1 Departments of Psychiatry, 2 Radiology, 3 Neurosurgery, and 4 Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06510
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ABSTRACT |
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Dhankhar, Ajay, Bruce E. Wexler, Robert K. Fulbright, Terry Halwes, Andrew M. Blamire, and Robert G. Shulman. Functional magnetic resonance imaging assessment of the human brain auditory cortex response to increasing word presentation rates. J. Neurophysiol. 77: 476-483, 1997. In an investigation of the auditory cortex response to speech, six subjects were studied using echo-planar functional magnetic resonance imaging (fMRI) at 2.1T. The subjects were asked to listen to English nouns presented at various rates ranging from 0 words per minute (wpm) to 130 wpm while fMRI images encompassing their primary and posterior superior secondary auditory cortices were acquired. An asymmetric spin echo imaging sequence was used with an induced T2 weighting of 50 ms to allow for transverse relaxation effects. Images were acquired in two or four axial-oblique slices with a repetition time of 3.75 or 7.5 s, in plane resolution of 6 × 3 mm, and a slice thickness of 5 mm. Localized activation centered over grey matter was consistently observed in all subjects in the transverse temporal gyrus (TTG), the transverse temporal sulcus (TTS), and the posterior superior aspect of the superior temporal gyrus (STG). The total activated volume and the integrated signal response in bilateral primary and posterior superior secondary auditory cortices increased with increasing rate of word presentation, peaking at 90 wpm (with some intersubject variability) with a subsequent fall at 130 wpm. There were no significant differences in the rate dependence of the signal response in bilateral primary and bilateral posterior superior secondary auditory cortices (P < 0.05).
Auditory processing in the human brain has been investigated extensively using several different stimuli including tones, syllables, and words. The array of techniques include cytoarchitectural mapping (Galaburda and Sanides 1980 Experimental setup
Six subjects (4 female, 2 male) were studied at 2.1T on a modified Bruker Biospec I (Bruker, Billerica, MA) whole-body spectrometer equipped with active shielded gradient coils (Oxford Magnet Technology, Oxford, UK). One female subject was studied twice to examine the reproducibility of the results. All subjects were right-handed, defined as writing and doing at least five of seven everyday tasks with their right hands (Wexler and Halwes 1985 Imaging protocol
Four contiguous, multislice, T1-weighted sagittal images (image matrix = 128 × 128; slice thickness = 5 mm; inversion time TIR = 750 ms; echo time TE = 18 ms; repetition time TR = 2.2 s) were acquired through the midline of the brain (the interhemispheric sagittal plane). The coordinates of the anterior commissure (AC) and the posterior commissure (PC) used in the standard Talairach-Tournoux coordinate system were noted using these images (Talairach and Tournoux 1988 Tasks
Stimuli were single syllable, common English nouns recorded by a male speaker. Words that were verbs as well as nouns (e.g., box, map) were excluded unless their use as a verb was far less common than their use as a noun. No word was presented twice. Stimuli were presented at 0 (resting), 10, 50, 90, and 130 wpm in 1-min stimulation blocks. Two or three blocks were presented at each rate, with the first presentation in ascending order of frequency (0, 10, 50, 90, 130 wpm), the second presentation in descending order, and the third presentation in random order (50, 90, 0, 130, 10 wpm).
Data analysis
LOCALIZATION OF ACTIVATION.
Data analysis was performed off-line on a Vaxstation 3200 computer (Digital Equipment, Maynard, MA) equipped with a SkyWarrior array processor (Sky Computers, Lowell, MA). For each set of 16 images in a single subject, the static baseline was removed by subtracting the mean of the four pretask images (So) on a voxel by voxel basis from every image in the series. This generated a new series of 16 difference images ( MOTION.
