Journal of Neurolinguistics 16 (2003) 407–416 www.elsevier.com/locate/jneuroling
Functional magnetic resonance imaging (fMRI) during a language comprehension task I.A. Malogiannisa, C. Valakib, N. Smyrnisa,*, M. Papathanasioud, I. Evdokimidisc, P. Barase, A. Mantasc, D. Kelekisd, G.N. Christodouloua a
Department of Psychiatry, National University of Athens, Medical School, Aeginition Hospital, 72 Vas. Sofias Ave., Athens GR-11528, Greece b Cognitive Science Laboratory, Department of Methodology History and Theory of Science, National University of Athens, Panepistimioupolis, Zografou, Athens, Greece c Department of Neurology, National University of Athens, Medical School, Aeginition Hospital, 72 Vas. Sofias Ave., Athens GR-11528, Greece d nd 2 Laboratory of Radiology, National University of Athens, Medical School, Sismanoglio General Hospital, 1 Sismanogliou St., Marousi 15126, Athens, Greece e Philips Medical Systems, 14 Sarantaporou and Metonos, Holargos, Athens, Greece
Abstract Previous magnetoencephalography (MEG) studies in healthy right-handed subjects have shown activation in the left posterior lateral aspect of temporal lobe accompanied by sources in the supramarginal gyrus (Broadmann areas 21,22) during language comprehension tasks. We used the method of functional magnetic resonance imaging to determine whether a similar comprehension task in which participants had to discriminate between feminine and neuter abstract nouns elicited activation in the same regions of the temporal lobes. A baseline condition was also used that required participants to discriminate between two different pitch tones. All six subjects showed significant activity in left superior and middle temporal gyrus (Broadmann areas 21,22) and five of them showed maximum activation in this area. Our results are in agreement with those of the MEG studies, demonstrating the concordance of the two methods and the validity of this task. q 2003 Elsevier Science Ltd. All rights reserved. Keywords: functional magnetic resonance imaging; MEG; Language comprehension; Language lateralization
* Corresponding author. Tel.: þ 30-210-7293244-5. E-mail address:
[email protected] (N. Smyrnis). 0911-6044/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0911-6044(03)00024-1
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1. Introduction Higher cognitive activity, such as reading and listening comprehension, is mediated by cerebral mechanisms specific to each task. For years, studies had to rely on evidence from neurological disorders, brain damage (Rasmussen & Milner, 1977), and more recently on stimulation performed during surgery, in view of accomplishing two different goals: establishing hemisphere dominance (lateralization), and localizing the anatomical structures that support language functions within the language dominant hemisphere (localization). One commonly used lateralization technique is the intracarodid amobarbital test (Wada test), which measures the relative contribution of the two hemispheres to language and memory functions across the two hemispheres (Loring et al., 1990; Wada & Rasmussen, 1960; Woods, Dodrill, & Ojemann, 1988). Although the Wada test is currently used to determine hemispheric dominance for language, it has several important limitations. It is an invasive procedure with reported complications between 3 and 5% (Dion, Gates, Fox, Barnett, & Blom, 1987; Rausch et al., 1993). Many patients find the paralysis and speech arrest induced by the procedure to be distressing (Desmond et al., 1995). Moreover, it provides information only about lateralization of language mechanisms, not about their precise location. Another technique, which is often used for localization of the cortical areas involved in language processing, is extraoperative (using subdural grids) (Lesser, Gordon, & Uematsu, 1994), or intraoperative (Luders et al., 1986; Ojemann, 1983, 1993) cortical electrical stimulation mapping. This is also an invasive method, carrying significant risk and requiring an awake and cooperative patient. The development of functional neuroimaging techniques have brought radical change by allowing direct observation of brain processes. Localization of cortical functions in patients who are about to undergo brain surgery, such as patients with tumors, arteriovenous malformations and epilepsy, is of great importance in order to avoid resection of eloquent cortex. Localization of language areas pre-operatively is particularly important for epilepsy patients, who have a higher incidence of atypical cortical language representation than do healthy individuals (Papanicolaou et al., 1999; Simos et al., 1999), and patients with slow growing lesions, which can result in intra-hemispheric reorganization. Moreover, the development of functional imaging techniques for measuring brain activation offers the possibility of a non-invasive alternative to the Wada test and cortical electrical stimulation mapping. Several positron emission tomography (PET) (Demonet et al., 1992; Demonet, Price, Wise, & Frackowiak, 1994; Petersen, Fox, Posner, Mintum, & Raichle, 1988; Price et al., 1996; Zatorre, Evans, Meyer, & Gjedde, 1992), functional magnetic resonance imaging (fMRI) (Binder et al., 1995, 1997; Cuenod et al., 1995; McCarthy, Blamire, Rothmn, Gruetter, & Shulman, 1993) and magnetoencephalography (MEG) (Papanicolaou et al., 1999; Simos, Breier, Zouridakis, & Papanicalaou, 1998) studies have investigated language lateralization and localization in healthy subjects. Recently MEG studies have also been conducted, where the resulting maps have been compared with Wada test (Breier et al., 1999) and cortical electrical stimulation mapping (Papanicolaou et al., 1999; Simos et al., 1999). In these studies a nearly perfect concordance between MEG and the Wada test, and cortical electrical stimulation mapping of receptive language-specific brain areas was found.
