Biology subjects

Craven, A. R.

Publications and source records attributed to Craven, A. R..

4 recordsLinked to original sources

bioRxiv2023

The intra-individual reliability of 1H-MRS measurement in the anterior cingulate cortex across one year

Magnetic resonance spectroscopy (MRS) is the primary method that can measure the levels of metabolites in the brain in vivo. To achieve its potential in clinical usage, the reliability of the measurement requires further articulation. Although there are many studies that investigate the reliability of gamma-aminobutyric acid (GABA), comparatively few studies have investigated the reliability of other brain metabolites, such as glutamate (Glu), N-acetyl-aspartate (NAA), creatine (Cr), phosphocreatine (PCr), or myo-inositol (mI), which all play a significant role in brain development and functions. In addition, previous studies which predominately used only two measurements (two datapoints) failed to provide the details of the time effect (e.g., time-of-day) on MRS measurement within subjects. Therefore, in this study, MRS data located in the anterior cingulate cortex (ACC) were repeatedly recorded across one year leading to at least 25 sessions for each subject with the aim of exploring the variability of other metabolites by using the index coefficient of variability (CV); the smaller the CV, the more reliable the measurements. We found that the metabolites of NAA, tNAA, and tCr showed the smallest CVs (between 1.61 and 4.90 %), and the metabolites of Glu, Glx, mI, and tCho showed modest CVs (between 4.26 and 7.89 %). Furthermore, we found that the concentration reference of the ratio to water with tissue correction results in smaller CVs compared to the ratio to tCr. In addition, we did not find any time-of-day effect on the MRS measurements. Collectively, the results of this study indicate that the MRS measurement is reasonably reliable in quantifying the levels of metabolites. Key pointsThe MRS measurement is reliable within subject. The ratio to water provides more reliable results compared to the ratio to tCr. The ratio to water is recommended as the internal concentration reference.

neuroscience↗

bioRxiv2023

GABA, glutamatergic dynamics and BOLD contrast concurrently assessed using functional MR spectroscopy during a cognitive task

A recurring issue in functional neuroimaging is how to link task-driven hemodynamic BOLD-fMRI responses to underlying neurochemistry at the synaptic level. Glutamate and GABA, the major excitatory and inhibitory neurotransmitters respectively, are typically measured with MR spectroscopy (MRS) sequences in a resting state, in the absence of a task. We propose to resolve this disconnect by applying a novel method to concurrently acquire BOLD, Glx and GABA measurements from a single voxel, using a locally adapted MEGA-PRESS sequence implementation which incorporates unsuppressed water reference signals at a regular interval, allowing continuous assessment of BOLD-related linewidth variation for fMRS applications. Healthy subjects (N = 81) performed a cognitive task (Eriksen Flanker) which was presented visually in a task-OFF, task-ON block design, with individual event stimulus timing varied with respect to the MRS readout. BOLD data acquired with the adapted MEGA-PRESS sequence were correlated with data acquired using a standard fMRI EPI sequence as a means of validating the concurrent approach: a significant (although moderate) correlation was observed, specific to the fMRS-targeted region of interest. We additionally present a novel linear model for extracting modelled spectra associated with discrete functional stimuli, building on well-established processing and quantification tools. Behavioural outcomes from the Flanker task, and activation patterns from the BOLD-fMRI sequence, were as expected from the literature. fMRS-assessed BOLD response correlated strongly with slowing of response time in the incongruent Flanker condition. Moreover, there was a significant increase in measured Glx levels (~8.8%), between task-OFF and task-ON periods. These findings verify the efficacy of our functional task and analysis pipelines for the simultaneous assessment of BOLD and metabolite fluctuations in a single voxel. As well as providing a robust basis for further work using these techniques, we also identify a number of clear directions for further refinement in future studies. HighlightsO_LIConcurrent measurement of temporally resolved metabolite estimates and local BOLD-related signal changes is demonstrated C_LIO_LIIn-vivo, GABA-edited functional 1H-MRS data were collected from 81 healthy subjects whilst they performed a cognitive task C_LIO_LIRobust task-related increases in measured Glutamate+Glutamine were observed in the Anterior Cingulate Cortex C_LIO_LIModerate correlation was observed between BOLD contrast strength as assessed by fMRS and fMRI techniques, specific to the prescribed region C_LIO_LIA novel technique for extraction of block- or event-related sub-spectra is demonstrated C_LI Graphical AbstractA novel sequence adaption for concurrent measurement of GABA-edited spectroscopy and functional BOLD changes is demonstrated on N=81 healthy subjects. Significant changes in measured Glutamate+Glutamine concentration are found, along with the expected behavioural and BOLD effects in response to a Flanker task. O_FIG O_LINKSMALLFIG WIDTH=170 HEIGHT=200 SRC="FIGDIR/small/539017v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@e06295org.highwire.dtl.DTLVardef@1683a30org.highwire.dtl.DTLVardef@1c45f7aorg.highwire.dtl.DTLVardef@1587cf0_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Comparison of seven modelling algorithms for GABA-edited 1H-MRS

