C H A P T E R S E V E N T E E N

Neurobiological and Behavioral

Studies of Skilled and Impaired

Word Reading

Stephen J. Frost

Rebecca Sandak

W. Einar Mencl

Nicole Landi

Dina Moore

Gina Della Porta

Jay G. Rueckl

Leonard Katz

Kenneth R. Pugh

Haskins Laboratories, New Haven, CT

Extensive behavioral research over the past several decades has examined the factorsthat govern the successful acquisition of reading skills and identification of thecause(s) of reading failure (Grigorenko, 2001; Pugh et al., 2000a). Research on theneurobiology of reading acquisition and development in skilled and impaired read-ers has benefited in recent years from rapid advances in several neuroimaging tech-nologies (e.g., Positron Emission Tomography (PET); functional Magnetic ResonanceImaging (fMRI); Magnetoencephology (MEG)). This chapter will review behavioralstudies of skilled reading and reading disability, and will describe how these func-tional imaging methods have been used in parallel with behavioral research toexamine the role of component processes and the functional brain organization forlanguage and reading in children and adults with and without reading disability(Papanicolaou et al., 2004).

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BEHAVIORAL STUDIES OF SKILLED READING

A central question in behavioral studies of skilled reading concerns the role ofphonological processing in mediating lexical access. Different classes of modelshave been put forward to address this question. Purely orthographic access models(Baron, 1973), and phonological coherence models (Van Orden, Pennington, &Stone, 1990) each assume singular lexical access codes; graphemic in the former,and phonologically-mediated in the latter. By contrast, dual-process accounts incor-porate two independent mechanisms or routes for accessing meaning: (1) by map-ping from spelling to the lexicon and then obtaining phonological informationthrough a lexical lookup procedure or (2) by mapping from spelling to a phono-logical code and then to the lexicon (“phonologically mediated access”) (Coltheart,1978; Coltheart, Rastle, Perry, Langdon, & Ziegler, 2001; Paap & Noel, 1991). A num-ber of alternative models do not assume multiple independent mechanisms, butinstead posit interactive bi-directional links with a cooperative division of laborbetween orthographic, phonological, and semantic processes to support efficientword recognition (Harm & Seidenberg, 1999; Plaut, McClelland, Seidenberg, &Patterson, 1996; Seidenberg & McClelland, 1989).

With regard to the evidence for the role of phonology in skilled word recogni-tion, many studies have now demonstrated that phonological access is early andautomatic (see R. Frost, 1998 for review). Using a semantic categorization task, VanOrden found that participants produced more false positive responses to words thatwere homophones or pseudohomophones of category exemplars than for spellingfoils (e.g., categorizing ROWS/ROZE as a flower more often than the control foilROBS/REEZ) (Van Orden, 1987; Van Orden et al., 1988). This effect persisted, evenat brief exposure durations, indicating that phonological recoding occurred early inprocessing and mediated activation of meaning. Moreover, because pseudohomo-phones are not represented lexically, Van Orden et al. concluded that the effectmust occur prior to lexical access.

Findings using brief exposure paradigms, such as backward masking and prim-ing, point to an early and robust influence of phonology on lexical access (Lesch &Pollatsek, 1993; Lukatela, Frost, & Turvey, 1999; Lukatela & Turvey, 1994a, 1994b;Perfetti & Bell, 1991; Perfetti, Bell & Delany, 1988). For example, Perfetti and col-leagues found significantly better identification rates when briefly presented targetwords were followed by pseudoword masks that were phonologically similar thanwhen they were graphemically similar, suggesting that phonological informationwas automatically extracted from the pseudoword mask and contributed to theidentification of the target (Perfetti & Bell, 1991; Perfetti et al., 1988). Furthermore,Lukatela and Turvey (1994a; see also Lesch & Pollatsek, 1993) observed associativepriming, pseudo-associative priming, and pseudohomophonic associative primingrelative to matched controls. At a short prime-target interval robust priming of thetarget word FROG was obtained for TOAD, TOWED, and TODE. At a long intervalboth TOAD and TODE effects were observed, but TOWED effects were eliminated.The authors concluded that the initial access code must be phonological in nature,with orthographic constraints coming into play relatively late.

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Cross-language studies have provided additional evidence indicating that lexicalaccess is mediated by the assembly of pre-lexical phonological codes. A unique fea-ture of Serbo-Croatian is that it has one spoken form, but two written alphabets (theRoman and Cyrillic) that share characters, some of which are pronounced the samein both alphabets (i.e., common letters) and some of which are pronounced differ-ently in the two alphabets (i.e., phonologically ambiguous letters). This featureallows researchers to combine the characters such that letter strings have one ormore phonological interpretations, depending on whether the phonologicallyambiguous characters are interpreted as Cyrillic or Roman. Studies of readers whoare competent in both written forms produce slower word naming and lexical deci-sion latencies for letter strings composed of phonologically ambiguous and com-mon letters compared to letter strings composed of phonologically unique andcommon letters (Lukatela, Popadic, Ognjenovic, & Turvey, 1980) and that the sizeof the effect is positively correlated with the number of phonologically ambiguousletters (Feldman & Turvey, 1983). Moreover, this phonological ambiguity effect canbe reduced by using an alphabetic prime composed of phonologically unique let-ters that effectively specify the target’s script (Lukatela, Feldman, et al., 1989). Thereis also growing evidence that readers of Mandarin are sensitive to the sub-lexicalphonological information contained in the phonetic components of compoundwords (see Perfetti, Liu, & Tan, 2005 for review). Studies have shown that homo-phonic characters that are unrelated in meaning produce slower decision latenciesand higher error rates than control stimuli in semantic similarity judgments (Perfetti &Zhang, 1995). Experiments in Chinese using the backward masking paradigm haveshown that briefly exposed target words are better identified when a followingmask is a homophone (Tan, Hoosain, & Peng, 1995), paralleling results in English(Perfetti et al., 1998). Although language differences have been reported relative tothe size or type of phonological unit that governs lexical access (e.g., see theGerman/English comparison study of Ziegler et al., 2001; Goswami, Ziegler, et al.,2003), the key point is that the findings converge to indicate that word recognitionin skilled adult readers does not appear to differ in fundamental ways across lan-guages and orthographies despite differences in the complexity of the mappingbetween a language’s written form and its spoken form (Carello, Turvey, & Lukatela,1992; Perfetti, 1985).

