Sex Differences in Lateralization Revealed in the Posterior Language Areas

Kenji Kansaku1,2, Akira Yamaura2 and Shigeru Kitazawa1

1 Neuroscience Section, Information Science Division, Electrotechnical Laboratory, Tsukuba and , 2 Department of Neurological Surgery, Chiba University School of Medicine, Chiba, Japan


    Abstract
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Notes
 References
 
It has been hypothesized that language functions are more strongly lateralized to the left hemisphere in males than in females. Previous anatomical data and patient studies have suggested that the posterior language areas should exhibit sex differences. However, neuroimaging studies to date have only provided support for differences in the anterior language areas. To look for differences in the posterior language areas, functional magnetic resonance imaging scans were obtained while male and female subjects listened attentively to a story read aloud and to the same story replayed in reverse. Comparing activation in the superior and the middle temporal gyri during a story to activation during reverse replay of the story showed lateralization to the left in males but not in females. There was no lateralization in either sex when comparing activation during random fragmentation of the story to reverse replay. In the angular and the supramarginal gyri, however, activation was lateralized to the left hemisphere in both sexes, unlike the sex-dependent activation of the posterior temporal lobes. We infer that females use the posterior temporal lobes more bilaterally during linguistic processing of global structures in a narrative than males do.


    Introduction
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Notes
 References
 
It has been proposed that language is more strongly lateralized in males than females (Levy, 1972Go; Hampson and Kimura, 1992Go; Kimura, 1999Go). The strongest evidence supporting this hypothesis is that males have a higher incidence of aphasia after lesions to the left hemisphere (McGlone, 1977Go; Inglis and Lawson, 1981Go). This functional difference led investigators to search for anatomical correlates. The planum temporale, which contributes to the phonological processing of auditory input (Binder et al., 1996Go), is reported to be more asymmetric in males (Kulynych et al., 1994Go). The isthmus of the corpus callosum, which contains commissural fibers connecting the posterior language areas (de Lacoste et al., 1985Go), is reported to be larger in females, relative either to the total area of the corpus callosum (Witelson, 1989Go; Steinmetz et al., 1992Go) or to the forebrain volume (Steinmetz et al., 1995Go, 1996Go; Jäncke et al., 1997Go). It has been suggested that these anatomical findings are responsible for the more symmetrical representation of language in females (Witelson, 1989Go).

The lesion and anatomical data emphasized the role of posterior regions in this sex difference. However, neuroimaging studies to date have provided support for differences only in the anterior perisylvian areas (Shaywitz et al., 1995Go; Pugh et al., 1996Go; Jaeger et al., 1998Go). In these studies revealing the sex difference in the anterior areas, one using past-tense generation tasks (Jaeger et al., 1998Go) and the others using a rhyme-judgement task (Shaywitz et al., 1995Go; Pugh et al., 1996Go), semantic processing was not required.

To detect sex differences in the posterior language areas, it is important to activate the posterior language areas that appear to be involved in critical aspects of language comprehension (Damasio, 1992Go). One possible way to do this is to require semantic judgements about words, but this does not work well (Frost et al., 1999Go). Another approach is to ask subjects to comprehend global aspects of a whole story, since this activates more areas in the posterior regions than are activated by simple word lists alone (Mazoyer et al., 1993Go).

Our study focused on sex differences in the degree of language lateralization in the brain, with special focus on the posterior language areas. Functional magnetic resonance imaging (fMRI) was performed while male and female subjects listened attentively to an essay read aloud (forward condition) and to a recording of the same essay played in reverse (reverse condition). Sex differences in activation were noted in the posterior language areas.


    Materials and Methods
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Notes
 References
 
Subjects

Forty-seven volunteer healthy subjects, 22 males (age 22–47 years) and 25 females (age 20–43 years) participated in the experiments. All the subjects were neurologically normal and strongly right-handed according to the Edinburgh Inventory (Oldfield, 1971Go). The subjects were university students, university graduates or college graduates. The studies received approval from the institutional human review committee. All subjects gave written informed consent according to institutional guidelines.

Task

In each experiment, the subjects were instructed to close their eyes and listen attentively to sound stimuli delivered through headphones for 380 s. The stimulus amplitude, which remained constant across subjects, had an average sound pressure level of 97 dB at the distal end of the audio system (Resonance Technology, Northridge, CA). Beforehand, the subjects were told that the sound stimuli contained a story and that several questions about the story would be asked after the experiment. Each experiment consisted of nine epochs: five control epochs alternating with four narrative epochs. The first control epoch was 60 s long and all the other epochs were 40 s long.

Three types of experiments were carried out. In experiment 1, to observe the whole extent of activation elicited by listening to a narrative, the narrative of a short essay (160 s) was delivered during the four test epochs (epochs 2, 4, 6 and 8) and no sound was delivered during the control epochs. In experiment 2, to exclude activation elicited by processing of auditory signals in general, the narrative was delivered during the test epochs and the preceding test epochs were replayed in reverse during each control epoch. In experiment 3, to eliminate activation caused by the processing of global structures in sentences, the narrative was cut into pieces of 1 s duration and the pieces were randomly presented in each test epoch (permuted stimuli), and the reverse replay of the preceding test epoch was delivered during each control epoch.

Six short essays were read aloud and the voice was digitally sampled (44.1 kHz) and recorded with a PC (Power Mac 9600/200MP, Apple Computer, Cupertino, CA). Three sound sequences for experiments 1, 2 and 3 were prepared for each essay using Matlab software (MathWorks, Natic, MA) on the PC and were re-recorded on a mini-disk. A mini-disk player (Sony, Tokyo, Japan) was used to play one of the 18 sound sequences during each experiment.

Nineteen male and 21 female subjects participated once each in experiments 1, 2 and 3, and three male and four female subjects participated once each in experiments 1 and 2. Sequences from the six essays were randomly assigned to each subject so that the subject listened to a story only once. The order of the experiments was balanced among the subjects.

Immediately after each experiment, the subject was required to respond orally to a set of questions prepared for each essay. The scores (perfect score = 10) by males were 8.4 ± 1.2 (mean ± SD, n = 17), 8.8 ± 0.9 (n = 16) and 1.0 ± 1.2 (n = 13) in experiment 1, 2 and 3, respectively. The scores by females were 8.6 ± 1.0 (n = 14), 8.4 ± 1.2 (n = 14) and 0.9 ± 1.1 (n = 10), respectively. Thus, as expected, all subjects understood little when presented with the fragmented stories and reverse replay (experiment 3). An analysis of variance showed that the number of correct answers to these questions did not depend significantly on sex (df = 1, F = 0.84, P = 0.36), the order of the experiments (df = 2, F = 2.0, P = 0.15) or the essay content (df = 5, F = 0.46, P = 0.65), but depended on the type of experiment (df = 2, F = 270, P < 0.0001).

Imaging

BOLD contrast image volumes (Ogawa et al., 1993Go) were acquired at 3.0 T (GE-ANMR system, GE-Signa Horizon LX system, Milwaukee, WI) using gradient-echo echo-planar imaging (TR/TE = 3999 ms/20 ms, FA = 90°, slice thickness/gap = 7/3 mm, FOV = 20 x 20 cm2, matrix size = 64 x 64). Eight axial slices were obtained from 19 male and 19 female subjects. Fifteen coronal slices were obtained from three male subjects and five female subjects, and 15 sagittal slices were obtained from one female subject. To overcome difficulties in observing activations in the poles, we improved magnetic field homogeneity by using not only linear but also second order shims (Spielman et al., 1998Go). Accordingly, we were able to observe activations in the dorsal part of the poles although we still failed in most subjects to observe activations in the ventral part of the poles (Fig. 2Go). Ninety-five sequential images of each slice were collected during each experiment. Anatomic images of the same slices were acquired using a conventional technique (heavy T2-weighted images; TR/TE = 6000 ms/180 ms). In addition, 3-D anatomic images were acquired using a 3-D spoiled gradient-echo technique (TR/TE = 33 ms/4 ms).



View larger version (31K):
[in this window]
[in a new window]
 
Figure 2. Composite images of the distribution of activated areas during experiment 2 (forward versus reverse) comparing data from three typical female subjects (a,b,c) with data from three typical male subjects (d,e,f). All the activated cortical volumes in each hemisphere are shown in red on a semi-transparent 3-D anatomic image of each subject (gray). Note the difference in the activated areas in the right hemispheres. (f) Various regions of interest: the superior temporal gyrus (STG, 1), middle temporal gyrus (MTG, 2), inferior temporal gyrus (ITG, 3), temporoparietal cortex (TPC, 4) and inferior frontal gyrus (IFG, 5). The STG, MTG and ITG were combined into another region of interest, the temporal gyri (TG).

