The Neural Signature of Impaired Inhibitory Control in Individuals with Heroin Use Disorder.

Heroin addiction imposes a devastating toll on society, with little known about its neurobiology. Excessive salience attribution to drug over nondrug cues/reinforcers, with concomitant inhibitory control decreases, are common mechanisms underlying drug addiction. Although inhibitory control alterations generally culminate in prefrontal cortex (PFC) hypoactivations across drugs of abuse, patterns in individuals with heroin addiction (iHUDs) remain unknown. We used a stop-signal fMRI task designed to meet recent consensus guidelines in mapping inhibitory control in 41 iHUDs and 24 age- and sex-matched healthy controls (HCs). Despite group similarities in the stop-signal response time (SSRT; the classic inhibitory control measure), compared with HCs, iHUDs exhibited impaired target detection sensitivity (proportion of hits in go vs false alarms in stop trials; p = 0.003). Additionally, iHUDs exhibited lower right anterior PFC (aPFC) and dorsolateral PFC (dlPFC) activity during successful versus failed stops (the hallmark inhibitory control contrast). Lower left dlPFC/supplementary motor area (SMA) activity was associated with slower SSRT specifically in iHUDs and lower left aPFC activity with worse target sensitivity across all participants (p < 0.05 corrected). Importantly, in iHUDs, lower left SMA and aPFC activity during inhibitory control was associated with shorter time since last use and higher severity of dependence, respectively (p < 0.05 corrected). Together, results revealed lower perceptual sensitivity and hypoactivations during inhibitory control in cognitive control regions (e.g., aPFC, dlPFC, SMA) as associated with task performance and heroin use severity measures in iHUDs. Such neurobehavioral inhibitory control deficits may contribute to self-control lapses in heroin addiction, constituting targets for prevention and intervention efforts to enhance recovery.SIGNIFICANCE STATEMENT Heroin addiction continues its deadly impact, with little known about the neurobiology of this disorder. Although behavioral and prefrontal cortical impairments in inhibitory control characterize addiction across drugs of abuse, these patterns remain underexplored in heroin addiction. Here, we illustrate a significant behavioral impairment in target discrimination in individuals with heroin addiction compared with matched healthy controls. We further show lower engagement during inhibitory control in the anterior and dorsolateral prefrontal cortex (key regions that regulate cognitive control) as associated with slower stopping, worse discrimination, and heroin use measures. Mapping the neurobiology of inhibitory control in heroin addiction for the first time, we identify potential treatment targets inclusive of prefrontal cortex-mediated cognitive control amenable for neuromodulation en route to recovery.

Common and distinct fronto-striatal volumetric changes in heroin and cocaine use disorders.

Different drugs of abuse impact the morphology of fronto-striatal dopaminergic targets in both common and unique ways. While dorsal striatal volume tracks with addiction severity across drug classes, opiates impact ventromedial prefrontal cortex (vmPFC) and nucleus accumbens (NAcc) neuroplasticity in preclinical models, and psychostimulants alter inhibitory control, rooted in cortical regions such as the inferior frontal gyrus (IFG). We hypothesized parallel grey matter volume changes associated with human heroin or cocaine use disorder: lower grey matter volume of vmPFC/NAcc in heroin use disorder and IFG in cocaine use disorder, and putamen grey matter volume to be associated with addiction severity measures (including craving) across both. In this cross-sectional study, we quantified grey matter volume (P < 0.05-corrected) in age/sex/IQ-matched individuals with heroin use disorder (n = 32, seven females), cocaine use disorder (n = 32, six females) and healthy controls (n = 32, six females) and compared fronto-striatal volume between groups using voxel-wise general linear models and non-parametric permutation-based tests. Overall, individuals with heroin use disorder had smaller vmPFC and NAcc/putamen volumes than healthy controls. Bilateral lower IFG grey matter volume patterns were specifically evident in cocaine versus heroin use disorders. Correlations between addiction severity measures and putamen grey matter volume did not reach nominal significance level in this sample. These results indicate alterations in dopamine-innervated regions (in the vmPFC and NAcc) in heroin addiction. For the first time we demonstrate lower IFG grey matter volume specifically in cocaine compared with heroin use disorder, suggesting a signature of reduced inhibitory control, which remains to be tested directly using select behavioural measures. Overall, results suggest substance-specific volumetric changes in human psychostimulant or opiate addiction, with implications for fine-tuning biomarker and treatment identification by primary drug of abuse.

