Cerebral Mechanisms Involved in Word Reading in Dyslexic Children: a Magnetic Source Imaging Approach

P.G. Simos, J.I. Breier, J.M. Fletcher1, E. Bergman2 and A.C. Papanicolaou

Vivian L. Smith Center for Neurologic Research, Department of Neurosurgery and , 1 Pediatrics, The University of Texas — Houston Medical School and , 2 Texas Reading Institute, Houston, TX, USA


    Abstract
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Notes
 References
 
The purpose of the present investigation was to describe spatiotemporal brain activation profiles during word reading using magnetic source imaging (MSI). Ten right-handed dyslexic children with severe phonological decoding problems and eight age-matched non-impaired readers were tested in two recognition tasks, one involving spoken and the other printed words. Dyslexic children's activation profiles during the printed word recognition task consistently featured activation of the left basal temporal cortices followed by activation of the right temporoparietal areas (including the angular gyrus). Non-impaired readers showed predominant activation of left basal followed by left temporoparietal activation. In addition, we were able to rule out the hypothesis that hypoactivation of left temporoparietal areas in dyslexics was due to a more general cerebral dysfunction in these areas. Rather, it seems likely that reading difficulties in developmental dyslexia are associated with an aberrant pattern of functional connectivity between brain areas normally involved in reading, namely ventral visual association cortex and temporoparietal areas in the left hemisphere. The interindividual consistency of activation profiles characteristic of children with dyslexia underlines the potential utility of this technique for examining neurophysiological changes in response to specific educational intervention approaches.


    Introduction
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Notes
 References
 
Developmental reading disability (dyslexia) affects a significant proportion of otherwise normal children. It is believed that the core deficit in dyslexia is in the operation of a decoding process that performs grapheme to phoneme conversions at a sublexical level, known as phonological assembly (Coltheart et al., 1993Go). Although phonological analysis is by definition required for reading aloud and for performing phonological similarity judgements on pseudowords (such as DOFE and HOAF), it is also believed to be critically involved in silent reading of real words by skilled readers (Seidenberg and McClelland, 1989Go; Seidenberg et al., 1994Go; Van Orden, 1987Go).

Functional imaging methods are uniquely suited to provide information regarding the brain mechanisms that support the cognitive processes, such as word recognition and phonological decoding, which, in turn, make reading possible. This undertaking has two essential requirements: first, researchers must identify the anatomical regions that as components of the mechanism of reading show increased levels of neurophysiological activity when individuals perform this function, i.e. when they read; second, researchers must also describe functional connections between these regions in order to learn more about the specific role of each area in the mechanism of reading. Although several methods can be used in search of information of the former type, information of the latter type has been elusive.

In search of brain areas involved in reading, modern ‘functional’ imaging methods examine task-related changes in cerebral activation as indices of regional cortical engagement. Although not specific to reading, these studies suggest that the activation profile associated with this function involves the superior and middle temporal gyri, inferior parietal areas (angular and supramarginal gyri) (Price et al., 1994Go; Pugh et al., 1996Go; Rumsey et al., 1997), certain visual association areas and possibly also the left inferior frontal gyrus (Pugh et al., 1996Go). There is evidence of reduced activation of these areas during reading in adults with dyslexia (Rumsey et al., 1992Go; Eden and Zeffiro, 1998Go; Shaywitz et al., 1998Go; Pugh et al., 2000aGo). These studies, however, rely on measures of blood flow/metabolism, which can serve as indirect indices of regional neurophysiological activity. In addition, these measures are primarily capable of providing profiles of relative activation (i.e. activation in task A in comparison with task B). Such profiles are meaningful on a group basis but may not capture the details of individual neuronal activity profiles.

