Functional MRI of sentence comprehension in children with dyslexia: beyond word recognition

Sentence comprehension (SC) studies in typical and impaired readers suggest that reading for meaning involves more extensive brain activation than reading isolated words. Thus far, no reading disability/dyslexia (RD) studies have directly controlled for the word recognition (WR) components of SC tasks, which is central for understanding comprehension processes beyond WR. This experiment compared SC to WR in 29, 9-14 year olds (15 typical and 14 impaired readers). The SC-WR contrast for each group showed activation in left inferior frontal and extrastriate regions, but the RD group showed significantly more activation than Controls in areas associated with linguistic processing (left middle/superior temporal gyri), and attention and response selection (bilateral insula, right cingulate gyrus, right superior frontal gyrus, and right parietal lobe). Further analyses revealed this overactivation was driven by the RD group's response to incongruous sentences. Correlations with out-of-scanner measures showed that better word- and text-level reading fluency was associated with greater left occipitotemporal activation, whereas worse performance on WR, fluency, and comprehension (reading and oral) were associated with greater right hemisphere activation in a variety of areas, including supramarginal and superior temporal gyri. Results provide initial foundations for understanding the neurobiological correlates of higher-level processes associated with reading comprehension.     

Brain basis of phonological awareness for spoken language in children and its disruption in dyslexia

Phonological awareness, knowledge that speech is composed of syllables and phonemes, is critical for learning to read. Phonological awareness precedes and predicts successful transition from language to literacy, and weakness in phonological awareness is a leading cause of dyslexia, but the brain basis of phonological awareness for spoken language in children is unknown. We used functional magnetic resonance imaging to identify the neural correlates of phonological awareness using an auditory word-rhyming task in children who were typical readers or who had dyslexia (ages 7-13) and a younger group of kindergarteners (ages 5-6). Typically developing children, but not children with dyslexia, recruited left dorsolateral prefrontal cortex (DLPFC) when making explicit phonological judgments. Kindergarteners, who were matched to the older children with dyslexia on standardized tests of phonological awareness, also recruited left DLPFC. Left DLPFC may play a critical role in the development of phonological awareness for spoken language critical for reading and in the etiology of dyslexia.     

Brain mechanisms for reading words and pseudowords: an integrated approach

The present study tested two predictions of dual-process models of reading: (i) that the brain structures involved in sublexical phonological analysis and those involved in whole-word phonological access during reading are different; and (ii) that reading of meaningful items, by means of the addressed phonology process, is mediated by different brain structures than reading of meaningless letter strings. We obtained brain activation profiles using Magnetic Source Imaging and, in addition, pronunciation latencies during reading of: (i) exception words (primarily involving addressed phonology and having meaning), (ii) pseudohomophones (requiring assembled phonology and having meaning), and (iii) pseudowords (requiring assembled phonology but having no meaning). Reading of meaningful items entailed a high degree of activation of the left posterior middle temporal gyrus (MTGp) and mesial temporal lobe areas, whereas reading the meaningless pseudowords was associated with much reduced activation of these two regions. Reading of all three types of print resulted in activation of the posterior superior temporal gyrus (STGp), inferior parietal and basal temporal areas. In addition, pronunciation speed of exception words correlated significantly with the onset of activity in MTGp but not STGp, whereas the opposite was true for pseudohomophones and pseudowords. These findings are consistent with the existence of two different brain mechanisms that support phonological processing in word reading: one mechanism that subserves assembled phonology and depends on the posterior part of STGp, and a second mechanism that is responsible for pronouncing words with rare print-to-sound correspondences and does not necessarily involve this region but instead appears to depend on MTGp.     