Examining nutrition among a sample of 3- to 5-year-old children living in rural Jamaica.

BACKGROUND: The period of early childhood, defined as three to five years of age, is an important and distinct stage in childhood development. Changes in dietary patterns and composition of diets are exposing children in developing countries to over-nutrition as well as under-nutrition. OBJECTIVE: To describe the nutritional status, dietary patterns, and socio-economic conditions of three to five-year-old children living in rural Jamaica. SAMPLE: A convenience sample of 142 children was recruited over a three-year period. MEASUREMENTS: Height and weight measurements were collected. Household dietary patterns and socio-economic indicators were available from a small group (n = 6) of parents. RESULTS: Children experiencing both under-nutrition and over-nutrition were identified. Nine percent (n = 13) could be classified as moderately to severely under-nourished, and 6.9% (n = 10) classified as overweight. Frying was a common cooking method, and fruits and vegetables were eaten often. CONCLUSIONS: Economic and political changes may place children in developing countries at risk for over-nutrition as well as under-nutrition. The school setting may be an important place to address nutritional issues. This analysis describes the nutritional status of a sample of three to five-year-old children living in rural Jamaica and provides suggestions for future research.

Functional architecture of intracellular oscillations in hippocampal dendrites.

Fast electrical signaling in dendrites is central to neural computations that support adaptive behaviors. Conventional techniques lack temporal and spatial resolution and the ability to track underlying membrane potential dynamics present across the complex three-dimensional dendritic arbor in vivo. Here, we perform fast two-photon imaging of dendritic and somatic membrane potential dynamics in single pyramidal cells in the CA1 region of the mouse hippocampus during awake behavior. We study the dynamics of subthreshold membrane potential and suprathreshold dendritic events throughout the dendritic arbor in vivo by combining voltage imaging with simultaneous local field potential recording, post hoc morphological reconstruction, and a spatial navigation task. We systematically quantify the modulation of local event rates by locomotion in distinct dendritic regions and report an advancing gradient of dendritic theta phase along the basal-tuft axis, then describe a predominant hyperpolarization of the dendritic arbor during sharp-wave ripples. Finally, we find spatial tuning of dendritic representations dynamically reorganizes following place field formation. Our data reveal how the organization of electrical signaling in dendrites maps onto the anatomy of the dendritic tree across behavior, oscillatory network, and functional cell states.

Female survivors of child sexual abuse: finding voice through research participation.

It is unclear whether survivors of trauma are at risk of emotional or psychological distress when they participate in research because there is little data on the subjective experience of research study participants and how they make meaning from their participation in research. This qualitative descriptive study explored the experience of research participation by survivors of childhood sexual abuse. We interviewed 12 female survivors and identified themes. Participants noted both positive personal and societal benefits of study participation and reported no harm due to their research participation. Study findings can help researchers understand the perspectives of participants regarding the benefits of taking part in violence research and can help allay concerns over causing participants undue psychological distress.

Abuse experiences, substance use, and reproductive health in women seeking care at an emergency department.

INTRODUCTION: Abuse experiences can have negative health consequences for women. Many women present to the emergency department for episodic, nonemergent care and may have unique needs as survivors of abuse. The purpose of this study was to describe child sexual abuse experiences, intimate partner violence, substance use, and reproductive health outcomes in a sample of adult women who were seeking care from a rural emergency department to better understand the health care needs of this unique population. METHODS: One hundred forty-five adult women (18-45 years old) were recruited at an emergency department in the southeastern United States. Questionnaires were used to assess for demographic characteristics, history of child sexual abuse (CSA), intimate partner violence, reproductive health, and substance use. RESULTS: In the sample, 42.8% of women (n = 62) reported a positive history of CSA and 34.7% of women (n = 49) experienced intimate partner physical violence during the past year. More than 46% of the women (n = 65) had harmful drinking patterns in the past year and more than 50% reported some type of substance use in the past 3 months. Women who experienced CSA had a significantly greater number of lifetime sexual partners, were more likely to report pain with sexual intercourse, and were more likely to report a medical history of an abnormal Papanicolaou smear. DISCUSSION: The women in this sample had high rates of abuse, harmful drinking patterns, and substance use and were at risk for sexually transmitted infections. Through screening for lifetime violence, including sexual violence, emergency nurses can be an important liaison between women who have experienced CSA and appropriate referrals within the health care system.

Naturalistic drug cue reactivity in heroin use disorder: orbitofrontal synchronization as a marker of craving and recovery.

