Investigating the function of the ventral visual reading pathway and its involvement in acquired reading disorders

This thesis investigated the role of the left ventral occipitotemporal (vOT) cortex and how damage to this area causes peripheral reading disorders. Functional magnetic resonance imaging (fMRI) studies in volunteers demonstrated that the left vOT is activated by written words over numbers or perceptually-matched baselines, irrespective of the word’s location on the visual field. Mixed results were observed for the comparison of words versus false font stimuli. This response profile suggests that the left vOT is preferentially activated by words or word-like stimuli, due to either: (1) bottom-up specialisation for processing familiar word-forms; (2) top-down task-dependent modulation, or (3) a combination of the two. Further studies are proposed to discriminate between these possibilities. Thirteen patients with left occipitotemporal damage participated in the rehabilitation and fMRI studies. The patients were impaired on word, text and letter reading. A structural analysis showed that damage to the left occipitotemporal white matter, in the vicinity of the inferior longitudinal fasciculus, was associated with slow word reading speed. The fMRI study showed that the patients had reduced activation of the bilateral posterior superior temporal sulci relative to controls. Activity in this area correlated with reading speed. The efficacy of intensive whole-word recognition training was tested. Immediately after the training, trained words were read faster than untrained words, but the effects did not persist until the follow-up assessment. Hence, damage to the left vOT white matter impairs rapid whole-word recognition and is resistant to rehabilitation. The final study investigated the role of spatial frequency (SF) in the lateralisation of vOT function. Lateralisation of high and low SF processing was demonstrated, concordant with the lateralisation for words and faces to the left and right vOT respectively. A perceptual basis for the organisation of vOT cortex might explain why left vOT damage is resistant to treatment

Does growth in private schooling contribute to Education for All? Evidence from a longitudinal, two cohort study in Andhra Pradesh, India

This paper informs debates about the potential role for low-fee private schooling in achieving Education for All goals in India. It reports ‘Young Lives’ longitudinal data for two cohorts (2,906 children) in the state of Andhra Pradesh. Eight year olds uptake of private schooling increased from 24 per cent (children born in 1994-5) to 44 per cent (children born in 2001-2). Children from rural areas, lower socioeconomic backgrounds and girls continue to be under represented. While some access gaps decreased, the gender gap seems to be widening. Evidence on risks to equity strengthen the case for an effectively regulated private sector, along with reforms to government sector schools

Orthographic neighborhood effects during lateralized lexical decision are abolished with bilateral presentation

Words presented to the right visual field (RVF) are processed more rapidly than those in the left visual field (LVF), presumably because of more direct links to the language dominant left cerebral hemisphere. This effect is moderated by a word’s orthographic neighborhood size (N), with LVF facilitation and RVF inhibition for words with a large N. Across two experiments, we sought to further examine lateralized N effects. Experiment 1 examined how hemispheric dominance for language influenced lateralized N effects, in 140 left-handers using a visual half-field task with bilateral presentation. Neither participants with a right ear advantage on a dichotic listening task nor participants with no right ear advantage showed the expected N effect, making the results ambiguous: it could be that left-handers fail to show N effects, or the effect could be abolished by some procedural aspect. Experiment 2 looked to test these options by testing 56 right-handers who responded to the same stimulus set under the original bilateral presentation condition and under unilateral presentation. N effects were found under unilateral but not bilateral presentation. We had adopted bilateral presentation because it had been recommended as better than unilateral presentation for controlling fixation and visual stimulation; our results indicate that this is not a minor methodological modification: it can dramatically affect lateralized N effects. (PsycInfo Database Record (c) 2022 APA, all rights reserved

Measurement of language laterality using functional transcranial Doppler ultrasound: a comparison of different tasks [version 2; referees: 2 approved]

Background: Relative blood flow in the two middle cerebral arteries can be measured using functional transcranial Doppler sonography (fTCD) to give an index of lateralisation as participants perform a specific task. Language laterality has mostly been studied with fTCD using a word generation task, but it is not clear whether this is optimal. Methods: Using fTCD, we evaluated a sentence generation task that has shown good reliability and strong left lateralisation in fMRI. We interleaved trials of word generation, sentence generation and list generation and assessed agreement of these tasks in 31 participants (29 right-handers). Results: Although word generation and sentence generation both gave robust left-lateralisation, Bland-Altman analysis showed that these two methods were not equivalent. The comparison list generation task was not systematically lateralised, but nevertheless laterality indices (LIs) from this task were significantly correlated with the other two tasks. Subtracting list generation LI from sentence generation LI did not affect the strength of the laterality index. Conclusions: This was a pre-registered methodological study designed to explore novel approaches to optimising measurement of language lateralisation using fTCD. It confirmed that sentence generation gives robust left lateralisation in most people, but is not equivalent to the classic word generation task. Although list generation does not show left-lateralisation at the group level, the LI on this task was correlated with left-lateralised tasks. This suggests that word and sentence generation involve adding a constant directional bias to an underlying continuum of laterality that is reliable in individuals but not biased in either direction. In future research we suggest that consistency of laterality across tasks might have more functional significance than strength or direction of laterality on any one task

