Neuroanatomy of dyslexia: An allometric approach.

Despite evidence for a difference in total brain volume between dyslexic and good readers, no previous neuroimaging study examined differences in allometric scaling (i.e. differences in the relationship between regional and total brain volumes) between dyslexic and good readers. The present study aims to fill this gap by testing differences in allometric scaling and regional brain volume differences in dyslexic and good readers. Object-based morphometry analysis was used to determine grey and white matter volumes of the four lobes, the cerebellum and limbic structures in 130 dyslexic and 106 good readers aged 8-14 years. Data were collected across three countries (France, Poland and Germany). Three methodological approaches were used as follows: principal component analysis (PCA), linear regression and multiple-group confirmatory factor analysis (MGCFA). Difference in total brain volume between good and dyslexic readers was Cohen's d = 0.39. We found no difference in allometric scaling, nor in regional brain volume between dyslexic and good readers. Results of our three methodological approaches (PCA, linear regression and MGCFA) were consistent. This study provides evidence for total brain volume differences between dyslexic and control children, but no evidence for differences in the volumes of the four lobes, the cerebellum or limbic structures, once allometry is taken into account. It also finds no evidence for a difference in allometric relationships between the groups. We highlight the methodological interest of the MGCFA approach to investigate such research issues.

Multi-parameter machine learning approach to the neuroanatomical basis of developmental dyslexia.

Despite decades of research, the anatomical abnormalities associated with developmental dyslexia are still not fully described. Studies have focused on between-group comparisons in which different neuroanatomical measures were generally explored in isolation, disregarding potential interactions between regions and measures. Here, for the first time a multivariate classification approach was used to investigate grey matter disruptions in children with dyslexia in a large (N = 236) multisite sample. A variety of cortical morphological features, including volumetric (volume, thickness and area) and geometric (folding index and mean curvature) measures were taken into account and generalizability of classification was assessed with both 10-fold and leave-one-out cross validation (LOOCV) techniques. Classification into control vs. dyslexic subjects achieved above chance accuracy (AUC = 0.66 and ACC = 0.65 in the case of 10-fold CV, and AUC = 0.65 and ACC = 0.64 using LOOCV) after principled feature selection. Features that discriminated between dyslexic and control children were exclusively situated in the left hemisphere including superior and middle temporal gyri, subparietal sulcus and prefrontal areas. They were related to geometric properties of the cortex, with generally higher mean curvature and a greater folding index characterizing the dyslexic group. Our results support the hypothesis that an atypical curvature pattern with extra folds in left hemispheric perisylvian regions characterizes dyslexia. Hum Brain Mapp 38:900-908, 2017. © 2016 Wiley Periodicals, Inc.

How reliable are gray matter disruptions in specific reading disability across multiple countries and languages? Insights from a large-scale voxel-based morphometry study.

The neural basis of specific reading disability (SRD) remains only partly understood. A dozen studies have used voxel-based morphometry (VBM) to investigate gray matter volume (GMV) differences between SRD and control children, however, recent meta-analyses suggest that few regions are consistent across studies. We used data collected across three countries (France, Poland, and Germany) with the aim of both increasing sample size (236 SRD and controls) to obtain a clearer picture of group differences, and of further assessing the consistency of the findings across languages. VBM analysis reveals a significant group difference in a single cluster in the left thalamus. Furthermore, we observe correlations between reading accuracy and GMV in the left supramarginal gyrus and in the left cerebellum, in controls only. Most strikingly, we fail to replicate all the group differences in GMV reported in previous studies, despite the superior statistical power. The main limitation of this study is the heterogeneity of the sample drawn from different countries (i.e., speaking languages with varying orthographic transparencies) and selected based on different assessment batteries. Nevertheless, analyses within each country support the conclusions of the cross-linguistic analysis. Explanations for the discrepancy between the present and previous studies may include: (1) the limited suitability of VBM to reveal the subtle brain disruptions underlying SRD; (2) insufficient correction for multiple statistical tests and flexibility in data analysis, and (3) publication bias in favor of positive results. Thus the study echoes widespread concerns about the risk of false-positive results inherent to small-scale VBM studies.

