A preliminary investigation of worry, cortical amyloid burden, and stressor-evoked brain and cardiovascular reactivity in older adults.

Worry is a transdiagnostic symptom common to many neurocognitive disorders of aging, including early stages of Alzheimer's disease and related dementias (ADRD). Severe worry is associated with amyloid burden in cognitively intact older adults, yet the mechanisms underlying this association are not well understood. We hypothesize that this relationship involves altered brain and cardiovascular reactivity to acute stressors, a brain-body phenotype that also increases risk for cardiovascular disease.

Establishing connectivity through microdissections of midbrain stimulation-related neural circuits.

Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomofunctional mechanisms governing human behaviour, in addition to the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. Although the ventral tegmental area has been targeted successfully with deep brain stimulation for different neuropsychiatric diseases, the axonal connectivity of the region is not fully understood. Here, using fibre microdissections in human cadaveric hemispheres, population-based high-definition fibre tractography and previously reported deep brain stimulation hotspots, we find that the ventral tegmental area participates in an intricate network involving the serotonergic pontine nuclei, basal ganglia, limbic system, basal forebrain and prefrontal cortex, which is implicated in the treatment of obsessive-compulsive disorder, major depressive disorder, Alzheimer's disease, cluster headaches and aggressive behaviours.

Early Infant Prefrontal Cortical Microstructure Predicts Present and Future Emotionality.

Background: High levels of infant negative emotionality (NE) and low positive emotionality (PE) predict future emotional and behavioral problems. The prefrontal cortex (PFC) supports emotional regulation, with each PFC subregion specializing in specific emotional processes. Neurite orientation dispersion and density imaging estimates microstructural integrity and myelination via the neurite density index (NDI) and dispersion via the orientation dispersion index (ODI), with potential to more accurately evaluate microstructural alterations in the developing brain.

Manual segmentation of the paraventricular nucleus of the hypothalamus and the dorsal and ventral bed nucleus of stria terminalis using multimodal 7 Tesla structural MRI: probabilistic atlases for a stress-control triad.

The paraventricular nucleus of the hypothalamus (PVN) is uniquely capable of proximal control over autonomic and neuroendocrine stress responses, and the bed nucleus of the stria terminalis (BNST) directly modulates PVN function, as well as playing an important role in stress control itself. The dorsal BNST (dBNST) is predominantly preautonomic, while the ventral BNST (vBNST) is predominantly viscerosensory, receiving dense noradrenergic signaling. Distinguishing the dBNST and vBNST, along with the PVN, may facilitate our understanding of dynamic interactions among these regions.

Neural Network Functional Interactions Mediate or Suppress White Matter-Emotional Behavior Relationships in Infants.

Background: Elucidating the neural basis of infant positive emotionality and negative emotionality can identify biomarkers of pathophysiological risk. Our goal was to determine how functional interactions among large-scale networks supporting emotional regulation influence white matter (WM) microstructural-emotional behavior relationships in 3-month-old infants. We hypothesized that microstructural-emotional behavior relationships would be differentially mediated or suppressed by underlying resting-state functional connectivity (rsFC), particularly between default mode network and central executive network structures.

Changes in brain response to urgency before and after treatment of urgency urinary incontinence with onabotulinumtoxin A.

Introduction: To better understand the role of the brain in urgency urinary incontinence (UUI), we used onabotulinumtoxin A (BoNTA) as a probe to evaluate changes in the brain's response to urgency in successful and unsuccessful treatment. Because BoNTA acts peripherally, brain changes observed should represent a reaction to changes in bladder function caused by BoNTA, or changes in the brain's compensatory mechanisms, rather than a direct effect of BoNTA on the brain.

Methods: We recruited 20 women aged over 60 years with nonneurogenic UUI who were to undergo treatment with onabotulinum A toxin injected intravesically.

Childhood Threat Is Associated With Lower Resting-State Connectivity Within a Central Visceral Network.

Childhood adversity is associated with altered or dysregulated stress reactivity; these altered patterns of physiological functioning persist into adulthood. Evidence from both preclinical animal models and human neuroimaging studies indicates that early life experience differentially influences stressor-evoked activity within central visceral neural circuits proximally involved in the control of stress responses, including the subgenual anterior cingulate cortex (sgACC), paraventricular nucleus of the hypothalamus (PVN), bed nucleus of the stria terminalis (BNST) and amygdala. However, the relationship between childhood adversity and the resting-state connectivity of this central visceral network remains unclear.

Are All Anxieties Created Equal? Stress-related Networks and Anxiety Phenotypes in Old Age.

Objective: The dysregulation of stress-related networks due to chronic symptoms such as severe worry and/or rumination is one of the putative pathways linking anxiety in late-life with cognitive decline and increased cardiovascular burden. Symptoms such as severe worry or rumination respond poorly to standard treatment and drive the morbidity associated with anxiety in older adults. We assessed if any of the neural networks anchored in the stress-related regions of interest (ROIs) are associated with distinct anxiety phenotypes (worry, rumination and global anxiety).

Patterns of Infant Amygdala Connectivity Mediate the Impact of High Caregiver Affect on Reducing Infant Smiling: Discovery and Replication.

Background: Behavioral research indicates that caregiver mood disorders and emotional instability in the early months following childbirth are associated with lower positive emotionality and higher negative emotionality in infants, but the neural mechanisms remain understudied.