 
Data Analysis

Statistical parametric mapping (SPM 96, Wellcome Department of Cognitive Neurology, Institute of Neurology, University College London, London, UK) was used initially to detect head movement; data with a head movement of <0.6 mm (one-fifth of the pixel size) were used for further analysis (Kansaku et al., 1998Go). This criterion was met for 17 (77% of 22), 16 (73% of 22) and 13 (68% of 19) male subjects, and 14 (56% of 25), 14 (56% of 25) and 10 (48% of 21) female subjects in experiments 1, 2 and 3, respectively.

For group analyses, SPM 96 (Friston et al., 1995Go) was used. For each individual subject, scans were realigned to the first image, stereotactically normalized and smoothed with a Gaussian filter (10 mm full width at half maximum, FWHM). A high-pass filter with a cut-off frequency of 0.5 cycles per min was used to exclude low-frequency confounding effects in the time series. A fixed-response, boxcar model was used to characterize condition effects. The SPM {Z} was thresholded at a Z value of 3.09 (P = 0.001, uncorrected).

In addition to group analyses, the data from each subject were analyzed. Sequential data of 90 images per slice, excluding the first five images, were correlated with a boxcar function that consisted of five alternating control epochs (5 x 40 s) and four test epochs (4 x 40 s). The boxcar function was shifted by 0 and 4 s and the correlation coefficients were calculated repeatedly; the larger correlation coefficient was assigned to each voxel. The criterion for activity was taken to be any instance of two or more contiguous voxels having a correlation coefficient greater than 0.3 (P < 0.0041). These active voxels were smoothed using a 5 mm FWHM spatial filter, and then fused with a 3-D anatomic volume prepared for each subject using the iMIPS program (iMIPS, Pembroke, MA). Three contiguous sagittal slices 10 mm thick were resliced from the lateral ends of the composite 3-D volume of activation. The activated volumes in the temporal lobes, temporoparietal cortex and inferior frontal gyrus were measured on the contiguous sagittal slices using MEDx software (Sensor Systems, Sterling, VA).


    Results
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Notes
 References
 
Group Analysis

Figure 1aGo shows the differential activation between the for- ward and no voice conditions (experiment 1) across female subjects. Activation was distributed bilaterally over the primary auditory cortex and the superior temporal gyrus (STG). The differential activation was also bilaterally distributed in male subjects (Fig. 1dGo).



View larger version (32K):
[in this window]
[in a new window]
 
Figure 1. Distribution of activated areas displayed on transparent brain hemispheres during experiment 1 (forward condition versus no voice condition; a,d), experiment 2 (forward condition versus reverse condition; b,e) and experiment 3 (permuted condition versus reverse condition; c, f) shown separately for female (a,b,c; n = 14, 14, 10) and male (d,e,f; n = 17, 16, 13) subjects. Color dots represent pixels for Z-scores > 3.09 in the group analysis. Talairach coordinates (Talairach and Tournoux-1988Go) and Z-scores of the activated regions are listed in Table 1Go.

 
Differential activation between the forward and reverse conditions (experiment 2) was distributed bilaterally over the middle temporal gyrus (MTG; Fig. 1bGo, Table 1Go) in females, whereas differential activation was found only in the left hemisphere over the left superior and middle temporal gyri (Fig. 1eGo, Table 1Go) in males.


View this table:
[in this window]
[in a new window]
 
Table 1 Group analysis of areas of activation
 
The sex differences in the posterior language areas only became apparent when effects of activations caused by the narrative were compared with the activations caused by reverse replay of the narrative (Fig. 1b,eGo). This shows that the sex differences resulted mainly from processing the narrative rather than primary processing of auditory stimuli. However, it was still unclear whether the sex differences depended on processing global structure in the narrative or whether local structure was sufficient. To examine this point further, we prepared another series of sound stimuli designed to maintain local structures for up to 1 s while disrupting the global structure in the original narrative. We cut the narrative into pieces of 1 s duration and delivered the pieces in random order during test epochs. The permuted stimuli were replayed in reverse during control epochs. In this experiment, experiment 3, the activation in males and females appeared to be the same (Fig. 1c,fGo). Differential activation was distributed over the left STG and right MTG in both sexes. To summarize: males show large asymmetry in processing intact narratives whereas females do not. When there is little global semantic structure, the areas activated appear to be the same in both sexes. Thus, we conclude the sex difference is specific for global semantic structure.