From a concept to a word in a syntactically complete sentence: an fMRI study on spontaneous language production in an overt picture description task.

Spontaneous language has rarely been subjected to neuroimaging studies. This study therefore introduces a newly developed method for the analysis of linguistic phenomena observed in continuous language production during fMRI. Most neuroimaging studies investigating language have so far focussed on single word or - to a smaller extent - sentence processing, mostly due to methodological considerations. Natural language production, however, is far more than the mere combination of words to larger units. Therefore, the present study aimed at relating brain activation to linguistic phenomena like word-finding difficulties or syntactic completeness in a continuous language fMRI paradigm. A picture description task with special constraints was used to provoke hesitation phenomena and speech errors. The transcribed speech sample was segmented into events of one second and each event was assigned to one category of a complex schema especially developed for this purpose. The main results were: conceptual planning engages bilateral activation of the precuneus. Successful lexical retrieval is accompanied - particularly in comparison to unsolved word-finding difficulties - by the left middle and superior temporal gyrus. Syntactic completeness is reflected in activation of the left inferior frontal gyrus (IFG) (area 44). In sum, the method has proven to be useful for investigating the neural correlates of lexical and syntactic phenomena in an overt picture description task. This opens up new prospects for the analysis of spontaneous language production during fMRI.

Computer-assisted analysis of spontaneous speech: quantification of basic parameters in aphasic and unimpaired language.

Although generally accepted as an important part of aphasia assessment, detailed analysis of spontaneous speech is rarely carried out in clinical practice mostly due to time limitations. The Aachener Sprachanalyse (ASPA; Aachen Speech Analysis) is a computer-assisted method for the quantitative analysis of German spontaneous speech that allows for a detailed assessment by means of linguistic basic parameters in an acceptable amount of time. It has previously been proven sensitive for monitoring changes over time. In this study, we present data of 52 aphasic participants whose spontaneous speech was analyzed retrospectively before and after an intensive therapy program. The measured changes are evaluated with reference to normative data of 60 non-brain-damaged speakers. Results confirm good sensitivity to document changes over time. Clinical relevance of changes is assessed with reference to critical score ranges derived from the normative data. Findings provide further evidence of the clinical applicability and usefulness of ASPA.

Word frequency effects in the left IFG in dyslexic and normally reading children during picture naming and reading.

Word frequency effects have been reported in numerous neuroimaging studies with typically reading adults, emphasising the role of the left inferior frontal gyrus (LIFG). Within LIFG, different cytoarchitectonic modules (areas 44 and 45) have been related to phonological vs. lexico-semantic processing, respectively. This fMRI study investigated the differential impact of word frequency on LIFG activation in reading and picture naming in primary school children with and without developmental dyslexia. All children showed the typical LIFG frequency effect in both tasks. The effect was comparable in a fronto-orbital region anterior-inferior adjacent to area 45. During reading but not picture naming, a second effect was observed in area 44. Here, the fMRI effect for lexical frequency was stronger for the dyslexic than the normal readers. These findings demonstrate the neural underpinnings of a selective deficit in dyslexic children in the graphemic input lexicon, whereas abstract lexical representations appear to be processed equally well in dyslexic and normally reading children. To conclude, the present fMRI study demonstrated differential impact of word frequency on LIFG activation in primary school children during reading but not picture naming. Apart from extending previous knowledge from studies with adults to childhood, the study sheds further light on a potential neural mechanism for deficient grapheme-to-phoneme conversion in dyslexic children.

Neuro-cognitive foundations of word stress processing - evidence from fMRI.

BACKGROUND: To date, the neural correlates of phonological word stress processing are largely unknown. METHODS: In the present study, we investigated the processing of word stress and vowel quality using an identity matching task with pseudowords. RESULTS: In line with previous studies, a bilateral fronto-temporal network comprising the superior temporal gyri extending into the sulci as well as the inferior frontal gyri was observed for word stress processing. Moreover, we found differences in the superior temporal gyrus and the superior temporal sulcus, bilaterally, for the processing of different stress patterns. For vowel quality processing, our data reveal a substantial contribution of the left intraparietal cortex. All activations were modulated by task demands, yielding different patterns for same and different pairs of stimuli. CONCLUSIONS: Our results suggest that the left superior temporal gyrus represents a basic system underlying stress processing to which additional structures including the homologous cortex site are recruited with increasing difficulty.

