At-risk individuals display altered brain activity following stress

Stress is a major risk factor for almost all psychiatric disorders, however, the underlying neurobiological mechanisms remain largely elusive. In healthy individuals, a successful stress response involves an adequate neuronal adaptation to a changing environment. This adaptive response may be dysfunctional in vulnerable individuals, potentially contributing to the development of psychopathology. In the current study, we investigated brain responses to emotional stimuli following stress in healthy controls and at-risk individuals. An fMRI study was conducted in healthy male controls (N = 39) and unaffected healthy male siblings of schizophrenia patients (N = 39) who are at increased risk for the development of a broad range of psychiatric disorders. Brain responses to pictures from the International Affective Picture System (IAPS) were measured 33 min after exposure to stress induced by the validated trier social stress test (TSST) or a control condition. Stress-induced levels of cortisol, alpha-amylase, and subjective stress were comparable in both groups. Yet, stress differentially affected brain responses of schizophrenia siblings versus controls. Specifically, control subjects, but not schizophrenia siblings, showed reduced brain activity in key nodes of the default mode network (PCC/precuneus and mPFC) and salience network (anterior insula) as well as the STG, MTG, MCC, vlPFC, precentral gyrus, and cerebellar vermis in response to all pictures following stress. These results indicate that even in the absence of a psychiatric disorder, at-risk individuals display abnormal functional activation following stress, which in turn may increase their vulnerability and risk for adverse outcomes

A comparison of methods to harmonize cortical thickness measurements across scanners and sites

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LME INT), (2) LME that models both site-specific random intercepts and age-related random slopes (LME INT+ SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2-81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3-85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (X-2 (3) = 63.704, p < 0.001) as well as casecontrol differences in age-related cortical thinning (X-2 (3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (X-2 (3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.Stress-related psychiatric disorders across the life spa

Neural correlates of inhibition and contextual cue processing related to treatment response in PTSD

Thirty to fifty percent of posttraumatic stress disorder (PTSD) patients do not respond to treatment. Understanding the neural mechanisms underlying treatment response could contribute to improve response rates. PTSD is often associated with decreased inhibition of fear responses in a safe environment. Importantly, the mechanism of effective treatment (psychotherapy) relies on inhibition and so-called contextual cue processing. Therefore, we investigate inhibition and contextual cue processing in the context of treatment. Forty-one male war veterans with PTSD and 22 healthy male war veterans (combat controls) were scanned twice with a 6- to 8-month interval, in which PTSD patients received treatment (psychotherapy). We distinguished treatment responders from nonresponders on the base of percentage symptom decrease. Inhibition and contextual cue processing were assessed with the stop-signal anticipation task. Behavioral and functional MRI measures were compared between PTSD patients and combat controls, and between responders and nonresponders using repeated measures analyses. PTSD patients showed behavioral and neural deficits in inhibition and contextual cue processing at both time points compared with combat controls. These deficits were unaffected by treatment; therefore, they likely represent vulnerability factors or scar aspects of PTSD. Second, responders showed increased pretreatment activation of the left inferior parietal lobe (IPL) during contextual cue processing compared with nonresponders. Moreover, left IPL activation predicted percentage symptom improvement. The IPL has an important role in contextual cue processing, and may therefore facilitate the effect of psychotherapy. Hence, increased left IPL activation may represent a potential predictive biomarker for PTSD treatment response

Predicting Treatment Outcome in PTSD : A Longitudinal Functional MRI Study on Trauma-Unrelated Emotional Processing

In about 30-50% of patients with posttraumatic stress disorder (PTSD), symptoms persist after treatment. Although neurobiological research has advanced our understanding of PTSD, little is known about the neurobiology underlying persistence of PTSD. Two functional MRI scans were collected from 72 war veterans with and without PTSD over a 6-To 8-month interval, during which PTSD patients received trauma-focused therapy. All participants performed a trauma-unrelated emotional processing task in the scanner. Based on post-Treatment symptom severity, a distinction was made between remitted and persistent patients. Behavioral and imaging measures of trauma-unrelated emotional processing were compared between the three groups (remitted patients, N=21; persistent patients, N=22; and combat controls, N=25) with repeated-measures (pre-and post-Treatment) analyses. Second, logistic regression was used to predict treatment outcome. Before and after treatment, persistent patients showed a higher dorsal anterior cingulate cortex (dACC) and insula response to negative pictures compared with remitted patients and combat controls. Before treatment, persistent patients showed increased amygdala activation in response to negative pictures compared with remitted patients. The remitted patients and combat controls did not differ on the behavioral or imaging measures. Finally, higher dACC, insula, and amygdala activation before treatment were significant predictors of symptom persistence. Our results highlight a pattern of brain activation that may predict poor response to PTSD treatment. These findings can contribute to the development of alternative or additional therapies. Further research is needed to elucidate the heterogeneity within PTSD and describe how differences in neural function are related to treatment outcome. Such approaches are critical for defining parameters to customize PTSD treatment and improve treatment response rates

Global drivers of cryptocurrency infrastructure adoption

A vast digital eco-system of entrepreneurship and exchange has sprung up with Bitcoin?s digital infrastructure at its core. We explore the worldwide spread of infrastructure necessary to maintain and grow Bitcoin as a system (Bitcoin nodes) and infrastructure enabling the use of bitcoins for everyday economic transactions (Bitcoin merchants). Specifically, we investigate the role of legal, criminal, financial and social determinants of the adoption of Bitcoin infrastructure. We offer some support for the view that the adoption of cryptocurrency infrastructure is driven by perceived failings of traditional financial systems, in that the spread of Bitcoin infrastructure is associated with low trust in banks and the financial system among inhabitants of a region, and with the occurrence of country-level inflation crises. On the other hand, our findings also suggest that active support for Bitcoin is higher in locations with well-developed banking services. Finally, we find support for the view that bitcoin adoption is also partly driven by cryptocurrencies? usefulness in engaging in illicit trade