Individual Analysis

The group analysis showed that sex differences, left dominant activation in males versus bilateral activation in females, were most apparent in experiment 2. The sex difference in experiment 2 was apparent even when the data were analyzed subject by subject (Fig. 2Go). Bilateral activation was apparent in three typical female subjects (Fig. 2a–cGo), whereas the activation was left dominant in three typical male subjects (Fig. 2d–fGo). However, the activated areas were distributed not only over the superior and middle temporal gyri, as expected from the group analysis, but also in the inferior frontal gyrus (Fig. 2b–dGo) and temporoparietal cortex (Figs. 2a,b,d,fGo). Accordingly, we measured the volume of activation in each subject for the three experiments for five regions of interest: the STG (1 in Fig. 2fGo), MTG (2), inferior temporal gyrus (ITG, 3), temporoparietal cortex (TPC, 4) and inferior frontal gyrus (IFG, 5). The total volume of activation in the three temporal gyri (TG, 1 + 2 + 3) was also calculated. The data are summarized in Table 2Go and Figure 3Go.


View this table:
[in this window]
[in a new window]
 
Table 2 Median volumes of activation
 


View larger version (25K):
[in this window]
[in a new window]
 
Figure 3. Cortical volumes of activation (ordinate) in the temporal gyri (TG; a,b,c) and temporoparietal cortex (TPC; d,e,f) during experiments 1 (a,d), 2 (b,e) and 3 (c,f), shown by sex and hemisphere. Each box plot shows the 10th, 25th, 50th, 75th and 90th percentiles of distribution. Significant differences are indicated by brackets containing one (P < 0.05; Wilcoxon signed rank test) or two (P < 0.005) asterisks.

 
Activation in the Temporal Lobe

As expected from the observations in Figure 2Go, the volume of activation in the right temporal gyri (TG, median = 14 ml, Fig. 3bGo) was as large as that in the left TG (15 ml) in females. In males, the median volume of activation in the left TG (22 ml) was almost twice as large as that in the right TG (12 ml). The difference between the volumes of activation in the right and left TG was not significant in females (P = 0.78), but was significant in males (P = 0.0005, Wilcoxon signed rank test). In male subjects, the dominance of activation in the left TG was detected in experiments 1 (P = 0.013, Fig. 3aGo) and 2, but the significant lateralization disappeared in experiment 3 (P = 0.97, Fig. 3cGo). The significant lateralization disappeared because the activation in the TG decreased on the left (17 ml from 22 ml in experiment 2, Table 2Go), but increased significantly on the right (19 ml from 12 ml; P = 0.023, Wilcoxon signed rank test). In females, bilateral activation in the TG occurred in experiments 1, 2 and 3; accordingly, the difference between the activation in the left and right TG was not significant in all three experiments.

As a direct measure of lateralization in the TG, we calculated the difference between the volumes activated in the left and right TG (the degree of lateralization in the TG) for each subject (Fig. 4Go). An analysis of variance was used to determine which of three factors (sex, the experiment and the number of correct answers to the post-experimental questions) affected the degree of lateralization. The number of correct answers was categorized into two groups (high and low) in each experiment, according to whether the score was higher or lower than the mean score for that experiment (Fig. 4d–fGo). The analysis of variance showed that (i) the degree of lateralization did not depend on the number of correct answers (df = 1, F = 0.86, P = 0.36), but depended on sex (df = 1, F = 11.1, P = 0.0013) and the experiment (df = 2, F = 5.63, P = 0.0054); and (ii) the effects of interactions were not significant (P > 0.7), except the interaction between sex and the experiment (df = 1, F = 6.0, P = 0.0039).



