There is growing public concern about neurodegenerative changes (e.g., Chronic Traumatic Encephalopathy) that may occur chronically following clinically apparent and clinically silent (i.e., sub-concussive blows) pediatric mild traumatic brain injury (pmTBI). However, there are currently no biomarkers that clinicians can use to objectively diagnose patients or predict those who may struggle to recover. Non-invasive neuroimaging, electrophysiological and neuromodulation biomarkers have promise for providing evidence of the so-called "invisible wounds" of pmTBI. Our systematic review, however, belies that notion, identifying a relative paucity of high-quality, clinically impactful, diagnostic or prognostic biomarker studies in the sub-acute injury phase (36 studies on unique samples in 28 years), with the majority focusing on adolescent pmTBI. Ultimately, well-powered longitudinal studies with appropriate control groups, as well as standardized and clearly-defined inclusion criteria (time post-injury, injury severity and past history) are needed to truly understand the complex pathophysiology that is hypothesized (i.e., still needs to be determined) to exist during the acute and sub-acute stages of pmTBI and may underlie post-concussive symptoms.

Algorithms that are capable of capturing subject-specific abnormalities (SSA) in neuroimaging data have long been an area of focus for diverse neuropsychiatric conditions such as multiple sclerosis, schizophrenia, and traumatic brain injury. Several algorithms have been proposed that define SSA in patients (i.e., comparison group) relative to image intensity levels derived from healthy controls (HC) (i.e., reference group) based on extreme values. However, the assumptions underlying these approaches have not always been fully validated, and may be dependent on the statistical distributions of the transformed data. The current study evaluated variations of two commonly used techniques ("pothole" method and standardization with an independent reference group) for identifying SSA using simulated data (derived from normal, t and chi-square distributions) and fractional anisotropy maps derived from 50 HC. Results indicated substantial group-wise bias in the estimation of extreme data points using the pothole method, with the degree of bias being inversely related to sample size. Statistical theory was utilized to develop a distribution-corrected z-score (DisCo-Z) threshold, with additional simulations demonstrating elimination of the bias and a more consistent estimation of extremes based on expected distributional properties. Data from previously published studies examining SSA in mild traumatic brain injury were then re-analyzed using the DisCo-Z method, with results confirming the evidence of group-wise bias. We conclude that the benefits of identifying SSA in neuropsychiatric research are substantial, but that proposed SSA approaches require careful implementation under the different distributional properties that characterize neuroimaging data.

Background Treatment of urgency urinary incontinence has focused on pharmacologically treating detrusor overactivity. Recent recognition that altered perception of internal stimuli (interoception) plays a role in urgency urinary incontinence suggests that exploration of abnormalities of brain function in this disorder could lead to better understanding of urgency incontinence and its treatment. Objectives 1) To evaluate the relationship between bladder filling, perceived urgency and activation at brain sites within the interoceptive network in urgency urinary incontinence 2) To identify coactivation of other brain networks that could affect interoception during bladder filling in urgency incontinence 3) To demonstrate interaction between these sites prior to bladder filling by evaluating their resting state connectivity Study Design We performed an observational cohort study using functional magnetic resonance imaging to compare brain function in 53 women with urgency urinary incontinence and 20 Controls. Whole-brain voxel-wise ANCOVAs were performed to examine differences in functional brain activation between groups during a task consisting of bladder filling, hold (static volume) and withdrawal phases. The task was performed at three previously established levels of baseline bladder volume, the highest exceeding strong desire to void volume. All women continuously rated their urge on a 0–10 point Likert scale throughout the task and a mixed measures ANOVA was used to test for differences in urge ratings. Empirically derived regions of interest from analysis of activation during the task were used as seeds for examining group differences in resting state functional connectivity. Results In both urgency urinary incontinent participants and Controls changes in urge ratings were greatest during bladder filling initiated from a high baseline bladder volume and urgency incontinent participants’ rating changes were greater than Controls. During this bladder filling phase urgency incontinent participant’s activation of the interoceptive network was greater than Controls, including in the left insula and the anterior and middle cingulate cortex. Urgency Incontinent Participant’s activation was also greater than Controls at sites in the Ventral Attention Network and Posterior Default Mode Network. Urgency incontinent participant’s connectivity was greater than Controls between a middle cingulate seed point and the Dorsal Attention Network, a “top down” attentional network. Control connectivity was greater between the mid-cingulate seed point and the Ventral Attention Network, a “bottom up” attentional network, Conclusions Increasing urge was associated with greater urgency incontinent participant than Control activation of the interoceptive network and activation in networks that are determinants of self-awareness (Default Mode Network) and of response to unexpected external stimuli (Ventral Attention Network). Differences in connectivity between interoceptive networks and opposing attentional networks (Ventra...