Eliciting dyslexic symptoms in proficient readers by simulating deficits in grapheme-to-phoneme conversion and visuo-magnocellular processing.

Among the cognitive causes of dyslexia, phonological and magnocellular deficits have attracted a substantial amount of research. Their role and their exact impact on reading ability are still a matter of debate, partly also because large samples of dyslexics are hard to recruit. Here, we report a new technique to simulate dyslexic symptoms in normal readers in two ways. Although difficulties in grapheme-to-phoneme conversion were elicited by manipulating the identifiability of written letters, visual-magnocellular processing deficits were generated by presenting letters moving dynamically on the screen. Both factors were embedded into a lexical word-pseudoword decision task with proficient German readers. Although both experimental variations systematically increased lexical decision times, they did not interact. Subjects successfully performed word-pseudoword distinctions at all levels of simulation, with consistently longer reaction times for pseudowords than for words. Interestingly, detecting a pseudoword was more difficult in the grapheme-to-phoneme conversion simulation as indicated by a significant interaction of word type and letter shape. These behavioural effects are consistent with those observed in 'real' dyslexics in the literature. The paradigm is thus a potential means of generating novel hypotheses about dyslexia, which can easily be tested with normal readers before screening and recruiting real dyslexics.

Taboo: a novel paradigm to elicit aphasia-like trouble-indicating behaviour in normally speaking individuals.

Two important research lines in neuro- and psycholinguistics are studying natural or experimentally induced slips of the tongue and investigating the symptom patterns of aphasic individuals. Only few studies have focused on explaining aphasic symptoms by provoking aphasic symptoms in healthy speakers. While all experimental techniques have so far dealt with the single word or the sentence level, the current study intended to provoke aphasia-like trouble-indicating behaviour (i.e. prepairs and repairs) in the spontaneous language production of unimpaired speakers. In their descriptions of complex pictures, the participants were requested to avoid particular words terming central elements of the pictures. The results show that the error pattern provoked by the novel "taboo" paradigm resembled substantially the pattern of aphasic individuals. Consequently, the paradigm is applicable for further studies, e.g. for bringing forward the understanding of spontaneous language production or for comparing the neurofunctional basis of errors in healthy and aphasic speakers.

Cognitive levels of performance account for hemispheric lateralisation effects in dyslexic and normally reading children.

Recent theories of developmental dyslexia explain reading deficits in terms of deficient phonological awareness, attention, visual and auditory processing, or automaticity. Since dyslexia has a neurobiological basis, the question arises how the reader's proficiency in these cognitive variables affects the brain regions involved in visual word recognition. This question was addressed in two fMRI experiments with 19 normally reading children (Experiment 1) and 19 children with dyslexia (Experiment 2). First, reading-specific brain activation was assessed by contrasting the BOLD signal for reading aloud words vs. overtly naming pictures of real objects. Next, ANCOVAs with brain activation during reading the individuals' scores for all five cognitive variables assessed outside the scanner as covariates were performed. Whereas the normal readers' brain activation during reading showed co-variation effects predominantly in the right hemisphere, the reverse pattern was observed for the dyslexics. In particular, middle frontal gyrus, inferior parietal cortex, and precuneus showed contralateral effects for controls as compared to dyslexics. In line with earlier findings in the literature, these data hint at a global change in hemispheric asymmetry during cognitive processing in dyslexic readers, which, in turn, might affect reading proficiency.

Interaction of phonological awareness and 'magnocellular' processing during normal and dyslexic reading: behavioural and fMRI investigations.