Systematic empirical investigations of the validity and reliability of individual brain activation profiles are rare. In our research we have used magnetoencephalography, otherwise known as magnetic source imaging (MSI), to investigate the role of cortical areas in language functions. We have established the concurrent validity of MSI protocols through extensive clinical studies, where MSI data were compared directly with the results of invasive functional mapping techniques, including the Wada procedure and electrical stimulation mapping (Breier et al., 1999aGo; Papanicolaou et al., 1999Go; Simos et al., 1999aGo,bGo). MSI is unique among other functional imaging techniques for its ability to provide spatiotemporal brain activation profiles that reflect not only where activity occurs in the brain but also when this activity occurs in relation to the presentation of an external stimulus. In this way information can be drawn more directly regarding which areas participate in reading and also how these areas might interact with each other, in real time, to enable such complex cognitive functions. The latter type of information is very critical in order to determine functional connections between brain areas that show increased activation in the context of reading tasks in the effort to describe the brain mechanism serving word recognition.

Using MSI, we have described in two studies the spatiotemporal activation profile associated with phonological decoding in neurologically intact adult volunteers without reading problems (Breier et al., 1998Go, 1999bGo). This profile features, initially, bilateral activation of occipital regions, followed by left basal temporal activation, which is in turn followed by activation in left posterior temporal and inferior parietal (i.e. temporoparietal) regions. A clear predominance of left over right hemisphere activation of basal temporal and temporoparietal areas was noted consistently across participants. Given the similarity in both degree and timing of activity in basal temporal areas between words and pseudowords (Breier et al., 1998Go, 1999bGo; Helenius et al., 1999Go; Salmelin et al., 1996Go), this activity probably reflects the engagement of neurophysiological processes involved in pre-lexical analysis of print. We have also obtained evidence for an aberrant brain activation profile in dyslexic children associated with phonological decoding of pseudowords (Simos et al., 2000Go). This profile was notable for a virtual lack of activation in left temporoparietal areas coupled with a corresponding increase in activity in homologous right hemisphere regions.

The present study had two main goals: first, to examine if the aberrant activation profile obtained in our previous study with dyslexic children generalizes to real-word reading by using a task that does not make explicit demands for phonological decoding. To achieve this goal we compared the spatiotemporal activation profiles, obtained during a printed-word recognition task from a different group of neurologically intact children with dyslexia, with those of age-matched non-dyslexic children. Given evidence that dyslexics may develop, and rely increasingly upon, alternative reading strategies in order to compensate for their poor phonological decoding skills (Johnston et al., 1991Go; Olson et al., 1985Go), it is important to examine children diagnosed with reading problems rather than adults with a history of dyslexia. Unfortunately, with only few notable exceptions (Richards et al., 2000Go), previous imaging studies on dyslexia sampled the latter population. Second, to determine whether hypoactivation of the left posterior temporal and temporoparietal areas in children with dyslexia is associated with a more general cerebral dysfunction of these areas (Eden and Zeffiro, 1998Go). For this purpose all children enrolled in this study were also tested on an auditory version of the printed-word recognition task which by definition involves phonological analysis of the (spoken) word stimuli. In previous studies we have shown that activity sources obtained in the two tasks colocalize in portions of temporoparietal cortex involved in phonological analysis of both spoken and printed words (Simos et al., 1998aGo, 1999aGo). Given that in non-impaired readers activity maps in these areas are very similar across the two tasks with respect to both the onset (latency) and the degree of regional activation, any deviation from this pattern in the impaired readers might indicate a regional functional deficit that is specific to reading.


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

Ten children (eight males, mean age 12.6, range 10–17 years) who presented with mild to severe reading difficulties and eight non-impaired readers (five males, mean age 12.9, range 8–16 years) were examined. All children had full-scale IQ scores (WISC III) in the normal range (the group mean for impaired readers was 102.2 ± 7.6 and 109.8 ± 9.0 for non-impaired readers). Impaired readers scored below the 30th percentile on the Word Attack subtest of the WJ-R Battery (Woodcock and Johnson, 1989Go), suggesting the presence of a severe impairment in phonological decoding skills. In contrast, all non-impaired readers scored above the 80th percentile on this test. All participants were right-handed, had English as their primary language and had no history of hearing deficit or visual impairment.

