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  • Inhibitory engrams in perception and memory.

    21 May 2018

    Nervous systems use excitatory cell assemblies to encode and represent sensory percepts. Similarly, synaptically connected cell assemblies or "engrams" are thought to represent memories of past experience. Multiple lines of recent evidence indicate that brain systems create and use inhibitory replicas of excitatory representations for important cognitive functions. Such matched "inhibitory engrams" can form through homeostatic potentiation of inhibition onto postsynaptic cells that show increased levels of excitation. Inhibitory engrams can reduce behavioral responses to familiar stimuli, thereby resulting in behavioral habituation. In addition, by preventing inappropriate activation of excitatory memory engrams, inhibitory engrams can make memories quiescent, stored in a latent form that is available for context-relevant activation. In neural networks with balanced excitatory and inhibitory engrams, the release of innate responses and recall of associative memories can occur through focused disinhibition. Understanding mechanisms that regulate the formation and expression of inhibitory engrams in vivo may help not only to explain key features of cognition but also to provide insight into transdiagnostic traits associated with psychiatric conditions such as autism, schizophrenia, and posttraumatic stress disorder.

  • Uncoupling protein 2 haplotype does not affect human brain structure and function in a sample of community-dwelling older adults.

    14 May 2018

    Uncoupling protein 2 (UCP2) is a mitochondrial membrane protein that plays a role in uncoupling electron transport from adenosine triphosphate (ATP) formation. Polymorphisms of the UCP2 gene in humans affect protein expression and function and have been linked to survival into old age. Since UCP2 is expressed in several brain regions, we investigated in this study whether UCP2 polymorphisms might 1) affect occurrence of neurodegenerative or mental health disorders and 2) affect measures of brain structure and function. We used structural magnetic resonance imaging (MRI), diffusion-weighted MRI and resting-state functional MRI in the neuroimaging sub-study of the Whitehall II cohort. Data from 536 individuals aged 60 to 83 years were analyzed. No association of UCP2 polymorphisms with the occurrence of neurodegenerative disorders or grey and white matter structure or resting-state functional connectivity was observed. However, there was a significant effect on occurrence of mood disorders in men with the minor alleles of -866G>A (rs659366) and Ala55Val (rs660339)) being associated with increasing odds of lifetime occurrence of mood disorders in a dose dependent manner. This result was not accompanied by effects of UCP2 polymorphisms on brain structure and function, which might either indicate that the sample investigated here was too small and underpowered to find any significant effects, or that potential effects of UCP2 polymorphisms on the brain are too subtle to be picked up by any of the neuroimaging measures used.

  • PET Tau and Amyloid-β Burden in Mild Alzheimer's Disease: Divergent Relationship with Age, Cognition, and Cerebrospinal Fluid Biomarkers.

    18 May 2018

    BACKGROUND: Combining PET amyloid-β (Aβ) and tau imaging may be critical for tracking disease progression in Alzheimer's disease (AD). OBJECTIVE: We sought to characterize the relationship between Aβ and tau ligands as well as with other measures of pathology. METHODS: We conducted a multi-center observational study in early AD (MMSE >20) participants aged 50 to 85 y. The schedule included cognitive assessments (ADAS-Cog) and CSF measurement of Aβ and tau at baseline and 6 months; PET-CT imaging with Aβ ([18F]AV45) and tau ([18F]AV1451) ligands at baseline. RESULTS: 22 participants took part in the study with 20 completing its 6-month duration and 12 having both tau and amyloid PET. The PET biomarker analysis revealed a strong negative correlation between age and tau in multiple regions. Entorhinal cortex tau and age interacted significantly in terms of cognitive change over 6 months which may have been to older participants deteriorating faster despite lower levels of cortical tau. Cortical Aβ associated with entorhinal cortex tau while CSF tau/Aβ ratio correlated strongly with cortical tau but not Aβ. CONCLUSION: The negative relationship between age and cortical tau whereby younger patients with mild AD had relatively greater tau burden is potentially important. It suggests that younger-age onset AD may be primarily driven by tau pathology while AD developing later may depend on a multitude of pathological mechanisms. These data also suggest that PET-tau performs better than PET-amyloid in predicting the best validated AD diagnostic marker- the CSF total tau/Aβ ratio.

  • Improving data availability for brain image biobanking in healthy subjects: Practice-based suggestions from an international multidisciplinary working group.

    14 May 2018

    Brain imaging is now ubiquitous in clinical practice and research. The case for bringing together large amounts of image data from well-characterised healthy subjects and those with a range of common brain diseases across the life course is now compelling. This report follows a meeting of international experts from multiple disciplines, all interested in brain image biobanking. The meeting included neuroimaging experts (clinical and non-clinical), computer scientists, epidemiologists, clinicians, ethicists, and lawyers involved in creating brain image banks. The meeting followed a structured format to discuss current and emerging brain image banks; applications such as atlases; conceptual and statistical problems (e.g. defining 'normality'); legal, ethical and technological issues (e.g. consents, potential for data linkage, data security, harmonisation, data storage and enabling of research data sharing). We summarise the lessons learned from the experiences of a wide range of individual image banks, and provide practical recommendations to enhance creation, use and reuse of neuroimaging data. Our aim is to maximise the benefit of the image data, provided voluntarily by research participants and funded by many organisations, for human health. Our ultimate vision is of a federated network of brain image biobanks accessible for large studies of brain structure and function.