All acquired EPI data were subjected to a three-step examination for motion contamination. 1) Image series were viewed as a movie to detect movement of the perimeter of the head. 2) Center-of-mass (COM) algorithm: the image series were recreated by setting the intensities of all the voxels outside the brain to 0. Hence, artifactual fluctuations of voxels outside the brain did not influence our investigation for COM deviations. The COM of every image in the recreated series was calculated.Using the first image in the series as a standard, the(xi, yi) deviation of the COM for the subsequent images was plotted against time to reveal the temporal pattern of motion. Image series showing a COM shift 30% of a voxel in x or y directions were discarded. Particular attention was paid to COM shifts coinciding with the onset and/or the cessation of the task, where an even more stringent standard of >20% shift in x or y was enforced. 3) Activated regions that showed persistence of response after stimulus cessation were treated with suspicion. Data sets that consistently produced activations showing such behavior were discarded.
Brain mapping
Localized activations in the primary and secondary auditory cortices were consistently observed in all subjects at all the presented rates except the 0 wpm (resting) state. In no instance did any subject show significant activation at the 0 wpm rate. Figure 1 shows statistical probability maps for a typical subject at the four presentation rates, thresholded at a t-value of 1.83 (P < 0.05) and color coded for values above that. The images are averages of three repeats of each task as described earlier. In Fig. 1A, three distinct ROIs were observed bilaterally and have been so marked with numerals in each hemisphere on the 90 wpm overlayed image. ROIs 1 and 2 are primary auditory cortex activations mapping to lateral and medial TTG respectively (BA 41, Heschl's gyrus). ROI 1 in the right hemisphere and ROI 2 in the left extend across the TTS into the STG. ROI 3 maps to the posterior and superior aspect of the STG in both the hemispheres (BA 22 and 42). In the left hemisphere, this represents an activation of Wernicke's area. The activations followed sulcal folds from the lower to the upper slice and were seen again in a slice 7 mm superior to the slice shown.
Rate dependence of the activations
Figure 1A shows a comparison of the activation profiles at different word presentation rates for a typical subject. At 10 wpm, ROIs 1 and 2 are activated weakly. There are increases in their activated volumes and
Although fMRI previously has been used successfully to localize brain activations during visual, sensory, and motor tasks (Blamire et al. 1992
INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References
), clinico-pathological correlates of patients with lesions or auditory deficiencies (Benson 1979
), open brain electrical stimulation recordings (Penfield and Rasmussen 1950
), evoked potentials (Celesia 1976
; Hari 1991
) positron emission tomography (PET) (Lauter et al. 1985
; Mazziotta et al. 1982
; Petersen et al. 1988
; Wise et al. 1991
) and functional magnetic resonance imaging (fMRI) (Binder et al. 1994
a,b). Although anatomic boundaries between different auditory processing areas are not precisely known, and may vary among individuals, it is generally well recognized that the primary auditory cortex is located on the transverse temporal gyrus (TTG or Heschl's gyrus), which is Brodmann's Area (BA) 41, while the secondary auditory (or association) cortex is in surrounding regions on the superior temporal gyrus (STG) encompassing Brodmann's Areas 21, 22, 42, and 52 (Celesia 1976
; Talairach and Tournoux 1988
).
; Mazziotta et al. 1982
; Petersen et al. 1988
; Wise et al. 1991
). However, speech stimuli produced larger and more widespread activations posteriorly and superiorly and activated the left hemisphere to a greater degree than the right. This was speculated to be related to the specialized role of the left hemisphere in semantic processing (Wise et al. 1991
; Zatorre et al. 1992
). Recently, Binder et al. (1994
a) have demonstrated the feasibility of using MRI to perform functional studies of auditory processing despite a constant background scanner noise. Using words, non-words, text, and white noise as stimuli, they report localized activation patterns in the TTG and the STG consistent with previous PET studies.
used PET to compare blood flow changes associated with different rates of stimulus presentation. They instructed subjects to listen passively while single-syllable nouns were presented at rates of 10, 30, 50, 70, and 90 words per minute (wpm). When they searched for voxels that showed linear increases in blood flow across the range of stimulation rates, they found that such voxels were present in bilateral primary auditory areas and the secondary auditory area in the right hemisphere. However, a search they conducted for voxels where the regional cerebral blood flow (rCBF) difference between rest and 10 wpm was significantly greater than the average rCBF difference between each word presentation rate yielded voxels located in, and limited to, the left posterior secondary auditory cortex.
b).