MSI Data Acquisition

Each participant was tested on two word recognition tasks, one involving printed and the other spoken words. In each task a different list of 63 words was used with a frequency of occurrence >20 per million in the corpus of second grade-level reading material according to the norms provided by Zeno and associates (Zeno et al., 1995Go). For each task, 33 words from each list were used as targets and the remaining 30 were used as distractors distributed in three blocks. The target stimuli were repeated in a different random order in each block mixed with 10 new distractors. Printed words were presented for 1 s in order to prevent potential contamination of the event-related field record by visual offset responses. The interstimulus interval varied randomly between 3 and 4 s across trials. The order of task presentation and the responding hand used to indicate the detection of a target word were counterbalanced across participants. Printed words were projected through a Sharp LCD projector (Model XG-E690U) on a white screen located ~1.5 m in front of the participant and subtended 1.0–4.0 and 0.5° of horizontal and vertical visual angle, respectively. The spoken word stimuli were produced by a native speaker of English with a flat intonation (duration between 300 and 750 ms; mean 450 ms). Spoken utterances were digitized with a sampling rate of 22 000 Hz and 16-bit resolution, stored on a portable computer that was also used for stimulus presentation and delivered binaurally via two 5-m-long plastic tubes terminating in ear inserts at an intensity of 80 dB SPL at the participant's outer ear.

The principles underlying the MSI method as well as MSI data collection and analysis methods are described in detail elsewhere (Simos et al., 1998aGo,bGo, 1999aGo). In the present study, MSI data were recorded in a magnetically shielded room with a whole-head neuromagnetometer (WH2500, 4D Neuroimaging, San Diego, CA) consisting of 148 magnetometer coils. The precise location of the intracranial sources of the observed evoked fields were computed every 4 ms for a period of 1 s after the onset of the auditory or printed word stimuli using standard algorithms (Sarvas, 1987Go). Reliably localized activity sources [i.e. those passing a 0.90 best-fit correlation criterion; see (Simos et al., 1998aGo,bGo, 1999aGo)] were co-registered on structural magnetic resonance imaging (MRI) scans obtained from each participant and the anatomical location of each source was determined using a standard MRI atlas (Damasio, 1995Go).

The degree (indicated by the number of reliably localized activity sources in a given area) and timing of regional activation (indicated by the earliest latency after stimulus onset at which activity sources were observed in a given area) were analyzed separately. The validity of the former measure as an index of regional activation has been established in several studies involving neurologically intact volunteers and patients (Simos et al., 1998bGo, 1999aGo; Zouridakis et al., 1998Go; Breier et al., 1999aGo; Papanicolaou et al., 1999Go). On the basis of previous MSI studies on reading (Breier et al., 1998Go, 1999bGo; Simos et al., 2000Go), we examined the following areas: the posterior third portion of the superior temporal gyrus (STGp), the posterior third portion of the middle temporal gyrus (MTGp), the supramarginal gyrus (SMG), the angular gyrus (ANG) and the basal temporal cortex (BTC), comprising the fusiform and lingual gyri.


    Results
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Notes
 References
 
To ensure that target words could be read with a high degree of accuracy by children in both groups, each subject was asked to read the target word list aloud prior to the MSI recording session (the exposure duration and rate of presentation of printed words were identical to those used during the actual experiment). Group mean error rates were 4.1 ± 3.2% for the impaired and 2.2 ± 2.2% [t(14.43) = 2.08, P = 0.056) for the non-impaired readers, indicating near-perfect performance by both groups.

Figures 1 and 2GoGo display the locations of clusters of activity sources projected onto the brain surface in the two groups of children during the visual and auditory word recognition tasks, respectively. Note that each circle marks the location of a single cluster in a single subject, preserving information regarding intersubject variability in activation profiles. The most striking pattern that can be discerned by visual inspection of the figures is the near-complete absence of activity sources in the left posterior temporal and temporoparietal region in the group of dyslexic children, and the dense concentration of source clusters in homologous areas in the right hemisphere.