View larger version (24K):
[in this window]
[in a new window]
 
Figure 4. Distribution of the difference of the activated volumes in the left and right temporal gyri shown by sex and experiment (a,b,c), and shown by the number of correct answers and experiment (d,e,f). The number of correct answers was categorized into two groups (high and low) in each experiment, according to whether the score was higher or lower than the mean score (8.5, 8.6, 0.96) for that experiment (d,e,f). Positive values in the ordinate indicate larger activation on the left than on the right, thus there is left dominant activation in the temporal gyri.

 
The results of the ANOVA are directly confirmed in Figure 4Go. In experiment 1 (Fig. 4aGo), the volume of lateralization was distributed around zero in females, and the distribution was slightly shifted to a more positive (left dominant) range in males; the difference in the two distributions was significant (P = 0.047, Mann–Whitney U test). In experiment 2 (Fig. 4bGo), activation was left dominant in all but one male, while they were distributed around zero in females; the sex difference was significant (P = 0.001). In experiment 3 (Fig. 4cGo), no significant difference was found between the distributions for males and females (P = 0.85). In contrast, no significant difference was detected when the degree of lateralization was compared between groups with high and low numbers of correct answers (high and low scores; Fig. 4d–fGo). The resulting P-values were 0.55, 0.48 and 0.50 for experiments 1, 2 and 3, respectively.

These results show that activation in the TG was more left dominant in males than in females in experiment 2. A significant sex difference was also detected in experiment 1, but the sex difference disappeared in experiment 3, when the stimuli during the test epochs lost the global structures in the narratives. These observations were similar when the activations were analyzed separately for the STG and MTG, although no significant left dominance was found in the STG of male subjects in experiment 1 (Table 2Go). Activation occurred in a smaller volume in the ITG than in the STG and MTG. Consequently, no significant left dominance was found in any experiments in both sexes in the ITG (Table 2Go).

Activation in the IFG

Sex-dependent left dominant activation was also found in the IFG (Table 2Go). In experiment 2, activation in the IFG was lateralized significantly (P = 0.008) in male subjects, but not (P = 0.59) in females. In experiment 1, lateralization in the IFG was marginally significant in males (P = 0.061), but not in females (P = 0.21). In experiment 3, lateralization was not significant in either males (P = 0.22) or females (P = 0.26).

Activation in the TPC

In contrast to the sex-dependent (male-specific) left dominance in the TG and IFG, activation in the TPC was left dominant in both sexes in experiments 1 (Fig. 3dGo) and 2 (Fig. 3eGo). In experiment 3, left dominance was not significant in either sex (Fig. 3fGo). It is worth noting that in male subjects the volume of activation in the right TPC in experiment 3 (median = 5.9 ml, Table 2Go) was significantly larger (P = 0.033) than that in experiment 2 (0.60 ml), although activation in the left TPC in experiment 3 was not significantly different from that in experiment 2 (P = 0.81).


    Discussion
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Notes
 References
 
Based on data from cortical lesions, it has been postulated that females utilize both hemispheres more equally during linguistic processing than males, who tend to be left hemisphere dominant (Levy, 1972Go; McGlone, 1977Go; Inglis and Lawson, 1981Go; Hampson and Kimura, 1992Go; Kulynych et al., 1994Go; Kimura, 1999Go). This idea is supported by fMRI and PET studies. However, the evidence from imaging showed differences primarily in anterior language areas (mainly the inferior frontal gyrus) during limited events such as phonological matching (Shaywitz et al., 1995Go; Pugh et al., 1996Go) and past-tense generation (Jaeger et al., 1998Go). Our study shows that males also have strong asymmetry in posterior language areas, primarily the superior and middle temporal gyri, whereas females do not.

Methodological Considerations

Several methodological factors in our study design were important in identifying sex differences in the posterior language areas. First, we avoided non-semantic tasks (Shaywitz et al., 1995Go; Pugh et al., 1996Go) and a semantic judgement task of words (Frost et al., 1999Go). A previous PET study (Mazoyer et al., 1993Go) suggested that listening to a whole story preferentially activates the posterior language regions. Therefore we required subjects to listen attentively to whole stories. Our result also shows differential activation in the posterior regions (Mazoyer et al., 1993Go) when comparing activation during stories to no sound (experiment 1); in male subjects activation was found in the left MTG and the bilateral STG. Even when we simply compared activation during stories to no sound (experiment 1) we were able to detect male-specific left dominant activation in the MTG by measuring the volume of activation in individual subjects (individual analysis), although the sex difference was not detected in the group analysis under this condition.

