Methodological considerations in assessment of language lateralisation with fMRI: a systematic review

The involvement of the right and left hemispheres in mediating language functions has been measured in a variety of ways over the centuries since the relative dominance of the left hemisphere was first known. Functional magnetic resonance imaging (fMRI) presents a useful non-invasive method of assessing lateralisation that is being increasingly used in clinical practice and research. However, the methods used in the fMRI laterality literature currently are highly variable, making systematic comparisons across studies difficult. Here we consider the different methods of quantifying and classifying laterality that have been used in fMRI studies since 2000, with the aim of determining which give the most robust and reliable measurement. Recommendations are made with a view to informing future research to increase standardisation in fMRI laterality protocols. In particular, the findings reinforce the importance of threshold-independent methods for calculating laterality indices, and the benefits of assessing heterogeneity of language laterality across multiple regions of interest and tasks. This systematic review was registered as a protocol on Open Science Framework: https://osf.io/hyvc4/

Measuring language lateralisation with different language tasks: a systematic review

Language lateralisation refers to the phenomenon in which one hemisphere (typically the left) shows greater involvement in language functions than the other. Measurement of laterality is of interest both to researchers investigating the neural organisation of the language system and to clinicians needing to establish an individual’s hemispheric dominance for language prior to surgery, as in patients with intractable epilepsy. Recently, there has been increasing awareness of the possibility that different language processes may develop hemispheric lateralisation independently, and to varying degrees. However, it is not always clear whether differences in laterality across language tasks with fMRI are reflective of meaningful variation in hemispheric lateralisation, or simply of trivial methodological differences between paradigms. This systematic review aims to assess different language tasks in terms of the strength, reliability and robustness of the laterality measurements they yield with fMRI, to look at variability that is both dependent and independent of aspects of study design, such as the baseline task, region of interest, and modality of the stimuli. Recommendations are made that can be used to guide task design; however, this review predominantly highlights that the current high level of methodological variability in language paradigms prevents conclusions as to how different language functions may lateralise independently. We conclude with suggestions for future research using tasks that engage distinct aspects of language functioning, whilst being closely matched on non-linguistic aspects of task design (e.g., stimuli, task timings etc); such research could produce more reliable and conclusive insights into language lateralisation. This systematic review was registered as a protocol on Open Science Framework: https://osf.io/5vmpt/

Randomized trial of iReadMore word reading training and brain stimulation in central alexia

Central alexia is an acquired reading disorder co-occurring with a generalized language deficit (aphasia). We tested the impact of a novel training app, ‘iReadMore’, and anodal transcranial direct current stimulation of the left inferior frontal gyrus, on word reading ability in central alexia. The trial was registered at www.clinicaltrials.gov (NCT02062619). Twenty-one chronic stroke patients with central alexia participated. A baseline-controlled, repeated-measures, crossover design was used. Participants completed two 4-week blocks of iReadMore training, one with anodal stimulation and one with sham stimulation (order counterbalanced between participants). Each block comprised 34 h of iReadMore training and 11 stimulation sessions. Outcome measures were assessed before, between and after the two blocks. The primary outcome measures were reading ability for trained and untrained words. Secondary outcome measures included semantic word matching, sentence reading, text reading and a self-report measure. iReadMore training resulted in an 8.7% improvement in reading accuracy for trained words (95% confidence interval 6.0 to 11.4; Cohen’s d = 1.38) but did not generalize to untrained words. Reaction times also improved. Reading accuracy gains were still significant (but reduced) 3 months after training cessation. Anodal transcranial direct current stimulation (compared to sham), delivered concurrently with iReadMore, resulted in a 2.6% (95% confidence interval −0.1 to 5.3; d = 0.41) facilitation for reading accuracy, both for trained and untrained words. iReadMore also improved performance on the semantic word-matching test. There was a non-significant trend towards improved self-reported reading ability. However, no significant changes were seen at the sentence or text reading level. In summary, iReadMore training in post-stroke central alexia improved reading ability for trained words, with good maintenance of the therapy effect. Anodal stimulation resulted in a small facilitation (d = 0.41) of learning and also generalized to untrained items