  • Structural brain correlates of interpersonal violence: Systematic review and voxel-based meta-analysis of neuroimaging studies.

    26 April 2018

    Owing to inconsistent nomenclature and results, we have undertaken a label-based review and anatomical likelihood estimation (ALE) meta-analysis of studies measuring the quantitative association between regional grey matter (GM) volume and interpersonal violence. Following PRISMA guidelines, we identified studies by searching 3 online databases (Embase, Medline, PsycInfo) and reference lists. Thirty-five studies were included in the label-based review, providing information for 1288 participants and 86 brain regions. Per region, 0-57% of the results indicated significant reductions in GM volume, while 0-23% indicated significant increases. The only region for which more than half of all results indicated significant reductions was the parietal lobe. However, these results were dispersed across subregions. The ALE meta-analysis, which included 6 whole-brain voxel-based morphometry studies totaling 278 participants and reporting 144 foci, showed no significant clusters of reduced GM volume. No material differences were observed when excluding experiments using reactive violence as outcome or subjects diagnosed with psychopathy. Possible explanations for these findings are phenomenological and etiological heterogeneity, and insufficient power in the label-based review and ALE meta-analysis to detect small effects. We recommend that future studies distinguish between subtypes of interpersonal violence, and investigate mediation by underlying emotional and cognitive processes.

  • Distinct resting-state functional connections associated with episodic and visuospatial memory in older adults.

    14 May 2018

    Episodic and spatial memory are commonly impaired in ageing and Alzheimer's disease. Volumetric and task-based functional magnetic resonance imaging (fMRI) studies suggest a preferential involvement of the medial temporal lobe (MTL), particularly the hippocampus, in episodic and spatial memory processing. The present study examined how these two memory types were related in terms of their associated resting-state functional architecture. 3T multiband resting state fMRI scans from 497 participants (60-82 years old) of the cross-sectional Whitehall II Imaging sub-study were analysed using an unbiased, data-driven network-modelling technique (FSLNets). Factor analysis was performed on the cognitive battery; the Hopkins Verbal Learning test and Rey-Osterreith Complex Figure test factors were used to assess verbal and visuospatial memory respectively. We present a map of the macroscopic functional connectome for the Whitehall II Imaging sub-study, comprising 58 functionally distinct nodes clustered into five major resting-state networks. Within this map we identified distinct functional connections associated with verbal and visuospatial memory. Functional anticorrelation between the hippocampal formation and the frontal pole was significantly associated with better verbal memory in an age-dependent manner. In contrast, hippocampus-motor and parietal-motor functional connections were associated with visuospatial memory independently of age. These relationships were not driven by grey matter volume and were unique to the respective memory domain. Our findings provide new insights into current models of brain-behaviour interactions, and suggest that while both episodic and visuospatial memory engage MTL nodes of the default mode network, the two memory domains differ in terms of the associated functional connections between the MTL and other resting-state brain networks.

  • PEAR: PEriodic And fixed Rank separation for fast fMRI.

    7 May 2018

    PURPOSE: In functional MRI (fMRI), faster acquisition via undersampling of data can improve the spatial-temporal resolution trade-off and increase statistical robustness through increased degrees-of-freedom. High-quality reconstruction of fMRI data from undersampled measurements requires proper modeling of the data. We present an fMRI reconstruction approach based on modeling the fMRI signal as a sum of periodic and fixed rank components, for improved reconstruction from undersampled measurements. METHODS: The proposed approach decomposes the fMRI signal into a component which has a fixed rank and a component consisting of a sum of periodic signals which is sparse in the temporal Fourier domain. Data reconstruction is performed by solving a constrained problem that enforces a fixed, moderate rank on one of the components, and a limited number of temporal frequencies on the other. Our approach is coined PEAR - PEriodic And fixed Rank separation for fast fMRI. RESULTS: Experimental results include purely synthetic simulation, a simulation with real timecourses and retrospective undersampling of a real fMRI dataset. Evaluation was performed both quantitatively and visually versus ground truth, comparing PEAR to two additional recent methods for fMRI reconstruction from undersampled measurements. Results demonstrate PEAR's improvement in estimating the timecourses and activation maps versus the methods compared against at acceleration ratios of R = 8,10.66 (for simulated data) and R = 6.66,10 (for real data). CONCLUSIONS: This paper presents PEAR, an undersampled fMRI reconstruction approach based on decomposing the fMRI signal to periodic and fixed rank components. PEAR results in reconstruction with higher fidelity than when using a fixed-rank based model or a conventional Low-rank + Sparse algorithm. We have shown that splitting the functional information between the components leads to better modeling of fMRI, over state-of-the-art methods.

  • Gradient and shim pre-emphasis by inversion of a linear time-invariant system model.

