditionally somatosensory areas to tactile stimulation is determined by interactions between the tactile input and complex task-related cognitive processes. It is important to emphasize, however, that our failure to detect effects of stimulation frequency on BOLD signals in the somatosensory cortices in the tactile threshold-tracking task does not imply that the neural processes in these areas are not influenced by stimulation frequency. This is almost certainly not the case. For example, the three frequencies we used in this study primarily excite three different types of cutaneous mechanoreceptors whose signals have been shown to be processed in small, intermingled, clusters (∼500 μm in diameter) within the monkey primary somatosensory cortex (Friedman et al., 2004; Sur, Wall, & Kaas, 1984). The small scale of this organization would be missed using the mass-univariate fMRI analysis that we used. However, high-resolution fMRI combined with recent advances in and multivariate pattern analysis (Diedrichsen, Ridgway, Friston, & Wiestler, 2011; Swisher et al., 2010) might help address this organization.

Acknowledgments

This work was funded by the Swedish Research Council Project 08667, the Strategic Research Program in Neuroscience at the Karolinska Institute, and the County of Västerbotten. J. A. P. received a salary award from the Human Frontier Science Program. We thank M. Andersson, A. Bäckström, and G. Westling for their technical support and B. Edin and L. Nyberg for their comments on the manuscript.

Reprint requests should be sent to Per F. Nordmark, Department of Integrative Medical Biology, Physiology Section, Umeå University, SE 90187 Umeå, Sweden, or via e-mail: per.nordmark@physiol.umu.se.

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