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Imaging studies on neuronal network formation provide relevant information as to how the brain matures during adolescence. We used a novel imaging approach combining well-established MRI measures of local functional connectivity that jointly provide qualitatively different information relating to the functional structure of the cerebral cortex. To investigate the adolescent transition into adulthood, we comparatively assessed 169 preadolescents aged 8-12 years and 121 healthy adults. Whole-brain functional connectivity maps were generated using multi-distance measures of intracortical neural activity coupling defined within iso-distant local areas. Such Iso-Distant Average Correlation (IDAC) measures therefore represent the average temporal correlation of a given brain unit, or voxel, with other units situated at increasingly separated iso-distant intervals. The results indicated that between-group differences in the functional structure of the cerebral cortex are extensive and implicate part of the lateral prefrontal cortex, a medial frontal/anterior cingulate region, the superior parietal lobe extending to the somatosensory strip and posterior cingulate cortex, and local connections within the visual cortex, hippocampus, amygdala and insula. We thus provided detail of the cerebral cortex functional structure maturation during the transition to adulthood, which may serve to establish more accurate links between adolescent performance gains and cerebral cortex maturation. Remarkably, our study provides new information as to the cortical maturation processes in prefrontal areas relevant to executive functioning and rational learning, medial frontal areas playing an active role in the cognitive appraisal of emotion and anxiety, and superior parietal cortices strongly associated with bodily self-consciousness in the context of body image formation., Competing Interests: Declaration of Competing Interest The authors report no financial interests or potential conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

Human functional magnetic resonance imaging (fMRI) studies suggest that the ventromedial prefrontal cortex (vmPFC) contributes to the learned discrimination of threat and safety signals, although its precise contribution to these processes remains unclear. One hypothesis is that the vmPFC supports the positive affective processing of safety signals linked to their implicit stress-relieving properties. We set out to test this hypothesis and to examine the specificity of vmPFC responses to safety signal processing versus its high level of 'default mode' activity. Sixty participants completed an fMRI conditioning task that involved the generation of a conditioned threat (CS+) and safety (CS-) signal following the completion of a pre-conditioning baseline. Confirming past findings, activation of the vmPFC and other midline cortical and parietal areas - broadly resembling the default mode network - robustly discriminated between the CS- and CS+. However, when adjusting for this network's characteristic 'baseline' activity, only a subset of regions, including the vmPFC, was activated by the CS-. Regional selectivity for safety signal processing was confirmed by demonstrating a significant correlation between the magnitude of vmPFC responses and self-rated positive affect evoked by the CS-. Taken together, our current findings confirm a link between human vmPFC activity and the positive affective processing of safety signals. We discuss these findings with regards a broader model of human vmPFC function and its suggested higher-order contribution to emotionally adaptive behavior., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The lateral surface of the right frontal lobe has a relevant role in modulating behavioral responses to aversive stimuli and may significantly influence pain experience. Imaging studies suggest that this modulatory role is multifaceted, but no studies have assessed the regional specialization of this cortex on the basis of its response dynamics during pain processing. We aimed to investigate functional specialization within the right lateral frontal cortex using a dynamic fMRI approach. Brain responses to a mechanical painful stimulus and a preceding anticipatory cue (auditory tone) were assessed in 25 healthy subjects. Functional data were decomposed into 15 sequential activation maps covering the full anticipation-painful stimulation cycle using a finite impulse response (FIR) analysis approach. Movie sequences showing the temporal evolution of brain activation illustrate the findings. A region involving premotor-prefrontal cortices was activated soon after the anticipatory cue and showed a significant correlation with both anterior cingulate cortex activation and subjective pain ratings. The frontal operculum also showed a significant anticipatory response, but the most robust activation followed painful stimulation onset and was strongly correlated with insula activation. The anterior prefrontal cortex showed full activation during late painful stimulation and was negatively correlated with pain unpleasantness. In conclusion, different elements within the right lateral frontal cortex showed distinct activation dynamics in response to painful stimulation, which would suggest relevant regional specialization during pain processing. These findings are congruent with the broad functional role of the right frontal cortex and its influence on crucial aspects of human behavior., (Copyright 2010 Elsevier Inc. All rights reserved.)

The high comorbidity of obsessive-compulsive disorder (OCD) with major depressive disorder (MDD) suggests common neurobiological substrates. We assessed the contribution of lifetime MDD to brain structural alterations in OCD using magnetic resonance imaging. OCD patients with (n=33) or without (n=39) lifetime MDD, and 72 control subjects were assessed. Comparative region of interest (ROI) analyses assessed the contribution of lifetime MDD to gray matter volume alterations in OCD patients. Interregional correlations of gray matter volume were also examined and voxelwise analyses were performed to identify alterations in other brain regions. OCD patients with lifetime MDD showed a larger reduction of medial orbitofrontal cortex (mOFC) gray matter volume. Both OCD groups showed distinct correlations of mOFC gray matter volume with other relevant brain regions. For patients with MDD, this involved the medial frontal gyrus, and right insula and amygdala regions, whereas for those OCD patients without MDD, the rostral anterior cingulate cortex was involved. Our findings support existing evidence suggesting a non-specific involvement of mOFC alterations in a range of neuropsychiatric disorders. Nevertheless, volume reduction in this region, together with an abnormal pattern of interregional correlations with other emotion-relevant brain areas, may contribute to explain the diathesis for MDD comorbidity in OCD.

