Maria Tziraki | The University of Sheffield (original) (raw)

Papers by Maria Tziraki

Supplementary Materials. Table S1. MRI sequence parameters and scan time duration for a complete ... more Supplementary Materials. Table S1. MRI sequence parameters and scan time duration for a complete imaging acquisition lasting approximately 45 min (including scout sequences and planning time). Table S2. Baseline descriptive data. Table S3. Baseline clinical findings. Table S4. Adverse events. Table S5. Week 4 intermediate outcomes. Table S6. Quantification of MAPK outcomes at baseline and endpoint. Table S7. A comparison of the mutation data in the SANTA sample to previously reported data from a clinic referred NF1 sample (see text). Figure S1. a) Spectrum obtained from 3 × 3 × 3 voxel placed in deep grey matter of a 5-year-old child using MEGA-PRESS suppression scheme at 3T (top, non-edited subspectrum; bottom, GABA-edited spectrum) showing signals from amino-acid protons (AA), choline-containing compounds (cho), creatine + phosphocreatine (cr), N-acetylaspartate (NAA), GABA and glutamate + glutamine (Glx). b) Figure depicting example output of AMARES Model fitting in jMRUI. Figure...

This paper describes the key basic elements required for a successful multi‐parametric MRI data a... more This paper describes the key basic elements required for a successful multi‐parametric MRI data acquisition in awake children with autism. The procedure was designed by taking into account methodological challenges arising from the acquisition of Resting State fMRI (RS fMRI) data, and factors such as cost, time, and staff availability. The ultimate aim was to prepare an imaging preparation protocol with high transferability to the whole autism spectrum, adaptable for use in a multi‐site research with multiple time points. As part of a randomized pharmaco‐intervention study, 31 children aged 4–10 years with Neurofibromatosis 1 and autism underwent MR imaging at baseline and end of intervention. The protocol consisted of tailored habituation instructions including gradual exposure to scanner noise, a social stories booklet, positive incentive strategies, and Play Therapy support. Success rate for initial acquisition was 71% for GABA+ MR spectroscopy at either location, 87% for perfusi...

Background: Monogenic causes of autism such as Neurofibromatosis Type 1 (NF1), with known neurobi... more Background: Monogenic causes of autism such as Neurofibromatosis Type 1 (NF1), with known neurobiology from animal models, provide a key method in autism biological research. Multimodal magnetic resonance imaging (MRI) can be profoundly effective in examining this phenotypic heterogeneity, but its utility in child subjects has been limited by implementation challenges such as the need for sedation, which is incompatible with the use of advanced imaging methods such as Resting State functional MRI (RS fMRI). Aim: To develop and implement an awake multimodal imaging protocol for use in an intervention trial with young children with NF1-Autism Methods: Feasibility was tested on children (n=30; mean age 8.5 years) enrolled in a world first placebo-controlled simvastatin trial in NF1 autism. Derived from literature review scanning protocol in awake children included 1) High resolution T1 volume; 2) RS fMRI; 3) Diffusion imaging; 4) Arterial Spin Labelling 5) GABA Proton magnetic resonanc...

Molecular autism, 2018

Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social an... more Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Thirty subjects had a mean age of 8.1 years (SD 1.8). Simvastatin was well tolerated. The amount of imaging data varied by test. Simvastatin...

Neuropsychologia, Jan 17, 2016

Our brain constantly receives tactile information from the body's surface. We often only beco... more Our brain constantly receives tactile information from the body's surface. We often only become aware of this information when directing our attention towards the body. Here, we report a study investigating the behavioural and neural response when selecting a target amongst distractor vibrations presented simultaneously to several locations either across the hands or body. Comparable visual search studies have revealed the N2pc as the neural correlate of visual selective attention. Analogously, we describe an enhanced negativity contralateral to the tactile target side. This effect is strongest over somatosensory areas and lasts approximately 200 ms from the onset of the somatosensory N140 ERP component. Based on these characteristics we named this electrophysiological signature of attentional tactile target selection during tactile search the N140-central-contralateral (N140cc). Furthermore, we present supporting evince that the N140cc reflects attentional enhancement of target...

Molecular Autism

Background: Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue t... more Background: Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/ behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods: A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Results: Thirty subjects had a mean age of 8.1 years (SD 1.8). Simvastatin was well tolerated. The amount of imaging data varied by test. Simvastatin treatment was associated with (i) increased frontal white matter MRS GABA (t(12) = − 2.12, p = .055), GABA/Glx ratio (t(12) = − 2.78, p = .016), and reduced grey nuclei Glx (ANCOVA p < 0.05, Mann-Whitney p < 0.01); (ii) increased ASL perfusion in ventral diencephalon (Mann-Whitney p < 0.01); and (iii) decreased ADC in cingulate gyrus (Mann-Whitney p < 0.01). Machine-learning classification of imaging outcomes achieved 79% (p < .05) accuracy differentiating groups at endpoint against chance level (64%, p = 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met 'clinical responder' criteria for behavioural outcome. Conclusions: We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network. Trial registration: EU Clinical Trial Register (EudraCT) 2012-005742-38 (www.clinicaltrialsregister.eu

Molecular autism, 2018

Neuropsychologia, Jan 17, 2016

Molecular Autism