Faculty Bibliography

Spreading depolarization (SD) is a sudden, large, and synchronous depolarization of principal cells which also involves interneurons and astrocytes. It is followed by depression of neuronal activity, and it slowly propagates across brain regions like cortex or hippocampus. SD is considered to be mechanistically relevant to migraine, epilepsy, and traumatic brain injury (TBI), but there are many questions about its basic neurophysiology and spread. Research into SD in hippocampus using slices is often used to gain insight and SD is usually triggered by a focal stimulus with or without an altered extracellular buffer. Here, we optimize an in vitro experimental model allowing us to record SD without focal stimulation, which we call spontaneous. This method uses only an altered extracellular buffer containing 0 mM Mg²⁺ and 5 mM K⁺ and makes it possible for simultaneous patch and extracellular recording in a submerged chamber plus intrinsic optical imaging in slices of either sex. We also add methods for quantification and show the quantified optical signal is much more complex than imaging alone would suggest. In brief, acute hippocampal slices were prepared with a chamber holding a submerged slice but with flow of artificial cerebrospinal fluid (aCSF) above and below, which we call interface-like. As soon as slices were placed in the chamber, aCSF with 0 Mg²⁺/5 K⁺ was used. Most mouse slices developed SD and did so in the first hour of 0 Mg²⁺/5 K⁺ aCSF exposure. In addition, prolonged bursts we call seizure-like events (SLEs) occurred, and the interactions between SD and SLEs suggest potentially important relationships. Differences between rats and mice in different chambers are described. Regarding optical imaging, SD originated in CA3 and the pattern of spread to CA1 and the dentate gyrus was similar in some ways to prior studies but also showed interesting differences. In summary, the methods are easy to use, provide new opportunities to study SD, new insights, and are inexpensive. They support previous suggestions that SD is diverse, and also suggest that participation by the dentate gyrus merits greater attention.

Automatic emotion regulation (AER) plays a vital role in the neuropathology underlying both suicide and self-harm via modifying emotional impact effortlessly. However, both the effortless account and the neural mechanisms of AER are undetermined. To investigate the neural changes at AER, we collected functional MRI (fMRI) in 31 participants who attended to neutral and disgust pictures in three conditions: watching, goal intention (GI), and reappraisal by implementation intention (RII). Results showed that RII (but not GI) decreased negative feelings and bilateral amygdala activity without increasing cognitive efforts, evidenced by the reduced effort rating and less prefrontal engagement during RII compared with during watching and GI. These emotion-regulatory effects of RII cannot be explained by emotional habituation, as the supplementary experiment (N = 31) showed no emotional habituation effects when the same disgust pictures were presented repeatedly three times for each watching and GI condition. Task-based network analysis showed both RII and GI relative to watching increased functional connectivities (FCs) of the ventral anterior cingulate cortex to the left insula and right precuneus during conditions, two FCs subserving goal setup. However, RII relative to GI exhibited weaker FCs in brain networks subserving effortful control, memory retrieval, aversive anticipation, and motor planning. In these FCs, the FC intensity of putamen-operculum/lingual and paracentral-superior temporal gyri positively predicted regulatory difficulty ratings. These findings suggest that the setup of implementation intention automatizes emotion regulation by reducing the online mobilization of emotion-coping neural systems.