Numerous questions surround the nature of reward processing in the developing adolescent brain, particularly in regard to polysubstance use. We therefore sought to examine incentive-elicited brain activation in the context of three common substances of abuse (cannabis, tobacco, and alcohol). Due to the role of the nucleus accumbens (NAcc) in incentive processing, we compared activation in this region during anticipation of reward and loss using a monetary incentive delay (MID) task. Adolescents (ages 14–18; 66% male) were matched on age, gender, and frequency of use of any common substances within six distinct groups: cannabis-only (n = 14), tobacco-only (n = 34), alcohol-only (n = 12), cannabis + tobacco (n = 17), cannabis + tobacco + alcohol (n = 17), and non-using controls (n = 38). All groups showed comparable behavioral performance on the MID task. The tobacco-only group showed decreased bilateral nucleus accumbens (NAcc) activation during reward anticipation as compared to the alcohol-only group, the control group, and both polysubstance groups. Interestingly, no differences emerged between the cannabis-only group and any of the other groups. Results from this study suggest that youth who tend toward single-substance tobacco use may possess behavioral and/or neurobiological characteristics that differentiate them from both their substance-using and non-substance-using peers.

This study suggests that low-frequency midline theta activity is selectively disrupted during proactive cognitive control in SPs. The disrupted midline theta activity may reflect a failure of SPs to proactively recruit cognitive control processes.

The role of ventral versus dorsolateral prefrontal regions in instantiating proactive and reactive cognitive control remains actively debated, with few studies parsing cue versus probe‐related activity. Rapid sampling (460 ms), long cue–probe delays, and advanced analytic techniques (deconvolution) were therefore used to quantify the magnitude and variability of neural responses during the AX Continuous Performance Test (AX‐CPT; N = 46) in humans. Behavioral results indicated slower reaction times during reactive cognitive control (AY trials) in conjunction with decreased accuracy and increased variability for proactive cognitive control (BX trials). The anterior insula/ventrolateral prefrontal cortex (aI/VLPFC) was commonly activated across comparisons of both proactive and reactive cognitive control. In contrast, activity within the dorsomedial and dorsolateral prefrontal cortex was limited to reactive cognitive control. The instantiation of proactive cognitive control during the probe period was also associated with sparse neural activation relative to baseline, potentially as a result of the high degree of neural and behavioral variability observed across individuals. Specifically, the variability of the hemodynamic response function (HRF) within motor circuitry increased after the presentation of B relative to A cues (i.e., late in HRF) and persisted throughout the B probe period. Finally, increased activation of right aI/VLPFC during the cue period was associated with decreased motor circuit activity during BX probes, suggesting a possible role for the aI/VLPFC in proactive suppression of neural responses. Considered collectively, current results highlight the flexible role of the VLPFC in implementing cognitive control during the AX‐CPT task but suggest large individual differences in proactive cognitive control strategies.

Acceleration parameters have been utilized for the last six decades to investigate pathology in both human and animal models of traumatic brain injury (TBI), design safety equipment, and develop injury thresholds. Previous large animal models have quantified acceleration from impulsive loading forces (i.e., machine/object kinematics) rather than directly measuring head kinematics. No study has evaluated the reproducibility of head kinematics in large animal models. Nine (five males) sexually mature Yucatan swine were exposed to head rotation at a targeted peak angular velocity of 250 rad/s in the coronal plane. The results indicated that the measured peak angular velocity of the skull was 51% of the impulsive load, was experienced over 91% longer duration, and was multi- rather than uni-planar. These findings were replicated in a second experiment with a smaller cohort (N = 4). The reproducibility of skull kinematics data was mostly within acceptable ranges based on published industry standards, although the coefficients of variation (8.9% for peak angular velocity or 12.3% for duration) were higher than the impulsive loading parameters produced by the machine (1.1 vs. 2.5%, respectively). Immunohistochemical markers of diffuse axonal injury and blood–brain barrier breach were not associated with variation in either skull or machine kinematics, suggesting that the observed levels of variance in skull kinematics may not be biologically meaningful with the current sample sizes. The findings highlight the reproducibility of a large animal acceleration model of TBI and the importance of direct measurements of skull kinematics to determine the magnitude of angular velocity, refine injury criteria, and determine critical thresholds.

Parsing multisensory information from a complex external environment is a fundamental skill for all organisms. However, different organizational schemes currently exist for how multisensory information is processed in human (supramodal; organized by cognitive demands) versus primate (organized by modality/cognitive demands) lateral prefrontal cortex (LPFC). Functional magnetic resonance imaging results from a large cohort of healthy controls (N = 64; Experiment 1) revealed a rostral-caudal stratification of LPFC for auditory versus visual attention during an audio-visual Stroop task. The stratification existed in spite of behavioral and functional evidence of increased interference from visual distractors. Increased functional connectivity was also observed between rostral LPFC and auditory cortex across independent samples (Experiments 2 and 3) and multiple methodologies. In contrast, the caudal LPFC was preferentially activated during visual attention but functioned in a supramodal capacity for resolving multisensory conflict. The caudal LPFC also did not exhibit increased connectivity with visual cortices. Collectively, these findings closely mirror previous nonhuman primate studies suggesting that visual attention relies on flexible use of a supramodal cognitive control network in caudal LPFC whereas rostral LPFC is specialized for directing attention to auditory inputs (i.e., human auditory fields).