. Using fMRI, we wished to characterize the changes in regional brain activation with increased processing load. In addition, we were interested particularly in clarifying the differences, if any, in the rate dependence of activation in the primary and the posterior secondary auditory cortices. A preliminary report on this research has been presented earlier (Dhankhar et al. 1994
).
METHODS
Abstract
Introduction
Methods
Results
Discussion
References
). All were native English speakers. None had any prior history of hearing deficits or neurologic or psychiatric illness. All subjects gave informed written consent for the experiment as approved by the Human Investigation Committee of the Yale University School of Medicine. Subjects performed the experiment voluntarily and were paid an hourly stipend as compensation.
). T1 weighted axial-oblique images parallel to the AC-PC line and perpendicular to the midline were then used to localize two (in 4 subjects) or four (in 2 subjects) contiguous slices that included the transverse temporal gyrus (TTG or Heschl's gyrus) and the posterior-superior aspect of the STG. In the two subjects for whom four slices were obtained, we also imaged the STG inferior and anterior to the TTG. The slices typically spanned a region 0-30 mm above the AC-PC line.
). This was in addition to nonlocalized hand shimming of first order coils. Two-dimensional time of flight MR angiograms were acquired (TE = 40 ms) in all cases to localize large blood vessels in each selected slice.
). The multislice EPI images were acquired with a TR of 3.75 (2 acquired slices) or 7.5 s (4 acquired slices), an image matrix of 64 × 64 with a nominal inplane resolution of 6 × 3 mm, and a slice thickness of 5 mm. Four dummy scans per slice were acquired prior to data collection to achieve steady-state magnetization.
S) revealing task-related intensity changes. Statistical maps based on paired Student's t-test comparisons between the pretask and the task periods were created as previously described (McCarthy et al. 1993
). The first image acquired during stimulus presentation in every slice was not included in the t-test calculation, allowing for a 3.75-s delay in the rise of the fMRI signal (Blamire et al. 1992
). T-images of the repeated sets for each frequency were averaged together, resulting in the final t-image for a performed task for each subject. The final t-images were thresholded at a t value of 1.83 (P < 0.05, 9 df). The method used here has the relative advantage over other similar methods (Blamire et al. 1992
; Shaywitz et al. 1995
) in that it involves no filtering, cluster-analysis or other user-modulated image processing routines. Minimal postprocessing manipulation of data was required for the subsequent comparisons that had to be made in this study. Anatomic localization was performed by linearly interpolating the final t-test image to a matrix size of 128 × 128 and superimposing it on the T1 weighted scout image of the same slice. Activated pixels are depicted on a color scale.
; Celesia 1976
; Galaburda and Sanides 1980
; Steinmetz and Seitz 1991
; Talairach and Tournoux 1988
). This was done individually for every subject, thereby taking into account intersubject variability in anatomy. For each of the four segregated anatomic regions (2 in each hemisphere), we counted significantly activated voxels (P < 0.05) at each rate; calculated time courses of activation, the percent
S/So, and the average percent
S/So (images 6-12) during activation of the significantly activated voxels; calculated the integrated signal change within a region, which we defined as the product of the average percent
S/So and the number of significantly activated voxels; and calculated the Talairach-Tournoux coordinates of the center of the region.
RESULTS
Abstract
Introduction
Methods
Results
Discussion
References
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FIG. 1.
A: patterns of activation in an axial-oblique image of 1 subject. Color overlays represent t-test comparisons between pretask and task periods where performed task was passive listening to words presented binaurally at 0, 10, 50, 90, and 130 words per minute (wpm). T-images have been thresholded at a value of 1.83 (P < 0.05). In this subject, no activation was seen at 0 wpm, and that image has therefore not been presented. Same color scale has been applied to all the rates with hotter colors representing increasing t-values in range 1.83-7.00. Three different regions of interest (ROIs) in left hemisphere have been labelled in 90 wpm image. ROI 1 = lateral transverse temporal gyrus (TTG); ROI 2 = medial TTG; ROI 3 = posterior superior superior temporal gyrus (STG; see Fig. 2 and text for details). B: observed activations at 10, 50, 90, and 130 wpm in same subject shown in A but from data acquired 5 wk earlier (t > 1.83, P < 0.05). C: time course of the primary auditory cortex activation in left hemisphere of inferior slice (ROI 1 + ROI 2 in A, 90 wpm). Percentage S/So of 18 pixels comprising this ROI has been plotted as a function of acquired image number. Horizontal bar on abscissa represents active task period (images 5-12).