Movies captivate groups of individuals (the audience), especially if they contain themes of common motivational interest to the group. In drug addiction, a key mechanism is maladaptive motivational salience attribution whereby drug cues outcompete other reinforcers within the same environment or context. We predicted that while watching a drug-themed movie, where cues for drugs and other reinforcers share a continuous narrative context, fMRI responses in individuals with heroin use disorder (iHUD) will preferentially synchronize during drug scenes. Results revealed such drug-biased synchronization in the orbitofrontal cortex (OFC), ventromedial and ventrolateral prefrontal cortex, and insula. After 15 weeks of inpatient treatment, there was a significant reduction in this drug-biased shared response in the OFC, which correlated with a concomitant reduction in dynamically-measured craving, suggesting synchronized OFC responses to a drug-themed movie as a neural marker of craving and recovery in iHUD.

Recovery of inhibitory control prefrontal cortex function in inpatients with heroin use disorder: a 15-week longitudinal fMRI study.

Importance: Heroin addiction and related mortality impose a devastating toll on society, with little known about the neurobiology of this disease or its treatment. Poor inhibitory control is a common manifestation of prefrontal cortex (PFC) impairments in addiction, and its potential recovery following treatment is largely unknown in heroin (or any drug) addiction. Objective: To study inhibitory control brain activity in iHUD and HC, before and after 15 weeks of inpatient treatment in the former. Design: A longitudinal cohort study (11/2020-03/2022) where iHUD and HC underwent baseline and follow-up fMRI scans. Average follow-up duration: 15 weeks. Setting: The iHUD and HC were recruited from treatment facilities and surrounding neighborhoods, respectively. Participants: Twenty-six iHUD [40.6±10.1 years; 7 (29.2%) women] and 24 age-/sex-matched HC [41.1±9.9 years; 9 (37.5%) women]. Intervention: Following the baseline scan, inpatient iHUD continued to participate in a medically-assisted program for an average of 15 weeks (abstinence increased from an initial 183±236 days by 65±82 days). The HC were scanned at similar time intervals. Main Outcomes and Measures: Behavioral performance as measured by the stop-signal response time (SSRT), target detection sensitivity (d', proportion of hits in go vs. false-alarms in stop trials), and brain activity (blood-oxygen level dependent signal differences) during successful vs. failed stops in the stop signal task. Results: As we previously reported, at time 1 and as compared to HC, iHUD exhibited similar SSRT but impaired d' [t(38.7)=2.37, p=.023], and lower anterior and dorsolateral PFC (aPFC, dlPFC) activity (p<.001). Importantly, at time 2, there were significant gains in aPFC and dlPFC activity in the iHUD (group*session interaction, p=.002); the former significantly correlated with increases in d' specifically in iHUD (p=.012). Conclusions and Relevance: Compared to HC, the aPFC and dlPFC impairments in the iHUD at time 1 were normalized at time 2, which was associated with individual differences in improvements in target detection sensitivity. For the first time in any drug addiction, these results indicate a treatment-mediated inhibitory control brain activity recovery. These neurobehavioral results highlight the aPFC and dlPFC as targets for intervention with a potential to enhance self-control recovery in heroin addiction.

Balancing the needs of the scientist and the subject in trauma research.

All participants in research are vulnerable to some extent. Survivors of trauma are often sought as participants for research studies and may be at an increased risk of emotional or psychological distress as a result of research participation. Scientists need to pay careful attention to issues of informed consent and the potential harm and benefits from research participation. This article explores challenges of selecting a sample, informed consent, and study continuation when conducting research with survivors of trauma.

Use of an audit in violence prevention research.

Auditing is an effective tool for articulating the trustworthiness and credibility of qualitative research. However, little information exists on how to conduct an audit. In this article, the authors illustrate their use of an audit team to explore the methods and preliminary findings of a study aimed at identifying the relevant and challenging problems experienced by urban teenagers. This study was the first in a series of studies to improve the ecological validity of violence prevention programs for high-risk urban teenagers, titled Identifying Essential Skills for Violence Prevention. The five phases of this audit were engaging the auditor, becoming familiar with the study, discussing methods and determining strengths and limitations, articulating audit findings, and planning subsequent research. Positioning the audit before producing final results allows researchers to address many study limitations, uncover potential sources of bias in the thematic structure, and systematically plan subsequent steps in an emerging design.

A profile of certification for pediatric nurses.