Between 15% to 20% of youth meet diagnostic criteria for anxiety, yet most do not receive treatment due to workforce shortages, under-detection, or barriers that dissuade families from seeking services in traditional settings. Equine-assisted services (EAS) include several promising approaches to reach populations who do not access traditional therapies. Few studies using rigorous methods have been conducted on EAS for youth. This study examined feasibility and outcomes of a 10-session Cognitive Behavioral Therapy (CBT)-based adaptive riding intervention (hereafter called Reining in Anxiety) delivered by trained equine professionals. Forty-one youth 6- 16 years of age were recruited from GallopNYC, an adaptive horseback riding center in the NYC metro area. Youth were randomized to an experimental group (n=22) or services as usual (n=19), a standard adaptive riding group (services as usual or SAU). Severity of anxiety symptoms, anxiety in close relationships, and emotional self-efficacy were assessed at baseline and at the end of treatment. Fidelity to the manual was excellent, ranging from 88.9% to 100%. There was a non-significant trend in the experimental group towards greater improvement with higher number of sessions completed. Youth in the Reining in Anxiety group displayed significant reductions in anxiety (t=4.426, df=38, p=0.042) and improvement in emotional self-efficacy at posttest (t=4.132, df=38, p=0.049) in comparison to the SAU group. No significant differences were found between groups for anxiety in close relationships. This study suggests that a CBT-based adaptive riding intervention delivered by non-mental health equine professionals following a detailed manual can reduce youth anxiety symptoms and be delivered with fidelity by riding instructors. These findings have implications for families seeking non-traditional services. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

The COVID-19 pandemic continues to cause an immense psychosocial strain worldwide. Excessive use of the internet during these psychologically trying times, fueled by physical isolation as a result of lockdowns, has translated into dysfunctional behaviors. A growing body of evidence suggests an unprecedented increase in internet use and consumption of online pornography during the pandemic, and possibly even directly caused by it. In this review, the authors report data from relevant sources to show the rise in pornography use during lockdowns in different countries worldwide. In addition to a brief overview of the neurobiology of internet addiction broadly and problematic online pornography use specifically, similarities with substance use disorders are explained. Further, the current status of the debate about defining diagnostic criteria is discussed. Finally, the review sheds light on the potential detrimental outcomes during the future post-pandemic "re-adaptation," while simultaneously offering preventative and management strategies for harm reduction. The authors conclude that foresightedness with utilizing existing tools and therapies and exercising appropriate amounts of caution could go a long way in addressing the challenges that lie ahead in the post-pandemic era.

Down syndrome (DS) is the primary genetic cause of intellectual disability (ID), which is due to the triplication of human chromosome 21 (HSA21). In addition to ID, HSA21 trisomy results in a number of neurological and physiological pathologies in individuals with DS, including progressive cognitive dysfunction and learning and memory deficits which worsen with age. Further exacerbating neurological dysfunction associated with DS is the concomitant basal forebrain cholinergic neuron (BFCN) degeneration and onset of Alzheimer's disease (AD) pathology in early mid-life. Recent single population RNA sequencing (RNA-seq) analysis in the Ts65Dn mouse model of DS, specifically the medial septal cholinergic neurons of the basal forebrain (BF), revealed the mitochondrial oxidative phosphorylation pathway was significantly impacted, with a large subset of genes within this pathway being downregulated. We further queried oxidative phosphorylation pathway dysregulation in Ts65Dn mice by examining genes and encoded proteins within brain regions comprising the basocortical system at the start of BFCN degeneration (6 months of age). In select Ts65Dn mice we demonstrate significant deficits in gene and/or encoded protein levels of Complex I-V of the mitochondrial oxidative phosphorylation pathway in the BF. In the frontal cortex (Fr Ctx) these complexes had concomitant alterations in select gene expression but not of the proteins queried from Complex I-V, suggesting that defects at this time point in the BF are more severe and occur prior to cortical dysfunction within the basocortical circuit. We propose dysregulation within mitochondrial oxidative phosphorylation complexes is an early marker of cognitive decline onset and specifically linked to BFCN degeneration that may propagate pathology throughout cortical memory and executive function circuits in DS and AD.

The Social Emotional Behavioral (SEB) Team of the National Children's Study (NCS) was tasked with making recommendations for assessment of important aspects of social-emotional health and function in children. This paper describes the constructs recommended for assessment along with the rationale for their assessment. These constructs, representing aspects of Social Relationships, Social Capital, Temperament, Negative Affect, Externalizing Behavior, Social Competence, Self-efficacy, Self-image, Psychological well-being, Ethnic/racial Socialization, Perceived Discrimination, Sexual Orientation, Religiosity, and Perceived Stress and Resilience were identified as being critical to the understanding of children's health and development from birth to age 21.