We investigated whether phonological deficits are a consequence of magnocellular processing deficits in dyslexic and control children. In Experiment 1, children were tested for reading ability, phonological awareness, visuo-magnocellular motion perception, and attention shifting (sometimes considered as magnocellular function). A two-step cluster analysis of the behavioural scores revealed four clusters of children. Phonological awareness was correlated with attention (cluster musical sharp1) or motion detection (cluster musical sharp2), whereas attention and motion detection were correlated in cluster musical sharp3. In cluster musical sharp4, all variables were uncorrelated. In Experiment 2, the same variables plus auditory discrimination were tested with fMRI in a sub-sample of Experiment 1. Although dyslexics had reduced activation in visual or auditory cortex during motion detection or auditory discrimination, respectively, they had increased right frontal activation in areas 44 and 45 in all 'magnocellular' (including auditory) tasks. In contrasts, during phonological decisions, there was higher activation for good readers than dyslexics in left areas 44 and 45. Together, the two experiments give insight into the interplay of phonological and magnocellular processing during reading. Distinct left versus right frontal effects reveal partly different underlying neural mechanisms. These data contradict the view that phonological processing deficits in dyslexia necessarily result from impaired magnocellular functioning.

The role of phonological awareness in treatments of dyslexic primary school children.

The present study investigated whether phonological awareness training is an effective intervention to significantly improve reading in German dyslexic third and fourth graders with a phonological awareness deficit, and whether these children can equally benefit from a phonology-based reading training or a visually-based reading training. German speaking dyslexic elementary school children (n=30; M=9.8 years) were matched by forming triplets based on IQ, reading quotient and phonological awareness and then randomly assigned to one out of three interventions (n=10): a phonological awareness training, a phonology-based reading training (phonics instruction), and a visually-based reading training (repeated reading of sight words). A total of 20 training sessions (30 minutes each) were distributed over four weeks. Typical readers (n=10; M=9.5 years) were assigned to the control group. Phonological awareness training directly improves reading comprehension in German dyslexic children with a phonological awareness deficit. However, these children can equally benefit from a visually-based reading training. In contrast, the phonology-based reading training has a direct selective effect on decoding but not on reading comprehension. Despite divergent short-term patterns, long-term improvement of reading comprehension and decoding is similar across all training groups, irrespective of the training method. Phonological awareness may but does not need to be part of reading remediation in dyslexic children with a phonological deficit when learning to read a consistent orthography. Rather, a visually-based reading strategy might compensate for the phonological deficit in dyslexic children after the initial stage of reading acquisition.

Shared vs. specific brain activation changes in dyslexia after training of phonology, attention, or reading.

Whereas the neurobiological basis of developmental dyslexia has received substantial attention, only little is known about the processes in the brain during remediation. This holds in particular in light of recent findings on cognitive subtypes of dyslexia which suggest interactions between individual profiles, training methods, and also the task in the scanner. Therefore, we trained three groups of German dyslexic primary school children in the domains of phonology, attention, or visual word recognition. We compared neurofunctional changes after 4 weeks of training in these groups to those in untrained normal readers in a reading task and in a task of visual attention. The overall reading improvement in the dyslexic children was comparable over groups. It was accompanied by substantial increase of the activation level in the visual word form area (VWFA) during a reading task inside the scanner. Moreover, there were activation increases that were unique for each training group in the reading task. In contrast, when children performed the visual attention task, shared training effects were found in the left inferior frontal sulcus and gyrus, which varied in amplitude between the groups. Overall, the data reveal that different remediation programmes matched to individual profiles of dyslexia may improve reading ability and commonly affect the VWFA in dyslexia as a shared part of otherwise distinct networks.

The direction of word stress processing in German: evidence from a working memory paradigm.

There are contradicting assumptions and findings on the direction of word stress processing in German. To resolve this question, we asked participants to read tri-syllabic non-words and stress ambiguous words aloud. Additionally, they also performed a working memory (WM) task (2-back task). In non-word reading, participants' individual WM capacity was positively correlated with assignment of main stress to the antepenultimate syllable, which is most distant to the word's right edge, while a (complementary) negative correlation was observed with assignment of stress to the ultimate syllable. There was no significant correlation between WM capacity and stress assignment to the penultimate syllable, which has been claimed to be the default stress pattern in German. In reading stress ambiguous words, a similar but non-significant pattern was observed as in non-word reading. In sum, our results provide first psycholinguistic evidence supporting leftward stress processing in German. Our results do not lend support to the assumption of penultimate default stress in German. A specification of the lemma model is proposed which seems able to reconcile our findings and apparently contradicting assumptions and evidence.

Experimental induction of reading difficulties in normal readers provides novel insights into the neurofunctional mechanisms of visual word recognition.