Laterality of temporoparietal causal connectivity during the prestimulus period correlates with phonological decoding task performance in dyslexic and typical readers

We examined how effective connectivity into and out of the left and right temporoparietal areas (TPAs) to/from other key cortical areas affected phonological decoding in 7 dyslexic readers (DRs) and 10 typical readers (TRs) who were young adults. Granger causality was used to compute the effective connectivity of the preparatory network 500 ms prior to presentation of nonwords that required phonological decoding. Neuromagnetic activity was analyzed within the low, medium, and high beta and gamma subbands. A mixed-model analysis determined whether connectivity to or from the left and right TPAs differed across connectivity direction (in vs. out), brain areas (right and left inferior frontal and ventral occipital-temporal and the contralateral TPA), reading group (DR vs. TR), and/or task performance. Within the low beta subband, better performance was associated with increased influence of the left TPA on other brain areas across both reading groups and poorer performance was associated with increased influence of the right TPA on other brain areas for DRs only. DRs were also found to have an increase in high gamma connectivity between the left TPA and other brain areas. This study suggests that hierarchal network structure rather than connectivity per se is important in determining phonological decoding performance.     

Conjoint and extended neural networks for the computation of speech codes: the neural basis of selective impairment in reading words and pseudowords

The computation of speech codes (i.e. phonology) is an important aspect of word reading. Understanding the neural systems and mech- anisms underlying phonological processes provides a foundation for the investigation of language in the brain. We used high-resolution three-dimensional positron emission tomography (PET) to investigate neural systems essential for phonological processes. The burden of neural activities on the computation of speech codes was maximized by three rhyming tasks (rhyming words, pseudowords and words printed in mixed letter cases). Brain activation patterns associated with these tasks were compared with those of two baseline tasks involving visual feature detection. Results suggest strong left lateralized epicenters of neural activity in rhyming irrespective of gender. Word rhyming activated the same brain regions engaged in pseudoword rhyming, suggesting conjoint neural networks for phonological processing of words and pseudowords. However, pseudoword rhyming induced the largest change in cerebral blood flow and activated more voxels in the left posterior prefrontal regions and the left inferior occipital-temporal junction. In addition, pseudoword rhyming activated the left supramarginal gyrus, which was not apparent in word rhyming. These results suggest that rhyming pseudowords requires active participation of extended neural systems and networks not observed for rhyming words. The implications of the results on theories and models of visual word reading and on selective reading dysfunctions after brain lesions are discussed.     

Brain activation during sentence comprehension among good and poor readers

This study sought to increase current understanding of the neuropsychological basis of poor reading ability by using fMRI to examine brain activation during a visual sentence comprehension task among good and poor readers in the third (n = 32) and fifth (n = 35) grades. Reading ability, age, and the combination of both factors made unique contributions to cortical activation. The main finding was of parietotemporal underactivation (less activation than controls) among poor readers at the 2 grade levels. A positive linear relationship (spanning both the poor and good readers) was found between reading ability and activation in the left posterior middle temporal and postcentral gyri and in the right inferior parietal lobule such that activation increased with reading ability. Different developmental trajectories characterized good and poor readers in the left angular gyrus: activation increased with age among good readers, a change that failed to occur among poor readers. The parietotemporal cortex is discussed in terms of its role in reading acquisition, with the left angular gyrus playing a key role. It is proposed that the functioning of the cortical network underlying reading is dependent on a combination of interacting factors, including physiological maturation, neural integrity, skill level, and the nature of the task.     

Word reading and posterior temporal dysfunction in amnestic mild cognitive impairment

Patient studies that combine functional magnetic resonance imaging with chronometric analysis of language dysfunction may reveal the critical contribution of brain areas to language processes as well as shed light on disease pathogenesis. In amnestic mild cognitive impairment (MCI), a prodromal stage of Alzheimer's disease, we examined whether the brain system for associative-semantic judgments with words or with pictures is affected and how this relates to off-line chronometric analysis of word reading and picture naming. A consecutive memory clinic-based series of 13 amnestic MCI patients as well as 13 matched controls participated. One area, the lower bank of the posterior third of the left superior temporal sulcus (STS), showed a significant group-by-task interaction: In controls, it was activated during the associative-semantic condition with words compared with the visuoperceptual control condition but not when the same tasks were compared with pictures as input. In MCI, this word-specific activation was significantly reduced. Response amplitude correlated (r = 0.90) with the steepness of the slope of the time-accuracy curve for word reading. Our data provide converging evidence for a critical contribution of the lower bank of the left posterior STS to mapping word form onto word meaning (lexical-semantic retrieval).     