    30 April 2018

    PURPOSE: The goal of this contribution is to enhance the fidelity and switching speed of gradient and shim fields by advancing pre-emphasis toward broadband and full cross-term correction. THEORY AND METHODS: The proposed approach is based on viewing gradient and shim chains as linear, time-invariant (LTI) systems. Pre-emphasis is accomplished by inversion of a broadband digital system model. In the multiple-channel case, it amounts to a matrix of broadband filters that perform concerted self- and cross-term correction. This approach is demonstrated with gradients and shims up to the third order in a 7 Tesla whole-body MR system. RESULTS: Pre-emphasis by LTI model inversion is first verified by studying settling speeds and response behavior without and with the correction. It is then demonstrated for rapid shim updating, achieving substantially enhanced fidelity of field dynamics and shim settling within approximately 1 ms. In single-shot echo-planar imaging (EPI) acquisitions in vivo, this benefit is shown to translate into enhanced geometric fidelity. CONCLUSIONS: The fidelity of gradient and shim dynamics can be greatly enhanced by pre-emphasis based on inverting a general LTI system model. Permitting shim settling on the millisecond scale, broadband multiple-channel pre-emphasis promises to render higher-order shimming fully versatile at the level of MRI sequence design. Magn Reson Med 78:1607-1622, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

  • Single-shot spiral imaging enabled by an expanded encoding model: Demonstration in diffusion MRI.

    3 May 2018

    PURPOSE: The purpose of this work was to improve the quality of single-shot spiral MRI and demonstrate its application for diffusion-weighted imaging. METHODS: Image formation is based on an expanded encoding model that accounts for dynamic magnetic fields up to third order in space, nonuniform static B0 , and coil sensitivity encoding. The encoding model is determined by B0 mapping, sensitivity mapping, and concurrent field monitoring. Reconstruction is performed by iterative inversion of the expanded signal equations. Diffusion-tensor imaging with single-shot spiral readouts is performed in a phantom and in vivo, using a clinical 3T instrument. Image quality is assessed in terms of artefact levels, image congruence, and the influence of the different encoding factors. RESULTS: Using the full encoding model, diffusion-weighted single-shot spiral imaging of high quality is accomplished both in vitro and in vivo. Accounting for actual field dynamics, including higher orders, is found to be critical to suppress blurring, aliasing, and distortion. Enhanced image congruence permitted data fusion and diffusion tensor analysis without coregistration. CONCLUSION: Use of an expanded signal model largely overcomes the traditional vulnerability of spiral imaging with long readouts. It renders single-shot spirals competitive with echo-planar readouts and thus deploys shorter echo times and superior readout efficiency for diffusion imaging and further prospective applications. Magn Reson Med 77:83-91, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

  • Experimental Neurology

    15 January 2013


    Our goal is to define how activity in large populations of neurons is coordinated in healthy movement and how such coordination may go awry in diseases, translating this information in to improved treatment for Parkinson’s Disease and other disorders of movement.

  • Neuromuscular Disorders

    15 January 2013


    We work to translate an understanding of the molecular mechanisms of disease at the neuromuscular synapse into treatments. Our work led us to be commissioned to provide a National Advisory and Diagnostic Service for congenital myasthenic syndromes.

  • Neural Injury Group

    19 February 2013


    Our aim is to gain a better understanding of the response of the peripheral nervous system to injury in order to develop strategies to promote peripheral nerve repair and to prevent the development of neuropathic pain. To do this we employ a variety of multi-disciplinary techniques ranging from transgenic models to human psychophysical studies and genetics.

  • Pain, Palliative and Supportive Care (PaPaS) Review Group

    15 January 2013


    The Cochrane Pain, Palliative and Supportive Care (PaPaS) Review Group is based at the Oxford Pain Relief Unit, Churchill Hospital.

  • Oxford Respiratory Group

    15 January 2013


    The Oxford Respiratory Group works collaboratively on a range of projects dedicated to Respiratory Control. Professor Pandit's group studies anaesthetic effects on oxygen sensing and also focusses on clinical research related to effects of anaesthetics on respiration and anaesthetic techniques on the lungs and airway.

  • Respiratory Physiology and Biomedical Engineering Group

    13 May 2014


    We work on modelling and monitoring disordered ventilation and gas exchange in acute and chronic lung disease.

  • Oxford Airway Group

    15 January 2013


    We strive to continually improve airway management in anaesthesia with a focus on minimising risk associated with difficult airways.

  • Circadian and Visual Neuroscience (Foster)

    15 January 2013


    Our research interests range across the neurosciences but with specific interests in circadian, visual and behavioural neuroscience.

  • Circadian and Visual Neuroscience (Peirson)

    15 January 2013


    Our research focuses on the non-image forming function of the eye, including how the light environment regulates sleep and circadian rhythms and how these responses are affected in disease.

  • Retinal Cell Biology and Degeneration

    15 January 2013


    The discovery of a novel inner retinal photoreceptor cell, driving non-visual functions, has had a significant impact on the retinal neuroscience field. My research focuses on understanding the physiology and function of these photosensitive retinal ganglion cells.