Robust and Task-Independent Spatial Profile of the Visual Word Form Activation in Fusiform Cortex

Written language represents a special category of visual information. There is strong evidence for the existence of a cortical region in ventral occipitotemporal cortex for processing the visual form of written words. However, due to inconsistent findings obtained with different tasks, the level of specialization and selectivity of this so called visual word form area (VWFA) remains debated. In this study, we examined category selectivity for Chinese characters, a non-alphabetic script, in native Chinese readers. In contrast to traditional approaches of examining response levels in a restricted predefined region of interest (ROI), a detailed distribution of the BOLD signal across the mid-fusiform cortical surface and the spatial patterns of responses to Chinese characters were obtained. Results show that a region tuned for Chinese characters could be consistently found in the lateral part of the left fusiform gyrus in Chinese readers, and this spatial pattern of selectivity for written words was not influenced by top-down tasks such as phonological or semantic modulations. These results provide strong support for the robust spatial coding of category selective response in the mid-fusiform cortex, and demonstrate the utility of the spatial distribution analysis as a more meaningful approach to examine functional magnetic resonance imaging (fMRI) data

Methodological considerations in assessment of language lateralisation with fMRI: a systematic review

The involvement of the right and left hemispheres in mediating language functions has been measured in a variety of ways over the centuries since the relative dominance of the left hemisphere was first known. Functional magnetic resonance imaging (fMRI) presents a useful non-invasive method of assessing lateralisation that is being increasingly used in clinical practice and research. However, the methods used in the fMRI laterality literature currently are highly variable, making systematic comparisons across studies difficult. Here we consider the different methods of quantifying and classifying laterality that have been used in fMRI studies since 2000, with the aim of determining which give the most robust and reliable measurement. Recommendations are made with a view to informing future research to increase standardisation in fMRI laterality protocols. In particular, the findings reinforce the importance of threshold-independent methods for calculating laterality indices, and the benefits of assessing heterogeneity of language laterality across multiple regions of interest and tasks. This systematic review was registered as a protocol on Open Science Framework: https://osf.io/hyvc4/

Methodological considerations in assessment of language lateralisation with fMRI: a systematic review

The involvement of the right and left hemispheres in mediating language functions has been measured in a variety of ways over the centuries since the relative dominance of the left hemisphere was first known. Functional magnetic resonance imaging (fMRI) presents a useful non-invasive method of assessing lateralisation that is being increasingly used in clinical practice and research. However, the methods used in the fMRI laterality literature currently are highly variable, making systematic comparisons across studies difficult. Here we consider the different methods of quantifying and classifying laterality that have been used in fMRI studies since 2000, with the aim of determining which give the most robust and reliable measurement. Recommendations are made with a view to informing future research to increase standardisation in fMRI laterality protocols. In particular, the findings reinforce the importance of threshold-independent methods for calculating laterality indices, and the benefits of assessing heterogeneity of language laterality across multiple regions of interest and tasks. This systematic review was registered as a protocol on Open Science Framework: https://osf.io/hyvc4/

Testing the interhemispheric deficit theory of dyslexia using the visual half-field technique

A deficit in interhemispheric transfer has been proposed as a neuropsychological theory of dyslexia. The role of interactions between the hemispheres during word recognition is demonstrated in two behavioural effects robustly reported using the visual half field paradigm. The well-established recognition advantage for right visual field (RVF) words over left visual field (LVF) words reflects the additional processing costs associated with callosal transfer of LVF word representations to the language specialised left hemisphere. Additionally, a further gain in recognition for bilateral presentation of a word is attributed to cooperative interactions between the hemispheres. These recognition advantages can therefore be seen as behavioural indices of the efficiency of callosal transfer. This study aimed to replicate the finding of an absence of the bilateral advantage in developmental dyslexia, previously reported by Henderson, Barca and Ellis (2007). 47 dyslexic and 43 control adult participants were tested, and no significant difference found in the size of their bilateral advantages. Our data did however replicate the previous finding of an increased RVF advantage in right handed dyslexic participants caused by poorer accuracy for LVF words. This evidence provides partial support for the interhemispheric deficit theory of dyslexia, suggesting an impairment in the transfer of visual word information from the right to the left hemisphere during reading.</p

