Understanding the behavioural and neurological response to word reading training paired with anodal tDCS in participants with Central Alexia

Central alexia (CA) is an acquired reading disorder co-occurring with a generalised language deficit (aphasia). In my thesis, through a series of three experiments, I aim to explore the reading network of 23 patients with CA and how it responds to a training application (app) called iReadMore. It is hoped that improving our understanding of the mechanisms of neural plasticity following therapy for post-stroke CA will lead to the development of more effectively targeted therapies. The introduction outlines models of reading and our current understanding of neuroplasticity in post-stroke aphasia. Of particular importance is the view of aphasia as a network disorder. Accordingly, this thesis investigates the effective connectivity observed when reading, rather than activation within individual regions. In the first results chapter, I compare the reading networks of CA and control participants using dynamic causal modelling (DCM) for magnetoencephalography (MEG) data. This analysis aims to identify potentially damaged and adapted connections within the reading network of CA participants. I then report the results of a clinical trial investigating the effects of iReadMore training, paired with anodal transcranial Direct Current Stimulation (A-tDCS). This chapter aims to identify if iReadMore training improves single word reading aloud, and if A-tDCS provides an additive effect on training. In the final results chapter, I use DCM for MEG to explore training induced changes in the reading network of CA patients. This chapter aims to identify the neural mechanisms by which iReadMore training is effective. In chapter six, I take each of the results chapters in turn and discuss the main findings, limitations and potential future research directions. I also discuss reading therapy for CA and the clinical use of DCM as two broader topics touched upon by this thesis

Evaluation of Leading Modern Public Libraries: Final report prepared for the Leading Modern Public Libraries Steering Group by Information Management Associates and the Centre for the Public Library and Information in Society, University of Sheffield, December 2006.

Presents findings of the external evaluation of the Leading Modern Public Libraries (LMPL) national leadership development programme, undertaken by Information Management Associates (IMA) with the Centre for the Public Library and Information in Society (CPLIS), University of Sheffield, February 2005-June 2006. The LMPL programme is a key component of the action plan for the Department for Culture Media & Sport (DCMS) Framework for the Future strategy for public libraries in England and Wales. Evaluation methods included a literature review, document analysis, participant observation, critical incident interviews, and pre- and post-program questionnaires. The program was judged successful, with reservations about participant selection

Using Simulated Family Presence to Decrease Agitation in Older Hospitalized Delirious Patients: A Randomized Controlled Trial

Background: Simulated family presence has been shown to be an effective nonpharmacological intervention to reduce agitation in persons with dementia in nursing homes. Hyperactive or mixed delirium is a common and serious complication experienced by hospitalized patients, a key feature of which is agitation. Effective nonpharmacological interventions to manage delirium are needed. Objectives: To examine the effect of simulated family presence through pre-recorded video messages on the agitation level of hospitalized, delirious, acutely agitated patients. Design: Single site randomized control trial, 3 groups x 4 time points mixed factorial design conducted from July 2015 to March 2016. Setting: Acute care level one trauma center in an inner city of the state of Connecticut, USA. Participants: Hospitalized patients experiencing hyperactive or mixed delirium and receiving continuous observation were consecutively enrolled (n = 126), with 111 participants completing the study. Most were older, male, Caucasian, spouseless, with a pre-existing dementia. Methods: Participants were randomized to one of the following study arms: view a one minute family video message, view a one minute nature video, or usual care. Participants in experimental groups also received usual care. The Agitated Behavior Scale was used to measure the level of agitation prior to, during, immediately following, and 30 minutes following the intervention. Results: Both the family video and nature video groups displayed a significant change in median agitation scores over the four time periods (p \u3c .001), whereas the control group did not. The family video group had significantly lower median agitation scores during the intervention period (p \u3c .001) and a significantly greater proportion (94%) of participants experiencing a reduction in agitation from the pre-intervention to during intervention (p \u3c .001) than those viewing the nature video (70%) or those in usual care only (30%). The median agitation scores for the three groups were not significantly different at either of the post intervention time measurements. When comparing the proportion of participants experiencing a reduction in agitation from baseline to post intervention, there remained a statistically significant difference (p = .001) between family video(60%) and usual care (35.1%) immediately following the intervention Conclusion: This work provides preliminary support for the use of family video messaging as a nonpharmacological intervention that may decrease agitation in selected hospitalized delirious patients. Further studies are necessary to determine the efficacy of the intervention as part of a multi-component intervention as well as among younger delirious patients without baseline dementia

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

The Architect Who Lost the Ability to Imagine: The Cerebral Basis of Visual Imagery.

While the loss of mental imagery following brain lesions was first described more than a century ago, the key cerebral areas involved remain elusive. Here we report neuropsychological data from an architect (PL518) who lost his ability for visual imagery following a bilateral posterior cerebral artery (PCA) stroke. We compare his profile to three other patients with bilateral PCA stroke and another architect with a large PCA lesion confined to the right hemisphere. We also compare structural images of their lesions, aiming to delineate cerebral areas selectively lesioned in acquired aphantasia. When comparing the neuropsychological profile and structural magnetic resonance imaging (MRI) for the aphantasic architect PL518 to patients with either a comparable background (an architect) or bilateral PCA lesions, we find: (1) there is a large overlap of cognitive deficits between patients, with the very notable exception of aphantasia which only occurs in PL518, and (2) there is large overlap of the patients' lesions. The only areas of selective lesion in PL518 is a small patch in the left fusiform gyrus as well as part of the right lingual gyrus. We suggest that these areas, and perhaps in particular the region in the left fusiform gyrus, play an important role in the cerebral network involved in visual imagery