FUNCTIONAL IMAGING STUDIES OF SKILLED READING

Given the importance of phonological information evidenced from behavioralstudies of skilled reading, identifying the neuroanatomical correlates of phonologyand their interaction with orthographic and lexico-semantic component processesrepresents an important step toward understanding the functional architecture ofreading and reading failure. Evidence from functional imaging studies indicates thatskilled word recognition requires the development of a highly organized corticalsystem that integrates processing of orthographic, phonological, and lexico-seman-tic features of words (see Pugh et al., 2000a; and Sarkari et al., 2002 for reviews).This system broadly includes two posterior sub-systems in the left hemisphere (LH):

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a ventral (occipitotemporal) and a dorsal (temporoparietal) system, and a third area,anterior to the other two, centered in and around the inferior frontal gyrus.

The ventral system includes a left inferior occipitotemporal/fusiform area andextends anteriorly into the middle and inferior temporal gyri. It has been suggestedthat the occipitotemporal (OT) region functions as a pre-semantic visual word formarea (VWFA) by some researchers (c.f., Cohen et al., 2002, but see Price et al., 2003for an alternative account). Importantly, the functional specificity of this regionappears to be late developing and critically related to the acquisition of reading skill(Booth et al., 2001; Shaywitz et al., 2002). Because of its critical role in skilled read-ing, we refer to this putative VWFA more neutrally as the ventral “skill zone.” Moreanterior foci within the ventral system extending into the middle to inferior temporalgyri (MTG, ITG) appear to be semantically tuned (Fiebach et al., 2002; Simos et al.,2002; Tagamets et al., 2000). The ventral system, particularly more posterior aspects,is also fast-acting in response to linguistic stimuli in skilled readers but not in RDindividuals (Salmelin et al., 1996). It should be noted that there is some disagreementin the literature about the precise localization of critical sub-regions comprising theventral system (Price et al., 2003). Nevertheless, recent studies examining both tim-ing and stimulus-type effects suggest that moving anteriorly through this ventral sys-tem, sub-regions respond to word and word-like stimuli in a progressively abstractedand linguistic manner (Tagamets et al., 2000; Tarkiainen et al., 2003).

The more dorsal temporoparietal system broadly includes the angular gyrus(AG) and supramarginal gyrus (SMG) in the inferior parietal lobule, and the poste-rior aspect of the superior temporal gyrus (Wernicke’s Area). Among their otherfunctions (e.g., attentionally controlled processing) the areas within this systemseem to be involved in mapping visual percepts of print onto the phonological andsemantic structures of language (Black and Behrmann 1994). In skilled readers, cer-tain regions within the LH temporoparietal system (particularly the SMG) respondwith greater activity to pseudowords than to familiar words (Price et al., 1996; Simoset al., 2002; Xu et al., 2001). This finding, along with our developmental studies(Shaywitz et al., 2002) suggests that the temporoparietal system plays a role in thetypes of phonological analyses that are relevant to learning new material.

The anterior system centered in posterior aspects of the inferior frontal gyrus(IFG) appears to be associated with phonological recoding during reading, amongother functions (e.g., phonological memory, syntactic processing); the more ante-rior aspects of IFG seem to play a role in semantic retrieval (Poldrack et al., 1999).The phonologically relevant components of this multi-functional system have beenfound to function in silent reading and in naming (see Fiez and Petersen 1998 forreview; Pugh et al., 1997) and like the temporoparietal system, is more stronglyengaged by low-frequency words (particularly, words with irregular/inconsistentspelling-to-sound mappings) and pseudowords than by high-frequency words(Fiebach et al., 2002; Fiez and Peterson 1998). We have speculated that this ante-rior system operates in close conjunction with the temporoparietal system to decodenew words during normal reading development (Pugh et al., 2000b).