Second, the selection of the control stimuli was important. Significant sex differences in lateralization were revealed in both the individual and group analyses, when we used a reverse presentation of the narrative as the control stimuli (experiment 2). Since the sound stimuli under the forward and reverse conditions were identical in volume and frequency distribution, the observed differences are most likely attributable to the processing of language, not processing of auditory signals in general. To study whether the processing of global structures in the narrative, such as sentences, was responsible for inducing the sex differences, or whether the processing of local structures, such as a train of words, was sufficient, we used permuted stimuli that maintained local, but not global, structure for up to 1 s. When we did this, differential activation was found bilaterally in both sexes (experiment 3). Taking the results of these experiments together (experiments 2 and 3), we conclude that sex differences in these posterior cortical areas are probably attributable to the processing of more global structures, such as sentences, not to the processing of local structure.

Finally, the use of a 3 T machine, through its relatively high signal-to-noise ratio (Gati et al., 1997Go), probably played an important role in detection of sex differences, when present.

Cortical Areas with Lateralization in Both Sexes

Significant lateralization was found in both sexes in the temporo- parietal cortex (experiments 1 and 2). This is an interesting finding, given the possibility that the temporoparietal cortex may be involved in phonological processing of word forms (Petersen et al., 1988Go, 1989Go), and that hemispheric specialization arises from interhemispheric conduction delay (Ringo et al., 1994Go). Ringo et al. suggested that processing of phonemes is most likely to be lateralized to one hemisphere, because inter- hemispheric communication leaves little time for the auditory analysis of phonemes. Subjects can understand speech at a presentation rate of ~30 ms per phoneme, while the average myelinated fiber would have a one-way interhemispheric delay of 25 ms. Phonological processing must therefore be localized within a single hemisphere, because an interhemispheric delay of that magnitude (25 ms) would be confusing when processing phonemes that arrive every 30 ms. Our observation of lateralized activation in the TPC in both sexes agrees well with this conjecture, as well as with the suggested role of the temporoparietal cortex in phonological processing (Petersen et al., 1988Go, 1989Go).

Cortical Areas with Sex Differences in Lateralization

Sex differences in language lateralization were most apparent in the temporal lobe. Females showed no significant lateralization in any of the three temporal gyri, but males showed significant left hemisphere lateralization in the STG and MTG. It is probable that sentence processing is one of the main functions of these cortical areas, because the left MTG in males was activated only by meaningful stories, not by word lists, sentences with pseudo-words or semantically anomalous sentences (Mazoyer et al., 1993Go). Because the sex differences disappeared when global structures were removed from auditory stimuli (experiment 3), and because a recent extensive fMRI study (Frost et al., 1999Go) using a semantic judgement task of words failed to detect substantive sex differences, we suggest that sex differences only become apparent when the subjects are required to process the global structures of sentences.

According to Ringo's conjecture (Ringo et al., 1994Go), these observed sex differences in lateralization might reflect sex differences in the interhemispheric communication between the posterior language areas, and thus might reflect sex differences in the commissural fibers connecting the posterior language areas. In fact, the isthmus of the corpus callosum, which contains commissural fibers connecting the posterior language areas (de Lacoste et al., 1985Go), is larger in females relative to the total area of the corpus callosum (Witelson, 1989Go; Steinmetz et al., 1992) and the forebrain volume (Steinmetz et al., 1995Go, 1996Go; Jäncke et al., 1997Go). It is possible that the relatively larger isthmus promotes more efficient communication between the hemispheres, allowing females to represent higher and less time-critical functions, such as processing sentences bilaterally.

Male-specific lateralization was also found in the anterior language area, the inferior frontal gyrus, in experiment 2 (Table 2Go). The male-specific lateralization in the inferior frontal gyrus agrees with previous imaging studies (Shaywitz et al., 1995Go; Pugh et al., 1996Go; Jaeger et al., 1998Go) that reported bilateral activation of the inferior frontal gyrus in females and lateralized activation in males.

