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Professor Krishna Singh BSc Dunelm, PhD Open

Professor Krishna Singh

BSc Dunelm, PhD Open

Professor, Head of Human Electrophysiology

School of Psychology

Email
singhkd@cardiff.ac.uk
Telephone
+44(0)29 2087 4690
Campuses
Cardiff University Brain Research Imaging Centre, Maindy Road, Cardiff, CF24 4HQ

Overview

Research

My research uses non-invasive imaging of the human brain using magnetic resonance imaging (MRI) and Magnetoencephalography (MEG).

Originally from a Physics background, I now consider myself to be a Neuroscientist - working at the interface between methodological development and clinical and cognitive neuroscience applications. I help support broader multidisciplinary research across the College of Biomedical and Life Sciences, as Theme Lead for Mind, Brain and Neuroscience.

I arrived in Cardiff in 2005 to help lead the new Cardiff University Brain Research Imaging Centre (CUBRIC). Here, my main role is to facilitate multimodal neuroimaging research in cognitive and clinical applications, with a specific remit to champion non-invasive human electrophysiology research using EEG and MEG. As part of this, I have helped build cross-disciplinary research collaborations across Cardiff University, including with colleagues in the Schools of Medicine and Biosciences, within Cardiff's Neuroscience and Mental Health Research Insititute. This has led to collaborative research programmes in Epilepsy, Schizophrenia and Alzheimer’s disease, including studies of electrophysiological markers of genetic risk.

I also help build and sustain the UK’s highly-collaborative MEG scientific community, through our MEG-UK Partnership. I recently led an MRC-funded Partnership grant that linked all UK MEG research groups together in developing common training, acquisition and analysis approaches for MEG research, as well as creating a multisite multi-platform database of MEG data.

Teaching summary

I am Module leader for one of the modules on our Neuroimaging MSc, PST512: “Introduction to Neuroimaging Methods. This is a course which is designed to give students insight into the principles behind modern non-invasive neuroimaging techniques. Topics covered include: The principles of MRI and structural imaging, DTI, fMRI, TMS, TDCS, neurophysiology, EEG and MEG.

Biography

Undergraduate education

1984 – 1987: Collingwood College, University of Durham. BSc in Physics (First Class Hons)

Postgraduate education

1987 – 1991: Department of Physics, The Open University, Milton Keynes. PhD in Physics.

Employment

2000 - 2005: Senior Lecturer, School of Life and Health Sciences, Aston University.

1998 - 2000: Lecturer. MARIARC, School of Medicine, Liverpool University.

1996 - 1998: Research Fellow. Psychology, Royal Holloway College, University of London.

1992 - 1996: Research Fellow. Department of Vision Sciences, Aston University, Birmingham.

1991 - 1992: Research Fellow. Department of Physics, The Open University, Milton Keynes.

Publications

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Teaching

I am Module leader for one of the modules on our Neuorimaging MSc, PST512: “Introduction to Neuroimaging Methods. This is a course which is designed to give students insight into the principles behind modern non-invasive neuroimaging techniques. Topics covered include: The principles of MRI and structural imaging, DTI, fMRI, TMS, TDCS, neurophysiology, EEG and MEG.

Research Programmes

  • fMRI and MEG studies of human visual cortex, including the relationship between the haemodynamic response and cortical oscillatory activity e.g. Singh et al., Neuroimage 2002, vol 16.
  • Studies demonstrating that Magnetoencephalography (MEG) can provided sensitive and time-resolved markers of pharmacological action, enabling both mechanistic insights and electrophysiological evidence of novel target engagement in multiple receptor systems: GABA (10.1002/hbm.23283,10.1016/j.neuroimage.2017.08.034), AMPA (10.1177/0269881117736915, 10.1016/j.cortex.2016.03.004) and NMDA (10.1016/j.euroneuro.2015.04.012, 10.1016/j.neuroimage.2020.117189).
  • Oscillatory biomarkers in health and disease: Recently, I have become interested in using MEG measured oscillatory parameters to help characterise synaptic function in diseases that are thought to depend on impairments to these systems, such as Schizophrenia and Epilepsy. For example, together with clinical colleagues, we showed an impairment of normal beta desynchronisation in patients with juvenile myoclonic epilepsy (Hamandi et al., Clinical Neurophysiology 2011, vol 122(11)). In a recent MEG study, we showed that young healthy carriers of the APOE4 risk gene showed oscillatory hyper-connectivity and hyper-activity across the cortex, in regions similar to those that showed reduced connectivity in older people with established Alzheimer's disease (eLife 2019;8:e36011).
  • Recently, with colleagues from the School of Medicine, we showed how visual gamma responses were impaired in chronic Schizophrenia, and that, using neurophysiologically-informed modelling (DCM), we could gain insight into how these arose from a disruption of the normal coupling within/between inhibitory interneurons and pyramidal cells - methods that will be crucially important in the proposed project (Schizophrenia Bulletin, sbz066).
  • The use of Magnetic Resonance Spectroscopy to assess variability in neurotransmitters (such as GABA) and how this determines both oscillatory dynamics and function (Muthukumaraswamy et al., PNAS 2009, vol 106; Edden et al., J. Neurosci. 2009, vol 29(50)).
  • Studying how individual variability in the brain's structure and function leads to variability in perceptual and cognitive performance: For example, we showed that performance on visual orientation discrimination was correlated with individual variability in both GABA concentration and visual gamma frequency in healthy humans. (Edden et al., J. Neurosci. 2009, vol 29(50)).