More recently, the functional neuroanatomy of visual word recognition in read-ing has been investigated in mature readers in a variety of languages (which employ

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both alphabetic and non-alphabetic writing systems) (e.g., Chee et al., 1999;Fiebach et al., 2002; Kuo et al., 2003, 2004; Paulesu et al., 2000; Salmelin et al.,1996). Neuroimaging studies of alphabetic languages broadly implicate the same setof LH cortical regions (including occipitotemporal, temporoparietal, and inferiorfrontal networks) identified in English-language studies (see Pugh et al., 2005).These common networks are almost always engaged by skilled readers irrespectiveof the specific language and/or writing system under investigation. Language-spe-cific differences usually appear to be a matter of degree, not of kind. That is, in onelanguage, the reading-relevant constituents of a neural network might be more orless activated than in another language, but the general circuitry appears similar inits taxonomic organization (Paulesu et al., 2000). For example, Kuo et al. (2003)examined covert naming of high-frequency and low-frequency Chinese charactersand observed greater activation in left premotor/inferior frontal regions and the leftinsula for low-frequency characters relative to high-frequency characters. Theseareas have been implicated in phonological processing in English; in particular, theinferior frontal gyrus is more strongly engaged by low-frequency words and pseu-dowords than by high-frequency words (Fiebach et al., 2002; Fiez & Peterson,1998). Moreover, high-frequency characters produced greater activation in the mid-dle temporal/angular gyrus, which have been implicated in lexical-semantic pro-cessing in neuroimaging studies of English word recognition (Fiebach et al., 2002;Price et al., 1997; Simos et al., 2002) and the precuneus, previously implicated invisual imagery (Fletcher et al., 1996). In a subsequent study, Kuo and colleagueshad participants perform homophone judgments and physical judgments on realcharacters, pseudo-characters (novel combinations of legal semantic and phoneticradicals that follow the positional architecture of Chinese characters), and Koreanhangul-like nonsense figures (Kuo et al., 2004). A number of regions important fororthographic-to-phonological mapping in English were also more active for thehomophone judgment relative to the character judgment in Chinese. These regionsincluded the inferior frontal gyrus, inferior parietal lobule/supramarginal gyrus, andthe fusiform gyrus. Note that some differences have been reported for Mandarinreading with increased reading-related activation at both superior parietal (Kuo et al.,2003), and left middle frontal regions (Tan et al., 2001); however, overall the read-ing networks appear to be largely similar to those observed for alphabetic writingsystems (Kuo et al., 2003, 2004).

BEHAVIORAL STUDIES OF READING DISABILITY

Significant progress has been made in understanding the cognitive and linguisticskills that must be in place to insure adequate reading development in children(Brady & Shankweiler 1991; Bruck 1992; Fletcher et al., 1994; Liberman et al., 1974;Rieben and Perfetti 1991; Shankweiler et al., 1995; Stanovich & Siegel 1994; see alsoPiasta & Wagner, this volume). With regard to reading disability, it has been arguedthat the reading difficulties experienced by some children may result from difficultieswith processing speed (Wolf & Bowers, 1999), rapid auditory processing (Tallal, 1980),general language deficits (Scarborough & Dobrich, 1990), or visual deficits (Cornelissen &

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Hansen, 1998). However, there is growing consensus that for the majority ofstruggling readers, a core difficulty in reading manifests itself as a deficiency within thelanguage system and, in particular, a deficiency at the level of phonological analysis(Liberman et al., 1974; Stanovich et al., 1984; Wagner & Torgesen, 1987).

Deficits in behavioral performance are most evident at the level of single wordand pseudoword reading; reading disabled (RD) individuals are both slow and inac-curate relative to nonimpaired (NI) readers. Many lines of evidence converge on theconclusion that the word and pseudoword reading difficulties in RD individuals are,to a large extent, manifestations of more basic deficits at the level of rapidly assem-bling the phonological code represented by a token letter string (Bradley & Bryant,1983; Liberman et al., 1989). Phonological assembly refers to the operations associ-ated with mapping from the orthographic to the phonological form in printed wordidentification. The failure to develop efficient phonological assembly skill in wordand pseudoword reading, in turn, appears to stem from difficulties – at the earlieststages of literacy training – in attaining fine-grained phonemic awareness.Phonological awareness in general, is defined as the metalinguistic understandingthat spoken words can be decomposed into phonological primitives, which in turncan be represented by alphabetic characters (Brady & Shankweiler, 1991; Bruck, 1992;Fletcher et al., 1994; Liberman et al., 1974; Rieben & Perfetti, 1991; Shankweiler et al.,1995; Stanovich & Siegel 1994).

As for why RD readers should have exceptional difficulty developing phonologi-cal awareness, the etiological underpinnings of this difficulty are still actively beinginvestigated and the question of whether such language-level challenges might, insome children at least, be linked to more basic deficits in one of the above-mentioneddomains is much debated. Nonetheless, a large body of evidence directly relatesdeficits in phonological awareness to difficulties in learning to read: phonologicalawareness measures predict later reading achievement (Bradley & Bryant, 1983;Stanovich et al., 1984; Torgesen et al., 1994); deficits in phonological awareness con-sistently separate RD and nonimpaired children (Fletcher et al., 1994; Stanovich &Siegel, 1994); phonological deficits persist into adulthood (Bruck, 1992; Felton et al.,1990; Shaywitz et al., 1999) and instruction in phonological awareness promotes theacquisition of reading skills (Ball & Blachman, 1991; Bradley & Bryant, 1983; Foormanet al., 1998; Torgesen et al., 1992; Wise & Olson, 1995). For children with adequatephonological skills, the process of phonological assembly in word and pseudowordreading becomes highly automated, efficient, and, as the evidence above suggests,continues to serve as an important component in rapid word identification even formature skilled readers (R. Frost, 1998).

