We used a new theory of the biological basis of the Big Five personality traits to generate hypotheses about the association of each trait with the volume of different brain regions. Controlling for age, sex, and whole-brain volume, results from structural magnetic resonance imaging of 116 healthy adults supported our hypotheses for four of the five traits: Extraversion, Neuroticism, Agreeableness, and Conscientiousness. Extraversion covaried with volume of medial orbitofrontal cortex, a brain region involved in processing reward information. Neuroticism covaried with volume of brain regions associated with threat, punishment, and negative affect. Agreeableness covaried with volume in regions that process information about the intentions and mental states of other individuals. Conscientiousness covaried with volume in lateral prefrontal cortex, a region involved in planning and the voluntary control of behavior. These findings support our biologically based, explanatory model of the Big Five and demonstrate the potential of personality neuroscience (i.e., the systematic study of individual differences in personality using neuroscience methods) as a discipline.

SUMMARY Arthopods, such as Ixodes ticks, serve as vectors for many human pathogens. The arthropod gut presents a pivotal microbial entry point and determines pathogen colonization and survival. We show that the gut microbiota of Ixodes scapularis, a major vector of the Lyme disease spirochete Borrelia burgdorferi, influence spirochete colonization of ticks. Perturbing the gut microbiota of larval ticks reduced Borrelia colonization, with dysbiosed larvae displaying decreased expression of the transcription factor STAT. Diminished STAT expression corresponded to lower expression of peritrophin, a key glycoprotein scaffold of the glycan-rich mucus-like peritrophic matrix (PM) that separates the gut lumen from the epithelium. The integrity of the I. scapularis PM was essential for B. burgdorferi to efficiently colonize the gut epithelium. These data elucidate a functional link between the gut microbiota, STAT-signaling, and pathogen colonization in the context of the gut epithelial barrier of an arthropod vector.

While the Talairach atlas remains the most commonly used system for reporting coordinates in neuroimaging studies, the absence of an actual 3-D image of the original brain used in its construction has severely limited the ability of researchers to automatically map locations from 3-D anatomical MRI images to the atlas. Previous work in this area attempted to circumvent this problem by constructing approximate linear and piecewise-linear mappings between standard brain templates (e.g. the MNI template) and Talairach space. These methods are limited in that they can only account for differences in overall brain size and orientation but cannot correct for the actual shape differences between the MNI template and the Talairach brain. In this paper we describe our work to digitize the Talairach atlas and generate a non-linear mapping between the Talairach atlas and the MNI template that attempts to compensate for the actual differences in shape between the two, resulting in more accurate coordinate transformations. We present examples in this paper and note that the method is available freely online as a Java applet.

This work examines the influence of changes in baseline activity on the intrinsic functional connectivity fMRI (fc-fMRI) in humans. Baseline brain activity was altered by inducing anesthesia (sevoflurane end-tidal concentration 1%) in human volunteers and fc-fMRI maps between the pre-anesthetized and anesthetized conditions were compared across different brain networks. We particularly focused on low-level sensory areas (primary somatosensory, visual, and auditory cortices), the thalamus, and pain (insula), memory (hippocampus) circuits, and the default mode network (DMN), the latter three to examine higher-order brain regions. The results indicate that, while fc-fMRI patterns did not significantly differ (p b 0.005; 20-voxel cluster threshold) in sensory cortex and in the DMN between the pre-and anesthetized conditions, fc-fMRI in high-order cognitive regions (i.e. memory and pain circuits) was significantly altered by anesthesia. These findings provide further evidence that fc-fMRI reflects intrinsic brain properties, while also demonstrating that 0.5 MAC sevoflurane anesthesia preferentially modulates higher-order connections.