Recent Key Research Papers

  • Dima DC, Adams R, Linden SC, Baird A, Smith J, Foley S, Perry G, Routley BC, Magazzini L, Drakesmith M, Williams N, Doherty J, van den Bree MBM, Owen MJ, Hall J, Linden DEJ, Singh KD (2020) Electrophysiological network alterations in adults with copy number variants associated with high neurodevelopmental risk. Translational Psychiatry10(1), 324 (PMCID: PMC7506525). In this resting-state MEG paper, we show that oscillatory connectivity is different in people carrying rare genetic variants, such as 22q11 deletions, and that machine-learning approaches allow cross-group classification. The results show that while some electrophysiological features are CNV-specific, others reflect more convergent neurobiological processes.
  • Shaw AD, Knight L, Freeman TCA, Williams GM, Moran, Friston KJ, Walters TR and Singh KD. (2020). Oscillatory, computational and behavioural evidence for impaired GABAergic inhibition in schizophrenia, Schizophrenia Bulletin, 46(2), 345-353. (PMCID: PMC7442335). Using MEG, MR spectroscopy and visual psychophysics, we identify several data features that differ in chronic schizophrenia, compared to controls. Many of these disease-related changes in gamma oscillations, GABA and orientation discrimination can be linked to reductions in GABAergic inhibition – this is made explicit via neurophysiologically-informed modelling (DCM).
  • Shaw AD, Muthukumaraswamy SD, Saxena N, Sumner RL, Adams NE, Moran RJ, Singh KD (2020). Generative modelling of the thalamo-cortical circuit mechanisms underlying the neurophysiological effects of ketamine. Neuroimage. 221:117189. (PMCID pending). We show how DCM-modelling of source-localised MEG data, measured before and during ketamine infusion, can investigate receptor-specific circuit changes induced by this NMDA antagonist. Our optimised model can be deployed in other drug studies and also in disease-cohort studies where neurotransmitter-specific modulations are hypothesised, such as NMDAR impairments in Schizophrenia or genetic risk of Schizophrenia.
  • Koelewijn L., Lancaster T.M., Linden D., Dima D.C., Routley B.C., Magazzini L., Barawi K., Brindley L., Adams R., Tansey K.E., Bompas A., Tales A., Bayer A., Singh K.D. (2019). Oscillatory hyperactivity and hyperconnectivity in young APOE-e4 carriers and hypoconnectivity in Alzheimer’s disease. eLife 2019;8:e36011 (PMCID PMC6491037), 10.7554/eLife.36011. Using resting-state MEG in young carriers of APOE-e4, we found oscillatory hyperactivity/hyperconnectivity compared to non-carriers. This is consistent with animal data showing hyperactivity associated with amyloid-beta and later disease transition. In an older cohort, we also identified hypoconnectivity in people with Alzheimer’s. This suggests possible early electrophysiological markers of dementia risk that could help understand/predict later transition.
  • Shaw, A.D., Moran, R.J., Muthukumaraswamy, S.D., Brealy J., Linden D.E., Friston, K.J., Singh, K.D. (2017). Neurophysiologically-informed markers of individual variability and pharmacological manipulation of human cortical gamma. NeuroImage. 161, pp. 19-31, (PMCID 5692925). We show how modelling of MEG-measured visual cortex gamma oscillations, using a computational model derived from animal studies of V1, can provide insight into the synaptic physiology underlying human individual variability and the target and dynamics of drugs targeting specific receptors/neurotransmitters.
  • Singh KD. Which “neural activity” do you mean? (2012) fMRI, MEG, oscillations and neurotransmitters. Neuroimage, 62(2): 1121-1130 (PMID 22248578). Here, I reviewed the relationship between fMRI-BOLD and direct electrophysiological measures from MEG/EEG. The idea is that fMRI is often described as measuring “neural activity” but that, in reality, it is a correlate of a complex mixture of electrophysiological signals that are related to both excitation and inhibition, which is poorly understood and may vary across the brain and people.