In terms of the characteristics of reading disability across languages, the extantevidence shows many similarities and few differences in profiles of RD acrossorthographies. Like disabled readers in English, many RD readers, specifically readersof regular orthographies with transparent spelling-to-sound correspondences: (a) havea family history of RD (Lyytinen, 2004a, 2004b); (b) show the larger lexicality, length,and grain-size effects relative to nonimpaired readers (Ziegler et al., 2003); and(c) exhibit signs of reduced distinctiveness (precision) in their phonological rep-resentations in the lexicon (Elbro, 1998; Elbro et al., 1998; Goswami, 2000; Ziegler &

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Goswami, 2005). Unlike English, in which RD readers are both slow and inaccurate,errors in regular orthographies are rare; however, wide individual differences occurin reading speed and the slowest readers are considered to have RD (Landerl et al.,1997; Wimmer & Mayringer, 2002). Nonetheless, the evidence provides some sup-port for the hypothesis that RD is attributable to the same core phonological deficitin all languages. In line with previous theoretical work at Haskins (Fowler, 1991),Goswami and colleagues have proposed that reduced precision in representing andprocessing phonological information may be the universal hallmark of RD(Goswami, 2000; Ziegler & Goswami, 2005). The transparency of the spelling-to-sound correspondences in regular orthographies like Finnish, allows the yokedprocesses of phonemic awareness and analysis to develop earlier and more fully(even in RD) than is possible given the additional challenges facing readers of amore irregular orthography. Even though decoding will be more accurate by RDchildren in regular orthographies, the imprecision (and potentially reduced accessi-bility) of their phonological knowledge about words still impedes routinization andsubsequent fluency. Although plausible and parsimonious, there is not yet sufficientevidence favoring this hypothesis over the notion that RD may arise for differentreasons in different languages. Until longitudinal data are collected across orthogra-phies using repeated administrations of the same array of cognitive and literacymeasures (and neurobiological indices) interpretations of available cross-languagecomparisons will remain inconclusive.

FUNCTIONAL IMAGING STUDIES OF READING DISABILITY

Evidence for Altered Circuits in Reading Disability

There are clear functional differences between NI and RD readers with regard toactivation patterns in dorsal, ventral, and anterior sites during reading tasks. In dis-abled readers, a number of functional imaging studies have observed LH posteriorfunctional disruption, at both dorsal and ventral sites during phonological process-ing tasks (Brunswick et al., 1999; Paulesu et al., 2001; Pugh et al., 2000a, 2000b;Salmelin et al., 1996; Shaywitz et al., 1998; 2002; Temple et al., 2001). This disrup-tion is instantiated as a relative under-engagement of these regions specificallywhen processing linguistic stimuli (words and pseudowords) or during tasks thatrequire decoding. This functional anomaly in posterior LH regions has beenobserved consistently in children (Shaywitz et al., 2002) and adults (Salmelin et al.,1996; Shaywitz et al., 1998). Hypoactivation in three key dorsal and ventral sites,including cortex within the temporoparietal region, the angular gyrus, and the ven-tral OT skill zone is detectable as early as the end of kindergarten in children whohave not reached important milestones in learning to read (Simos et al., 2002).

Most neuroimaging studies have attempted to isolate specific brain regions whereactivation patterns discriminate RD from NI readers (e.g., Rumsey et al., 1997;Shaywitz et al., 1998; Simos et al., 2002; Temple et al., 2001). However, work in read-ing disability (Horwitz et al., 1998; Pugh et al., 2000a, 2000b) employing functionalconnectivity analyses has also provided important insights into functional differences

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between RD and NI readers in word recognition. In this approach, the primaryaim is to consider relations among distinct brain regions that function cooperativelyas circuits to process information during reading (Friston, 1994). For example,Horwitz, Rumsey and Donohue (1998) examined correlations (within task/acrosssubjects) between activation levels in the LH angular gyrus and other brain sitesduring two reading aloud tasks (exception word and nonword naming).Correlations between the LH angular gyrus and occipital and temporal lobe siteswere strong and significant in NI readers and weak in RD readers. Such a resultsuggests a breakdown in functional connectivity across the major components ofthe LH posterior reading system. A subsequent study examining functional con-nectivity between the angular gyrus and occipital and temporal lobe sites on tasksthat systematically varied demands made on phonological assembly showed thatfor RD readers LH functional connectivity was disrupted on word and nonwordreading tasks as reported by Horwitz et al., (1998); however, there appeared tobe no dysfunction on the tasks which tapped metaphonological judgments only(e.g., a single letter rhyme task), or complex visual-orthographic coding only(e.g., an orthographic case judgment task). The results are most consistent witha specific phonological deficit hypothesis: Our data suggest that a breakdown infunctional connectivity among components of the LH posterior system manifestsonly when orthographic to phonological assembly is required. The notion of adevelopmental lesion, one that would disrupt functional connectivity in this sys-tem across all types of cognitive behaviors, is not supported by this result.Moreover, we found that on word and nonword reading tasks RH homologuesappear to function in a compensatory manner for RD readers; correlations werestrong and stable in this hemisphere for both reading groups with higher valuesin RD readers.