The role of orthographic neighbourhood effects in lateralized lexical decision: a replication study and meta-analysis

The effect of orthographic neighbourhood size (N) on lexical decision reaction time differs when words are presented in the left or right visual fields. Evidence suggests a facilitatory N effect (i.e., faster reaction times for words with larger neighbourhoods) in the left visual field. However, the N effect in the right visual field remains controversial: it may have a weaker facilitative role or it may even be inhibitory. In a pre-registered online experiment, we replicated the interaction between N and visual field and provided support for an inhibitory N effect in the right visual field. We subsequently conducted a pre-registered systematic review and meta-analysis to synthesise the available evidence and determine the direction of N effects across visual fields. Based on the evidence, it would seem the effect is inhibitory in the right visual field. Furthermore, the size of the N effect is considerably smaller in the right visual field. Both studies revealed considerable heterogeneity between participants and studies, and we consider the implications of this for future work

How does iReadMore therapy change the reading network of patients with central alexia?

Central alexia (CA) is an acquired reading disorder co-occurring with a generalised language deficit (aphasia). The roles of perilesional and ipsilesional tissue in recovery from post-stroke aphasia are unclear. We investigated the impact of reading training (using iReadMore, a therapy app) on the connections within and between the right and left hemisphere of the reading network of patients with CA. In patients with pure alexia, iReadMore increased feedback from left inferior frontal region (IFG) to the left occipital (OCC) region. We aimed to identify if iReadMore therapy was effective through a similar mechanism in CA patients.Participants with chronic post-stroke CA (n=23) completed 35 hours of iReadMore training over four weeks. Reading accuracy for trained and untrained words was assessed before and after therapy. The neural response to reading trained and untrained words in the left and right OCC, ventral occipitotemporal (vOT) and IFG was examined using event-related magnetoencephalography.The training-related modulation in effective connectivity between regions was modelled at the group level with Dynamic Causal Modelling.iReadMore training improved participants' reading accuracy by an average of 8.4% (range: -2.77 to 31.66) while accuracy for untrained words was stable. Training increased regional sensitivity in bilateral frontal and occipital regions, and strengthened feedforward connections within the left hemisphere. Our data suggests that iReadMore training in these patients modulates lower-order visual representations, as opposed to higher-order, more abstract ones, in order to improve word reading accuracy.SIGNIFICANCE STATEMENTThis is the first study to conduct a network-level analyses of therapy effects in participants with post-stroke central alexia. When patients trained with iReadMore (a multimodal, behavioural, mass practice, computer-based therapy), reading accuracy improved by an average 8.4% on trained items. A network analysis of the magnetoencephalography data associated with this improvement revealed an increase in regional sensitivity in bilateral frontal and occipital regions and strengthening of feedforward connections within the left hemisphere. This indicates that in CA patients iReadMore engages lower-order, intact resources within the left hemisphere (posterior to their lesion locations) to improve word reading. This provides a foundation for future research to investigate reading network modulation in different CA subtypes, or for sentence level therapy

Generalized models for quantifying laterality using functional transcranial Doppler ultrasound

We consider how analysis of brain lateralization using functional transcranial Doppler ultrasound (fTCD) data can be brought in line with modern statistical methods typically used in functional magnetic resonance imaging (fMRI). Conventionally, a laterality index is computed in fTCD from the difference between the averages of each hemisphere's signal within a period of interest (POI) over a series of trials. We demonstrate use of generalized linear models (GLMs) and generalized additive models (GAM) to analyze data from individual participants in three published studies (N = 154, 73 and 31), and compare this with results from the conventional POI averaging approach, and with laterality assessed using fMRI (N = 31). The GLM approach was based on classic fMRI analysis that includes a hemodynamic response function as a predictor; the GAM approach estimated the response function from the data, including a term for time relative to epoch start (simple GAM), plus a categorical index corresponding to individual epochs (complex GAM). Individual estimates of the fTCD laterality index are similar across all methods, but error of measurement is lowest using complex GAM. Reliable identification of cases of bilateral language appears to be more accurate with complex GAM. We also show that the GAM-based approach can be used to efficiently analyze more complex designs that incorporate interactions between tasks

Dissociation of sensitivity to spatial frequency in word and face preferential areas of the fusiform gyrus