Dissociation of normal feature analysis and deficient processing of letter-strings in dyslexic adults.

Neuroimaging studies have revealed that the functional organization of reading differs between developmentally dyslexic and non-impaired individuals. However, it is not clear how early in the reading process the differences between fluent and dyslexic readers start to emerge. We studied cortical activity of ten dyslexic adults using magnetoencephalography (MEG), as they silently read words or viewed symbol-strings which were clearly visible or degraded with Gaussian noise. This method has previously been used to dissociate between analysis of local features and pre-lexical word processing in fluent adult readers. Signals peaking around 100 ms after stimulus onset and originating in the postero-medial extrastriate cortex were associated with increasing local luminance contrast in the noise patches. These early visual responses were similar in dyslexic and non-impaired readers. In contrast, the letter-string-specific responses peaking around 150 ms predominantly in the left inferior occipito-temporal cortex in fluent readers were undetectable in dyslexic readers. Thus, while the early visual processing seems intact in dyslexic adults, the pattern of cortical activation starts to differ from that of fluent readers at the point where letter-string-specific signals first emerge during reading.     

Organization of language areas in bilingual patients: a cortical stimulation study

OBJECT: In an attempt to gain a better understanding of how multiple languages are represented in the human brain, the authors studied bilingual patients who underwent surgery for brain tumors, during which the authors mapped cortical language sites by using electrostimulation. METHODS: Reading, counting, and word retrieval tasks were studied in 12 right-handed bilingual patients with no language deficit. All bilingual patients were native to France. One patient spoke four languages. The patients constituted a nonhomogeneous group in terms of language proficiency or age of acquisition. Languages were evaluated and classified into three major groups, depending on proficiency and date of acquisition. Strict conditions of language site validation were applied, separating typical anomia sites from speech arrest or other language sites (such as hesitation sites). A total of 30 speech arrest sites, 16 anomia sites, and three sites of language difficulties (not typically classified as speech arrest) were found throughout the 26 language studies performed. Strict overlapping of language areas (for all language tasks) was found in five patients, whereas the remaining seven had at least one area that was language-specific and sometimes task-specific. Specific areas for a particular language were found for word retrieval tasks (anomia) in eight sites (50%) but also in six (20%) of the reading or counting sites (speech arrest), either in frontal (three patients) or in temporoparietal (four patients) regions. Among the four early bilingual patients tested (languages acquired before the age of 7 years), three had language-specific cortical areas. Interestingly, six patients in this series who had a discrepancy between two languages did not have more cortical areas devoted to the less proficient language (with acknowledgment of the limit in cortical exposure available for testing by the craniotomy). CONCLUSIONS: In this series, the authors found that bilingual patients could have common but also different cortical areas for both languages in temporoparietal areas and in frontal areas. In some cases, the authors found that language tasks such as counting, reading, or word retrieval in different languages can be sustained by language- and task-specific cortical areas. In bilingual patients, cortical mapping should ideally be performed using different language tasks in all languages in which the patient is fluent.     

Gradual recovery from dyslexia and related serial magnetoencephalographic changes in the lexicosemantic centers after resection of a mesial temporal astrocytoma. Case report

Letter-perception centers are not held in as high regard as motor- and language-related cortices during planning of neurosurgical procedures, and there have been no reports suggesting cortical reorganization of reading ability. The authors describe a patient with a left mesial temporal glioma in whom two letter-perception centers (the anterior portion of the left superior temporal gyrus and the left fusiform gyrus) were successfully localized before surgery by performing magnetoencephalography (MEG) during reading tasks. Control MEG examinations of 15 healthy volunteers were also performed to assist in a careful interpretation of patient results. Although a radical resection of the mesial temporal glioma, which involved the left fusiform gyrus, caused severe dyslexia, the patient's impaired reading skills improved gradually during a 1-year postoperative period. In the meantime, the spared left superior temporal gyrus displayed an overshot recovery of MEG responses. During the postoperative period there was no obvious recovery in MEG signals and no compensatory activity in the contralateral fusiform gyrus. This case demonstrates that lexicosemantic centers involved in the reading process can be noninvasively localized using MEG and that the results obtained are highly reliable for surgical planning. The results of the repeated MEG reflected sequentially the patient's recovery from dyslexia. This is the first report in which MEG studies have been shown to predict preoperatively the risk of dyslexia and demonstrate its serial physiological recovery.     

The role of semantics and grammatical class in the neural representation of words

On the basis of neuropsychological and functional imaging evidence, meaning and grammatical class (particularly the verb-noun distinction) have been proposed as organizational principles of linguistic knowledge in the brain. However, previous studies investigating verb and noun processing have been confounded by the presence of systematic correlations between word meaning and grammatical class. In this positron emission tomography study, we investigated implicit word processing using stimuli that allowed the effects of semantic and grammatical properties to be examined independently, without grammatical-semantic confounds. We found that left hemisphere cortical activation during single-word processing was modulated by word meaning, but not by grammatical class. Motor word processing produced significant activation in left precentral gyrus, whereas sensory word processing produced significant activation in left inferior temporal and inferior frontal regions. In contrast to previous studies, there were no effects of grammatical class in left inferior frontal gyrus (IFG). Instead, we found semantic-based differences within left IFG: anterior, but not posterior, left IFG regions responded preferentially to sensory words. These findings demonstrate that the neural substrates of implicit word processing are determined by semantic rather than grammatical properties and suggest that word comprehension involves the activation of modality-specific representations linked to word meaning.     

Probing the pathophysiology of auditory/verbal hallucinations by combining functional magnetic resonance imaging and transcranial magnetic stimulation

Functional magnetic resonance imaging and repetitive transcranial magnetic stimulation (rTMS) were used to explore the pathophysiology of auditory/verbal hallucinations (AVHs). Sixteen patients with schizophrenia-spectrum disorder were studied with continuous or near continuous AVHs. For patients with intermittent hallucinations (N = 8), blood oxygenation level-dependent (BOLD) activation maps comparing hallucination and nonhallucination periods were generated. For patients with continuous hallucinations (N = 8) correlations between BOLD signal time course in Wernicke's area, and other regions were used to map functional coupling to the former. These maps were used to identify 3-6 cortical sites per patient that were probed with 1-Hz rTMS and sham stimulation. Delivering rTMS to left temporoparietal sites in Wernicke's area and the adjacent supramarginal gyrus was accompanied by a greater rate of AVH improvement compared with sham stimulation and rTMS delivered to anterior temporal sites. For intermittent hallucinators, lower levels of hallucination-related activation in Broca's area strongly predicted greater rate of response to left temporoparietal rTMS. For continuous hallucinators, reduced coupling between Wernicke's and a right homologue of Broca's area strongly predicted greater left temporoparietal rTMS rate of response. These findings suggest that dominant hemisphere temporoparietal areas are involved in expressing AVHs, with higher levels of coactivation and/or coupling involving inferior frontal regions reinforcing underlying pathophysiology.     

Attenuated brain response to auditory word stimulation with sevoflurane: a functional magnetic resonance imaging study in humans

BACKGROUND: Functional magnetic resonance imaging offers a compelling, new perspective on altered brain function but is sparsely used in studies of anesthetic effect. To examine effects on verbal memory encoding, the authors imaged human brain response to auditory word stimulation using functional magnetic resonance imaging at different concentrations of an agent not previously studied, and tested memory after recovery. METHODS: Six male volunteers were studied breathing 0.0, 2.0, and 1.0% end-tidal sevoflurane (awake, deep, and light states, respectively) via laryngeal mask. In each condition, they heard 15 two-syllable English nouns via closed headphones. Each word was repeated 15 times (1/s), followed by 15 s of rest. Blood oxygenation level-dependent brain activations during blocks of stimulation versus rest were assessed with a 3-T Siemens Trio scanner and a 20-voxel spatial extent threshold. Memory was tested approximately 1.5 h after recovery with an auditory recognition task (chance performance = 33% correct). RESULTS: Scans showed widespread activations (P < 0.005, uncorrected) in the awake state, including bilateral superior temporal, frontal, and parietal cortex, right occipital cortex, bilateral thalamus, striatum, hippocampus, and cerebellum; more limited activations in the light state (bilateral superior temporal gyrus, right thalamus, bilateral parietal cortex, left frontal cortex, and right occipital cortex); and no significant auditory-related activation in the deep state. During recognition testing, subjects correctly selected 77 +/- 12% of words presented while they were awake as "old," versus 32 +/- 15 and 42 +/- 8% (P < 0.01) correct for the light and deep stages, respectively. CONCLUSIONS: Sevoflurane induces dose-dependent suppression of auditory blood oxygenation level-dependent signals, which likely limits the ability of words to be processed during anesthesia and compromises memory.     