S/S0) of those voxels in the primary auditory cortex with P < 0.05 in the left hemisphere (ROI 1 + ROI 2 in Fig. 1A). The percentage signal change (percent
S/So) of the 18 voxels comprising this ROI has been plotted as a function of the acquired image number. The horizontal bar on the abscissa represents the active task period (images 5-12; stimulus started immediately after image 4 was acquired). Signal intensity started to rise after the onset of the task (image 4) and had reached its mean activated value 3.75 s later, when the subsequent image was acquired. At the 90 wpm rate, the maximum signal increase was 5.6% of the pretask baseline while the mean signal change for images 6-12 was 4.6%. Signal decay followed cessation of the task, with a time lag as shown of 11.3 s to reach the baseline value. At 90 wpm, the mean
S/So of activated voxels of all the subjects studied was 6.4%. The average delay for the signal rise to peak after commencement of the task was 3.8 s, with a much slower time lag before return to baseline of 10.5 s.
S/So values as the rate increases to 50 wpm and to 90 wpm. At 130 wpm, the activated volumes and
S/So values fall. ROI 3 also showed a similar rate dependent behavior of the activated volume and
S/So even though there was a large region activated at 10 wpm. This subject (female) demonstrated an unusually strong left dominance in both the primary and the secondary regions at all rates. This was observed to a lesser extent in the other subjects (see later).
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FIG. 2.
Histogram of voxels in bilateral primary and posterior superior secondary auditory cortices (average of 6 subjects). Vertical lines represent t = 0 and t = 1.83.
. The average volume of each of our four segregated regions was 14 ± 4 ml and the Talairach coordinates were x = ±47 ± 6, y =
23 ± 4, and z = 12 ± 3 mm for bilateral primary auditory cortices and x = ±60 ± 9, y =
33 ± 5, and z = 14 ± 4 mm for bilateral posterior superior secondary auditory cortices. Note that our activated ROIs for each subject were entirely contained within the 14 ± 4 ml defined regions and were highly similar in location and size to the approximately 15-ml voxels of Price et al. For the integrated signal thus defined, we again observed a rise in the signal with increasing rate of word presentation from 10 to 90 wpm in each of the four cortical regions investigated.
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FIG. 3.
Rate dependent increase in integrated signal at P < 0.05 in bilateral primary and posterior superior secondary auditory cortices. Integrated signal is defined as volume of activation multiplied by average S/So and is a measure of total activity. Anatomic definition of the areas was performed using T1 weighted scout images.
,1 we searched for individual voxels in each subject that had a t-value of
1.83 (P < 0.05) at the 10 wpm rate but then showed no significant change in t-value with increasing rate.2 An insignificantly small number of pixels were selected by our algorithm (P < 0.05). The process was repeated after smoothing the data with a 20-mm Gaussian sphere, but we still saw no regions satisfying this condition. However, even after smoothing, a search for voxels showing a t-value rising with rate consistently resulted in at least a few voxels in the ROIs (data not shown).
. We performed thisANOVA and again found the effects of cortex and therate-cortex interaction to be nonsignificant (P < 0.34and P < 0.58, respectively), whereas the primary effect of rate remained highly significant (P < 0.001).
DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References
; Kim et al. 1993
; McCarthy et al. 1993
), the investigation of auditory processing presents a special challenge. Background noise generated by the gradients required for image formation potentially raises the baseline typically used to calculate the difference in the NMR signal in the pretask and the task states. However, our results show that fMRI clearly demonstrates the ability to detect distinct brain activity in primary and secondary auditory cortices, in agreement with the recent results of Binder et al. (1994
a,b).
a,b; Petersen et al. 1988
; Zatorre et al. 1992
).