Because the evidence from neuroimaging studies of skilled reading indicates thatdifferent languages and orthographies engage common circuits during reading, wemight expect language-invariant neurobiological signatures to be associated withreading disability as well. The evidence to date from alphabetic languages is sup-portive of this expectation (Paulesu et al., 2001; Salmelin et al., 1996; Shaywitzet al., 2002). Functional disruptions in LH posterior cortex (particularly the occipi-totemporal region) in RD individuals performing reading tasks during neuroimag-ing have been found in several languages that vary in the complexity of mappingsbetween printed and spoken forms (English, Finnish, German, French, and Italian).This common neurobiological signature, within a largely language-invariant cir-cuitry for reading in the LH, reinforces the notion of universality in RD. A recentstudy of Chinese RD readers (Siok et al., 2004) reported a language-specific differ-ence in the RD signature (specifically diminished activation of middle frontalregions for RD readers relative to controls). This finding has not been reported inalphabetic languages. However, these authors also found diminished activation inRD readers at the same LH ventral regions previously reported by Paulesu and othersin RD within alphabetic languages (Brunswick et al., 1999; Paulesu et al., 2001;Salmelin et al., 1996; Shaywitz et al., 2002).

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Potentially Compensatory Processing in Reading Disability.

Behaviorally, poor readers compensate for their inadequate phonological aware-ness and knowledge of letter-sound correspondences by over-relying on contextualcues to read individual words; their word reading errors tend to be visual or seman-tic rather than phonetic (see Perfetti 1985 for review). These behavioral markers ofreading impairment may be instantiated cortically by compensatory activation offrontal and RH regions. In our studies (Shaywitz et al., 1998, 2002), we observedprocessing in RD readers that we interpret as compensatory. We found that on tasksthat made explicit demands on phonological processing (pseudoword- and word-reading tasks), RD readers showed a disproportionately greater engagement of IFGand prefrontal dorsolateral sites than did NI readers (see also Brunswick et al., 1999;Salmelin et al., 1996 for similar findings). Evidence of a second, potentiallycompensatory, shift – in this case to posterior RH regions – comes from several findings.Using MEG, Sarkari et al. (2002) found an increase in the apparent engagement ofthe RH temporoparietal region in RD children. More detailed examination of thistrend, using hemodynamic measures, indicates that hemispheric asymmetries in activityin posterior temporal and temporoparietal regions (MTG and AG) vary significantlyamong reading groups (Shaywitz et al., 1998): there was greater right than LH acti-vation in RD readers but greater left than RH activation in NI readers. Rumsey et al.(1999) examined the relationship between RH activation and reading performancein their adult RD and NI participants and found that RH temporoparietal activationwas correlated with standard measures of reading performance only for RD readers(see also Shaywitz et al., 2002).

We hypothesize that the reason RD readers tend to strongly engage inferiorfrontal sites is their increased reliance on covert pronunciation (articulatory recod-ing) in an attempt to cope with their deficient phonological analysis of the printedword. In addition, their heightened activation of the posterior RH regions withreduced LH posterior activation suggests a process of word recognition that relieson letter-by-letter processing in accessing RH localized visuo-semantic representa-tions (or some other compensatory process) rather than relying on phonologicallystructured word recognition strategies. These differential patterns, especially theincreased activation in frontal regions might also reflect increased effort duringreading; under-engagement of LH posterior areas, particularly ventral sites, wouldnot be thought to reflect this increased effort, but rather the failure to engage theseareas likely precipitates any change in effort.

Neurobiological Effects of Successful Reading Remediation.

Converging evidence from other studies supports the notion that gains in reading skillresulting from intense reading intervention are associated with a more “normalized”localization of reading processes in the brain. In a recent MEG study, eight youngchildren with severe reading difficulties underwent a brief but intensive phonics-based remediation program (Simos et al., 2002). After intervention, the most salient

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change observed on a case-by-case basis was a robust increase in the apparentengagement of the LH temporoparietal region, accompanied by a moderate reduc-tion in the activation of the RH temporoparietal areas. Similarly, Temple et al. (2003)used fMRI to examine the effects of an intervention (FastForword) on the corticalcircuitry of a group of 8- to 12-year-old children with reading difficulties. After inter-vention, increased LH temporoparietal and inferior frontal increases were observed.Moreover, the LH increases correlated significantly with increased reading scores. Ina recent collaborative study with Dr. Benita Blachman of Syracuse University, weexamined three groups of young children (average age was 6.5 years at Time 1)with fMRI and behavioral indices (Shaywitz et al., 2004). A treatment RD groupreceived nine months of an intensive phonologically-analytic intervention(Blachman et al., 1999), and there were two control groups: a typically developingand an untreated RD group. Relative to RD controls, RD treatment participants showedreliable gains on reading measures (particularly on fluency-related measures). Pre-and post-treatment fMRI employed a simple cross modal (auditory/visual) forcedchoice letter match task. When RD groups were compared at post-treatment (Time2), reliably greater activation increases in LH reading related sites were seen in thetreatment group. When Time 2 and Time 1 activation profiles were directly con-trasted for each group it was evident that both RD treatment and typically devel-oping, but not RD controls, showed reliable increases in LH reading related sites.Prominent differences were seen in LH IFG, and importantly in LH ventral skillzone. These changes were quite similar to the NI controls as they also learned toread. Importantly, the treatment group returned one year post-treatment for a fol-low up fMRI scan and progressive LH ventral increases along with decreasing RHactivation patterns were observed even one year after treatment was concluded. Allthese initial neuroimaging treatment studies suggest that a critical neurobiologicalsignature of successful intervention, at least in younger children, appears to beincreased engagement of major LH reading-related circuits, and reduced compen-satory reliance on RH homologues.

