A resting state fMRI analysis pipeline for pooling inference across diverse cohorts: an ENIGMA rs-fMRI protocol.

Large-scale consortium efforts such as Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) and other collaborative efforts show that combining statistical data from multiple independent studies can boost statistical power and achieve more accurate estimates of effect sizes, contributing to more reliable and reproducible research. A meta- analysis would pool effects from studies conducted in a similar manner, yet to date, no such harmonized protocol exists for resting state fMRI (rsfMRI) data. Here, we propose an initial pipeline for multi-site rsfMRI analysis to allow research groups around the world to analyze scans in a harmonized way, and to perform coordinated statistical tests. The challenge lies in the fact that resting state fMRI measurements collected by researchers over the last decade vary widely, with variable quality and differing spatial or temporal signal-to-noise ratio (tSNR). An effective harmonization must provide optimal measures for all quality data. Here we used rsfMRI data from twenty-two independent studies with approximately fifty corresponding T1-weighted and rsfMRI datasets each, to (A) review and aggregate the state of existing rsfMRI data, (B) demonstrate utility of principal component analysis (PCA)-based denoising and (C) develop a deformable ENIGMA EPI template based on the representative anatomy that incorporates spatial distortion patterns from various protocols and populations.

Longitudinal brain volume changes in major depressive disorder.

Patients with major depressive disorder (MDD) exhibit gray matter volume (GMV) reductions in limbic regions. Clinical variables-such as the number of depressive episodes-seem to affect volume alterations. It is unclear whether the observed cross-sectional GMV abnormalities in MDD change over time, and whether there is a longitudinal relationship between GMV changes and the course of disorder. We investigated T1 structural MRI images of 54 healthy control (HC) and 37 MDD patients in a 3-Tesla-MRI with a follow-up interval of 3 years. The Cat12 toolbox was used to analyze longitudinal data (p < 0.05, FWE-corrected, whole-brain analysis; flexible factorial design). Interaction effects indicated increasing GMV in MDD in the bilateral amygdala, and decreasing GMV in the right thalamus between T1 and T2. Further analyses comparing patients with a mild course of disorder (MCD; 0-1 depressive episode during the follow-up) to patients with a severe course of disorder (SCD; > 1 depressive episode during the follow-up) revealed increasing amygdalar volume in MCD. Our study confirms structural alterations in limbic regions in MDD patients and an association between these impairments and the course of disorder. Thus, we assume that the reported volumetric alterations in the left amygdala (i.e. volumetric normalization) are reversible and apparently driven by the clinical phenotype. Hence, these results support the assumption that the severity and progression of disease influences amygdalar GMV changes in MDD or vice versa.

Formal thought disorders: from phenomenology to neurobiology.

Formal thought disorder (FTD) is present in most psychiatric disorders and in some healthy individuals. In this Review, we present a comprehensive, integrative, and multilevel account of what is known about FTD, covering genetic, cellular, and neurotransmitter effects, environmental influences, experimental psychology and neuropsychology, brain imaging, phenomenology, linguistics, and treatment. FTD is a dimensional, phenomenologically defined construct, which can be clinically subdivided into positive versus negative and objective versus subjective symptom clusters. Because FTDs have been traditionally linked to schizophrenia, studies in other diagnoses are scarce. Aetiologically, FTD is the only symptom under genetic influence in schizophrenia as shown in linkage studies, but familial communication patterns (allusive thinking) have also been associated with the condition. Positive FTDs are related to synaptic rarefication in the glutamate system of the superior and middle lateral temporal cortices. Cortical volume of the left superior temporal gyrus is decreased in patients with schizophrenia who have positive FTD in structural MRI studies and shows reversed hemispheric (right more than left) activation in functional MRI experiments during speech production. Semantic network dysfunction in positive FTD has been demonstrated in experiments of indirect semantic hyperpriming (reaction time). In acute positive FTD, antipsychotics are effective, but a subgroup of patients have treatment-resistant, chronic, positive or negative FTD. Specific psychotherapy as treatment for FTD has not yet been developed. With this solid data on the pathogenesis of FTD, we can now implement clinical studies to treat this condition.

Segment-specific and state-dependent targeting accuracy of the stick insect.

In its natural habitat, Carausius morosus climbs on the branches of bushes and trees. Previous work suggested that stick insects perform targeting movements with their hindlegs to find support more easily. It has been assumed that the animals use position information from the anterior legs to control the touchdown position of the ipsilateral posterior legs. Here we addressed the question of whether not only the hindleg but also the middle leg performs targeting, and whether targeting is still present in a walking animal when influences of mechanical coupling through the ground are removed. If this were the case, it would emphasize the role of underlying neuronal mechanisms. We studied whether targeting occurred in both legs, when the rostral neighboring leg, i.e. either the middle or the front leg, was placed at defined positions relative to the body, and analyzed targeting precision for dependency on the targeted position. Under these conditions, the touchdown positions of the hindlegs show correlation to the position of the middle leg parallel and perpendicular to the body axis, while only weak correlation exists between the middle and front legs, and only in parallel to the body axis. In continuously walking tethered animals, targeting accuracy of the hindlegs and middle legs parallel to the body axis barely differed. However, targeting became significantly more accurate perpendicular to the body axis. Our results suggest that a neural mechanism exists for controlling the touchdown position of the posterior leg but that the strength of this mechanism is segment specific and dependent on the behavioral context in which it is used.