Implications for the Function of the Right Hemisphere in Language Processing

When listening to stories, males showed activation strongly lateralized to the left temporal gyri and temporoparietal cortex (experiment 2). However, when listening to permuted story fragments lacking global structure (experiment 3), the activation in these two areas was no longer lateralized. The subjects were forced to infer the content of sound stimuli from the fragments of words and sentences that appeared in random order (experiment 3). Therefore, nonsyntactic integration mechanisms might have been fully activated under these conditions. This increased right hemisphere activation (experiment 3) is consistent with the recent idea that the right hemisphere is more involved in nonsyntactic integration mechanisms than in the syntactic mechanisms of language processes (Beeman and Chiarello, 1998Go).

The increased activation in the right hemisphere was found to be significant only in males, not in females, further suggesting that the function of the right hemisphere in language processing is sex-dependent. This point must be considered when examining the function of the right hemisphere in language processing, a topic of intense debate (Caplan et al., 1996Go; Hickok et al., 1996Go; Bavelier et al., 1998Go; Beeman and Chiarello, 1998Go; Paulesu and Mehler, 1998Go).


    Notes
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Notes
 References
 
This study was performed with the aid of special coordination funds for promoting science and technology from the Science and Technology Agency of the Japanese Government to S.K. We would like to express our appreciation to Drs B.J. Richmond, K. Kawano, F.A. Miles, T. Oishi, Y. Otsu and M. Sugishita for their critical and helpful comments in preparing this manuscript. We would also like to thank Drs T. Iijima, T. Takahashi, R. Xiao, N. Sadato, H. Yamada and Y. Sugase, and Messrs T. Hara and T. Tsukamoto for their help, and Dr Y. Nakajima for his encouragement.

Address correspondence to Shigeru Kitazawa, Neuroscience Section, Information Science Division, Electrotechnical Laboratory, 1-1-4 Umezono, Tsukuba 305-8568, Japan. Email: kitazawa{at}etl.go.jp.


    References
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Notes
 References
 
Bavelier D, Corina DP, Neville HJ (1998) Brain and language: a perspective from sign language. Neuron 21:275–278.[ISI][Medline]

Beeman M, Chiarello C (1998) Right hemisphere language comprehension. Mahwah, NJ: Erlbaum.

Binder JR, Frost JA, Hammeke TA, Rao SM, Cox RW (1996) Function of the left planum temporale in auditory and linguistic processing. Brain 119:1239–1247.[Abstract]

Caplan D, Hildebrandt N, Makris N (1996) Location of lesions in stroke patients with deficits in syntactic processing in sentence comprehension. Brain 119:933–949.[Abstract]

de Lacoste MC, Kirkpatrick JB, Ross ED (1985) Topography of the human corpus callosum. J Neuropathol Exp Neurol 44:578–591.[ISI][Medline]

Damasio AR (1992) Aphasia. N Engl J Med 326:531–539.[ISI][Medline]

Friston KJ, Holmes AP, Worsley KJ, Poline JB, Frith CD, Franckowiak RSJ (1995) Statistical parametric maps in functional imaging: a general linear approach. Human Brain Map 2:189–210.

Frost JA, Binder JR, Springer JA, Hammeke TA, Bellgowan PSF, Rao SM, Cox RW (1999) Language processing is strongly left lateralized in both sexes. Evidence from functional MRI. Brain 122:199–208.[Abstract/Free Full Text]

Gati JS, Menon RS, Ugurbil K, Rutt BK (1997) experimental determination of the BOLD field strength dependence in vessels and tissue. Magn Reson Med 38:296–302.[ISI][Medline]

Hampson E, Kimura D (1992) Sex differences and hormonal influences on cognitive function in humans. In: Behavioral endocrinology (Becker J, Breedlove S, Crews D, eds), pp. 357–398. Cambridge, MA: MIT Press.

