Biology subjects

Clarke, W. T.

Publications and source records attributed to Clarke, W. T..

4 recordsLinked to original sources

bioRxiv2020

GABA relates to functional connectivity changes and retention in visuomotor adaptation

Motor adaptation is fundamental to maintaining accurate movements under changing conditions, but the neurochemical basis of human motor adaptation is not well understood. Here, we used an ultra-high-field MR multimodal acquisition to address the hypothesis that M1 GABA and M1-Cerebellar functional connectivity would relate to retention of adaptation, but not acquisition of adaptation. As such, we demonstrate higher baseline M1 [GABA] relates to greater retention but does not relate to adaptation-acquisition. This relationship is mediated by change in M1-Cerebellar functional connectivity: higher M1 [GABA] relates to a decreased M1-Cerebellar connectivity, resulting in greater retention. These findings showed anatomical, neurochemical and behavioural specificity: As expected, no relationship was found between retention and a control metabolite, retention and connectivity change between control regions and between M1 [GABA] and behaviour in a control condition. The implication of a mechanistic link from neurochemistry to retention advances our understanding of population variability in retention and provides a step towards therapeutic interventions to restore motor abilities.

neuroscience↗

bioRxiv2020

A mechanism for hippocampal memory recall based on excitatory-inhibitory fluctuations in neocortex

The brain has a remarkable capacity to acquire and store memories that can later be selectively recalled. These processes are supported by the hippocampus which is thought to index memory recall by reinstating information stored across distributed neocortical circuits. However, the mechanism that supports this interaction remains unclear. Here, in humans, we show that recall of a visual cue from a paired associate is accompanied by a transient increase in the ratio between glutamate and GABA in visual cortex. Moreover, these excitatory-inhibitory fluctuations are predicted by activity in the hippocampus. These data suggest the hippocampus gates memory recall by indexing information stored across neocortical circuits using a disinhibitory mechanism.

neuroscience↗

bioRxiv2020

FSL-MRS: An end-to-end spectroscopy analysis package

PurposeWe introduce FSL-MRS, an end-to-end, modular, open-source magnetic resonance spectroscopy analysis toolbox. FSL-MRS provides spectroscopic data conversion, pre-processing, spectral simulation, fitting, quantitation and visualisation. MethodsFSL-MRS is modular. FSL-MRS programs operate on data in a standard format (NIfTI) capable of storing single voxel and multi-voxel spectroscopy, including spatial orientation information. FSL-MRS includes tools for pre-processing of raw spectroscopy data, including coil-combination, frequency and phase alignment, and filtering. A density matrix simulation program is supplied for generation of basis spectra from simple text-based descriptions of pulse sequences. Fitting is based on linear combination of basis spectra and implements Markov chain Monte Carlo optimisation for the estimation of the full posterior distribution of metabolite concentrations. Validation of the fitting is carried out on independently created simulated data, phantom data, and three in vivo human datasets (257 SVS and 8 MRSI datasets) at 3T and 7T. Interactive HTML reports are automatically generated by processing and fitting stages of the toolbox. FSL-MRS can be used on the command line or interactively in the Python language. ResultsValidation of the fitting shows low error in simulation (median error 11.9%) and in phantom (3.4%). Average correlation between a third-party toolbox (LCModel) and FSL-MRS was high (0.53-0.81) in all three in vivo datasets. ConclusionFSL-MRS is designed to be flexible and extensible to new forms of spectroscopic acquisitions. Custom fitting models can be specified within the framework for dynamic or multi-voxel spectroscopy. FSL-MRS is available as part of the FMRIB Software Library.

neuroscience↗

bioRxiv2020

Multi-centre, multi-vendor reproducibility of 7T QSM and R2* in the human brain: results from the UK7T study

We present the reliability of ultra-high field T2* MRI at 7T, as part of the UK7T Networks "Travelling Heads" study. T2*-weighted MRI images can be processed to produce quantitative susceptibility maps (QSM) and R2* maps. These reflect iron and myelin concentrations, which are altered in many pathophysiological processes. The relaxation parameters of human brain tissue are such that R2* mapping and QSM show particularly strong gains in contrast-to-noise ratio at ultra-high field (7T) vs clinical field strengths (1.5 - 3T). We aimed to determine the inter-subject and inter-site reproducibility of QSM and R2* mapping at 7T, in readiness for future multi-site clinical studies. MethodsTen healthy volunteers were scanned with harmonised single- and multi-echo T2*-weighted gradient echo pulse sequences. Participants were scanned five times at each "home" site and once at each of four other sites. The five sites had 1x Philips, 2x Siemens Magnetom, and 2x Siemens Terra scanners. QSM and R2* maps were computed with the Multi-Scale Dipole Inversion (MSDI) algorithm (https://github.com/fil-physics/Publication-Code). Results were assessed in relevant subcortical and cortical regions of interest (ROIs) defined manually or by the MNI152 standard space. Results and DiscussionMean susceptibility ({chi}) and R2* values agreed broadly with literature values in all ROIs. The inter-site within-subject standard deviation was 0.001 - 0.005 ppm ({chi}) and 0.0005 - 0.001 ms-1 (R2*). For {chi} this is 2.1-4.8 fold better than 3T reports, and 1.1-3.4 fold better for R2*. The median ICC from within- and cross-site R2* data was 0.98 and 0.91, respectively. Multi-echo QSM had greater variability vs single-echo QSM especially in areas with large B0 inhomogeneity such as the inferior frontal cortex. Across sites, R2* values were more consistent than QSM in subcortical structures due to differences in B0-shimming. On a between-subject level, our measured {chi} and R2* cross-site variance is comparable to within-site variance in the literature, suggesting that it is reasonable to pool data across sites using our harmonised protocol. ConclusionThe harmonized UK7T protocol and pipeline delivers on average a 3-fold improvement in the coefficient of reproducibility for QSM and R2* at 7T compared to previous reports of multi-site reproducibility at 3T. These protocols are ready for use in multi-site clinical studies at 7T.

neuroscience↗