Too hard to control: compromised pain anticipation and modulation in mild traumatic brain injury

Mild traumatic brain injury (MTBI) is a vulnerability factor for the development of pain-related conditions above and beyond those related to comorbid traumatic and emotional symptoms. We acquired functional magnetic resonance imaging (fMRI) on a validated pain anticipation task and tested the hypotheses that individuals with a reported history of MTBI, compared with healthy comparison subjects, would show increased brain response to pain anticipation and ineffective pain modulation after controlling for psychiatric symptoms. Eighteen male subjects with a reported history of blast-related MTBI related to combat, and eighteen healthy male subjects with no reported history of MTBI (healthy controls) underwent fMRI during an event-related experimental pain paradigm with cued high or low intensity painful heat stimuli. No subjects in either group met diagnostic criteria for current mood or anxiety disorder. We found that relative to healthy comparison subjects, after controlling for traumatic and depressive symptoms, participants with a reported history of MTBI showed significantly stronger activations within midbrain periaqueductual grey (PAG), right dorsolateral prefrontal cortex and cuneus during pain anticipation. Furthermore, we found that brain injury was a significant moderator of the relationship between anticipatory PAG activation and reported subjective pain. Our results suggest that a potentially disrupted neurocognitive anticipatory network may result from damage to the endogenous pain modulatory system and underlie difficulties with regulatory pain processing following MTBI. In other words, our findings are consistent with a notion that brain injury makes it more difficult to control acute pain. Understanding these mechanisms of dysfunctional acute pain processing following MTBI may help shed light on the underlying causes of increased vulnerability for the development of pain-related conditions in this population

Global Biobank Meta-analysis Initiative: Powering genetic discovery across human disease

Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)—a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits