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Laura E. Hughes

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6 papers
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6

YNICL Journal 2024 Journal Article

Frontotemporal lobar degeneration changes neuronal beta-frequency dynamics during the mismatch negativity response

  • Alistair Perry
  • Laura E. Hughes
  • Natalie E. Adams
  • Michelle Naessens
  • Niels A. Kloosterman
  • Matthew A. Rouse
  • Alexander G. Murley
  • Duncan Street

The consequences of frontotemporal lobar degeneration include changes in prefrontal cortical neurophysiology, with abnormalities of neural dynamics reported in the beta frequency range (14-30 Hz) that correlate with functional severity. We examined beta dynamics in two clinical syndromes associated with frontotemporal lobar degeneration: the behavioral variant of frontotemporal dementia (bvFTD) and progressive supranuclear palsy (PSP). Whilst these two syndromes are partially convergent in cognitive effects, they differ in disease mechanisms such as molecular pathologies and prefrontal atrophy. Whether bvFTD and PSP also differ in neurophysiology remains to be fully investigated. We compared magnetoencephalography from 20 controls, 23 people with bvFTD and 21 people with PSP (Richardson's syndrome) during an auditory roving oddball paradigm. We measured changes in low and high total beta power responses (14-22 and 22-30 Hz respectively) over frontotemporal cortex in the period of the mismatch negativity response (100-250 ms post-stimulus). In controls, we found increased 14-22 Hz beta power following unexpected sensory events (i.e. increased deviant versus standard response), from right prefrontal cortex. Relative to controls, PSP reversed the mismatch response in this time-frequency window, reflecting reduced responses to the deviant stimuli (relative to standard stimuli). Abnormal beta at baseline in PSP could account for the reduced task-modulation of beta. Across bvFTD and PSP groups, the beta response to deviant stimuli (relative to standard stimuli) correlated with clinical severity, but not with atrophy of the prefrontal source region. These findings confirm the proposed importance of higher-order cortical regions, and their beta-power generators, in sensory change detection and context-updating during oddball paradigms. The physiological effects are proposed to result from changes in synaptic density, cortical neurotransmitters and subcortical connections, rather than merely atrophy. Beta-power changes may assist clinical stratification and provide intermediate outcomes for experimental medicine studies of novel therapeutic strategies.

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YNIMG Journal 2022 Journal Article

A multi-site, multi-participant magnetoencephalography resting-state dataset to study dementia: The BioFIND dataset

  • Delshad Vaghari
  • Ricardo Bruna
  • Laura E. Hughes
  • David Nesbitt
  • Roni Tibon
  • James B. Rowe
  • Fernando Maestu
  • Richard N. Henson

Early detection of Alzheimer's Disease (AD) is vital to reduce the burden of dementia and for developing effective treatments. Neuroimaging can detect early brain changes, such as hippocampal atrophy in Mild Cognitive Impairment (MCI), a prodromal state of AD. However, selecting the most informative imaging features by machine-learning requires many cases. While large publically-available datasets of people with dementia or prodromal disease exist for Magnetic Resonance Imaging (MRI), comparable datasets are missing for Magnetoencephalography (MEG). MEG offers advantages in its millisecond resolution, revealing physiological changes in brain oscillations or connectivity before structural changes are evident with MRI. We introduce a MEG dataset with 324 individuals: patients with MCI and healthy controls. Their brain activity was recorded while resting with eyes closed, using a 306-channel MEG scanner at one of two sites (Madrid or Cambridge), enabling tests of generalization across sites. A T1-weighted MRI is provided to assist source localisation. The MEG and MRI data are formatted according to international BIDS standards and analysed freely on the DPUK platform (https://portal.dementiasplatform.uk/Apply). Here, we describe this dataset in detail, report some example (benchmark) analyses, and consider its limitations and future directions.

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YNICL Journal 2013 Journal Article

Reorganisation of brain networks in frontotemporal dementia and progressive supranuclear palsy

  • Laura E. Hughes
  • Boyd C.P. Ghosh
  • James B. Rowe

The disruption of large-scale brain networks is increasingly recognised as a consequence of neurodegenerative dementias. We assessed adults with behavioural variant frontotemporal dementia and progressive supranuclear palsy using magnetoencephalography during an auditory oddball paradigm. Network connectivity among bilateral temporal, frontal and parietal sources was examined using dynamic causal modelling. We found evidence for a systematic change in effective connectivity in both diseases. Compared with healthy subjects, who had focal modulation of intrahemispheric frontal-temporal connections, the patient groups showed abnormally extensive and inefficient networks. The changes in connectivity were accompanied by impaired responses of the auditory cortex to unexpected deviant tones (MMNm), despite normal responses to standard stimuli. Together, these results suggest that neurodegeneration in two distinct clinical syndromes with overlapping profiles of prefrontal atrophy, causes a similar pattern of reorganisation of large-scale networks. We discuss this network reorganisation in the context of other focal brain disorders and the specific vulnerability of functional brain networks to neurodegenerative disease.

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