The Lyme disease agent, Borrelia burgdorferi, colonizes the gut of the tick Ixodes scapularis, which transmits the pathogen to vertebrate hosts including humans. Here we show that B. burgdorferi colonization increases the expression of several tick gut genes including pixr, encoding a secreted gut protein with a Reeler domain. RNA interference-mediated silencing of pixr, or immunity against PIXR in mice, impairs the ability of B. burgdorferi to colonize the tick gut. PIXR inhibits bacterial biofilm formation in vitro and in vivo. Abrogation of PIXR function in vivo results in alterations in the gut microbiome, metabolome and immune responses. These alterations influence the spirochete entering the tick gut in multiple ways. PIXR abrogation also impairs larval molting, indicative of its role in tick biology. This study highlights the role of the tick gut in actively managing its microbiome, and how this impacts B. burgdorferi colonization of its arthropod vector.

Dr. Stein owns founders shares and stock options in Resilience Therapeutics and has stock options in Oxeia Biopharmaceuticals. Data Availability The GWAS summary statistics generated during and/or analyzed during the current study are available via dbGAP; the dbGaP accession assigned to the Million Veteran Program is phs001672.v1.p. The website is: https://www.ncbi.nlm.nih.gov/projects/gap/cgibin/study.cgi?study_id=phs001672.v1.p1 Additionally, the data that support the findings of this study are available from the corresponding authors upon request.

Converging data suggest recovery from injury in the preterm brain. We used functional Magnetic Resonance Imaging (fMRI) to test the hypothesis that cerebral connectivity involving Wernicke's area and other important cortical language regions would differ between preterm (PT) and term (T) control school age children during performance of an auditory language task. Fifty-four PT children (600 -1250 g birth weight) and 24 T controls were evaluated using an fMRI passive language task and neurodevelopmental assessments including: the Wechsler Intelligence Scale for Children -III (WISC -III), the Peabody Individual Achievement Test -Revised (PIAT-R) and the Peabody Picture Vocabulary Test -Revised (PPVT-R) at 8 years of age. Neural activity was assessed for language processing and the data were evaluated for connectivity and correlations to cognitive outcomes. We found PT subjects scored significantly lower on all components of the WISC -III (p < 0.009), the PIAT-R reading comprehension test (p = 0.013), and the PPVT-R (p = 0.001) compared to term subjects. Connectivity analyses revealed significantly stronger neural circuits in PT children between Wernicke's area and the right inferior frontal gyrus (R IFG, Broca's area homologue) and both the left and the right supramarginal gyri (SMG) components of the inferior parietal lobules (p ≤ 0.02 for all). We conclude that PT subjects employ neural systems for auditory language function at school age differently than T controls; these alterations may represent a delay in maturation of neural networks or the engagement of alternate circuits for language processing.

Background/Objectives Polypharmacy and prescribing potentially inappropriate medications (PIMs) are common among older persons. Appropriate prescribing requires robust communication and shared decision making about medications. This study examines the effect of TRIM (Tool to Reduce Inappropriate Medications), a web tool linking the electronic health record (EHR) to a clinical decision support system, on medication communication and prescribing. Design Randomized clinical trial Setting Primary care clinics at a VA Medical Center Participants 128 Veterans age 65 years and older prescribed ≥ 7 medications, randomized to receipt of TRIM or usual care. Intervention TRIM extracts medications and chronic conditions from the EHR and contains data entry screens for information obtained from brief chart review and telephonic patient assessment. These data serve as input for automated algorithms identifying medication reconciliation discrepancies, PIMs, and potentially inappropriate regimens. Clinician feedback reports summarize discrepancies and provide recommendations for deprescribing. Patient feedback reports summarize discrepancies and self-reported medication problems. Measurements Primary: subscales of the Patient Assessment of Care for Chronic Conditions (PACIC) related to shared decision making, clinician and patient communication; secondary: changes in medications. Results While 29.7% of TRIM participants versus 15.6% of control participants provided the highest PACIC ratings, the difference was nonsignificant. Adjusting for covariates and clustering of patients within clinicians, TRIM was associated with significantly more active patient communication and facilitative clinician communication, and with more medication-related communication among both. TRIM was significantly associated with correction of medication discrepancies, but had no effect on number of medications or reduction in PIMs. Conclusions TRIM improved communication around medications and accuracy of documentation. While there was no association with prescribing, the small sample size provided limited power to examine medication-related outcomes.