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Figure 1. Summary of the locations of active areas compiled from individual data for the visual word recognition task. Only later sources (after the resolution of modality-specific responses) are presented. Profiles from impaired readers are presented in the top row of images (a lateral view of the right hemisphere is on left side of figure and a view of the left hemisphere is on the right) and in the middle left-hand image (a view of the basal surface of the brain). Corresponding views from the non-impaired readers are shown in the middle right-hand image and in the bottom row of images. All individuals are represented, although some are represented by a greater number of clusters than others. Moreover, each individual showed activity sources in each of the principal areas shown in the figure (i.e. the temporoparietal and basal temporal cortex) and may be represented by more than one cluster in a particular area. Each cluster consists of a variable number of activity sources. Cluster size, in terms of numbers of temporally contiguous activity sources, is reflected in the size of the colored circles. The relative timing of onset of clusters of activity sources is represented along a color continuum that varies from lighter yellow, indicating earlier onset of activity, to darker red, indicating later onset of activity.

 


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Figure 2. Summary of the locations of active areas compiled from individual data for the auditory word recognition task. The layout, timing and amount of activity scales are the same as in Figure 1Go. It appears that impaired readers showed activity in temporoparietal cortices that was greater in degree as well as earlier in onset (after stimulus presentation) than non-impaired readers.

 
Degree of Regional Activation

Two sets of analyses were performed. The first set was conducted in order to test the hypothesis that impaired readers would display little or no activity in the left temporoparietal areas (STGp, MTGp and SMG) during the printed word recognition task but they would show a ‘normal’ pattern of activation in this area during the spoken word version of the task. Data for the ANG and BTC were not included in this analysis because, as expected given the nature of the task (Simos et al., 1998aGo,bGo), activity sources in these areas were not consistently found in all participants during the auditory task. The data were analyzed using a multivariate approach to ANOVA with three withinsubjects variables (task: auditory, visual; area: STGp, MTGp, SMG; and hemisphere: left, right). Group (dyslexic, non-dyslexic) was the between-subjects variable. The Bonferroni method was used for maintaining the family-wise Type I error under 0.05 when pairwise means comparisons were performed.

The analysis did not reveal significant main effects or interactions involving Area (see Fig. 3Go). Collapsing data from all three areas (STGp, MTGp and SMG) did not change the pattern of results, leading to a significant group x task x hemisphere interaction [F(1,16) = 12.79, P < 0.003] that was accounted for by a significant task x hemisphere interaction for the dyslexic group only [F(1,9) = 18.61, P < 0.002].






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Figure 3. Degree of activation in temporal and inferior parietal regions (indicated by the number of activity sources) in the auditory and visual word recognition tasks obtained from the two groups of children. The activity in the basal temporal regions and the angular gyrus was consistently found only during the visual task. Abbreviations: STGp, posterior superior temporal gyrus; MTGp, posterior middle temporal gyrus; SMG, supramarginal gyrus; ANG, angular gyrus; BTC, basal temporal cortex.

 
This pattern was apparent on a case-by-case basis: reliable activity in the left temporoparietal area was found in only one dyslexic child in the visual task (see Fig. 1Go) who, nonetheless, displayed substantially greater activity in the right homologous region. In contrast, all 10 dyslexic children displayed a greater degree of activation in the left compared with the right temporoparietal area during the auditory word recognition task. As is also evident from Figures 1 and 2GoGo, the auditory task was associated with significantly greater activation in the left temporoparietal area than the visual word recognition task in the dyslexic group only [t(9) = 10.89, P < 0.0001].

