Unnecessary reliance on multilevel modelling to analyse nested data in neuroscience: When a traditional summary-statistics approach suffices.

Nested data structures create statistical dependence that influences the effective sample size and statistical power of a study. Several methods are available for dealing with nested data, including the summary-statistics approach and multilevel modelling (MLM). Recent publications have heralded MLM as the best method for analysing nested data, claiming benefits in power over summary-statistics approaches (e.g., the t-test). However, when cluster size is equal, these approaches are mathematically equivalent. We conducted statistical simulations demonstrating equivalence of MLM and summary-statistics approaches for analysing nested data and provide supportive cases for the utility of the conventional summary-statistics approach in nested experiments. Using statistical simulations, we demonstrate that losses in power in the summary-statistics approach discussed in the previous literature are unsubstantiated. We also show that MLM sometimes suffers from frequent singular fit errors, especially when intraclass correlation is low. There are indeed many situations in which MLM is more appropriate and desirable, but researchers should be aware of the possibility that simpler analysis (i.e., summary-statistics approach) does an equally good or even better job in some situations.

No evidence for a relationship between social closeness and similarity in resting-state functional brain connectivity in schoolchildren.

Previous research suggests that the proximity of individuals in a social network predicts how similarly their brains respond to naturalistic stimuli. However, the relationship between social connectedness and brain connectivity in the absence of external stimuli has not been examined. To investigate whether neural homophily between friends exists at rest we collected resting-state functional magnetic resonance imaging (fMRI) data from 68 school-aged girls, along with social network information from all pupils in their year groups (total 5,066 social dyads). Participants were asked to rate the amount of time they voluntarily spent with each person in their year group, and directed social network matrices and community structure were then determined from these data. No statistically significant relationships between social distance, community homogeneity and similarity of global-level resting-state connectivity were observed. Nor were we able to predict social distance using a regularised regression technique (i.e. elastic net regression based on the local-level similarities in resting-state whole-brain connectivity between participants). Although neural homophily between friends exists when viewing naturalistic stimuli, this finding did not extend to functional connectivity at rest in our population. Instead, resting-state connectivity may be less susceptible to the influences of a person's social environment.

Inter-slice leakage and intra-slice aliasing in simultaneous multi-slice echo-planar images.

Simultaneous multi-slice (SMS) imaging is a popular technique for increasing acquisition speed in echo-planar imaging (EPI) fMRI. However, SMS data are prone to motion sensitivity and slice leakage artefacts, which spread signal between simultaneously acquired slices. Relevant to motion sensitivity, artefacts from moving anatomic structures propagate along the phase-encoding (PE) direction. This is particularly relevant for eye movement. As signal from the eye is acquired along with signal from simultaneously excited slices during SMS, there is potential for signal to spread in-plane and between spatially remote slices. After identifying an artefact temporally coinciding with signal fluctuations in the eye and spatially distributed in correspondence with multiband slice acceleration and parallel imaging factors, we conducted a series of small experiments to investigate eye movement artefacts in SMS data and the contribution of PE direction to the invasiveness of these artefacts. Five healthy adult volunteers were scanned during a blinking task using a standard SMS-EPI protocol with posterior-to-anterior (P ≫ A), anterior-to-posterior (A ≫ P) or right-to-left (R ≫ L) PE direction. The intensity of signal fluctuations (artefact severity) was measured at expected artefact positions and control positions. We demonstrated a direct relationship between eye movements and artefact severity across expected artefact regions. Within-brain artefacts were apparent in P ≫ A- and A ≫ P-acquired data but not in R ≫ L data due to the shift in artefact positions. Further research into eye motion artefacts in SMS data is warranted but researchers should exercise caution with SMS protocols. We recommend rigorous piloting of SMS protocols and switching to R ≫ L/L ≫ R PE where feasible.

Differences in white matter connectivity between treatment-resistant and treatment-responsive subtypes of schizophrenia.

Schizophrenia is a heterogeneous disorder exhibiting variable responsiveness to treatment between individuals. Previous work demonstrated that white matter abnormalities may relate to antipsychotic response but no study to date has examined differences between first-line treatment responders (FLR) and clozapine-eligible individuals receiving first-line antipsychotics. The current study aimed to establish whether differences in white matter structure exist between these two cohorts. Diffusion-weighted images were acquired for 15 clozapine-eligible and 10 FLR participants. Measures of fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) were obtained and between-group t-tests interrogating differences in FA were conducted. To investigate the neural basis of a decrease in FA, the significant cluster from FA analysis was masked and used to obtain mean RD and AD measures for that region. Those who were clozapine-eligible had significantly lower FA in the body of the corpus callosum (p < 0.05), associated with a significant increase in mean RD compared with FLR (p < 0.001). No difference in mean AD was observed for this region. These data reveal differences in diffusion measures between FLR and those eligible for clozapine and suggest that lower FA and greater RD in the corpus callosum could exist as a biomarker of treatment resistance in people with schizophrenia.

Increased sensorimotor network connectivity associated with clozapine eligibility in people with schizophrenia.

Schizophrenia is a heterogeneous disorder that exhibits variable responsiveness to treatment between individuals. Here we conducted a resting-state functional magnetic resonance imaging (rs-fMRI) study to determine whether resistance to first-line antipsychotics is reflected in resting-state connectivity. rs-fMRI data were collected from 15 people who had failed to respond to first-line antipsychotics (clozapine-eligible) and 10 first-line treatment responders (FLR). Image pre-processing and analysis were performed using FMRIB's software library (FSL). Data was decomposed into spatial and temporal components using independent components analysis. Connectivity within each independent component was compared between groups using t-tests and the Bonferroni correction for multiple comparisons. Gender was added as a covariate. Clozapine-eligible individuals exhibited enhanced functional connectivity within the sensorimotor network compared with FLR. Those eligible for clozapine showed additional connectivity with the precuneus compared with FLR. No other comparisons reached statistical significance and no effect of gender was observed. These data reveal differences in functional connectivity between FLR and those eligible for clozapine and suggest that greater connectivity between the SMN and precuneus may be indicative of treatment resistance in people with schizophrenia.