Over the past 15 years, more than 5,000 nurses have earned specialty nursing certification in pediatrics. While approximately 68% of these nurses have maintained this certification, many have allowed their certification to lapse. Surveys were conducted to describe differences between these two groups.

Sex trafficking and the exploitation of adolescents.

Human trafficking affects a surprisingly large number of adolescents around the globe. Women and girls make up the majority of sex trafficking victims. Nurses must be aware of sex trafficking as a form of sexual violence in the adolescent population. Nurses can play a role in identifying, intervening, and advocating for victims of human trafficking as they currently do for patients that are the victims of other types of violent crimes.

Analysis of the determinants of bba64 (P35) gene expression in Borrelia burgdorferi using a gfp reporter.

The bba64 (P35) gene of Borrelia burgdorferi, the agent of Lyme disease, encodes a surface-exposed lipoprotein. The expression of bba64 in vitro is tightly regulated and dependent on several environmental factors. In nature, its expression is induced in the tick vector during feeding and maintained during infection of the vertebrate host. The pattern of expression of bba64 suggests that it imparts a critical function to the pathogen. A previous study has shown that the expression of bba64 is down-regulated in the absence of RpoS, suggesting that the alternative sigma factor may be involved in its expression. A DNA-binding protein has also been shown to specifically recognize a sequence in the 5' regulatory region of the gene. Therefore, the contribution of these putative determinants to the differential expression of bba64 was investigated. The role of RpoS was critically evaluated by genetic complementation of the rpoS mutant using a chromosomally targeted copy of the wild-type gene. The results confirm that RpoS is indeed required for the expression of bba64. The role of the upstream DNA-binding site was examined using bba64 promoter-gfp transcriptional fusions in a shuttle vector. The DNA-binding site was studied by targeting mutations to an inverted repeat sequence (IRS), the most prominent feature within the binding site, as well as by deletion of the entire sequence upstream of the basal promoter. Quantitative assessment of gene expression demonstrated that neither the IRS nor the sequence upstream of the promoter was essential for expression. Moreover, the expression of the reporter (GFP) appeared to remain RpoS-dependent in all cases, based on the co-expression of GFP and OspC in a subpopulation of spirochaetes and the selective expression of GFP in the stationary phase. Collectively, the data indicate that RpoS is the sole determinant of differential bba64 expression in cultured spirochaetes.

Genital findings of women after consensual and nonconsensual intercourse.

After a sexual assault, forensic nurses, nurse practitioners, and physicians are called on to collect evidence, document any genital injuries, and testify about the significance of injuries. Recently, the scientific rigor of the research has been challenged in the courts.

Expression of the bmpB gene of Borrelia burgdorferi is modulated by two distinct transcription termination events.

bmp gene family 36 of Borrelia burgdorferi, the agent of Lyme disease, comprises four paralogs: bmpA, bmpB, bmpC, and bmpD. The bmpA and bmpB genes constitute an operon. All four genes have been found to be transcribed in cultured spirochetes. Expression from the bmpAB operon results in three distinct transcripts of 1.1, 1.6, and 2.4 kb, and the relative expression of bmpA mRNA is three- to fourfold greater than that of bmpB mRNA. However, thus far only expression of the BmpA protein has been demonstrated. Therefore, in this study we characterized the origins of the three transcripts and compared the relative expression of the BmpA and BmpB proteins. Northern blotting revealed that the three distinct transcripts originated from a single promoter located upstream of bmpA but terminated either 3' to the bmpA (1.1-kb RNA) or bmpB (2.4-kb RNA) gene or, most unusually, within the bmpB gene (1.6-kb RNA). Termination within the bmpB gene was associated with a functional Rho-independent transcription terminator. At the protein level, we also observed a 4.3-fold greater abundance of BmpA compared to that of BmpB. These studies identify a transcription termination mechanism in B. burgdorferi resulting in the disparate expression of the two genes of the bmpAB operon.

Two cases of anal fistula in girls evaluated for sexual abuse.

Anal fistulae are seen infrequently in the pediatric population. They are most commonly encountered in otherwise healthy boys less than 1 year of age. In the scant literature regarding pediatric anal fistulae, the majority of studies and case reports involve children less than 1 year of age. Within a 2-year period 2 school age girls presented to the authors' clinic with anal fistulae without history of a perianal abscess and without predisposing factors. Both of these children had a history of sexual abuse. We believe that in an otherwise healthy school age girl the appearance of an anal fistula should raise concern for the possibility of sexual abuse.