Structural neuroimaging studies have reported a variety of brain alterations between groups of obsessive-compulsive disorder (OCD) patients and healthy controls. However, the large heterogeneity in discrete anatomical measures that exists among patients prevents a clear discrimination of single patients from healthy subjects. This reduces the potential clinical applicability of structural neuroimaging studies. In the present study we assessed the feasibility of identifying OCD patients on the basis of whole-brain anatomical alterations. Whole-brain magnetic resonance images were collected from two consecutive samples of OCD outpatients (n=72 and n=30), and control subjects (n=72 and n=30). We computed the whole-brain (voxel-wise) pattern of structural difference between OCD patients and control subjects at the group level. A single expression value of this difference pattern was calculated for each subject, expressing their degree of 'OCD-like' anatomical alteration. Accuracy of patient classification based on these expression values was assessed using two validation approaches. Firstly, using a cross-validation method, we obtained a high classification accuracy (average of the sensitivity and specificity indices) of 93.1%. In a second assessment, which classified new groups of OCD patients and control subjects, overall accuracy was lower at 76.6%. Individual expression values for OCD patients were significantly correlated with overall symptom severity as measured by the Y-BOCS scale. Our results suggest that OCD patients can be identified on the basis of whole-brain structural alterations, although the accuracy of our approach may be limited by the inherent variability of psychiatric populations. Nevertheless, the anatomical characterization of individual patients may ultimately provide the psychiatrist with relevant biological information.

Delayed acquisition of developmental motor and cognitive milestones is a common clinical expression of many etiological processes. Imaging exams of developmentally delayed children often show no structural brain alterations despite suspicion of brain maturation delay. MRI studies increasingly suggest that white matter myelination finely reflects the progression in functional brain maturation. In this volumetric MRI study, we sought to evaluate whether developmental delay in children with normal conventional MRI exams is associated with reduced myelinated white matter. A total of 100 children (mean age, 4.4 years) with developmental delay and 50 normally developing age-matched control children underwent 3-D MRI to measure the volume of myelinated white matter. Patients showed a significant reduction in the relative content of myelinated white matter (accounting for 19.8% of brain volume in patients and 21.4% in control subjects, P = 0.005). The observed difference was equivalent to a 3.2-year myelination delay. Although the whole hemispheres were invariably symmetrical, the volume of myelinated white matter was asymmetrical in 30% of patients and 10% of control subjects (P = 0.006). We conclude that volumetric assessment of white matter may reveal a reduction in brain myelination beyond early childhood in developmentally delayed children showing normal brain appearance. This finding further emphasizes the view of white matter myelination as an indicator of functional brain maturation.

Improvements in in vivo imaging methods have boosted research on brain asymmetry aimed at further establishing putative anatomical substrates for brain functional lateralization and particularly to explain left-hemisphere specialization for language. We analyzed volume asymmetries for major anatomical divisions of the lateral (perisylvian) brain region and their relative white matter content. A total of 100 healthy right-handed subjects were examined with 3D magnetic resonance imaging (MRI). The insular plane was used to limit the lateral brain, and the sylvian fissure and central sulcus to define frontal, parietal, temporal, and temporo-parieto-occipital regions. Results revealed a frontal region showing similar volumes in both hemispheres, a parietal region and a temporal region both larger in the left hemisphere, and a temporo-parieto-occipital region with predominantly right-sided asymmetry. Volume measurements of the parietal, temporal, and temporo-parieto-occipital regions complemented each other and accounted for 58% of planum temporale area variations. All study regions showed significant asymmetry for relative white matter content (percentage of white matter relative to region volume). White matter asymmetry, however, was particularly relevant for the frontal and temporal regions showing a highly frequent left-sided pattern (frontal region, 90%; temporal region, 91% of subjects). Leftward asymmetry in these two regions occurred in both genders, although hemisphere differences were significantly larger in men. Results from this MRI volume analysis of structural asymmetries in the lateral brain region complement data obtained by other methods and suggest a high occurrence of leftward asymmetry for relative white matter content in language-related regions.

This study focused on investigating a possible relationship between interindividual variability in the morphology of the cingulate gyrus and behavioral styles. Using magnetic resonance images obtained from 100 healthy young volunteers (50 women and 50 men), we measured the surface area of the anterior cingulate gyrus and related it to the scores on the Temperament and Character Inventory. Anatomical data revealed that hemispheric asymmetry in the anterior cingulate gyrus surface area was very common (83% of cases) and that a prominent right anterior cingulate was more frequent in women than in men. In the correlational analysis, surface measurements of the right anterior cingulate gyrus accounted for a 24% score variance in Harm Avoidance. Both women and men with larger right anterior cingulate described themselves as experiencing greater worry about possible problems, fearfulness in the face of uncertainty, shyness with strangers, and fatigability. Furthermore, women reported overall higher scores in Harm Avoidance than men; these gender differences were largely explained by gender differences in the right anterior cingulate area in a covariate analysis. Our observations suggest that a large right anterior cingulate is related to a temperamental disposition to fear and anticipatory worry in both genders and that a higher prevalence of these traits in women may be coupled with a greater expansion of this brain region., ((C)2002 Elsevier Science (USA).)

The Sylvian fissure region gathers lateral frontotemporal cortices and subcortical structures that are frequently disturbed in patients with mood disorders. We have investigated possible CSF space changes in this brain region in severe melancholic depression. Fifty-seven patients and 37 control subjects received three-dimensional MRI. CSF volumes were obtained for cerebral CSF, lateral ventricles, and both Sylvian fissure regions. As a group, patients showed a significant CSF space enlargement that was prominent around the Sylvian fissure, particularly in the left hemisphere. Likewise, evident leftward asymmetry was more frequent in the patient group (patients 31.6%, controls 2.7%). The combination of CSF space enlargement and the pattern of Sylvian CSF asymmetry predicted the patient condition with 62.2% specificity and 82.5% sensitivity. We conclude that, in the context of a broad severity spectrum of imaging alterations in severe melancholic depression, asymmetrical CSF space enlargement may be evident in the Sylvian fissure region.