REFINING OUR ACCOUNT OF NEUROBIOLOGY

OF SKILLED WORD RECOGNITION

In a preliminary model (Pugh et al., 2000) we speculated that the temporoparietaland anterior systems are critical in learning to integrate orthographic, phonological,and semantic features of words whereas the ventral system develops, as a conse-quence of adequate learning during reading acquisition, to support fluent wordidentification in normally developing, but not reading disabled, individuals (seebelow for relevant data). This general taxonomy however, is both coarse-grainedand under-specified. To explore functional sub-specialization further we haverecently conducted a series of experiments with skilled readers as participants (Frostet al., 2005; Katz et al., in press; Mencl et al., 2005; Sandak et al., 2004). We exam-ined: phonological priming (Mencl et al., 2005), phonological/semantic tradeoffs(Frost et al., 2005), and critical factors associated with repetition effects (Katz et al.,in press) and adaptive learning (Sandak et al, 2004). This line of research is aimed

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at providing more information on both sub-specialization with the major LHregions, and how different component systems modulate processing in relation toone another during learning.

Phonological Priming

We have recently completed an fMRI study of phonological and orthographic prim-ing effects in printed word recognition (Mencl et al., 2005). Participants performed aprimed lexical decision task. Word prime-target pairs were either (1) both ortho-graphically and phonologically similar (bribe-TRIBE); (2) orthographically similar butphonologically dissimilar (couch-TOUCH); or (3) unrelated (lunch-SCREEN). Resultsrevealed that targets primed by phonologically dissimilar words evoked more activa-tion than targets primed by phonologically similar words in several LH cortical areashypothesized to underlie phonological processing: this modulation was seen in IFG,Wernicke’s area, and the SMG. Notably, this phonological priming effect was alsoobtained within the early-activating LH OT skill zone, consistent with the claim thatphonological coding influences lexical access at its earliest stages.

Tradeoffs Between Phonology and Semantics

Many previous studies have attempted to identify the neural substrates of ortho-graphic, phonological, and semantic processes in NI (Fiebach et al., 2002) and RD(Rumsey et al., 1997) cohorts. RD readers have acute problems in mapping fromorthography to phonology and appear to rely on semantic information to supple-ment deficient decoding skills (Plaut & Booth, 2000). NI readers too, appear toshow a trade-off between these component processes. Strain et al. (1996) providedbehavioral confirmation of this, demonstrating that the standard consistency effecton low-frequency words (longer naming latencies for words with inconsistentspelling-to-sound mappings such as PINT relative to words with consistent map-pings such as MILL) is attenuated for words that are highly imageable/concrete.Importantly, this interaction reveals that semantics can facilitate the processes asso-ciated with orthographic-to-phonological mapping in word recognition.

Using fMRI, we sought to identify the neurobiological correlates of thisphenomenon (Frost et al., 2005). A go/no-go naming paradigm was employed inan event-related fMRI protocol with word stimuli representing the crossing of fre-quency, imageability, and spelling-to-sound consistency. Higher activation for high-imageable words was found in middle temporal and posterior parietal sites. Incontrast, higher activation for inconsistent relative to consistent words was found inthe IFG, replicating findings by Fiez et al. (1999) and Herbster et al. (1997).Critically, analyses revealed that imageability was associated with reduced consis-tency-related activation in IFG but increased posterior parietal activation; thisappears to be the principal neural signature of the behavioral trade-off betweensemantics and phonology revealed by Strain and colleagues. This finding serves asan important step in the linking of neurobiological and computational models ofreading.

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Adaptive Learning

Previous studies have demonstrated that both increased familiarity with specificwords and increased reading skill are associated with a shift in the relative activa-tion of the cortical systems involved in reading, from predominantly dorsal to pre-dominantly ventral. In another line of research, we are carrying out functionalneuroimaging experiments in order to provide a more precise characterization ofthe means by which practice with unfamiliar words results in this shift, and to gaininsights into how these systems learn to read new words. In one study from ourgroup (Katz et al., in press) we found evidence for this shift as skilled readersacquired familiarity for words via repetition. In that study, we examined repetitioneffects (comparing activation for thrice repeated tokens relative to unrepeatedwords) in both lexical decision and overt naming. Across tasks, repetition was asso-ciated with facilitated processing as measured by reduced response latencies anderrors. Many sites, including IFG, SMG, supplementary motor area, and cerebellum,showed reduced activation for highly practiced tokens. Critically, a dissociation wasobserved within the ventral system: the OT skill zone showed practice-relatedreduction (like the SMG and IFG sites), whereas more anterior ventral sites, partic-ularly MTG, were stable or even showed increased activation with repetition. Thus,we concluded that a neural signature of increased efficiency in word recognition ismore efficient processing in dorsal, anterior, and posterior ventral sites, with stableor increased activation in more anterior middle and inferior temporal sites.

A second experiment (Sandak et al., 2004) examined whether the type of pro-cessing engaged in when learning a new word mediates how well that word islearned, and the cortical regions engaged when that word is subsequently read. Wesuspected that repetition alone is not sufficient to optimize learning; rather, wehypothesized that the quality of the lexical representations established when newwords are learned is affected by the type of processing engaged in during learning.Specifically, we predicted that, relative to attending to the orthographic features ofnovel words, learning conditions that stress phonological or semantic analysiswould speed naming and, in turn, cortical activation patterns similar to those char-acteristic of increased familiarity with words (as seen in Katz et al., in press). Priorto MRI scanning, participants completed a behavioral session in which theyacquired familiarity for three sets of pronounceable pseudowords while makingorthographic (consonant/vowel pattern), phonological (rhyme) or semantic (cate-gory) judgments. Note that in the semantic condition, participants learned a novelsemantic association for each pseudoword. Following training, participants com-pleted an event-related fMRI session in which they overtly named trained pseudo-words, untrained pseudowords, and real words.