Funding

  • £47210 from the Wellcome Trust ISSF (2020-201). Development of wearable, room-temperature and movement- tolerant MEG for adults and children at Cardiff University. Singh, Beltrachini, Vanderwert.
  • £165,055, Endeavour Project Grant from Epilepsy Research UK (2021-2024). Seeing inside: non-invasive brain mapping of epileptic activity (SINIMA). Hamandi, Singh, Murphy, Faulkner, Sieradzan.
  • £400,000 from the EPSRC (2020-2021) Core Equipment grant, Graham, Singh (Co- applicant), Murphy, Beltrachini, Holt, Lawrence, Charron.
  • £971,676 from the MRC (2018-2020) Integrating genetic, clinical and phenotypic data to advance stratification, prediction and treatment in mental health. Hall, Owen, Harwood, John, Murphy, Walters, O’Donovan, Atack, Jones, Rice, Holmans, Collishaw, Moore, Singh, Thapar.
  • £6.7M from the MRC (2014-2016) Enhancing UK's Clinical Research Capabilities and Technologies 2014. Ultra-High Field MRI: Advancing Clinical Neuroscientific Research in Experimental Medicine. Wise, Jones, Singh, Linden, Kauppinen (Bristol), Graham.
  • £4.9M from the Wellcome Trust (2016-2021) Multi-Scale and Multi-Modal Assessment of Coupling in the Healthy and DiseasedBrain. Jones, Assaf, Chambers, Graham, Jezzard (Oxford), Linden, Morris (Nottingham), Nutt (ICL), Sumner, Singh, Wise.
  • £2.9M from the EPSRC (2014-2019) National Facility for In Vivo MR Imaging of Human Tissue Microstructure. Jones, Alexander(UCL), Bowtell (Nottingham), Cercignani (Sussex), Dell’Acqua (KCL), Parker (Manchester), Singh, Wise, Miller (Oxford), Thomas.
  • £1.0M from the Wolfson Foundation (2014-2016) CUBRIC – The Cardiff University Brain Research Imaging Centre. Singh, Price, Jones, Wise, Linden, Graham, Chambers, Sumner.
  • £4.9M (FEC) (£654,159 to Cardiff) from the MRC. (2014-2019) MICA: STRATA - Schizophrenia: Treatment Resistance andTherapeutic Advances. Kapur, McCabe, Murray, McGuire, Howes, Rose, McCrone, Pickles, Talbot, Williams, Matthews, Deakins, Lewis, Emsley, Stone, Walters, Owen, Pocklington, Singh, Lawrie, McIntosh, Egerton, Doody, O’Neill, O’Donovan.
  • £44569 from the Wellcome Trust ISSF (2017-2018). Characterising alternations of neural dynamics in intractable epilepsy using neurophysiologically- informed models. Zhang, Singh, Hamandi, Cheng.
  • £38601 from the Wellcome Trust ISSF (2016-2016). Neurophysiologically- informed models and machine learning classificationof task-driven and resting state oscillatory dynamics in schizophrenia. Singh, Walters, Freeman, Zhang.
  • £307,019 from the Wellcome Trust. (2013-2016) Excitatory-inhibitory balance in adolescents at high genetic risk of mentaldisorder: A study of cortical gamma oscillations and GABA concentrations of 22q11.2 deletion syndrome. Doherty, Owen. Linden, Van den Bree, Singh.
  • £4.2M (FEC) (£925,580 to Singh as Cardiff PI) from the MRC. (2013-2018) Defining the disturbance in cortical glutamate andGABA function in psychosis, its origins and consequences. Deakin, Talbot, Gerhard, Hinz, Williams, Singh, Wilkinson, Walters, Freeman, Morris, Liddle, Brookes, Palaniyappan, Macdonald.
  • £1.5M (FEC) from the MRC. (2013-2019). Building multi-site clinical research capacity in Magnetoencephalography (MEG). Singh (PI), Hamandi, Gross, Kessler, Brookes, Morris, Henson, Barnes, Woolrich, Nobre, Litvak, Holliday, Furlong, Shtyrov, Green
  • £986,846 (FEC) from the MRC. (2013-2016) Behavioural and neurophysiological effects of schizophrenia risk genes: a multi-locus, pathway-based approach. Linden, O’Donovan, Owen, Holmans, Pocklington, Zammit, Hall, Singh, Jones, Davey-Smith.
  • £668,226 from the Wellcome Trust. (2013-2018). Dedicated Computing Infrastructure for CUBRIC. Jones, Singh, Wise.
  • £99,980 from Epilepsy Research UK. Magnetoencephalographic measures of abnormalsensory oscillations: A new window onphotosensitive epilepsy. (2010-2013). Hamandi, Singh and Muthukumaraswamy.
  • £195,000 from the Welsh Assembly Government (A4B): The Integrated Brain Imaging and Stimulation Project (IBIS). (2010-2013). Chambers, Singh, Wise, Jones and Jiles.
  • £165,000 from Bristol Research into Alzheimer’s and Care of the Elderly: Characterizing the functional and anatomical integrity ofvisual attention-related processing in Alzheimers disease. (2010-2013). Tales, Singh, Bayer, Jones and O’Sullivan.
  • £113,039 from The Waterloo Foundation: Advanced Neuro-imaging in BECTS. (2010-2013). Hamandi, Singh, et al.
  • £426,191 from the Wellcome Trust: See it, grab it: Control of automatic sensorimotor behaviour in health and disease. (2009-2012) Sumner, Husain, Singh and Rafal.
  • £4M from the Wellcome Trust: 4 yr PhD programme in integrative neuroscience. (2008-2014). Lead Applicants: Aggleton andCrunelli.
  • £176,933 from BBSRC (BBSB08035): Synthetic Aperture Magnetometry Studies of Stimulus Related Oscillatory Power Changesin Human Visual Cortex. (2004-2007). Singh.

