Abnormal functional connectivity in women with urgency urinary incontinence: Can we predict disease presence and severity in individual women using Rs-fcMRI/.

AIMS: To identify atypical brain functional connectivity in women with UUI and detrusor overactivity (DO) and to predict the presence/severity of UUI in individual women using connectivity features. METHODS: This is a cross-sectional study comparing brain functional connectivity in women with and without UUI. Validated symptom/quality of life questionnaires were used for phenotyping. Participants are females between ages 40 and 85 with daily UUI with DO (Cases, N = 16) and without UUI (Controls, N = 24). Functional MRI and Resting state connectivity MRI were obtained at empty/ full bladder. Multivariate pattern analysis (MVPA) was used to predict the presence and severity of UUI from connectivity data. RESULTS: There are significant differences in brain activation between cases and controls in eighteen brain regions irrespective of empty or full bladder. These include regions involved in attention (inferior partietal), decision making (inferior and superior frontal gyrus), primary motor and sensory (precentral and postcentral gyrus) functions. Women with UUI showed no change in connectivity with bladder filling in regions involved in interoception (insula), integration of afferent function (anterior cingulate), and decision making (middle frontal). MVPA of connectivity data showed robust classification of an individual woman as case or control (89% sensitivity, 83% specificity). Six connectivity features accurately predicted disease severity (R(2) = 0.81). CONCLUSION: We identified two mechanisms of abnormal bladder control, one involving atypical activation of brain regions, and another atypical functional integration across sensory, emotional, cognitive and motor regions. Connectivity information is robust enough to classify an individual as having UUI or not and to predict symptom severity. Neurourol. Urodynam. 35:564-573, 2016. © 2015 Wiley Periodicals, Inc.

Subtyping attention-deficit/hyperactivity disorder using temperament dimensions: toward biologically based nosologic criteria.

IMPORTANCE: Psychiatric nosology is limited by behavioral and biological heterogeneity within existing disorder categories. The imprecise nature of current nosologic distinctions limits both mechanistic understanding and clinical prediction. We demonstrate an approach consistent with the National Institute of Mental Health Research Domain Criteria initiative to identify superior, neurobiologically valid subgroups with better predictive capacity than existing psychiatric categories for childhood attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: To refine subtyping of childhood ADHD by using biologically based behavioral dimensions (i.e., temperament), novel classification algorithms, and multiple external validators. DESIGN, SETTING, AND PARTICIPANTS: A total of 437 clinically well-characterized, community-recruited children, with and without ADHD, participated in an ongoing longitudinal study. Baseline data were used to classify children into subgroups based on temperament dimensions and examine external validators including physiological and magnetic resonance imaging measures. One-year longitudinal follow-up data are reported for a subgroup of the ADHD sample to address stability and clinical prediction. MAIN OUTCOMES AND MEASURES: Parent/guardian ratings of children on a measure of temperament were used as input features in novel community detection analyses to identify subgroups within the sample. Groups were validated using 3 widely accepted external validators: peripheral physiological characteristics (cardiac measures of respiratory sinus arrhythmia and pre-ejection period), central nervous system functioning (via resting-state functional connectivity magnetic resonance imaging), and clinical outcomes (at 1-year longitudinal follow-up). RESULTS: The community detection algorithm suggested 3 novel types of ADHD, labeled as mild (normative emotion regulation), surgent (extreme levels of positive approach-motivation), and irritable (extreme levels of negative emotionality, anger, and poor soothability). Types were independent of existing clinical demarcations including DSM-5 presentations or symptom severity. These types showed stability over time and were distinguished by unique patterns of cardiac physiological response, resting-state functional brain connectivity, and clinical outcomes 1 year later. CONCLUSIONS AND RELEVANCE: Results suggest that a biologically informed temperament-based typology, developed with a discovery-based community detection algorithm, provides a superior description of heterogeneity in the ADHD population than does any current clinical nosologic criteria. This demonstration sets the stage for more aggressive attempts at a tractable, biologically based nosology.