No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.

Trauma-focused psychotherapy is the first-line treatment for posttraumatic stress disorder (PTSD) but 30–50% of patients do not benefit sufficiently. We investigated whether structural and resting-state functional magnetic resonance imaging (MRI/rs-fMRI) data could distinguish between treatment responders and non-responders on the group and individual level. Forty-four male veterans with PTSD underwent baseline scanning followed by trauma-focused psychotherapy. Voxel-wise gray matter volumes were extracted from the structural MRI data and resting-state networks (RSNs) were calculated from rs-fMRI data using independent component analysis. Data were used to detect differences between responders and non-responders on the group level using permutation testing, and the single-subject level using Gaussian process classification with cross-validation. A RSN centered on the bilateral superior frontal gyrus differed between responders and non-responder groups (PFWE < 0.05) while a RSN centered on the pre-supplementary motor area distinguished between responders and non-responders on an individual-level with 81.4% accuracy (P < 0.001, 84.8% sensitivity, 78% specificity and AUC of 0.93). No significant single-subject classification or group differences were observed for gray matter volume. This proof-of-concept study demonstrates the feasibility of using rs-fMRI to develop neuroimaging biomarkers for treatment response, which could enable personalized treatment of patients with PTSD.

Resting-state functional magnetic resonance imaging (rs-fMRI) data are 4-dimensional volumes (3-space + 1-time) that have been posited to reflect the underlying mechanisms of information exchange between brain regions, thus making it an attractive modality to develop diagnostic biomarkers of brain dysfunction. The enormous success of deep learning in computer vision has sparked recent interest in applying deep learning in neuroimaging. But the dimensionality of rs-fMRI data is too high (~20 M), making it difficult to meaningfully process the data in its raw form for deep learning experiments. It is currently not clear how the data should be engineered to optimally extract the time information, and whether combining different representations of time could provide better results. In this paper, we explored various transformations that retain the full spatial resolution by summarizing the temporal dimension of the rs-fMRI data, therefore making it possible to train a full three-dimensional convolutional neural network (3D-CNN) even on a moderately sized [~2,000 from Autism Brain Imaging Data Exchange (ABIDE)-I and II] data set. These transformations summarize the activity in each voxel of the rs-fMRI or that of the voxel and its neighbors to a single number. For each brain volume, we calculated regional homogeneity, the amplitude of low-frequency fluctuations, the fractional amplitude of lowfrequency fluctuations, degree centrality, eigenvector centrality, local functional connectivity density, entropy, voxel-mirrored homotopic connectivity, and autocorrelation lag. We trained the 3D-CNN on a publically available autism dataset to classify the rs-fMRI images as being from individuals with autism spectrum disorder (ASD) or from healthy controls (CON) at an individual level. We attained results competitive on this task for a combined ABIDE-I and II datasets of~66%. When all summary measures were combined the result was still only as good as that of the best single measure which was regional homogeneity (ReHo). In addition, we also applied the support vector machine (SVM) algorithm on the same dataset and achieved comparable results,