As predicted, we found that the type of processing (orthographic, phonological,or semantic) engaged in when learning a new word influences both how well thatword is learned, and the cortical regions engaged when that word is subsequentlyread. Behaviorally, phonological and semantic training resulted in speeded namingtimes relative to orthographic training. Of the three training conditions, we found thatonly phonological training was associated with both facilitated naming and the pattern

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of cortical activations previously implicated as characteristic of increased efficiency forword recognition (Katz et al., in press). We suggest that for phonologically traineditems, learning was facilitated by engaging in phonological processing during train-ing; this in turn resulted in efficient phonological processing (instantiated cortically asrelatively reduced activation in IFG and SMG) and efficient retrieval of pre-semanticlexical representations during subsequent naming (instantiated cortically as relativelyreduced activation in the OT skill zone). Semantic training also facilitated naming butwas associated with increased activation in areas previously implicated in semanticprocessing, suggesting that the establishment and retrieval of semantic representationscompensated for less efficient phonological processing for these items.

IMPLICATIONS OF RECENT FINDINGS

We had initially speculated that the temporoparietal and anterior systems are criti-cal in learning to integrate orthographic, phonological, and semantic features ofwords whereas the ventral system develops, as a consequence of adequate learn-ing during reading acquisition, to support fluent word identification in normallydeveloping, but not RD, individuals (Pugh et al., 2000). Our recent experimentsexamining phonological priming, phonological/semantic tradeoffs, and critical fac-tors associated with adaptive learning in reading have yielded findings that requireus to refine our initial taxonomy. These data allow for the development of a morefine-grained picture of the functional neuroanatomy and sub-specializations withinthese systems, illustrated in Figure 17-1. Across these studies identical sets of vox-els in the SMG (within the temporoparietal system), IFG (within the anterior sys-tem) and the OT skill zone (within the ventral system) showed (1) increasedactivation for pseudowords relative to words, (2) strong phonological primingeffects, and (3) repetition-related reductions that were most salient in the phono-logically-analytic training condition. This pattern strongly suggests a phonological“tuning” in these sub-regions. (It is particularly noteworthy that the developmentallycritical OT skill zone – the putative VWFA – by these data, appears to be phono-logically tuned. It makes good sense that this region should be so structured giventhe failure to develop this system in reading disability when phonological deficitsare one of the core features of this population). By contrast, the angular gyrus(within the temporoparietal system) and the middle/inferior temporal gyri (withinthe ventral system) appear to have more abstract lexico-semantic functions acrossour studies (see Price et al., 1997 for similar claims).

From these findings, we speculate that sub-regions within SMG and IFG operatein a yoked fashion to bind orthographic and phonological features of words duringlearning; these systems also operate in conjunction with the AG where these featuresare further yoked to semantic knowledge systems distributed across several corticalregions. Adequate binding, specifically adequate orthographic/phonological integra-tion, enables the development of the pre-semantic OT skill zone into a functional pat-tern identification system. As words become better learned, this area becomescapable of efficiently activating lexico-semantic subsystems in MTG/ITG, enablingthe development of a rapid ventral word identification system. RD individuals, with

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demonstrable anomalies in temporoparietal function (and associated difficultieswith phonologically analytic processing on behavioral tests), fail to adequately“train” ventral subsystems (particularly the OT skill zone) and thus develop com-pensatory responses in frontal and RH systems. In our view, this revised accountbetter lends itself to the architectural assumptions put forward in interactive mod-els (e.g., Harm and Seidenberg 1999) than with classic dual route models. The find-ings on stimulus-type effects, and especially the data on adaptive learning, do notreadily support the notion of independent dorsal and ventral reading pathways,with each coding different information. Instead, they suggest a set of phonologicallyor semantically tuned sub-systems that are widely distributed across both dorsal andventral cortex and appear to act cooperatively during fluent word reading and inadaptive learning.

FUTURE DIRECTIONS

In recent years, significant progress has been made in the study of reading andreading disability with the use of functional neuroimaging techniques. A good deal isnow known about the distributed neural circuitry for reading in skilled adult readers,the developmental trajectory toward this mature reading circuitry in normally devel-oping children, deviations from this trajectory in reading disability, and the ways inwhich intensive training for struggling younger readers alters brain organization forreading. Further advancement in developing an adequate theory of the neurobiologyof reading demands considerable progress in a number of domains.

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FIGURE 17.1 Components of the Reading System.

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One such domain is the area of functional connectivity. Studies of readingemploying functional connectivity analyses of reading and reading disability havebeen promising (Horwitz et al., 1998; Pugh et al., 2000; Shaywitz et al., 2002).However, this approach has largely been limited to assessments of with task/across-subject connectivity; extending the approach to assessments of within-subject con-nectivity is still in its early stages of development. Moreover, studies using bothhemodynamic and electrophysiological data to isolate correlated activation can becombined with emerging findings from diffusion weighted tensor imaging (DTI),which reveals axonal tracts connecting distributed neural subsystems across cortex.Indeed, a recent study using diffusion-weighted imaging analysis has documentedstructural anomalies in white matter tracts within the LH temporoparietal regionsuggesting a possible neural basis for the often seen functional anomalies in dis-abled readers (Klingberg et al., 2000). In addition, new developments in spectro-scopic imaging techniques can support more careful analyses of the basicneurochemistry of regions targeted by functional studies to investigate the etiologyof abnormal development.

