Imperial College London

DrSaraDe Simoni

Faculty of MedicineDepartment of Medicine

Honorary Research Associate
 
 
 
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s.de-simoni

 
 
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Burlington DanesHammersmith Campus

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Summary

 

Publications

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25 results found

Jenkins PO, De Simoni S, Bourke N, Fleminger J, Scott G, Towey D, Svensson W, Khan S, Patel M, Greenwood R, Cole J, Sharp DJet al., 2018, Dopaminergic abnormalities following traumatic brain injury, Brain, Vol: 141, Pages: 797-810, ISSN: 1460-2156

Traumatic brain injury can reduce striatal dopamine levels. The cause of this is uncertain, but is likely to be related to damage to the nigrostriatal system. We investigated the pattern of striatal dopamine abnormalities using 123I-Ioflupane single-photon emission computed tomography (SPECT) scans and their relationship to nigrostriatal damage and clinical features. We studied 42 moderate–severe traumatic brain injury patients with cognitive impairments but no motor parkinsonism signs and 20 healthy controls. 123I-Ioflupane scanning was used to assess dopamine transporter levels. Clinical scan reports were compared to quantitative dopamine transporter results. Advanced MRI methods were used to assess the nigrostriatal system, including the area through which the nigrostriatal projections pass as defined from high-resolution Human Connectome data. Detailed clinical and neuropsychological assessments were performed. Around 20% of our moderate–severe patients had clear evidence of reduced specific binding ratios for the dopamine transporter in the striatum measured using 123I-Ioflupane SPECT. The caudate was affected more consistently than other striatal regions. Dopamine transporter abnormalities were associated with reduced substantia nigra volume. In addition, diffusion MRI provided evidence of damage to the regions through which the nigrostriatal tract passes, particularly the area traversed by dopaminergic projections to the caudate. Only a small percentage of patients had evidence of macroscopic lesions in the striatum and there was no relationship between presence of lesions and dopamine transporter specific binding ratio abnormalities. There was also no relationship between reduced volume in the striatal subregions and reduced dopamine transporter specific binding ratios. Patients with low caudate dopamine transporter specific binding ratios show impaired processing speed and executive dysfunction compared to patients with normal levels. Taken toge

JOURNAL ARTICLE

Cole JH, Jolly A, De Simoni S, Bourke N, patel M, Scott G, Sharp Det al., 2018, Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury, Brain, Vol: 141, Pages: 822-836, ISSN: 1460-2156

Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of magnetic resonance imaging. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions, and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 moderate/severe traumatic brain injury patients (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (one-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterised using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarised regionally and compared with clinical and neuropsychological measures. Traumatic brain injury patients showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over one year was pronounced following traumatic brain injury. Traumatic brain injury patients lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates we

JOURNAL ARTICLE

Scott GPT, Zetterberg H, Jolly A, Cole JH, De Simoni S, Jenkins PO, Feeney C, Owen DR, Lingford-Hughes A, Howes O, Patel MC, Goldstone AP, Gunn RN, Blennow K, Matthews PM, Sharp DJet al., 2017, Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration, Brain, Vol: 141, Pages: 459-471, ISSN: 1460-2156

Survivors of a traumatic brain injury can deteriorate years later, developing brain atrophy and dementia. Traumatic brain injury triggers chronic microglial activation, but it is unclear whether this is harmful or beneficial. A successful chronic-phase treatment for traumatic brain injury might be to target microglia. In experimental models, the antibiotic minocycline inhibits microglial activation. We investigated the effect of minocycline on microglial activation and neurodegeneration using PET, MRI, and measurement of the axonal protein neurofilament light in plasma. Microglial activation was assessed using 11C-PBR28 PET. The relationships of microglial activation to measures of brain injury, and the effects of minocycline on disease progression, were assessed using structural and diffusion MRI, plasma neurofilament light, and cognitive assessment. Fifteen patients at least 6 months after a moderate-to-severe traumatic brain injury received either minocycline 100 mg orally twice daily or no drug, for 12 weeks. At baseline, 11C-PBR28 binding in patients was increased compared to controls in cerebral white matter and thalamus, and plasma neurofilament light levels were elevated. MRI measures of white matter damage were highest in areas of greater 11C-PBR28 binding. Minocycline reduced 11C-PBR28 binding (mean Δwhite matter binding = −23.30%, 95% confidence interval −40.9 to −5.64%, P = 0.018), but increased plasma neurofilament light levels. Faster rates of brain atrophy were found in patients with higher baseline neurofilament light levels. In this experimental medicine study, minocycline after traumatic brain injury reduced chronic microglial activation while increasing a marker of neurodegeneration. These findings suggest that microglial activation has a reparative effect in the chronic phase of traumatic brain injury.