Edited MRS sequences are widely used for studying GABA in the human brain. Several algorithms are available for modelling these data, deriving metabolite concentration estimates through peak fitting or a linear combination of basis spectra. The present study compares seven such algorithms, using data obtained in a large multi-site study. GABA-edited (GABA+, TE = 68 ms MEGA-PRESS) data from 222 subjects at 20 sites were processed via a standardised pipeline, before modelling with FSL-MRS, Gannet, AMARES, QUEST, LCModel, Osprey and Tarquin, using standardised vendor-specific basis sets (for GE, Philips and Siemens) where appropriate. After referencing metabolite estimates (to water or creatine), systematic differences in scale were observed between datasets acquired on different vendors hardware, presenting across algorithms. Scale differences across algorithms were also observed. Using the correlation between metabolite estimates and voxel tissue fraction as a benchmark, most algorithms were found to be similarly effective in detecting differences in GABA+. An inter-class correlation across all algorithms showed single-rater consistency for GABA+ estimates of around 0.38, indicating moderate agreement. Upon inclusion of a basis set component explicitly modelling the macromolecule signal underlying the observed 3.0 ppm GABA peaks, single-rater consistency improved to 0.44. Correlation between discrete pairs of algorithms varied, and was concerningly weak in some cases. Our findings highlight the need for consensus on appropriate modelling parameters across different algorithms, and for detailed reporting of the parameters adopted in individual studies to ensure reproducibility and meaningful comparison of outcomes between different studies. HighlightsO_LIGABA-edited MRS data from 222 healthy adults across 20 research sites were analyzed C_LIO_LIData were modelled using seven different algorithms, yielding GABA+ and Glx estimates C_LIO_LIModerate agreement was seen across all the tested algorithms C_LIO_LIAdding a component to represent co-edited macromolecule signals improved concordance C_LIO_LIBaseline modelling emerged as major factor differentiating outcomes C_LI

neuroscience↗

bioRxiv2020

Neural activity precedes conscious awareness of being in or out of a transient hallucinatory state

Auditory verbal hallucinations, or "hearing voices", is a remarkable state of the mind, occurring in psychiatric and neurological patients, and in a significant minority of the general population. An unexplained characteristic of this phenomenon is that it transiently fluctuates, with coming and going of episodes with time. We monitored neural activity with BOLD-fMRI second-by-second before and after participants indicated the start and end of a transient hallucinatory episode during the scanning session by pressing a response-button. We show that a region in the ventro-medial frontal cortex is activated in advance of conscious awareness of going in or out of a transient hallucinatory state. There was an increase in activity initiated a few seconds before the button-press for onsets, and a corresponding decrease in activity initiated a few seconds before the button-press for offsets. We identified the time between onset and offset button-presses, extracted the corresponding BOLD time-courses from nominated regions-of-interest, and analyzed changes in the signal from 10 seconds before to 15 seconds after the response-button was pressed, which identified onset and offset events. We suggest that this brain region act as a switch to turn on and off a hallucinatory episode. The results may have implications for new interventions for intractable hallucinations.

neuroscience↗