Avatar therapy for persecutory auditory hallucinations: What is it and how does it work?

We have developed a novel therapy based on a computer program, which enables the patient to create an avatar of the entity, human or non-human, which they believe is persecuting them. The therapist encourages the patient to enter into a dialogue with their avatar, and is able to use the program to change the avatar so that it comes under the patient's control over the course of six 30-min sessions and alters from being abusive to becoming friendly and supportive. The therapy was evaluated in a randomised controlled trial with a partial crossover design. One group went straight into the therapy arm: "immediate therapy". The other continued with standard clinical care for 7 weeks then crossed over into Avatar therapy: "delayed therapy". There was a significant reduction in the frequency and intensity of the voices and in their omnipotence and malevolence. Several individuals had a dramatic response, their voices ceasing completely after a few sessions of the therapy. The average effect size of the therapy was 0.8. We discuss the possible psychological mechanisms for the success of Avatar therapy and the implications for the origins of persecutory voices

Modulation of frontal effective connectivity during speech

Noninvasive neurostimulation methods such as transcranial direct current stimulation (tDCS) can elicit long-lasting, polarity-dependent changes in neocortical excitability. In a previous concurrent tDCS-fMRI study of overt picture naming, we reported significant behavioural and regionally specific neural facilitation effects in left inferior frontal cortex (IFC) with anodal tDCS applied to left frontal cortex (Holland et al., 2011). Although distributed connectivity effects of anodal tDCS have been modelled at rest, the mechanism by which 'on-line' tDCS may modulate neuronal connectivity during a task-state remains unclear. Here, we used Dynamic Causal Modelling (DCM) to determine: (i) how neural connectivity within the frontal speech network is modulated during anodal tDCS; and, (ii) how individual variability in behavioural response to anodal tDCS relates to changes in effective connectivity strength. Results showed that compared to sham, anodal tDCS elicited stronger feedback from inferior frontal sulcus (IFS) to ventral premotor (VPM) accompanied by weaker self-connections within VPM, consistent with processes of neuronal adaptation. During anodal tDCS individual variability in the feedforward connection strength from IFS to VPM positively correlated with the degree of facilitation in naming behaviour. These results provide an essential step towards understanding the mechanism of 'online' tDCS paired with a cognitive task. They also identify left IFS as a 'top-down' hub and driver for speech change

Identifying Abnormal Connectivity in Patients Using Dynamic Causal Modeling of fMRI Responses

Functional imaging studies of brain damaged patients offer a unique opportunity to understand how sensorimotor and cognitive tasks can be carried out when parts of the neural system that support normal performance are no longer available. In addition to knowing which regions a patient activates, we also need to know how these regions interact with one another, and how these inter-regional interactions deviate from normal. Dynamic causal modeling (DCM) offers the opportunity to assess task-dependent interactions within a set of regions. Here we review its use in patients when the question of interest concerns the characterization of abnormal connectivity for a given pathology. We describe the currently available implementations of DCM for fMRI responses, varying from the deterministic bilinear models with one-state equation to the stochastic non-linear models with two-state equations. We also highlight the importance of the new Bayesian model selection and averaging tools that allow different plausible models to be compared at the single subject and group level. These procedures allow inferences to be made at different levels of model selection, from features (model families) to connectivity parameters. Following a critical review of previous DCM studies that investigated abnormal connectivity we propose a systematic procedure that will ensure more flexibility and efficiency when using DCM in patients. Finally, some practical and methodological issues crucial for interpreting or generalizing DCM findings in patients are discussed

Systematic evaluation of high-level visual deficits and lesions in posterior cerebral artery stroke

Knowledge about the consequences of stroke on high-level vision comes primarily from single case studies of patients selected based on their behavioural profiles, typically patients with specific stroke syndromes like pure alexia or prosopagnosia. There are, however, no systematic, detailed, large-scale evaluations of the more typical clinical behavioural and lesion profiles of impairments in high-level vision after posterior cerebral artery stroke. We present behavioural and lesion data from the Back of the Brain project, to date the largest (N = 64) and most detailed examination of patients with cortical posterior cerebral artery strokes selected based on lesion location. The aim of the current study was to relate behavioural performance with faces, objects and written words to lesion data through two complementary analyses: (i) a multivariate multiple regression analysis to establish the relationships between lesion volume, lesion laterality and the presence of a bilateral lesion with performance and (ii) a voxel-based correlational methodology analysis to establish whether there are distinct or separate regions within the posterior cerebral artery territory that underpin the visual processing of words, faces and objects. Behaviourally, most patients showed more general deficits in high-level vision (n = 22) or no deficits at all (n = 21). Category-selective deficits were rare (n = 6) and were only found for words. Overall, total lesion volume was most strongly related to performance across all three domains. While behavioural impairments in all domains were observed following unilateral left and right as well as bilateral lesions, the regions most strongly related to performance mainly confirmed the pattern reported in more selective cases. For words, these included a left hemisphere cluster extending from the occipital pole along the fusiform and lingual gyri; for objects, bilateral clusters which overlapped with the word cluster in the left occipital lobe. Face performance mainly correlated with a right hemisphere cluster within the white matter, partly overlapping with the object cluster. While the findings provide partial support for the relative laterality of posterior brain regions supporting reading and face processing, the results also suggest that both hemispheres are involved in the visual processing of faces, words and objects

Ultra-low temperature dilatometry

This thesis presents research of two novel magnetic materials, LiHoF4 and Tb2Ti2O7. Experiments were performed at low temperatures and in an applied magnetic field to study thermal expansion and magnetostriction using a capacitive dilatometer designed during this project. This thesis presents 3 distinct topics. This manuscript begins with a thermodynamic description of thermal expansion and magnetostriction. The design of a capacitive dilatometer suitable for use at ultra-low temperatures and in high magnetic fields is presented. The thermal expansion of oxygen free high conductivity copper is used as a test of the absolute accuracy of the dilatometer. The first material studied using this dilatometer was LiHoF4. Pure LiHoF4 is a dipolar coupled Ising ferromagnet and in an applied transverse magnetic field is a good representation of the transverse field Ising model. An ongoing discrepancy between theoretical and experimental work motivates further study of this textbook material. Presented here are thermal expansion and magnetostriction measurements of LiHoF4 in an applied transverse field. We find good agreement with existing experimental work. This suggests that there is some aspect of LiHoF4 or the effect of quantum mechanical fluctuations at finite temperatures which is not well understood. The second material studied is the spin liquid Tb2Ti2O7. Despite theoretical predictions that Tb2Ti2O7 will order at finite temperature, a large body of experimental evidence demonstrates that spins within Tb2Ti2O7 remain dynamic to the lowest temperatures studied. In addition Tb2Ti2O7 also exhibits anomalous thermal expansion below 20K, giant magnetostriction, and orders in an applied magnetic field. Thermal expansion and magnetostriction measurements of Tb2Ti2O7 are presented in applied longitudinal and transverse fields. Zero-field thermal expansion measurements do not repeat the previously observed anomalous thermal expansion. A large feature is observed in thermal expansion at 100mK, in rough agreement with existing experimental work. Longitudinal and transverse magnetic fields were applied to Tb2Ti2O7. Longitudinal magnetostriction measurements show qualitatively di erent behavior than previous observations. These measurements were taken along di erent crystal axes so direct comparison cannot be made. Thermal expansion measurements in an applied transverse field show evolution with the strength of the applied field. This evolution may relate to an ordering transition, however difficulties in repeatability in a transverse field require that these results be repeated in an improved setup

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