As a group, dyslexic children showed distinct hemisphere differences in the relative degree of activation in temporoparietal areas across tasks: in the left hemisphere the auditory task was associated with 96.7% more sources than the visual task, whereas the opposite was true in the right hemisphere, with 38.3% more sources in the visual versus the auditory task. These trends were apparent in all impaired readers in the left hemisphere and in 9/10 cases in the right hemisphere. In contrast, non-dyslexic readers displayed a relative increase in the degree of activation in the auditory compared with the visual task in both the left (8.4%) and the right hemisphere (32.5%).

The second set of analyses examined in more detail the activation profile during the visual task in the two groups of children. Since significant effects involving area were not found in the first set of analyses, data from the three temporoparietal (TMP) areas (STGp, SMG and MTGp) were collapsed together. Given the nature of the task (Breier et al., 1998Go, 1999bGo), activity sources were also found in the ANG and BTC in both groups and, therefore, data from both areas were also included in the analyses. An ANOVA with area (TMP, ANG, BTC) and hemisphere as the within-subjects factors and group (dyslexic, nondyslexic) as the between-subjects factor revealed a significant three-way interaction [F(2,32) = 5.87, P < 0.0067]. Again, given that the mean number of activity sources in the ANG was not significantly different from the mean number of sources in the STGp, SMG and MTGp combined, data from all four temporoparietal areas were pooled together (indicated as TMP1). A subsequent ANOVA for area (TMP1 and BTC), hemisphere and group resulted in a significant group x area x hemisphere interaction [F(1,16) = 14.84, P < 0.0014]. Further tests showed a significantly greater degree of activation in the left than in the right TMP1 [t(7) = 3.4, P < 0.011] and BTC [t(7) = 2.8, P < 0.026] in the non-impaired group, and a difference in the opposite direction for TMP1 activation in the impaired group [t(9) = 3.1, P < 0.013] (see Fig. 3Go). In contrast, impaired readers showed greater left over right BTC activation [t(9) = 3.4, P < 0.01].

Temporal Course of Regional Activation

Figure 4Go displays the mean onset of activation in temporal and temporoparietal areas following the presentation of printed word stimuli in the two groups of children. Data from the left temporoparietal region (TMP1, which in this case included areas STGp, MTGp, SMG and ANG) in the dyslexic group and from the right BTC region in both groups are not reported due to insufficient number of observations. In general, basal temporal areas showed activity sources first followed by TMP1 activation. Bonferonni-corrected planned pairwise comparisons examined differences in the onset latency of regional activation within as well as across groups. Consistent with data from previous studies with adult participants (Breier et al., 1998Go, 1999bGo), in nonimpaired readers left BTC areas displayed activity earlier than temporoparietal areas in that hemisphere [t(7) = 3.30, P < 0.013]. In dyslexic children activity in left BTC areas was followed instead by right temporoparietal activation [t(9) = 3.40, P < 0.01]. Interestingly, the onset of activity in the left temporoparietal region was notably delayed with respect to the onset of activity in the homologous right hemisphere region in one dyslexic child (the only one who displayed any activity in left temporoparietal areas). Moreover, the timing of activity in right temporoparietal areas in dyslexic children was comparable to the timing of activity in homologous left hemisphere areas in non-impaired readers (dyslexic children: mean onset = 274 ± 109; non-dyslexic children: mean onset = 347 ± 216, P > 0.05). The onset latencies of left BTC activation were also very similar across groups (dyslexic children: mean onset = 200 ± 86; non-dyslexic children: mean onset = 213 ± 98, P > 0.05). Finally, inspection of Figure 2Go suggests the presence of group differences in the fine details of the spatiotemporal activation profiles obtained in the context of the auditory word recognition task. However, both the nature of the task and the small size of our sample do not permit a detailed examination of such differences.



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Figure 4. Mean onset latency of activation in temporoparietal regions (STGp, MTGp, SMG and ANG) and basal temporal areas (fusiform and lingual gyri) in the two groups of children during the visual task. Data from the right basal temporal areas in both groups and left temporoparietal regions in the dyslexics are not reported due to an insufficient number of observations for group mean estimation. Note that right temporoparietal regions in dyslexic children first became engaged at approximately the same time after stimulus onset as the homologous areas in the left hemisphere in non-dyslexic children. Abbreviations: TMP, temporoparietal areas; BTC, basal temporal cortex.