Hickok G, Bellugi U, Klima E S (1996) The neurobiology of sign language and its implications for the neural basis of language. Nature 381: 699–702.[ISI][Medline]

Inglis J, Lawson JS (1981) Sex differences in the effects of unilateral brain damage on intelligence. Science 212:693–695.[ISI][Medline]

Jäncke L, Jochen FS, Gottfried S, Yanxiong H, Helmuth S (1997) The relationship between corpus callosum size and forebrain volume. Cereb Cortex 7:48–56.[Abstract]

Jaeger JJ, Lockwood AH, Van Valin RD, Kemmerer DL, Murphy BW, Wack DS (1998) Sex differences in brain regions activated by grammatical and reading tasks. NeuroReport 9:2803–2807.[ISI][Medline]

Kansaku K, Kitazawa S, Kawano K (1998) Sequential hemodynamic activation of motor areas and the draining veins during finger movements revealed by cross-correlation between signals from fMRI. NeuroReport 9:1969–1974.[ISI][Medline]

Kimura D (1999) Sex and cognition. London: MIT Press.

Kulynych JJ, Vladar K, Jones DW, Weinberger DR (1994) Gender differences in the normal lateralization of the supratemporal cortex: MRI surface-rendering morphometry of Heschl's gyrus and the planum temporale. Cereb Cortex 4:107–118.[Abstract]

Levy J (1972) Lateral specialization of the human brain: behavioral manifestations and possible evolutionary basis. In: The biology of behavior (Kiger J, ed.), pp. 159–180. Corvallis, OR: Oregon State University.

Mazoyer BM, Tzourio N, Frank V, Syrota A, Murayama N, Levrier O, Salamon G, Dehaene S, Cohen L, Mehler J (1993) The cortical representation of speech. J Cogn Neurosci 5:467–479.[ISI]

McGlone J (1977) Sex differences in the cerebral organization of verbal functions in patients with unilateral brain lesions. Brain 100:775–793.[ISI][Medline]

Ogawa S, Menon RS, Tank DW, Kim SG, Merkle H, Ellermann JM, Ugurbil K (1993) Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. Biophys J 64:803–812.[Abstract]

Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh Inventory. Neuropsychologia 9:97–113.[ISI][Medline]

Paulesu E, Mehler J (1998) Right on in sign language. Nature 392: 233–234.[ISI][Medline]

Petersen SE, Fox PT, Posner MI, Mintum M, Raichle ME (1988) Positron emission tomographic studies of the cortical anatomy of single-word processing. Nature 331:585–589.[ISI][Medline]

Petersen SE, Fox PT, Posner MI, Mintum M, Raichle ME (1989) Positron emission tomographic studies of the processing of single words. J Cogn Neurosci 1:153–170.

Pugh KR, Shaywitz BA, Shaywitz SE, Constable RT, Skudlarski P, Fulbright RK, Bronen RA, Shankweiler DP, Katz L, Fletcher JM, Gore JC (1996) Cerebral organization of component processes in reading. Brain 119:1221–1238.[Abstract]

Ringo JL, Doty RW, Demeter S, Simard PY (1994) Time is of the essence: a conjecture that hemispheric specialization arises from interhemi- spheric conduction delay. Cereb Cortex 4:331–343.[Abstract]

Shaywitz BA, Shaywitz SE, Pugh KR, Constable RT, Skudlarski P, Fulbright RK, Bronen RA, Fletcher JM, Shankweiler DP, Katz L, Gore JC (1995) Sex differences in the functional organization of the brain for language. Nature 373:607–609.[ISI][Medline]

Spielman DM, Adalsteinsson E, Lim KO (1998) Quantitative assessment of improved homogeneity using higher-order shims for spectroscopic imaging of the brain. Magn Reson Med 40:376–382.[ISI][Medline]

Steinmetz H, Jäncke L, Kleinschmidt A, Schlaug G, Volkmann J, Huang Y (1992) Sex but no hand difference in the isthmus of the corpus callosum. Neurology 42:749–752.[Abstract]

Steinmetz H, Staiger JF, Schlaug SG, Huang Y, Jäncke L (1995) Corpus callosum and brain volume in women and men. NeuroReport 6: 1002–1004.[ISI][Medline]

Steinmetz H, Staiger JF, Schlaug SG, Huang Y, Jäncke L (1996) Inverse relationship between brain size and callosal connectivity. Natur- wissenschaften 83:221.

Talairach J, Tournoux P (1988) Coplanar stereotaxic atlas of the human brain: 3-dimensional proportional system: an approach to cerebral imaging. New York: Thieme.

Witelson SF (1989) Hand and sex differences in the isthmus and genu of the human corpus callosum. A postmortem morphological study. Brain 112:799–835.[Abstract]