Phonological and visual dysfunctions may result in reading deficits like those encountered in developmental dyslexia. Here, we use a novel approach to induce similar reading difficulties in normal readers in an event-related fMRI study, thus systematically investigating which brain regions relate to different pathways relating to orthographic-phonological (e.g. grapheme-to-phoneme conversion, GPC) vs. visual processing. Based upon a previous behavioural study (Tholen et al. 2011), the retrieval of phonemes from graphemes was manipulated by lowering the identifiability of letters in familiar vs. unfamiliar shapes. Visual word and letter processing was impeded by presenting the letters of a word in a moving, non-stationary manner. FMRI revealed that the visual condition activated cytoarchitectonically defined area hOC5 in the magnocellular pathway and area 7A in the right mesial parietal cortex. In contrast, the grapheme manipulation revealed different effects localised predominantly in bilateral inferior frontal gyrus (left cytoarchitectonic area 44; right area 45) and inferior parietal lobule (including areas PF/PFm), regions that have been demonstrated to show abnormal activation in dyslexic as compared to normal readers. This pattern of activation bears close resemblance to recent findings in dyslexic samples both behaviourally and with respect to the neurofunctional activation patterns. The novel paradigm may thus prove useful in future studies to understand reading problems related to distinct pathways, potentially providing a link also to the understanding of real reading impairments in dyslexia.

The neural correlates of agrammatism: Evidence from aphasic and healthy speakers performing an overt picture description task.

Functional brain imaging studies have improved our knowledge of the neural localization of language functions and the functional reorganization after a lesion. However, the neural correlates of agrammatic symptoms in aphasia remain largely unknown. The present fMRI study examined the neural correlates of morpho-syntactic encoding and agrammatic errors in continuous language production by combining three approaches. First, the neural mechanisms underlying natural morpho-syntactic processing in a picture description task were analyzed in 15 healthy speakers. Second, agrammatic-like speech behavior was induced in the same group of healthy speakers to study the underlying functional processes by limiting the utterance length. In a third approach, five agrammatic participants performed the picture description task to gain insights in the neural correlates of agrammatism and the functional reorganization of language processing after stroke. In all approaches, utterances were analyzed for syntactic completeness, complexity, and morphology. Event-related data analysis was conducted by defining every clause-like unit (CLU) as an event with its onset-time and duration. Agrammatic and correct CLUs were contrasted. Due to the small sample size as well as heterogeneous lesion sizes and sites with lesion foci in the insula lobe, inferior frontal, superior temporal and inferior parietal areas the activation patterns in the agrammatic speakers were analyzed on a single subject level. In the group of healthy speakers, posterior temporal and inferior parietal areas were associated with greater morpho-syntactic demands in complete and complex CLUs. The intentional manipulation of morpho-syntactic structures and the omission of function words were associated with additional inferior frontal activation. Overall, the results revealed that the investigation of the neural correlates of agrammatic language production can be reasonably conducted with an overt language production paradigm.

Longitudinal changes in brains of patients with fluent primary progressive aphasia.

Primary progressive aphasia (PPA) is a rare clinical dementia syndrome with predominant, progressive language impairment. Clinical symptoms, linguistic impairment and the course of the disease may vary considerably between patients. In order to capture these aspects, longitudinal assessments of neurofunctional changes in PPA including their relationship to behaviour and clinical symptoms are mandatory, ideally at intervals shorter than 1 year. Here, we report a longitudinal fMRI study investigating the development of lexical processing and their neural basis in PPA patients over 1year. Four logopenic PPA patients and four matched controls were scanned 3 times (T1, T2, T3, at 6months intervals) while performing a visual lexical decision task on German words and pseudowords. Group differences for the lexicality effect (pseudowords>words) were assessed at time point T1 and its longitudinal changes in the BOLD signal associated with the lexicality effect were analysed. Brain atrophy was assessed with a high-resolution MPRAGE sequence and analysed using deformation based morphometry (DBM). From the very beginning of the study, PPA patients showed reduced left-hemispheric and increased right-hemispheric activations compared to controls. During the progression of the disease, activation increased predominantly in left posterior middle temporal gyrus (pMTG) and inferior frontal junction area, whereas the same regions decreased in activity in control brains. Interestingly, DBM data showed that this increase in activation in PPA patients was accompanied by progressing atrophy in the same regions. At a behavioural level, the accuracy in the lexical decision task was comparably high for both groups during the whole period of examination, despite some large variability between patients. To conclude, the dissociation between (i) maintained high performance, (ii) increased activity in regions involved in lexical access such as pMTG, and (iii) progressive atrophy of the very same regions supports the notion of a compensatory mechanism in brains of PPA patients for maintaining language while brain atrophy is progressing. The activity increase within a left-lateralised fronto-temporal network seems vital for high-level performance, whereas initial right-hemispheric recruitment of homologue language regions, which is reminiscent of that in vascular aphasics, has no continuous impact on lexical performance.

