Gellersen, H. M. | Search bioRxiv

bioRxiv2021

Searching for Consistent Brain Network Topologies Across the Garden of (Shortest) Forking Paths

The functional interactions between regions of the human brain can be viewed as a network, empowering neuroscientists to leverage tools such as graph theory to obtain insight about brain function. However, obtaining a brain network from functional neuroimaging data inevitably involves multiple steps of data manipulation, which can affect the organisation (topology) of the resulting network and its properties. Test-retest reliability is a gold standard for both basic research and clinical use: a suitable data-processing pipeline for brain networks should recover the same network topology across repeated scan sessions of the same individual. Analyzing resting-state functional Magnetic Resonance Imaging (rs-fMRI) recordings from two test-retest studies across short (45 minutes), medium (2-4 weeks) and long term delays (5-16 months), we investigated the reliability of network topologies constructed by applying 576 unique pipelines to the same fMRI data, obtained from considering combinations of atlas type and size, edge definition and thresholding, and use of global signal regression. We adopted the portrait divergence, an information-theoretic criterion to measure differences in network topology across all scales, enabling us to quantify the influence of different pipelines on the overall organisation of the resulting network. Remarkably, our findings reveal that the choice of pipeline plays a fundamental role in determining how reproducible an individuals brain network topology will be across different scans: there is large and systematic variability across pipelines, such that an inappropriate choice of pipeline can distort the resulting network more than an interval of several months between scans. Across datasets and time-spans, we also identify specific combinations of data-processing steps that consistently yield networks with reproducible topology, enabling us to make recommendations about best practices to ensure high-quality brain networks.

neuroscience↗

bioRxiv2020

Memory precision of object-location binding is unimpaired in APOE ε4-carriers with spatial navigation deficits

Research suggests that tests of memory fidelity, feature binding and spatial navigation are promising for early detection of subtle behavioural changes related to Alzheimers disease (AD). In the absence of longitudinal data, one way of testing the early detection potential of cognitive tasks is through the comparison of individuals at different genetic risk for AD. Most studies have done so using samples aged 70 years or older. Here, we tested whether memory fidelity of long-term object-location binding may be a sensitive marker even among cognitively healthy individuals in their mid-60s by comparing participants at low and higher risk based on presence of the {varepsilon}4-allele of the apolipoprotein gene (n=26 {varepsilon}3{varepsilon}3, n=20 {varepsilon}3{varepsilon}4 carriers). We used a continuous report paradigm in a visual memory task that required participants to recreate the spatial position of objects in a scene. We employed mixture modelling to estimate the two distinct memory processes that underpin the trial-by-trial variation in localisation errors: retrieval success which indexes the proportion of trials where participants recalled any information about an objects position and the precision with which participants retrieved this information. Prior work has shown that these memory paradigms that separate retrieval success from precision are capable of detecting subtle differences in mnemonic fidelity even when retrieval success could not. Nonetheless, a Bayesian analysis found good evidence that {varepsilon}3{varepsilon}4 carriers did not remember fewer object locations (F(1, 42)=.450, p=.506, BF01 =3.02), nor was their precision for the spatial position of objects reduced compared to {varepsilon}3{varepsilon}3 carriers (F(1, 42)=.12, p=.726, BF01 =3.19). Because the participants in the sample presented here were a subset of a study on APOE effects on spatial navigation in the Sea Hero Quest game (Coughlan et al., 2019. PNAS, 116(9)), we obtained these data to contrast APOE effects on the two tasks within the same sample (n=33). Despite the smaller sample size, wayfinding deficits among {varepsilon}3{varepsilon}4 could be replicated (F(1, 33) =5.60, p=.024, BF10 =3.44). Object-location memory metrics and spatial navigation scores were not correlated (all r<.25, p>.1, 0<BF10 <3). These findings show spared object-location binding in the presence of a detrimental APOE {varepsilon}4 effect on spatial navigation. This suggests that the sensitivity of memory fidelity and binding tasks may not extend to individuals with one {varepsilon}4-allele in their early to mid-60s. The results provide further support to prior proposals that spatial navigation may be a sensitive marker for the earliest AD-dependent cognitive changes, even before episodic memory.

neuroscience↗