Methods: Using resting-state functional connectivity as a measure of the functional architecture of the early infant brain, we aimed to determine the extent to which connectivity between the amygdala, a key region supporting emotional learning and perception, and large-scale neural networks mediated the association between caregiver affect and anxiety and early infant negative emotionality and positive emotionality. Two samples of infants (first sample: n = 58; second sample: n = 31) 3 months of age underwent magnetic resonance imaging during natural sleep.

Opposing relationships of childhood threat and deprivation with stria terminalis white matter.

While stress may be a potential mechanism by which childhood threat and deprivation influence mental health, few studies have considered specific stress-related white matter pathways, such as the stria terminalis (ST) and medial forebrain bundle (MFB). Our goal was to examine the relationships between childhood adversity and ST and MFB structural integrity and whether these pathways may provide a link between childhood adversity and affective symptoms and disorders. Participants were young adults (n = 100) with a full distribution of maltreatment history and affective symptom severity.

Reduced postpartum hippocampal volume is associated with positive mother-infant caregiving behavior.

Background: Maternal caregiving is a complex set of behaviors that can be impacted by early life stress (ELS), yet human neurobiological mechanisms are not well understood.

Methods: Young mothers (n=137) were enrolled into a neuroimaging substudy of the longitudinal Pittsburgh Girls Study (PGS). Using data collected annually while subjects were ages 8-16, ELS was calculated as a composite score of poverty, trauma, and difficult life circumstances.

Integrative omics analysis identifies differential biological pathways that are associated with regional grey matter volume changes in major depressive disorder.

Background: Major depressive disorder (MDD) is accompanied by alterations in grey matter volume. However, the biological processes associated with regional structural perturbations remain elusive.

Methods: We applied integrative omics analysis to investigate specialized transcriptome signatures and translational determinants associated with regional grey matter variations in 2737 MDD patients relative to 3098 controls by summarizing the results from gene co-expression network analysis of Allen human brain transcriptome profiles in six donors, enrichment analysis of gene-sets and cellular structure from rodents and mediation analysis of BrainSpan proteome profile in six donors.

Limbic white matter structural integrity at 3 months prospectively predicts negative emotionality in 9-month-old infants: a preliminary study.

Background: Little is known about how early alterations in white matter relate to clinically relevant behaviors such as emotional dysregulation. Thus, our goal was to examine how the white matter structural integrity of key limbic (i.e.

Determining the key childhood and adolescent risk factors for future BPD symptoms using regularized regression: comparison to depression and conduct disorder.

Objective: Research has yielded factors considered critical to risk for borderline personality disorder (BPD). Yet, these factors overlap and are relevant to other disorders, like depression and conduct disorder (CD). Regularized regression, a machine learning approach, was developed to allow identification of the most important variables in large datasets with correlated predictors.

Interactions between childhood maltreatment and combat exposure trauma on stress-related activity within the cingulate cortex: a pilot study.

Childhood trauma may sensitize the brain, increasing vulnerability to maladaptive stress responses following adulthood trauma exposure. Previous work has identified the cingulum as a white matter pathway that may be sensitized to adulthood trauma by childhood maltreatment. In this pilot study of young adult male military veterans (N = 28), we examined regions of interest (ROIs) connected by the cingulum, including regions involved in cognitive processes and stress responses.

White Matter Integrity Underlying Depressive Symptoms in Dementia Caregivers.

Objective: We sought to determine whether the aspects of white matter connectivity implicated in major depression also relate to mild depressive symptoms in family dementia caregivers (dCGs).

Methods: Forty-one dCGs (average age=69 years, standard deviation=6.4) underwent a 7 Tesla 64-direction (12-minute) diffusion-weighted imaging sequence.

When worry may be good for you: Worry severity and limbic-prefrontal functional connectivity in late-life generalized anxiety disorder.

Background: Late-life generalized anxiety disorder (GAD) is one of the most common anxiety disorders in older adults. However, its neural markers have received relatively little attention. In this study, we explored the association between worry severity and limbic-prefrontal connectivity during emotional reactivity in late-life GAD.

Towards personalized, brain-based behavioral intervention for transdiagnostic anxiety: Transient neural responses to negative images predict outcomes following a targeted computer-based intervention.

Objective: Clinical anxiety is prevalent, highly comorbid with other conditions, and associated with significant medical morbidity, disability, and public health burden. Excessive attentional deployment toward threat is a transdiagnostic dimension of anxiety seen at both initial and sustained stages of threat processing. However, group-level observations of these phenomena mask considerable within-group heterogeneity that has been linked to treatment outcomes, suggesting that a transdiagnostic, individual differences approach may capture critical, clinically relevant information.

Using optimal combined moderators to define heterogeneity in neural responses to randomized conditions: Application to the effect of sleep loss on fear learning.

Comparing the neural outcomes of two randomized experimental groups is a primary aim of many functional neuroimaging studies. However, between-group effects can be obscured by heterogeneity in neural responses. Optimal Combined Moderator (OCM) approaches have previously been used to clarify heterogeneity in clinical outcomes following treatment randomization.

Childhood maltreatment moderates the effect of combat exposure on cingulum structural integrity.

Limbic white matter pathways link emotion, cognition, and behavior and are potentially malleable to the influences of traumatic events throughout development. However, the impact of interactions between childhood and later life trauma on limbic white matter pathways has yet to be examined. Here, we examined whether childhood maltreatment moderated the effect of combat exposure on diffusion tensor imaging measures within a sample of military veterans (N = 28).