Investigation into inconsistent lateralisation of language functions as a potential risk factor for language impairment

Disruption to language lateralisation has been proposed as a cause of developmental language impairments. In this study, we tested the idea that consistency of lateralisation across different language functions is associated with language ability. A large sample of adults with variable language abilities (N = 67 with a developmental disorder affecting language and N = 37 controls) were recruited. Lateralisation was measured using functional transcranial Doppler sonography (fTCD) for three language tasks that engage different language subprocesses (phonological decision, semantic decision and sentence generation). The whole sample was divided into those with consistent versus inconsistent lateralisation across the three tasks. Language ability (using a battery of standardised tests) was compared between the consistent and inconsistent groups. The results did not show a significant effect of lateralisation consistency on language skills. However, of the 31 individuals showing inconsistent lateralisation, the vast majority (84%) were in the disorder group with only five controls showing such a pattern, a difference that was higher than would be expected by chance. The developmental disorder group also demonstrated weaker correlations between laterality indices across pairs of tasks. In summary, although the data did not support the hypothesis that inconsistent language lateralisation is a major cause of poor language skills, the results suggested that some subtypes of language disorder are associated with inefficient distribution of language functions between hemispheres. Inconsistent lateralisation could be a causal factor in the aetiology of language disorder or may arise in some cases as the consequence of developmental disorder, possibly reflective of compensatory reorganisation

Profile of language abilities in a sample of adults with developmental disorders

This study investigated the profile of language abilities in a sample of high-achieving English speaking adults with developmental disorders. Ninety-seven adult participants were recruited: 49 with a dyslexia diagnosis (dyslexic group), 16 with a diagnosis of a different developmental disorder including dyspraxia, autism and SpLD (non-dyslexic developmental disorder group) and 32 with no diagnosis (non-disordered group). Dyslexic and non-dyslexic developmental disorder groups demonstrated similar impairments across measures of word reading, working memory, processing speed and oral language. Dyslexic participants showed the usual pattern of impaired phonological skills but spared non-verbal intelligence and vocabulary. There were also some suggestions of impaired structural oral language skills in this group. A data-driven clustering analysis found that diagnosis was not a reliable predictor of similarity between cases, with diagnostic categories split between data-driven clusters. Overall, the findings indicate that high-achieving adults with developmental disorders do demonstrate impairments that are likely to affect success in higher education, but that support needs should be assessed on a case-by-case basis, rather than according to diagnostic label

An updated investigation of the multidimensional structure of language lateralization in left- and right-handed adults: a test–retest functional transcranial Doppler sonography study with six language tasks

A previous study we reported in this journal suggested that left and right-handers may differ in their patterns of lateralization for different language tasks (Woodhead et al. 2019 R. Soc. Open Sci.6, 181801. (doi:10.1098/rsos.181801)). However, it had too few left-handers (N = 7) to reach firm conclusions. For this update paper, further participants were added to the sample to create separate groups of left- (N = 31) and right-handers (N = 43). Two hypotheses were tested: (1) that lateralization would be weaker at the group level in left-than right-handers; and (2) that left-handers would show weaker covariance in lateralization between tasks, supporting a two-factor model. All participants performed the same protocol as in our previous paper: lateralization was measured using functional transcranial Doppler sonography during six different language tasks, on two separate testing sessions. The results supported hypothesis 1, with significant differences in laterality between groups for four out of six tasks. For hypothesis 2, structural equation modelling showed that there was stronger evidence for a two-factor model in left than right-handers; furthermore, examination of the factor loadings suggested that the pattern of laterality across tasks may also differ between handedness groups. These results expand on what is known about the differences in laterality between left- and right-handers