Autonomic and brain morphological predictors of stress resilience

Stressful life events are an important cause of psychopathology. Humans exposed to aversive or stressful experiences show considerable inter-individual heterogeneity in their responses. However, the majority does not develop stress-related psychiatric disorders. The dynamic processes encompassing positive and functional adaptation in the face of significant adversity have been broadly defined as resilience. Traditionally, the assessment of resilience has been confined to self-report measures, both within the general community and putative high-risk populations. Although this approach has value, it is highly susceptible to subjective bias and may not capture the dynamic nature of resilience, as underlying construct. Recognizing the obvious benefits of more objective measures of resilience, research in the field has just started investigating the predictive value of several potential biological markers. This review provides an overview of theoretical views and empirical evidence suggesting that individual differences in heart rate variability (HRV), a surrogate index of resting cardiac vagal outflow, may underlie different levels of resilience toward the development of stress-related psychiatric disorders. Following this line of thought, recent studies describing associations between regional brain morphometric characteristics and resting state vagally-mediated HRV are summarized. Existing studies suggest that the structural morphology of the anterior cingulated cortex (ACC), particularly its cortical thickness, is implicated in the expression of individual differences in HRV. These findings are discussed in light of emerging structural neuroimaging research, linking morphological characteristics of the ACC to psychological traits ascribed to a high-resilient profile and abnormal structural integrity of the ACC to the psychophysiological expression of stress-related mental health consequences. We conclude that a multidisciplinary approach integrating brain structural imaging with HRV monitoring could offer novel perspectives about brain-body pathways in resilience and adaptation to psychological stres

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Reciprocal anatomical relationship between primary sensory and prefrontal cortices in the human brain

The human brain exhibits remarkable interindividual variability in cortical architecture. Despite extensive evidence for the behavioral consequences of such anatomical variability in individual cortical regions, it is unclear whether and how different cortical regions covary in morphology. Using a novel approach that combined noninvasive cortical functional mapping with whole-brain voxel-based morphometric analyses, we investigated the anatomical relationship between the functionally mapped visual cortices and other cortical structures in healthy humans. We found a striking anticorrelation between the gray matter volume of primary visual cortex and that of anterior prefrontal cortex, independent from individual differences in overall brain volume. Notably, this negative correlation formed along anatomically separate pathways, as the dorsal and ventral parts of primary visual cortex showed focal anticorrelation with the dorsolateral and ventromedial parts of anterior prefrontal cortex, respectively. Moreover, a similar inverse correlation was found between primary auditory cortex and anterior prefrontal cortex, but no anatomical relationship was observed between other visual cortices and anterior prefrontal cortex. Together, these findings indicate that an anatomical trade-off exists between primary sensory cortices and anterior prefrontal cortex as a possible general principle of human cortical organization. This new discovery challenges the traditional view that the sizes of different brain areas simply scale with overall brain size and suggests the existence of shared genetic or developmental factors that contributes to the formation of anatomically and functionally distant cortical regions

Structural abnormalities in cortical volume, thickness, and surface area in 22q11.2 microdeletion syndrome: Relationship with psychotic symptoms.