S/So with rate accompanied by a significant rise in the number of activated voxels in bilateral primary and posterior secondary auditory cortices. Precise definition of the volume of activation during a particular task condition is difficult because the volume depends on the somewhat arbitrary selection of a threshold for the t-value. However, as may be seen in Fig. 2, activation is more extensive at 90 wpm than it is at 50 wpm with any selected t threshold.
a,b; Price et al. 1992
). In addition, we have established an upper limit of the rate dependent increase with monosyllabic English noun stimulus by showing no significant increase in signal from 90 to 130 wpm, and, in fact, showing a trend toward a decrease in signal.
, as also should be the physiological response.
reported a linear rise in signal from 0 to 90 wpm in all the regions examined except Wernicke's area. Although our data agree with the PET results in bilateral primary and right secondary auditory cortices in so much as they show a steady rate dependent rise in signal, they do not show the sharp stepwise rise in Wernicke's area. In Wernicke's area, our results are indistinguishable from the other regions, in contrast to the PET results. Indeed, rate dependence of left posterior superior secondary cortex persisted even when we examined only the most posterior regions, thereby eliminating any possible mixing of primary auditory cortex voxels with Wernicke's area.
. We assessed this possibility by calculating Talairach-Tournoux coordinates for each of our four segregated regions. Of the six distinct regions identified by Price et al. (1992)
, the bilateral primary auditory activations were centered at x = ±50, y =
22, and z = 12 mm. The average Talairach coordinates for our primary activations were x = ±47 ± 6, y =
23 ± 4, and z = 12 ± 3 mm. The posterior superior temporal gyri activations in Price et al. (1992)
were centered at x = ±58, y =
34, and z = 12 mm. The average Talairach coordinates for these regions in our study were ±60 ± 9, y =
33 ± 5, and z = 14 ± 4 mm.
, we calculated an approximate lower estimate for the volume of activation of their ROIs to be to be 2 × 3 × 2.5 = 15 ml. On inspection of the Talairach coordinates of the ROIs that localized to the primary and posterior secondary auditory cortices of our six subjects, we found that the individual coordinates were contained within the above PET volume in every instance. We therefore can conclude that we investigated, and have reported the results for, anatomic regions highly similar to those identified in the PET study.
and searching our data for voxels activated at 10 wpm but showing no further increase in activation at higher stimulation rates, we failed to find any. Of course, the Price et al. study directly measured rCBF differences while the signal in fMRI is believed to be an indirect, albeit close, correlate of flow changes. Previous studies have established the technique as a reliable indicator of neuronal activation in human brain primary, sensory, and cognitive areas, so it is unlikely that the differences in our results stem from inherent methodological incompatibilities (for recent reviews, see Aine 1995
; Shulman et al. 1993
). Moreover, we find ourselves in excellent agreement with the localization of activation as well the rate dependence of the activation from 10 to 90 wpm in bilateral primary as well as right posterior secondary cortices.
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ACKNOWLEDGEMENTS |
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The authors thank Dr. Fahmeed Hyder for comments and Dr. Alex Stevens for assistance with the ANOVAs.
This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-34576.
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FOOTNOTES |
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1
The data processing of Price et al. (1992) involved an intersubject averaging of data, which included a 20-mm Gaussian smoothing filter to account for a scattering of anatomic structures between subjects. After creating t-statistical parametric maps of their condition means, they conducted a search for the voxels that showed a linear rise in signal with the presentation rate of heard words and found those to be located bilaterally in primary auditory cortices and medial STG and unilaterally in the right posterior superior STG. A search for voxels where the difference between rest and 10 wpm was greater than the average difference between each word presentation rate only showed voxels in the left superior posterior STG (Wernicke's Area).
2
Our search algorithm 1) accepted the t-statistical map (t > 1.83, P < 0.05) for the 10 wpm stimulus as input; 2) performed a linear regression through the t-images of 10, 50, 90, and 130 wpm for those voxels present in 1); and 3) returned the slope and the correlation coefficient.
Address reprint requests to A. Dhankjhar.
Received 11 December 1995; accepted in final form 3 September 1996.
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