More deeply, while neurobiological studies of word recognition, particularlythose identifying neurobiological signatures of reading disability, have generated agood deal of enthusiasm, it should be remembered that functional neuroimagingmeasures are not intrinsically explanatory; they simply describe brain organizationat a given point in development. Links between multiple indices of reading(dis)ability, including genetic risk/protective factors, brain structure and function,and cognitive deficits promise to constitute the core scientific foundation for ourunderstanding of neurodevelopmental disorders in the coming years; to progressivefrom descriptive neurobiological findings to potentially explanatory models. In anew project in our lab we are using a longitudinal design to characterize readingdevelopment in NI and RD cohorts of children by measuring developmentalchanges in reading performance (obtained during the early stages of reading acqui-sition through to the point where fluent reading is anticipated) using functionalneuroanatomy (fMRI), neurochemistry, measured with magnetic resonance spec-troscopy (MRS) and genetic analyses. By establishing meaningful links betweenbehavioral/cognitive skills that must be in place to read and neuroanatomical, neu-rochemical, and genetic measures, we can begin to develop an explanatory accountof neurocognitive divergences in typically developing and RD children (Grigorenko2001; Pugh et al., 2000a). That is, we believe that designs of this type will allowspecifications of the biological pathways predisposing for risk for the development ofRD and explorations of elements of these pathways that might be most suitable forpharmacological and behavioral intervention. While the goal of linking genetics,neurochemistry, functional neuroanatomy, and behavior in reading development isboth ambitious and, to some extent, exploratory, the goal of developing an adequateexplanatory model of observed divergences in RD with respect to brain and behaviorrequires such links to be made.

The neuroimaging studies of reading interventions to date indicate that the signa-ture of successful intervention in at-risk children is an increased response in criticalLH posterior regions (Shaywitz et al., in press; Simos et al., 2002; Temple et al.,

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2003). Each of these studies has utilized training programs that emphasize phono-logical awareness training to differing degrees. However, several pressing questionsremain. First, will similar remediation effects be obtained for older populations withpersistent reading difficulties? Moreover, are there specific etiological factors thatdistinguish children who demonstrate only minimal gains with treatment fromresponders? If so, might alternative instructional approaches be more effective forthese children? These are complex issues and demand large-scale studies that com-pare and contrast various interventions and examine interactions with individual dif-ference (Simos, et al., this volume) or subtype dimensions (Piasta & Wagner, thisvolume). Such contrastive research will greatly extend the utility of developmentalresearch of the neurobiology of word recognition.

In addition, there is a real need to find better markers of abnormal trajectoriesin very young (pre-school age) children, as well as to develop appropriate earlyinterventions. Whereas it is known that the development of phonemic awareness isstrongly and causally related to the development of reading skill (e.g., Bradley &Bryant, 1985; Wagner & Torgesen, 1987), little is known about the cognitive primi-tives underlying the development of phonemic awareness. Some researchers havesuggested that deficits in phonemic awareness in reading impaired children mayarise from a more basic deficit in speech perception (e.g., Mody et al., 1997) orauditory temporal processing (e.g., Tallal, 1980). Future behavioral and neuroimag-ing work needs to continue to examine the development of phonological aware-ness and reading in order to understand the etiology of reading disabilities atmultiple levels of analysis.

Finally, much behavioral research supports the notion that word recognitionengages common processes across languages and orthographies; however, at pre-sent there is much less cross-linguistic neuroimaging research on reading develop-ment, disability, and the effects of intervention. Although the initial evidence hasprovided support for a common neurobiological signature of both skilled andimpaired reading, some differences have been observed (Siok et al., 2004). Giventhe significant variability in orthographic form, orthographic-to-phonological map-pings, methods of reading instruction, and manifestations of reading disabilityacross languages and cultures, more work needs to be done in the area of cross-linguistic studies of reading, both in order to identify the neurobiological universalsof reading and to understand how the functional organization of reading varies withlanguage-specific features. Additionally, few cross-linguistic studies of literacyacquisition have employed well-matched longitudinal designs and samples, andnone have as yet included integrated neurobiological and behavioral measures. Asa result, it has been difficult to identify universal versus language-specific aspectsof skill acquisition by typically developing children and those with RD; such knowl-edge is crucial to a full theoretical and practical account of reading acquisition anddisability. Cross-linguistic neurocognitive research has the potential we think, toenhance significantly our current understanding of universal influences on learningto read.

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ACKNOWLEDGMENTS

This research was funded by NICHD grants F32-HD42391 to Rebecca Sandak, R01-HD40411 to Kenneth R. Pugh, and P01-HD01994 to Haskins Laboratories.

Portions of this chapter have appeared recently in: G. D. Rosen (ed.), DevelopingNew Pathways in the Study of the Dyslexic Brain. Baltimore: York Press (in press),J. Stein (ed) Kobe Dyslexia Conference papers (submitted), and Sandak, et al.,(2004). Scientific Studies of Reading: Special Issue on Neurobiology of Reading.

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