Effects of lexicality and word frequency on brain activation in dyslexic readers.

We investigated the neural basis of lexical access to written stimuli in adult dyslexics and normal readers via the Lexicality effect (pseudowords>words) and the Frequency effect (low>high frequent words). The participants read aloud German words (with low or high lexical frequency) or pseudowords while being scanned. In both groups, both Lexicality effect and Frequency effect involved Broca's region (areas 44 and 45). Whereas the effects were stronger for dyslexic than normal readers in area 44, area 45 showed the reverse pattern. These findings mimic recent results from an fMRI study on dyslexic primary school children, indicating that lexical access to written stimuli poses increased and enduring difficulties on dyslexic readers, at least in a language with a transparent orthography. Additionally, data from four compensated adult dyslexics are reported and discussed, which hint at the importance of both Broca's and Wernicke's region for recovery from childhood dyslexia.

Distinct neural signatures of cognitive subtypes of dyslexia: effects of lexicality during phonological processing.

The present study investigates the neurobiological basis of two subtypes of dyslexia with either a double deficit (concerning phonological awareness and rapid naming) or a single rapid naming deficit. We compared such groups of German dyslexic primary school children to each other and with good reading children in a phoneme deletion task performed during fMRI scanning. Children heard German words or pseudowords and repeated the remainder of the stimulus while deleting the initial phoneme (e.g. tear - _ear). In four conditions, the input stimulus (word or pseudoword) could either become another word or pseudoword as output. The word-word condition stuck out against all other conditions involving pseudowords: Dyslexics with a double deficit showed a strong response in left areas 44 and 45 in Boca's region, whereas dyslexics with rapid naming difficulties revealed a contralateral effect in right areas 44 and 45. These findings, which were obtained without presenting written or pictorial stimuli, reveal that a double deficit in dyslexia is not the sum of single deficits, but rather involves the interaction of lexical and phonological processing, making strong demands on the left inferior frontal cortex. In general, the results stress the importance of considering subtypes of dyslexia differentially in order to obtain better insights in the neurocognitive mechanisms of impaired and successful reading.

Distinct neural signatures of cognitive subtypes of dyslexia with and without phonological deficits.

Developmental dyslexia can be distinguished as different cognitive subtypes with and without phonological deficits. However, despite some general agreement on the neurobiological basis of dyslexia, the neurofunctional mechanisms underlying these cognitive subtypes remain to be identified. The present BOLD fMRI study thus aimed at investigating by which distinct and/or shared neural activation patterns dyslexia subtypes are characterized. German dyslexic fourth graders with and without deficits in phonological awareness and age-matched normal readers performed a phonological decision task: does the auditory word contain the phoneme/a/? Both dyslexic subtypes showed increased activation in the right cerebellum (Lobule IV) compared to controls. Subtype-specific increased activation was systematically found for the phonological dyslexics as compared to those without this deficit and controls in the left inferior frontal gyrus (area 44: phonological segmentation), the left SMA (area 6), the left precentral gyrus (area 6) and the right insula. Non-phonological dyslexics revealed subtype-specific increased activation in the left supramarginal gyrus (area PFcm; phonological storage) and angular gyrus (area PGp). The study thus provides the first direct evidence for the neurobiological grounding of dyslexia subtypes. Moreover, the data contribute to a better understanding of the frequently encountered heterogeneous neuroimaging results in the field of dyslexia.