PET Activation of Posterior Temporal Regions during Auditory Word Presentation and Verb Generation

Previous studies using positron emission tomography (PET) reportblood flow changes in superior and middle temple gyri associatedwith auditory and language tasks (Petersen et al., 1988, 1989;Wise et al., 1991; Demonet et al., 1992; Howard et al., 1992Sergent et al., 1992; Zatorre et al., 1992; Petrides et al.,1993; Raichle et al., 1994; Fiez et al., 1995). An importantissue is whether these changes reflect the activation of a singlefunctional region or multiple regions with distinct functionalcontributions. In the present study, we examined this issueby focusing upon two tasks for which we have previously reportedposterior temporal blood flow changes: listening to auditorilypresented words (Petersen et al., 1988, 1989), and generationof a verb in response to a visually presented noun (Raichleet al., 1994); see also Wise et al. (1991). We began by furthercharacterizing a left temporoparietal region of change previouslyassociated with auditory word presentation. This previouslyreported response was replicated, and the results were extendedby demonstrating presentation of pseudowords also produced activation.We next asked whether the activation associated with auditoryword presentation could be distinguished from that associatedwith the generation of verbs in response to visually presentednouns. It was found that the activations associated with thesetwo tasks could be both functionally and spatially dissociated.Thus, two posterior temporal areas associated with auditoryword presentation and verb generation appear to represent distinctareas concerned with word processing. More generally, the resultsdemonstrate an approach for assessing the independence of twoactivated areas.     

Attenuated Brain Response to Auditory Word Stimulation with Sevoflurane: A Functional Magnetic Resonance Imaging Study in Humans

Background: Functional magnetic resonance imaging offers a compelling, new perspective on altered brain function but is sparsely used in studies of anesthetic effect. To examine effects on verbal memory encoding, the authors imaged human brain response to auditory word stimulation using functional magnetic resonance imaging at different concentrations of an agent not previously studied, and tested memory after recovery.

Methods: Six male volunteers were studied breathing 0.0, 2.0, and 1.0% end-tidal sevoflurane (awake, deep, and light states, respectively) via laryngeal mask. In each condition, they heard 15 two-syllable English nouns via closed headphones. Each word was repeated 15 times (1/s), followed by 15 s of rest. Blood oxygenation level-dependent brain activations during blocks of stimulation versus rest were assessed with a 3-T Siemens Trio scanner and a 20-voxel spatial extent threshold. Memory was tested approximately 1.5 h after recovery with an auditory recognition task (chance performance = 33% correct).

Results: Scans showed widespread activations (P < 0.005, uncorrected) in the awake state, including bilateral superior temporal, frontal, and parietal cortex, right occipital cortex, bilateral thalamus, striatum, hippocampus, and cerebellum; more limited activations in the light state (bilateral superior temporal gyrus, right thalamus, bilateral parietal cortex, left frontal cortex, and right occipital cortex); and no significant auditory-related activation in the deep state. During recognition testing, subjects correctly selected 77 +/- 12% of words presented while they were awake as "old," versus 32 +/- 15 and 42 +/- 8% (P < 0.01) correct for the light and deep stages, respectively.     

