During the last two decades, our inner sense of time has been repeatedly studied with the help of neuroimaging techniques. These investigations have suggested the specific involvement of different brain areas in temporal processing. At least two distinct neural systems are likely to play a role in measuring time: One is mainly constituted of subcortical structures and is supposed to be more related to the estimation of time intervals below the 1-sec range (subsecond timing tasks), and the other is mainly constituted of cortical areas and is supposed to be more related to the estimation of time intervals above the 1-sec range (suprasecond timing tasks). Tasks can then be performed in motor or nonmotor (perceptual) conditions, thus providing four different categories of time processing. Our meta-analytical investigation partly confirms the findings of previous meta-analytical works. Both sub- and suprasecond tasks recruit cortical and subcortical areas, but subcortical areas are more intensely activated in subsecond tasks than in suprasecond tasks, which instead receive more contributions from cortical activations. All the conditions, however, show strong activations in the SMA, whose rostral and caudal parts have an important role not only in the discrimination of different time intervals but also in relation to the nature of the task conditions. This area, along with the striatum (especially the putamen) and the claustrum, is supposed to be an essential node in the different networks engaged when the brain creates our sense of time.

The pathological brain is characterized by distributed morphological or structural alterations in the grey matter, which tend to follow identifiable network-like patterns. We analysed the patterns formed by these alterations (increased and decreased grey matter values detected with the voxel-based morphometry technique) conducting an extensive transdiagnostic search of voxelbased morphometry studies in a large variety of brain disorders. We devised an innovative method to construct the networks formed by the structurally co-altered brain areas, which can be considered as pathological structural co-alteration patterns, and to compare these patterns with three associated types of connectivity profiles (functional, anatomical, and genetic). Our study provides transdiagnostical evidence that structural co-alterations are influenced by connectivity constraints rather than being randomly distributed. Analyses show that although all the three types of connectivity taken together can account for and predict with good statistical accuracy, the shape and temporal development of the co-alteration patterns, functional connectivity offers the better account of the structural co-alteration, followed by anatomic and genetic connectivity. These results shed new light on the possible mechanisms at the root of neuropathological processes and open exciting prospects in the quest for a better understanding of brain disorders.

By means of a novel methodology that can statistically derive patterns of co-alterations distribution from voxel-based morphological data, this study analyzes the patterns of brain alterations of three important psychiatric spectra-that is, schizophrenia spectrum disorder (SCZD), autistic spectrum disorder (ASD), and obsessive-compulsive spectrum disorder (OCSD). Our analysis provides five important results. First, in SCZD, ASD, and OCSD brain alterations do not distribute randomly but, rather, follow network-like patterns of co-alteration. Second, the clusters of co-altered areas form a net of alterations that can be defined as morphometric co-alteration network or co-atrophy network (in the case of gray matter decreases). Third, within this network certain cerebral areas can be identified as pathoconnectivity hubs, the alteration of which is supposed to enhance the development of neuronal abnormalities. Fourth, within the morphometric co-atrophy network of SCZD, ASD, and OCSD, a subnetwork composed of eleven highly connected nodes can be distinguished. This subnetwork encompasses the anterior insulae, inferior frontal areas, left superior temporal areas, left parahippocampal regions, left thalamus and right precentral gyri. Fifth, the co-altered areas also exhibit a normal structural covariance pattern which overlaps, for some of these areas (like the insulae), the co-alteration pattern. These findings reveal that, similarly to neurodegenerative diseases, psychiatric disorders are characterized by anatomical alterations that distribute according to connectivity constraints so as to form identifiable morphometric co-atrophy patterns.

HighlightsIn chronic pain, gray matter (GM) alterations are not distributed randomly across the brain.The pattern of co-alterations resembles that of brain connectivity.The alterations' distribution partly rely on the pathways of functional connectivity.This method allows us to identify tendencies in the distribution of GM co-alteration related to chronic pain.