JOURNAL ARTICLE

De Simoni S, Jenkins PO, Bourke N, Fleminger JJ, Hellyer PJ, Jolly AE, Patel MC, Cole J, Leech R, Sharp DJet al., 2017, Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury, Brain, Vol: 141, Pages: 148-164, ISSN: 1460-2156

Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of ex

JOURNAL ARTICLE

Jenkins PO, De Simoni S, Fleminger J, Bourke N, Jolly A, Cole J, Darian D, Sharp Det al., 2016, Disruption to the dopaminergic system after traumatic brain injury, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ Publishing Group, ISSN: 1468-330X

CONFERENCE PAPER

De Simoni S, Grover PJ, Jenkins PO, Honeyfield L, Quest R, Scott G, Wilson WH, Majewska P, Waldman AD, Patel MC, Sharp DJet al., 2016, Disconnection between the default mode network and medial temporal lobes in post-traumatic amnesia, Brain, Vol: 139, Pages: 3137-3150, ISSN: 0006-8950

Post-traumatic amnesia is very common immediately after traumatic brain injury. It is characterised by a confused, agitated state and a pronounced inability to encode new memories and sustain attention. Clinically, post-traumatic amnesia is an important predictor of functional outcome. However, despite its prevalence and functional importance, the pathophysiology of post-traumatic amnesia is not understood. Memory processing relies on limbic structures such as the hippocampus, parahippocampus and parts of the cingulate cortex. These structures are connected within an intrinsic connectivity network, the Default Mode Network. Interactions within the Default Mode Network can be assessed using resting state functional magnetic resonance imaging, which can be acquired in confused patients unable to perform tasks in the scanner. Here we used this approach to test the hypothesis that the mnemonic symptoms of post-traumatic amnesia are caused by functional disconnection within the Default Mode Network. We assessed whether the hippocampus and parahippocampus showed evidence of transient disconnection from cortical brain regions involved in memory processing. 19 traumatic brain injury patients were classified into post-traumatic amnesia and traumatic brain injury control groups, based on their performance on a paired associates learning task. Cognitive function was also assessed with a detailed neuropsychological test battery. Functional interactions between brain regions were investigated using resting-state functional magnetic resonance imaging. Together with impairments in associative memory patients in post-traumatic amnesia demonstrated impairments in information processing speed and spatial working memory. Patients in post-traumatic amnesia showed abnormal functional connectivity between the parahippocampal gyrus and posterior cingulate cortex. The strength of this functional connection correlated with both associative memory and information processing speed and normal

JOURNAL ARTICLE

Record C, De Simoni S, Feeney C, Sharp D, Nicholas R, Raffel Jet al., 2016, Improved cerebral blood flow after natalizumab treatment in multiple sclerosis, 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE Publications, Pages: 669-669, ISSN: 1352-4585

CONFERENCE PAPER

Jolly AE, De Simoni S, Cole JH, Sharp DJet al., 2016, Identifying cognitive impairment in TBI: A novel multivariate approach, International Brain Injury Association’s Eleventh World Congress on Brain Injury, Publisher: Taylor & Francis, Pages: 518-518, ISSN: 1362-301X

CONFERENCE PAPER

Jenkins P, De Simoni S, Fleminger J, Bourke N, Jolly A, Cole J, Towey D, Sharp Det al., 2016, Disruption to the dopaminergic system following traumatic brain injury, International Brain Injury Association’s Eleventh World Congress on Brain Injury, Publisher: Taylor & Francis, Pages: 670-670, ISSN: 1362-301X

CONFERENCE PAPER

De Simoni S, Kochaj R, Jenkins P, Cole J, Sharp Det al., 2016, Changes in cerebral blood flow and their relationship to cognition following traumatic brain injury, International Brain Injury Association’s Eleventh World Congress on Brain Injury, Publisher: Taylor & Francis, Pages: 605-605, ISSN: 1362-301X

CONFERENCE PAPER

Pollak TA, De Simoni S, Barimani B, Zelaya FO, Stone JM, Mehta MAet al., 2015, Phenomenologically distinct psychotomimetic effects of ketamine are associated with cerebral blood flow changes in functionally relevant cerebral foci: a continuous arterial spin labelling study, PSYCHOPHARMACOLOGY, Vol: 232, Pages: 4515-4524, ISSN: 0033-3158

JOURNAL ARTICLE

Jenkins P, Fleminger J, De-Simoni S, Jolly A, Gorgoraptis N, Hampshire A, Sharp Det al., 2015, HOME COMPUTERISED COGNITIVE TESTING FOR TBI IS FEASIBLE AND POPULAR, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050