 

    Discussion
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Notes
 References
 
The present results showed that the spatiotemporal activation profiles of children diagnosed with developmental dyslexia are markedly and consistently different from those obtained from age-matched non-dyslexic children. Brain activation profiles in children with dyslexia during word reading were characterized by: (i) markedly reduced left temporoparietal activation; (ii) markedly increased activation in homologous areas of the right hemisphere starting at approximately the same latency (after the onset of the printed word stimuli) as activity in the left temporo parietal regions in non-dyslexic children; and (iii) activity in ventral visual association cortices (basal temporal cortex) that was very similar in both degree and timing with the activity profile observed in the non-impaired readers. By virtue of the fact that MSI-based profiles of activation reveal both spatial and temporal aspects of brain function, the data presented here afford a closer look at the details of the mechanism that supports reading in children with developmental dyslexia. Whereas in non-impaired readers, this mechanism involves the early engagement of left basal temporal regions followed by engagement of left posterior temporal and temporoparietal areas, in impaired readers this mechanism consists mainly of early left basal temporal activation followed by engagement of right posterior temporal and temporoparietal areas. On the other hand, the activation of left temporoparietal areas during auditory word processing in impaired readers was virtually identical with the activation observed in non-impaired readers. Taken together, the data are consistent with the hypothesis that reading difficulties in developmental dyslexia are associated with an aberrant pattern of functional connections between brain areas normally involved in reading, rather than a general dysfunction of a particular area.

Specifically, the data presented above directly address a number of important questions regarding the pathophysiology of dyslexia. First, which aspect of the mechanism of reading is captured by the distinctly altered activation profiles observed in dyslexic children? Activation profiles of both impaired and nonimpaired readers obtained separately during real word (present study) and pseudoword reading (Simos et al., 2000Go) were very similar in both the degree and the temporal course of regional activation. Reading words or pseudowords involves a number of common processes, including visual-feature, orthographic and phonological analysis. Based on evidence that (i) visual and orthographic analysis depend heavily upon visual association areas (Salmelin et al., 1996Go; Breier et al., 1998Go, 1999bGo; Helenius et al., 1999Go) and that (ii) activation profiles for these areas are similar between impaired and non-impaired readers (present data and Simos et al., 2000), it is reasonable to surmise that neurophysiological processes responsible for the drastically altered activation profiles in dyslexic children are primarily those involved in phonological decoding. This would explain why, in dyslexic children, reading consistently fails to activate posterior temporal and inferior parietal areas that are known to be critically involved in phonological decoding or assembly (Eden and Zeffiro, 1998Go; Shaywitz et al., 1998Go; Pugh et al., 2000aGo). Such profile differences can account for some of the most prominent cognitive deficits displayed by children with reading problems, namely phonological decoding difficulties (Wagner and Torgesen, 1987Go; Stanovich, 1988Go; Liberman et al., 1989Go; Fletcher et al., 1994Go; Lyon, 1995Go; Foorman et al., 1996Go; McBride-Chang, 1996Go).

Secondly, what is the role of individual brain areas in the mechanism of reading in children with dyslexia? The most prominent difference in the activation profiles between impaired and non-impaired readers was the reduced activation in left temporoparietal regions and a corresponding increase in activity in homologous right hemisphere areas in dyslexic children. In contrast, neither degree nor timing of activity in basal temporal areas varied as a function of the presence of reading difficulties. We will examine each area separately below.

