Sharott Group

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Sharrott

Circuit mechanisms of dysfunction and development of therapy for brain disorders

Our group is focussed on developing and delivering novel methods of therapeutic brain stimulation for brain disorders for which existing approaches remain ineffective. This development is underpinned by fundamental insights into functional and dysfunctional computation at the level of populations of neurons in affected brain areas. We use a cross-species strategy, where preclinical experiments are used develop methods of modulating brain activity in real-time using lightweight approaches that can be readily deployed on human devices. 

Group Science

Our overarching aim is to identify systems-level mechanisms underlying fundamental brain functions and to use this understanding to develop brain stimulation-based technologies to treat brain disorders. A key principle of our strategy is to use forward and back-translation between studies in experimental animals and human subjects with deep brain electrodes.  In experimental animals, we investigate function and dysfunction at the level of spiking activity of many neurons in relevant brain areas (e.g. cortex, basal ganglia, thalamus, hippocampus) and use analytical techniques aimed at identifying computational processes at the population-scale. A key part of our work is to identify signals (e.g. features of local field potentials) that are recorded in humans that provide accurate information about these population-level dynamics. Increasingly, by utilising next-generation sense/stimulation devices, we can track such electrophysiological signatures of disease during weeks and months of treatment. By combining these different levels of information, we develop clinically tractable approaches that can promote functional activity and/or supress activities that lead to impaired cognition and behaviour. To achieve this, we focus on closed-loop approaches that can track these neural signatures in real-time and use this information to control the timing of deep brain or non-invasive stimulation in ways that restores function. Using this approach, we aim to identify novel, clinically tractable interventions that improve sleep, cognition and motor control in disorders including Parkinson’s disease, Alzheimer’s disease, stroke and schizophrenia.

Key Research Areas
  • Identifying population-level neural activity supporting motor control and decision making.

  • Cross-species development of novel brain stimulation approaches for brain disorders, including Parkinson’s disease and Alzheimer’s disease.

  • Development of novel closed-loop approaches for large-scale modulation of neural oscillations associated with motor control, memory and sleep.

Research Techniques
  • High-density electrophysiological recordings during complex behaviour

  • Closed-loop deep brain stimulation.

  • Clinical neurophysiology in people with deep brain electrodes for therapy.

 

Equality and Diversity

We are committed to fostering an inclusive work environment that celebrates diversity and promotes equal opportunity within our group and the wider MRC BNDU.

Group Leader
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Andrew Sharrott
Group News
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Photo of Camille Lasbareilles (seated) and Ioana Grigoras (standing) with members of the Unit’s Patient and Public Advisory Group.

Unit early-career researchers Camille Lasbareilles and Ioana Grigoras demonstrate transcranial magnetic stimulation to members of the Unit’s Patient and Public Advisory Group.

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A group photo of attendees at the Unit’s Science Day in winter 2023.

Attendees at the MRC BNDU’s Science Day in Winter 2023.

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Photo of a visiting In2scienceUK school pupil working at a lab bench.

In2scienceUK student gets involved with neuroanatomy research at the MRC BNDU.

Selected Publications
Unit Publication
McNamara CG
Rothwell M
Sharott A

2022. Cell Rep, 41(6):111616.

Unit Publication
van Rheede JJ
Feldmann LK
Busch JL
Fleming JE
Mathiopoulou V
Denison T
Sharott A
Kühn AA

2022. NPJ Parkinsons Dis, 8(1):88.

Unit Publication
Cagnan H
Mallet N
Moll CK
Gulberti A
Holt AB
Westphal M
Gerloff C
Engel AK
Hamel W
Magill PJ
Brown P
Sharott A
2019. Proc. Natl. Acad. Sci. U.S.A., 116:16095-16104.
Unit Publication
Holt AB
Kormann E
Gulberti A
Pötter-Nerger M
McNamara CG
Cagnan H
Baaske MK
Little S
Köppen JA
Buhmann C
Westphal M
Gerloff C
Engel AK
Brown P
Hamel W
Moll CK
Sharott A
2019. J. Neurosci., 39(6):1119-1134.
Unit Publication
Baaske MK
Kormann E
Holt AB
Gulberti A
McNamara CG
Pötter-Nerger M
Westphal M
Engel AK
Hamel W
Brown P
Moll CK
Sharott A
2020. Neurobiol. Dis., 146:105119.
Datasets and resources

Like other Groups at the MRC BNDU, we are committed to best practice in open research.  We have created and curated a range of primary data, metadata and related resources that can be readily downloaded by external users from the MRC BNDU's Data Sharing Platform. We are part of the team that created CHAMBER, a novel chemoarchitectonic atlas of mouse thalamus and other brain regions.

Sharott A
Doig N
Garas F
Vinciati F
Magill PJ
10.5287/bodleian:VYqnPkxkb