CONFERENCE PAPER

Shcherbinin S, Doyle O, Zelaya FO, de Simoni S, Mehta MA, Schwarz AJet al., 2015, Modulatory effects of ketamine, risperidone and lamotrigine on resting brain perfusion in healthy human subjects, PSYCHOPHARMACOLOGY, Vol: 232, Pages: 4191-4204, ISSN: 0033-3158

JOURNAL ARTICLE

Stone J, Kotoula V, Dietrich C, De Simoni S, Krystal JH, Mehta MAet al., 2015, Perceptual distortions and delusional thinking following ketamine administration are related to increased pharmacological MRI signal changes in the parietal lobe, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 29, Pages: 1025-1028, ISSN: 0269-8811

JOURNAL ARTICLE

Majewska P, Ribeiro Violante I, Lorenz R, De Simoni S, Sharp Det al., 2015, EEG characteristics of memory deficits in acute traumatic brain injury patients with post-traumatic amnesia, The Society of British Neurological Surgeons Meeting 2015

CONFERENCE PAPER

Jenkins P, De Simoni S, Grover P, Waldman A, Sharp Det al., 2014, HIPPOCAMPAL CONNECTIVITY AND POST-TRAUMATIC AMNESIA, Meeting of the Associatiion-of-British-Neurologists, Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050

CONFERENCE PAPER

Doyle OM, De Simoni S, Schwarz AJ, Brittain C, O'Daly OG, Williams SCR, Mehta MAet al., 2013, Quantifying the Attenuation of the Ketamine Pharmacological Magnetic Resonance Imaging Response in Humans: A Validation Using Antipsychotic and Glutamatergic Agents, JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, Vol: 345, Pages: 151-160, ISSN: 0022-3565

JOURNAL ARTICLE

De Simoni S, Schwarz AJ, O'Daly OG, Marquand AF, Brittain C, Gonzales C, Stephenson S, Williams SCR, Mehta MAet al., 2013, Test-retest reliability of the BOLD pharmacological MRI response to ketamine in healthy volunteers, NEUROIMAGE, Vol: 64, Pages: 75-90, ISSN: 1053-8119

JOURNAL ARTICLE

Stone JM, Dietrich C, Edden R, Mehta MA, De Simoni S, Reed LJ, Krystal JH, Nutt D, Barker GJet al., 2012, Ketamine effects on brain GABA and glutamate levels with 1H-MRS: relationship to ketamine- induced psychopathology, MOLECULAR PSYCHIATRY, Vol: 17, Pages: 664-665, ISSN: 1359-4184

JOURNAL ARTICLE

Marquand AF, O'Daly OG, De Simoni S, Alsop DC, Maguire RP, Williams SCR, Zelaya FO, Mehta MAet al., 2012, Dissociable effects of methylphenidate, atomoxetine and placebo on regional cerebral blood flow in healthy volunteers at rest: A multi-class pattern recognition approach, NEUROIMAGE, Vol: 60, Pages: 1015-1024, ISSN: 1053-8119

JOURNAL ARTICLE

Stone J, Dietrich C, Edden R, Mehta M, De Simoni S, Reed L, Krystal J, Nutt DJ, Barker Get al., 2012, Ketamine-induced changes in anterior cingulate glutamate levels correlate with positive symptom generation, EUROPEAN NEUROPSYCHOPHARMACOLOGY, Vol: 22, Pages: S52-S53, ISSN: 0924-977X

JOURNAL ARTICLE

Doyle OM, De Simoni S, Brammer MJ, Schwarz AJ, Mehta Met al., 2011, MULTIVARIATE PATTERN RECOGNITION APPLIED TO PHMRI: MODULATION OF THE KETAMINE RESPONSE, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A58-A58, ISSN: 0269-8811

CONFERENCE PAPER

Stone JM, Dietrich C, Reed L, Edden R, De Simoni S, Mehta MA, Krystal J, Barker Get al., 2011, EFFECT OF KETAMINE ON BRAIN GLUTAMATE AND GABA IN HEALTHY VOLUNTEERS, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A59-A59, ISSN: 0269-8811

CONFERENCE PAPER

De Simoni S, Schwarz AJ, O'Daly OG, Stephenson S, Williams SCR, Mehta MAet al., 2011, OPTIMISED DESIGN MATRIX FOR KETAMINE PHMRI IN HUMANS: RELIABILITY, EFFECT SIZE AND THE INFLUENCE OF MOTION, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A58-A58, ISSN: 0269-8811

CONFERENCE PAPER

Marquand AF, De Simoni S, O'Daly OG, Williams SCR, Mourao-Miranda J, Mehta MAet al., 2011, Pattern Classification of Working Memory Networks Reveals Differential Effects of Methylphenidate, Atomoxetine, and Placebo in Healthy Volunteers, NEUROPSYCHOPHARMACOLOGY, Vol: 36, Pages: 1237-1247, ISSN: 0893-133X

JOURNAL ARTICLE

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