Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen’s d=−0.293; P=1.71 × 10⁻²¹), left fusiform gyrus (d=−0.288; P=8.25 × 10⁻²¹) and left rostral middle frontal cortex (d=−0.276; P=2.99 × 10⁻¹⁹). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

Microstructure imaging from diffusion magnetic resonance (MR) data represents an invaluable tool to study non-invasively the morphology of tissues and to provide a biological insight into their microstructural organization. In recent years, a variety of biophysical models have been proposed to associate particular patterns observed in the measured signal with specific microstructural properties of the neuronal tissue, such as axon diameter and fiber density. Despite very appealing results showing that the estimated microstructure indices agree very well with histological examinations, existing techniques require computationally very expensive non-linear procedures to fit the models to the data which, in practice, demand the use of powerful computer clusters for large-scale applications. In this work, we present a general framework for Accelerated Microstructure Imaging via Convex Optimization (AMICO) and show how to re-formulate this class of techniques as convenient linear systems which, then, can be efficiently solved using very fast algorithms. We demonstrate this linearization of the fitting problem for two specific models, i.e. ActiveAx and NODDI, providing a very attractive alternative for parameter estimation in those techniques; however, the AMICO framework is general and flexible enough to work also for the wider space of microstructure imaging methods. Results demonstrate that AMICO represents an effective means to accelerate the fit of existing techniques drastically (up to four orders of magnitude faster) while preserving accuracy and precision in the estimated model parameters (correlation above 0.9). We believe that the availability of such ultrafast algorithms will help to accelerate the spread of microstructure imaging to larger cohorts of patients and to study a wider spectrum of neurological disorders.

Peak-based meta-analyses of neuroimaging studies create, for each study, a brain map of effect size or peak likelihood by convolving a kernel with each reported peak. A kernel is a small matrix applied in order that voxels surrounding the peak have a value similar to, but slightly lower than that of the peak. Current kernels are isotropic, i.e. the value of a voxel close to a peak only depends on the Euclidean distance between the voxel and the peak. However, such perfect spheres of effect size or likelihood around the peak are rather implausible: a voxel that correlates with the peak across individuals is more likely to be part of the cluster of significant activation or difference than voxels uncorrelated with the peak. This paper introduces anisotropic kernels, which assign different values to the different neighboring voxels based on the spatial correlation between them. They are specifically developed for Effect Size Signed Differential Mapping (ES-SDM), though might be easily implemented in other meta-analysis packages such as Activation Likelihood Estimation (ALE). The paper also describes the creation of the required correlation templates for gray matter / BOLD response, white matter, cerebrospinal fluid and fractional anisotropy. Finally, the new method is validated by quantifying the accuracy of the recreation of effect size maps from peak information. This empirical validation showed that the optimal degree of anisotropy and full-width of half-maximum (FWHM) might vary largely depending on the specific data meta-analyzed. However, it also showed that the recreation substantially improved and did not depend on the FWHM when full anisotropy was used. Based on these results, we recommend the use of fully anisotropic kernels in ES-SDM and ALE, unless optimal meta-analysis-specific parameters can be estimated based on the recreation of available statistical maps. The new method and templates are freely available at http://www.sdmproject.com/.

There is much current interest in identifying the anatomical and functional circuits that are the basis of the brain's computations, with hope that functional neuroimaging techniques will allow the in vivo study of these neural processes through the statistical analysis of the time-series they produce. Ideally, the use of techniques such as multivariate autoregressive (MAR) modelling should allow the identification of effective connectivity by combining graphical modelling methods with the concept of Granger causality. Unfortunately, current time-series methods perform well only for the case that the length of the time-series Nt is much larger than p , the number of brain sites studied, which is exactly the reverse of the situation in neuroimaging for which relatively short time-series are measured over thousands of voxels. Methods are introduced for dealing with this situation by using sparse MAR models. These can be estimated in a two-stage process involving (i) penalized regression and (ii) pruning of unlikely connections by means of the local false discovery rate developed by Efron. Extensive simulations were performed with idealized cortical networks having small world topologies and stable dynamics. These show that the detection efficiency of connections of the proposed procedure is quite high. Application of the method to real data was illustrated by the identification of neural circuitry related to emotional processing as measured by BOLD.