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More specifically, MEG normative studies during an aural language comprehension task involving the presentation of single words resulted in detection of sources of early components of the auditory evoked fields in the floor of the sylvian fissure bilaterally (primary auditory– sensory cortex) and the sources of the late components of the evoked fields in the posterior portion of the left superior and middle temporal gyrus (STG and MdTG, respectively). In addition, activation of the hippocampus was observed, predominantly in the left hemisphere (Papanicolaou et al., 1999; Simos et al., 1998).. These MEG studies were conducted using a language comprehension protocol, the results of which, as mentioned before, were validated through intra-operative stimulation. In addition to this protocol, several others, such as semantic categorization (Castillo et al., 2001), were used. Regardless of the different protocols used, these MEG studies have resulted in a similar pattern of brain activation for language comprehension, that is, a pattern that includes activation of STG, MTG and the medial temporal lobe (MTL). In the fMRI literature, different protocols have resulted in slightly different profiles of activation for language comprehension. Some fMRI results have been compared to the standard Wada test and cortical electrical stimulation in neurological patients (Brockway, 2000; Worthington et al., 1997). Some studies predict that fMRI tasks will replace Wada testing for language lateralization while giving additional localization information (Brockway, 2000). Other preliminary results mention poor concordance between intracarotid amytal testing and fMRI language testing (Worthington et al., 1997). A direct comparison of fMRI-derived auditory language comprehension maps with cortical stimulation (Schlosser, Luby, Spencer, Awad, & McCarthy, 1999) led to the conclusion that the spatial extent of the activation produced by fMRI and the spatial extent of stimulation-induced language disruption that was caused by direct cortical stimulation do not always correspond. A review of the fMRI literature shows a variety of results, some of which are less consistent with the patterns of activation traditionally related to the auditory processing of linguistic stimuli. For instance, activated cortical regions, revealed with fMRI, during presentation of simple speech stimuli included the lateral aspect of both temporal lobes, and in all subjects, bilateral superior temporal lobe (STL) signal increases. The response was nearly identical in right and left hemispheres (Binder et al., 1994). According to Creutzfeldt, Ojemann, and Lettich (1989), activation of STG during listening to language differs according to phonemic aspects, segmentation or the length of spoken words. Brain regions along the upper bank of the left and right superior temporal sulcus (STS) showed greater activity when subjects listened to vocal (speech or nonspeech) sounds, as opposed to non-vocal sounds (Belin, Zattore, Lafaille, Ahad, & Pike, 2000). During dichotic listening tasks, hemodynamic responses in the planum temporale (PT) and posterior STS were strongly left-lateralized, reflecting the specialization of these brain regions for language processing (Jancke, Buchanan, & Shah, 2001). Two different response patterns were found in multiple auditory areas and language-related areas (Hashimoto, Homae, Nakajima, & Miyashita, 2000). Less consistent with classical models, brain areas were found to be active in the left temporoparietal region outside the traditional Wernicke’s area and extensive left prefrontal regions outside Broca’s area, during phonetic and semantic analysis tasks of aurally presented words (Binder et al., 1997). Some studies show that while the left and right STG regions may be differentially
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involved in processing pragmatic and lexico-semantic information, the left inferior gyrus and the fusiform gyrus is involved in processing all three types of linguistic information (Kuperberg et al., 2000). Considering two auditory tasks (one semantic and one nonsemantic), the data averaged across subjects did not show obligatory activation of left inferior frontal and temporal language areas during non-semantic word tasks (Chee, O’Craven, Bergida, Rosen, & Savoy, 1999). Given the partial inconsistencies found in the fMRI results summarized above, as well as the fact that a correspondence between fMRI and intra-operative localization of the language-sensitive cortex is not yet clearly established (see also Rutten, Ramsey, van Rijen, Noordmans, & van Veelan, 2002), and given the validity of MEG language comprehension mapping, repeatedly verified through intra-operative stimulation, it appears that the MEG data are more trustworthy. Therefore, we undertook this fMRI study to determine whether we would obtain the same activation pattern as MEG, as long as our activation task required, as it did, word comprehension, no matter how the comprehended words might have been further processed.