Introduction22q11.2 deletion syndrome (22q11DS) represents one of the largest known genetic risk factors for psychosis, yet the neurobiological mechanisms underlying symptom development are not well understood. Here we conducted a cross-sectional study of 22q11DS to decompose cortical volume into its constituent parts, cortical thickness (CT) and surface area (SA), which are believed to have distinct neurodevelopmental origins.MethodsHigh-resolution T1-weighted scans were collected on 65 participants (31 22q11DS, 34 demographically comparable typically developing controls, 10-25 years old). Measures of cortical volume, CT, and SA were extracted from regions of interest using the FreeSurfer image analysis suite. Group differences and age-related trajectories in these structures, as well as their association with psychotic symptomatology, were assessed.ResultsRelative to controls, 22q11DS participants showed bilateral volumetric reductions in the inferior temporal cortex, fusiform gyrus, anterior cingulate, superior parietal cortex, and cuneus, which were driven by decreased SA in these regions. 22q11DS participants also had increased volumes, driven by increased CT, in bilateral insula regions. 22q11DS youth had increased CT in frontal regions, particularly middle frontal and medial orbitofrontal cortices. A pattern of age-associated cortical thinning was observed in typically developing controls in brain regions associated with visual and sensory information-processing (i.e., left pericalcarine cortex and fusiform gyrus, right lingual and postcentral cortices). However, this relationship was disrupted in 22q11DS participants. Finally, correlational analyses revealed that increased CT in right medial orbitofrontal cortex was associated with increased positive symptom severity in 22q11DS.ConclusionDifferential disruptions of CT and SA in distinct cortical regions in 22q11DS may indicate abnormalities in distinct developmental neural processes. Further, neuroanatomic abnormalities in medial frontal brain structures disproportionately affected in idiopathic schizophrenia were associated with psychotic symptom severity in 22q11DS youth, suggesting that disrupted biological processes in these cortical regions may underlie development of psychotic symptoms, both in 22q11DS and in the broader population

Exploration of gray matter correlates of cognitive training benefit in adolescents with chronic traumatic brain injury

Sustaining a traumatic brain injury (FBI) during adolescence has a profound effect on brain development and can result in persistent executive functioning deficits in daily life. Cognitive recovery from pediatric-TBI relies on the potential of neuroplasticity, which can be fostered by restorative training-programs. However the structural mechanisms underlying cognitive recovery in the immature brain are poorly understood. This study investigated gray matter plasticity following 2 months of cognitive training in young patients with TBI. Sixteen adolescents in the chronic stage of moderate-severe-TBI (9 male, mean age = 15y8m +/- 1y7m) were enrolled in a cognitive computerized training program for 8 weeks (5 times/week, 40 min/session). Pre-and post-intervention, and 6 months after completion of the training, participants underwent a comprehensive neurocognitive test-battery and anatomical Magnetic Resonance Imaging scans. We selected 9 cortical-subcortical Regions-Of-Interest associated with Executive Functioning (EF-ROIs) and 3 control regions from the Desikan-Killiany atlas. Baseline analyses showed significant decreased gray matter density in the superior frontal gyri p = 0.033, superior parietal gyri p = 0.015 and thalamus p = 0.006 in adolescents with TBI compared to age and gender matched controls. Linear mixed model analyses of longitudinal volumetric data of the EF-ROI revealed no strong evidence of training-related changes in the group with TBI. However, compared to the change over time in the control regions between post-intervention and 6 months follow-up, the change in the EF-ROIs showed a significant difference. Exploratory analyses revealed a negative correlation between the change on the Digit Symbol Substitution test and the change in volume of the putamen (r = - 0.596, p = 0.015). This preliminary study contributes to the insights of training-related plasticity mechanisms after pediatric-TBI

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Structural and functional differences in medial prefrontal cortex underlie distractibility and suppression deficits in ageing.

Older adults experience deficits in working memory (WM) that are acutely exacerbated by the presence of distracting information. Human neurophysiological studies have revealed that these changes are accompanied by a diminished ability to suppress visual cortical activity associated with task-irrelevant information. Although this is often attributed to deficits in top-down control from a prefrontal cortical source, this has not yet been directly demonstrated. Here we evaluate the neural basis of distraction's negative impact on WM and the impairment in neural suppression in older adults by performing structural and functional MRIs while older participants engage in tasks that require remembering relevant visual stimuli in the context of overlapping irrelevant stimuli. Analysis supports both an age-related distraction effect and neural suppression deficit, and extends our understanding by revealing an alteration in functional connectivity between visual cortices and a region in the default network, the medial prefrontal cortex (mPFC). Moreover, within the older population, the magnitude of WM distractibility and neural suppression are both associated with individual differences in cortical volume and activity of the mPFC, as well as its associated white-matter tracts