Watching the brain during meaning acquisition

Acquiring the meaning of a new word in a foreign language can be achieved either by rote memorizing or, similar to meaning acquisition during infancy, by extracting it from context. Little is known about the brain mechanisms involved in word learning. Here we demonstrate, using event-related brain potentials, the rapid development of a brain signature related to lexical and semantic processing during contextual word learning. Healthy volunteers engaged in a simple word-learning task were required to discover the meaning of a novel word from a context during silent reading. After 3 exposures, brain potentials to novel words in meaningful contexts were indistinguishable from real words, although this acquisition effect was not observed for novel words, for which sentence contexts allowed no meaning derivation. Furthermore, when the learned novel words were presented in isolation, an activation of their corresponding meaning was observed, although this process was slower than for real words.     

Memory traces for spoken words in the brain as revealed by the hemodynamic correlate of the mismatch negativity

The mismatch negativity response, considered a brain correlate of automatic preattentive auditory processing, is enhanced for word stimuli as compared with acoustically matched pseudowords. This lexical enhancement, taken as a signature of activation of language-specific long-term memory traces, was investigated here using functional magnetic resonance imaging to complement the previous electrophysiological studies. In passive oddball paradigm, word stimuli were randomly presented as rare deviants among frequent pseudowords; the reverse conditions employed infrequent pseudowords among word stimuli. Random-effect analysis indicated clearly distinct patterns for the different lexical types. Whereas the hemodynamic mismatch response was significant for the word deviants, it did not reach significance for the pseudoword conditions. This difference, more pronounced in the left than right hemisphere, was also assessed by analyzing average parameter estimates in regions of interests within both temporal lobes. A significant hemisphere-by-lexicality interaction confirmed stronger blood oxygenation level-dependent mismatch responses to words than pseudowords in the left but not in the right superior temporal cortex. The increased left superior temporal activation and the laterality of cortical sources elicited by spoken words compared with pseudowords may indicate the activation of cortical circuits for lexical material even in passive oddball conditions and suggest involvement of the left superior temporal areas in housing such word-processing neuronal circuits.     

Where, when and why brain activation differs for bilinguals and monolinguals during picture naming and reading aloud

Using functional magnetic resonance imaging, we found that when bilinguals named pictures or read words aloud, in their native or nonnative language, activation was higher relative to monolinguals in 5 left hemisphere regions: dorsal precentral gyrus, pars triangularis, pars opercularis, superior temporal gyrus, and planum temporale. We further demonstrate that these areas are sensitive to increasing demands on speech production in monolinguals. This suggests that the advantage of being bilingual comes at the expense of increased work in brain areas that support monolingual word processing. By comparing the effect of bilingualism across a range of tasks, we argue that activation is higher in bilinguals compared with monolinguals because word retrieval is more demanding; articulation of each word is less rehearsed; and speech output needs careful monitoring to avoid errors when competition for word selection occurs between, as well as within, language.     

Visual word recognition in the left and right hemispheres: anatomical and functional correlates of peripheral alexias

According to a simple anatomical and functional model of word reading, letters displayed in one hemifield are first analysed through a cascade of contralateral retinotopic areas, which compute increasingly abstract representations. Eventually, an invariant representation of letter identities is created in the visual word form area (VWFA), reproducibly located within the left occipito-temporal sulcus. The VWFA then projects to structures involved in phonological or lexico-semantic processing. This model yields detailed predictions on the reading impairments that may follow left occipitotemporal lesions. Those predictions were confronted to behavioural, anatomical and functional MRI data gathered in normals and in patients suffering from left posterior cerebral artery infarcts. In normal subjects, alphabetic stimuli activated both the VWFA and the right-hemispheric symmetrical region (R-VWFA) relative to fixation, but only the VWFA showed a preference for alphabetic strings over simple chequerboards. The comparison of normalized brain lesions with reading-induced activations showed that the critical lesion site for the classical syndrome of pure alexia can be tightly localized to the VWFA. Reading impairments resulting from deafferentation of an intact VWFA from right- or left-hemispheric input were dissected using the same methods, shedding light on the connectivity of the VWFA. Finally, the putative role of right-hemispheric processing in the letter-by-letter reading strategy was clarified. In a letter-by-letter reader, the R-VWFA assumed some of the functional properties normally specific to the VWFA. These data corroborate our initial model of normal word perception and underline that an alternative right-hemispheric pathway can underlie functional recovery from alexia.