Different cortical regions within the ventral occipitotemporal junction have been reported to show preferential responses to particular objects. Thus, it is argued that there is evidence for a left-lateralized visual word form area and a right-lateralized fusiform face area, but the unique specialization of these areas remains controversial. Words are characterized by greater power in the high spatial frequency (SF) range, whereas faces comprise a broader range of high and low frequencies. We investigated how these high-order visual association areas respond to simple sine-wave gratings that varied in SF. Using functional magnetic resonance imaging, we demonstrated lateralization of activity that was concordant with the low-level visual property of words and faces; left occipitotemporal cortex is more strongly activated by high than by low SF gratings, whereas the right occipitotemporal cortex responded more to low than high spatial frequencies. Therefore, the SF of a visual stimulus may bias the lateralization of processing irrespective of its higher order properties

Artificial intelligence-based decision support software to improve the efficacy of acute stroke pathway in the NHS: an observational study

IntroductionIn a drip-and-ship model for endovascular thrombectomy (EVT), early identification of large vessel occlusion (LVO) and timely referral to a comprehensive center (CSC) are crucial when patients are admitted to an acute stroke center (ASC). Several artificial intelligence (AI) decision-aid tools are increasingly being used to facilitate the rapid identification of LVO. This retrospective cohort study aimed to evaluate the impact of deploying e-Stroke AI decision support software in the hyperacute stroke pathway on process metrics and patient outcomes at an ASC in the United Kingdom.MethodsExcept for the deployment of e-Stroke on 01 March 2020, there were no significant changes made to the stroke pathway at the ASC. The data were obtained from a prospective stroke registry between 01 January 2019 and 31 March 2021. The outcomes were compared between the 14 months before and 12 months after the deployment of AI (pre-e-Stroke cohort vs. post-e-Stroke cohort) on 01 March 2020. Time window analyses were performed using Welch’s t-test. Cochran–Mantel–Haenszel test was used to compare changes in disability at 3 months assessed by modified Rankin Score (mRS) ordinal shift analysis, and Fisher’s exact test was used for dichotomised mRS analysis.ResultsIn the pre-e-Stroke cohort, 19 of 22 patients referred received EVT. In the post-e-Stroke cohort, 21 of the 25 patients referred were treated. The mean door-in-door-out (DIDO) and door-to-referral times in pre-e-Stroke vs. post-e-Stroke cohorts were 141 vs. 79 min (difference 62 min, 95% CI 96.9–26.8 min, p < 0.001) and 71 vs. 44 min (difference 27 min, 95% CI 47.4–5.4 min, p = 0.01), respectively. The adjusted odds ratio (age and NIHSS) for mRS ordinal shift analysis at 3 months was 3.14 (95% CI 0.99–10.51, p = 0.06) and the dichotomized mRS 0–2 at 3 months was 16% vs. 48% (p = 0.04) in the pre- vs. post-e-Stroke cohorts, respectively.ConclusionIn this single-center study in the United Kingdom, the DIDO time significantly decreased since the introduction of e-Stroke decision support software into an ASC hyperacute stroke pathway. The reduction in door-in to referral time indicates faster image interpretation and referral for EVT. There was an indication of an increased proportion of patients regaining independent function after EVT. However, this should be interpreted with caution given the small sample size. Larger, prospective studies and further systematic real-world evaluation are needed to demonstrate the widespread generalisability of these findings

Auditory training changes temporal lobe connectivity in Wernicke's aphasia: a randomised trial

Introduction Aphasia is one of the most disabling sequelae after stroke, occurring in 25%–40% of stroke survivors. However, there remains a lack of good evidence for the efficacy or mechanisms of speech comprehension rehabilitation. Trial Design This within-subjects trial tested two concurrent interventions in 20 patients with chronic aphasia with speech comprehension impairment following left hemisphere stroke: (1) phonological training using ‘Earobics’ software and (2) a pharmacological intervention using donepezil, an acetylcholinesterase inhibitor. Donepezil was tested in a double-blind, placebo-controlled, cross-over design using block randomisation with bias minimisation. Methods The primary outcome measure was speech comprehension score on the comprehensive aphasia test. Magnetoencephalography (MEG) with an established index of auditory perception, the mismatch negativity response, tested whether the therapies altered effective connectivity at the lower (primary) or higher (secondary) level of the auditory network. Results Phonological training improved speech comprehension abilities and was particularly effective for patients with severe deficits. No major adverse effects of donepezil were observed, but it had an unpredicted negative effect on speech comprehension. The MEG analysis demonstrated that phonological training increased synaptic gain in the left superior temporal gyrus (STG). Patients with more severe speech comprehension impairments also showed strengthening of bidirectional connections between the left and right STG. Conclusions Phonological training resulted in a small but significant improvement in speech comprehension, whereas donepezil had a negative effect. The connectivity results indicated that training reshaped higher order phonological representations in the left STG and (in more severe patients) induced stronger interhemispheric transfer of information between higher levels of auditory cortex