2. Methods 2.1. Subjects Six right handed healthy subjects (four male, two female) with a mean age of 30.66 years (range, 25 – 38) participated. All subjects gave informed consent for their participation. The study protocol was approved by the Aeginition Hospital Ethics committee. 2.2. fMRI image acquisition Neural activity was indexed by monitoring Blood Oxygenation Level Dependent (BOLD) signal changes with fMRI. Imaging was performed on a 1.5 Tesla scanner (Gyroscan MT-Intera 1.5T Philips Medical System, The Netherlands). T2-weighted images (TE 50 ms, TR 3 s, 64 £ 64 matrix, voxel size 3.59 £ 3.59 £ 4, FOV 3.70) were collected using single shot echoplanar imaging (EPI). Twenty-four sagittal 4 mm slices were acquired with 12 contiguous slices in each hemisphere, covering the whole brain. A series of 128 consecutive images were acquired simultaneously at each slice location. 2.3. fMRI activation task In this Greek language task, subjects had to discriminate between feminine and neuter abstract nouns. The activation task was alternated with a baseline condition where subjects had to discriminate between two different pitch tones. Stimuli were digitally recorded, and pure tones and words were presented with a PC computer. Each series of 128 images consisted of eight periods of linguistic activation during which subjects performed the gender discrimination task, alternating with eight periods of the baseline tone decision
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task. Each activation period lasted 24 s (48 s/cycle, 16 images per cycle, eight cycles), starting with the baseline condition. In the word comprehension task, subjects heard Greek abstract nouns that were either feminine or neuter and were instructed to lift their right index finger each time they heard a feminine noun. In the tone task, subjects heard a sequence of pure tones having a frequency of either 500 or 750 Hz and were instructed to lift their right index finger each time they heard the high pitch tone. The two tasks were matched for average stimulus intensity (100 Db SPL), stimulus duration (0.75 s), trial duration (3 s) and frequency of positive targets (one target every 8 s). All the subjects were given instructions and a brief practice before entering the scanner. 2.4. fMRI data analysis Images were analyzed with SPM 99 software (Wellcome Department of Neurology, UK). Scans were realigned to each other, in order to reduce the effects of head movement and then were normalized by transformation into the standard stereotactic coordinate system of Talairach and Tournoux (1988). The realigned and normalized images were smoothed by a 6 mm isotropic full-width, half-maximum Gaussian filter. Activation taskrelated effects (activation versus control) were investigated voxel by voxel for each subject to create statistical parametric t-maps and subsequently transformed into maps of z-scores. The threshold for significant activation differences at the level of individual voxels was at p , 0:05; corrected for multiple comparisons. Minimum cluster size was defined as five or more contiguous, in-plane significant voxels. For each activated region, the cluster with the greatest size is presented in Table 2. The coordinates for the local maxima (4 mm
Table 1 Activated regions Temporal
Left
Right
Frontal
Left
Right
MdTG (21) MdTG (22) MdTG (20) STG (22) STG (21) STG (38) STG (41) ITG (20) ITG (21)
1, 2, 3, 4, 5, 6 1, 5 4 1, 5 3 2
1, 2, 3, 4, 5, 6 5
MdFG (9) MdFG (46) MdFG (6) IFG (47) IFG (9) IFG (45) IFG (46) SFG (6) SFG (8) SFG (9)
1, 3, 6 1 5 2, 3, 5, 6 1, 2, 3 2, 3 4 2, 5 2
5 3
4
5 2 5 3 5
2, 5
5 2 5
Activated regions in left and right hemisphere in temporal and frontal cortex (Brodmann’s areas are in parentheses) for every subject (subject codes 1– 6). LMdTG and RMdTG: left and right middle temporal gyrus; LSTG and RSTG: left and right superior temporal gyrus; LITG and RITG: left and right inferior temporal gyrus; LMdFG and RMdFG: left and right middle frontal gyrus; LIFG and RIFG: left and right inferior frontal gyrus; LSFG and RSFG: left and right superior frontal gyrus.
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apart) of each cluster are also presented in the same table. The maximum focus of activation for each subject is defined as the cluster with the largest number of activated voxels for this subject.