Nine out of 10 impaired readers did not show any activation in left temporoparietal areas during word reading, while a tenth subject showed only minimal activation. This finding did not appear to be the result of failure to comply with task requirements, since children from both groups made very few errors in reading the target words aloud. Regions that showed marked hypoactivation included the posterior part of the superior temporal gyrus and the left inferior parietal lobule (angular and supramarginal gyri), which are known to play a crucial role in word recognition and reading (Geschwind, 1965Go; Greenblatt, 1976Go; Price et al., 1994Go; Pugh et al., 1996Go, 2000aGo). Moreover, we were able to rule out the possibility that left posterior temporal/ temporoparietal hypoactivation was due to a general inability to engage this region for encoding word stimuli (Eden et al., 1996Go) since the two groups showed comparable activation profiles during the auditory version of the word recognition task.

The lack of engagement of the left STGp during silent reading in impaired readers is interesting given that this area, which is part of the auditory association cortex, is believed to be critically involved in the phonological analysis of speech as well as in phonological assembly (Eden and Zeffiro, 1998Go; Shaywitz et al., 1998Go; Pugh et al., 2000aGo). This finding can be accounted for in a number of ways, two of which are presented below. One possibility is that this region does not participate at all in complex phonological analysis. This explanation appears unlikely in view of the fact that, on the auditory version of the word recognition task, children with dyslexia displayed strong activation in this region and did not differ significantly from the group of non-impaired readers. A second possibility is that activity in this region is normally coupled with activation in the left ANG, which was also dramatically reduced in the dyslexic compared with non-dyslexic children. Failure to engage the left ANG in tasks that require phonological decoding has recently been reported in imaging studies using functional MRI (fMRI) (Pugh et al., 2000aGo) and positron emission tomography (Horwitz et al., 1998Go), supporting earlier proposals that this area plays a crucial role in the conversion of print to sound (Geschwind, 1965Go; Greenblatt, 1976Go). This latter possibility is consistent with our observation that, in non-impaired readers, the left ANG typically becomes engaged immediately after left basal temporal areas and certainly before the onset of activation in the supramarginal and superior temporal gyri (Breier et al., 1999bGo). This tight temporal coupling of activation between the ventral visual association cortex and the ANG is in close agreement with evidence from lesion data, suggesting a crucial role of functional connections between the two areas in reading (Damasio and Damasio, 1983Go).

There are several indications in the data presented here that argue in favor of the hypothesis that right posterior temporal and temporoparietal areas show increased participation (and not merely increased activation) during reading in dyslexic children. These areas became engaged during reading to a greater extent than what would be expected given the amount of activation present during the auditory version of the task. Moreover, analyses on the timing of activity argue against the hypothesis that dyslexic's activation profiles reflect delayed, yet otherwise normal, word decoding. Specifically, right TMP regions in dyslexics first become active at about the same time (on average) as left TMP areas in the non-impaired readers. Stronger activation in the right posterior temporal and inferior parietal areas found in the impaired readers agrees with at least one previous report (Shaywitz et al., 1998Go).

Also, the degree of engagement of the left basal temporal areas, which are believed to be involved in pre-lexical analysis of print (i.e. early visual and/or orthographic analysis) (Breier et al., 1998Go; 1999bGo; Price et al., 1994Go; Pugh et al., 1996Go), appears to be indistinguishable between the two groups of children. Similarly, there were no significant group differences in the onset of activity in the left basal temporal regions. Although the overall profile of activity in the basal temporal areas does not differentiate between dyslexic and non-impaired readers, a more detailed examination of the engagement of these regions associated with various components of pre-lexical processing of print, such as featureand letter string-specific analysis, may reveal subtle group differences (Helenius et al., 1999Go).