Supervision

Postgraduate research interests

I am interested in supervising PhD projects in multi-modal functional neuroimaging methods and applications (MEG and fMRI), with a specific focus on vision and the underlying neurophysiology of MEG and BOLD-fMRI signals. A recent developing interest has been the dependency of these measures on GABAergic inhibition.

If you are interested in applying for a PhD, or for further information regarding my postgraduate research, please contact me directly (contact details available on the 'Overview' page), or submit a formal application.

Current students

Megan Godfrey 2016-

Laura Bloomfield 2016-

Melissa Wright 2016-

Marie-Lucie Read 2017-

Tom Chambers 2017-

Dominik Krzeminski 2017-

Hellen Yuan 2018-

Jacopo Barone 2018-

Stefan Brugger 2018-

Emily Lambe 2018-

Mengi Zhang 2020-

Past projects

Previous students

Dr Alexander Shaw 2011-2015, Research Associate, CUBRIC, Cardiff University

Dr Joanne Doherty 2013-2019, Clinical Research Fellow, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University

Dr Gemma Williams 2014-2018

Dr Diana Dima 2015-2018, Post-doctoral researcher at Johns Hopkins, USA.

Dr Benjamin Dunkley 2008-2011, Assistant Professor, University of Toronto, Canada.

Dr Rachael Stickland 2015-2019, Postdoctoral Fellow of Northwestern University, USA.

Dr Phoebe Asquith 2015-2019, Research Associate, School of Psychology, Cardiff University

Dr Bethany Routley 2013-2017, Science and Communications Officer, Cancer Research Wales

Dr Lorenzo Magazzini 2013-2017

Dr Mark Mikkelsen 2012-2015, Postdoctoral Fellow at The Johns Hopkins University, USA.

Dr Laura Knight  2012-2015, Cedar - Healthcare Technology Research Centre, Cardiff, Wales.

Dr Jennifer Brealy 2011-2015

Dr Claire Hanley 2012-2015, Lecturer in Psychology, Swansea University

Dr Panagiotis Kovanis 2010-2014

Dr Sian Robson 2010-2013, Research fellow, Centre for Genomic and Experimental Medicine, University of Edinburgh.

Dr Ian Fawcett 2002-2005