3. Results and discussion Table 1 shows the activated regions in left and right hemisphere in temporal and frontal cortex (Brodmann’s areas are in parentheses) for every subject (subject codes 1 – 6). It can be seen that all subjects activated the left MdTG, Brodmann area 21. In Fig. 1 activated regions are presented for each subject on a glass brain and superimposed on a T1 Template (SPM 99, Wellcome Department of Neurology, UK). The arrows indicate the maximum activated region. The maximum focus of activity was in the left MdTG for five of the six subjects. Only subject 5 had a different pattern with maximum activation in the right MdTG. Table 2 presents the Talairach and Tournoux (1988) coordinates of the maximally activated voxel for every subject and the brain regions to which these coordinates correspond, the Z-statistic for this voxel, the number of voxels that belong in the same cluster (Kc), and the corrected probablility for this cluster. It was observed that for five subjects a highly significant activation was found in the left temporal cortex (area 21). In subject 5 the maximally activated voxel was in the right temporal cortex (area 21), although this subject also exhibited a significantly activated region in the corresponding left temporal cortex. Some of the previous fMRI studies, mentioned in Section 1 above, that have used a language comprehension task similar to ours have found left hemisphere activation in the posterior-STS and middle temporal gyrus (Brodmann area 21/22), in the inferior and middle frontal gyri (Brodmann areas 9 and 44 –46), and the superior frontal gyrus. They also found smaller and less intense foci of activity in similar temporal and frontal regions of the right hemisphere (Binder et al., 1995, 1996). The activation patterns found in our study are thus consistent with those of previous studies. Our results also indicate that this fMRI study of speech comprehension has replicated the main findings of previous MEG studies (Papanicolaou et al., 1999; Simos et al., 1999). All of the subjects in our study showed activation of the left middle temporal gyrus (LMdTG-Brodmann area 21). For five of the six subjects, activation was found in the left temporal cortex (Broadmann 21). Only subject five displayed greater activation in right temporal cortex (Broadmann 21), but he also exhibited significant activation in the corresponding left temporal cortex. The left and right middle temporal gyrus (Broadmann areas 22 and part of 21) constitute part of the secondary auditory cortex. According to Luria (1973a,b) these areas play an essential part in distinguishing among simultaneously presented auditory stimuli, as well as the successive combinations of sounds with different pitch and rhythm. In subjects 1, 2, 3 and 5 activation was found in left and right STG (Broadmann areas 22,21 and 38). Previous MEG studies that made use of cortical electrical stimulation tests (arrest of repetition) concluded that this area is involved in the phonological processing of spoken (and written) stimuli. Left posterior STG seems
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Fig. 1. Activation regions are presented for each subject (S1–S6) on a glass brain and superimposed on a T1 Template (SPM 99, Wellcome Department of Neurology, UK). The arrows indicate the maximum activated region. The maximum focus of activity was in the LMdTG for five of the six subjects. Only subject 5 (S5) had a different pattern with maximum activation in the RMdTG.
to be an important component of the mechanism involved in assembled phonology, and neuroimaging studies performed on dyslexic readers report a lack of activation of this area during tasks that require phonological assembly operations. Our results are in agreement with the MEG studies that relate posterior STG to phonological processing (Simos et al., 2002).
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Table 2 Statistics for maximally activated region Subject
Kc
p corrected
Z
x; y; z
Activated regions)
1 2 3 4 5 6
299 217 212 394 187 60
,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001
Infinite Infinite Infinite Infinite Infinite 7.51
262, 224, 22 262, 22, 210 256, 214, 210 256, 226, 210 70, 224, 26 268, 226, 22
LMdTG (21) LMdTG (21) LMdTG (21) LMdTG (21) RMdTG (21) LMdTG (21)
Talairach and Tournoux (1988) coordinates of the maximally activated voxel for every subject and the brain regions that these coordinates correspond to, the Z-statistic for this voxel, the number of voxels that belong in the same cluster (Kc), and the p-value, corrected for this cluster.
In two subjects activation was also observed in right inferior temporal gyrus (RITG), and in one subject in the left inferior temporal gyrus (LITG). With the exception of subject 4, activation was also observed in the middle frontal gyrus (Broadmann 6, 9, 46). Only two subjects had activation in the superior frontal gyrus. As mentioned in Section 1, we expected that this fMRI experiment would show the same activation patterns as those elicited by MEG protocols that have been validated through comparison with the results of direct cortical stimulation mapping procedures, as long as the activation task required word comprehension, no matter how the comprehended words might be further processed. Compared to those protocols, we chose different stimuli and a different language comprehension task (gender discrimination) in a different language (Greek), in order to test their generality. In spite of these procedural differences, the pattern of our results summarized above matches closely with those obtained in the previously validated MEG studies. Consequently, we conclude that as long as the same cortical language comprehension circuits are engaged, the same patterns of activation emerge in spite of differences in specific stimuli, procedural details or even the type of functional imaging method used.
Acknowledgements This study was supported by National University of Athens internal funding. We would like to thank Prof. A. Papanicolaou for providing us with the study protocol.
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