Thirdly, are MSI-based aberrant activation profiles obtained from dyslexic children during reading sufficiently consistent on a case-by-case basis to have any practical application in the management of this disorder? We demonstrated that the features of the brain activation profile in dyslexia described above are extremely consistent across children who display severe phonological decoding difficulties. We have observed these features in all 21 children tested so far in two MSI paradigms. Such a level of intersubject consistency is uncommon in previous functional imaging studies on dyslexia, and may be due, at least in part, to the fact that the present sample consisted of children as opposed to adult readers. There is evidence that dyslexics may gradually resort to alternative strategies, such as visual/orthographic analysis, for word recognition in order to compensate for their difficulties with phonological decoding (Olson et al., 1985Go; Johnston et al., 1991Go). Provided that these strategies may depend on a different set of neurophysiological operations, brain activation profiles in individuals with developmental dyslexia may change with age. The consistency with which this phenomenon was obtained in every dyslexic individual in both studies is striking and clearly underlines a potential use of this technique as a tool for evaluating the effectiveness of educational intervention strategies that specifically target the ‘phonological core’ of developmental reading disability. Such results were not, however, surprising given that compelling evidence to the validity of individual MSI-derived maps of regional activation has been obtained by comparison with standard invasive techniques in large series of consecutive neurosurgical patients (Breier et al., 1999aGo; Papanicolaou et al., 1999Go; Simos et al., 1999aGo,bGo).

Certainly, the small size of the sample warrants some caution in interpreting these results, and we would like to evaluate a much larger sample in order to establish the relationships of the imaging findings with behavioral response data (e.g. error rates) and subject characteristics (e.g. IQ). However, it is also important to recognize that the children in this study were carefully evaluated. As expected, the groups differ in directions that would be expected in a comparison of children with and without dyslexia. However, although the expected difference in IQ scores was noted in the presented sample, all dyslexics have IQ scores in the normal range and the size of the difference is <0.5 standard deviations. This is hardly a comparison of upper and lower tails of the IQ distribution. Moreover, the notion that IQ per se has a significant explanatory weight in studies of dyslexia has been widely questioned either through studies of dyslexics who vary in IQ levels or through predictions of performance based on IQ. In the former, comparisons of dyslexics varying in IQ levels do not produce evidence for differences in cognitive performance, reading levels, hereditability, prognosis or response to treatment. For the latter, IQ scores also do not independently predict cognitive performance or response to treatment (Fletcher et al., 1994Go; Stanovich and Siegel, 1994Go). In fMRI studies, brain activation patterns are not found to vary in dyslexics who differed in IQ (Pugh et al., 2000bGo).

To conclude, the present data corroborate previous MSI findings of pronounced differences in spatiotemporal activation profiles between dyslexic and age-matched non-dyslexic children that are evident on a case-by-case basis. The identity and presumed functional role of the areas that show the most dramatic differences (left posterior superior temporal and inferior parietal cortex) support the view that developmental dyslexia, especially when associated with marked phonological processing difficulties, is linked to a functional deficit in the brain mechanism that supports phonological analysis of print. This deficit presents as a failure to engage left temporoparietal areas which, in normal readers, follows (and is possibly triggered by) activation of the left basal temporal areas. Given that, in children with dyslexia, processing of spoken words in a similar recognition task, results in equally strong activation of these regions compared with the non-impaired readers, our findings suggest that developmental dyslexia is associated with an aberrant pattern of functional connectivity between areas normally involved in reading, namely the basal temporal visual association areas and temporoparietal areas in the left hemisphere. The excellent interindividual consistency of the aberrant profile found in dyslexic children holds promise for a future use of this procedure to examine changes in brain function associated with specific intervention programs. Unfortunately, the auditory recognition task used in this study was not designed to selectively engage neurophysiological operations involved in acoustic and phonological analysis of spoken language, that is, operations which may be deficient in impaired readers. To address this issue, we have just initiated large-scale studies examining spatiotemporal activation profiles associated with specific aspects of phonological and lexical analysis of spoken and written language in well-characterized young children who experience problems with learning to read.


    Notes
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Notes
 References
 
The research presented in this article was partly supported by NSF Grant REC-9979968 to ACP.

Address correspondence to Panagiotis G. Simos, PhD, Department of Neurosurgery, The University of Texas — Houston Medical School, 6431 Fannin Suite 7.149, Houston, TX 77030, USA. Email: psimos{at}uth.tmc.edu.


    References
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Notes
 References
 
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