A care coordination program to support patients with hepatitis B virus at Kaiser Permanente Mid-Atlantic States.

BACKGROUND: Eliminating hepatitis B virus (HBV) is a significant worldwide challenge requiring innovative approaches for vaccination, screening, disease management, and the prevention of related conditions. Programs that support patients in accessing needed clinical services can help optimize access to preventive services and treatment resources for hepatitis B. METHODS: Here, we outline a coordinator-supported program (HBV Pathway) that connects patients infected with HBV to laboratory testing, imaging, and specialty care for treatment initiation and/or liver cancer surveillance (screening of high-risk patients for liver cancer). This study describes the HBV Pathway steps and reports sociodemographic factors of patients by initiation and completion. RESULTS: Results showed a 72.5% completion rate (defined as completing all Pathway steps including the final specialty visit) among patients who initiated the Pathway. Differences in completion were observed by age, race, ethnicity, and service area, with higher rates for younger ages, Asian race, non-Hispanic ethnicity, and lower rates for patients within one service area. Of those who completed the specialty visit, 59.5% were referred for hepatocellular carcinoma surveillance. CONCLUSIONS: The HBV Pathway offers dual benefits- care coordination support for patients to promote Pathway completion and a standardized testing and referral program to reduce physician burden. This program provides an easy and reliable process for patients and physicians to obtain updated clinical information and initiate treatment and/or liver cancer screening if needed.

Disrupted executive cerebro-cerebellar functional connectivity in alcohol use disorder.

BACKGROUND: Alcohol use disorder (AUD) affects 283 million people worldwide and its prevalence is increasing. Despite the role of the cerebellum in executive control and its sensitivity to alcohol, few studies have assessed its involvement in AUD-relevant functional networks. The goal of this study is to compare resting-state functional connectivity (FC) patterns in abstinent adults with a history of AUD and controls (CTL). We hypothesized that group differences in cerebro-cerebellar FC would be present, particularly within the frontoparietal/executive control network (FPN). METHODS: Twenty-eight participants completed a resting-state functional magnetic resonance imaging (rsfMRI) study. CTL participants had no history of AUD, comorbid psychological conditions, or recent heavy drinking and/or drug use. AUD participants had a history of AUD, with sobriety for at least 30 days prior to data collection. Multivariate pattern analysis, an agnostic, whole-brain approach, was used to identify regions with significant differences in FC between groups. Seed-based analyses were then conducted to determine the directionality and extent of these FC differences. Associations between FC strength and executive function were assessed using correlations with Wisconsin Card Sorting Test (WCST) performance. RESULTS: There were significant group differences in FC in nodes of the FPN, ventral attention network, and default mode network. Post hoc analyses predominantly identified FC differences within the cerebro-cerebellar FPN, with AUD showing significantly less FC within the FPN. In AUD, FC strength between FPN clusters identified in the multivariate pattern analysis (MVPA) analysis (Left Crus II, Right Frontal Cortex) was positively associated with performance on the WCST. CONCLUSIONS: Our results show less engagement of the FPN in individuals with AUD than in CTL. FC strength within this network was positively associated with performance on the WCST. These findings suggest that long-term heavy drinking alters cerebro-cerebellar FC, particularly within networks that are involved in executive function.

COVID-19 and Adolescent Outpatient Mental Health Service Utilization.

OBJECTIVE: The COVID-19 pandemic created challenges in accessing mental health (MH) services when adolescent well-being declined. Still, little is known about how the COVID-19 pandemic affected outpatient MH service utilization for adolescents. METHODS: Retrospective data were collected from electronic medical records of adolescents aged 12-17 years at Kaiser Permanente Mid-Atlantic States, an integrated health care system from January 2019 to December 2021. MH diagnoses included anxiety, mood disorder/depression, anxiety and mood disorder/depression, attention-deficit/hyperactivity disorder, or psychosis. We used interrupted time series analysis to compare MH visits and psychopharmaceutical prescribing before and after the COVID-19 onset. Analyses were stratified by demographics and visit modality. RESULTS: The study population of 8121 adolescents with MH visits resulted in a total of 61,971 (28.1%) of the 220,271 outpatient visits associated with an MH diagnosis. During 15,771 (7.2%) adolescent outpatient visits psychotropic medications were prescribed. The increasing rate of MH visits prior to COVID-19 was unaffected by COVID-19 onset; however, in-person visits declined by 230.5 visits per week (P < .001) from 274.5 visits per week coupled with a rise in virtual modalities. Rates of MH visits during the COVID-19 pandemic differed by sex, mental health diagnosis, and racial and ethnic identity. Psychopharmaceutical prescribing during MH visits declined beyond expected values by a mean of 32.8 visits per week (P < .001) at the start of the COVID-19 pandemic. CONCLUSIONS: A sustained switch to virtual visits highlights a new paradigm in care modalities for adolescents. Psychopharmaceutical prescribing declined requiring further qualitative assessments to improve the quality of access for adolescent MH.

Pride Medical at Capitol Hill: A New Lesbian, Gay, Bisexual, Transgender, Queer/Questioning plus (LGBTQ+) Patient Care Option at Kaiser Permanente Mid-Atlantic States.

When accessing medical care, lesbian, gay, bisexual, transgender, queer/questioning plus (LGBTQ+) individuals face many known challenges, including stigma, discrimination, and health disparities. Transgender and nonbinary individuals often encounter physicians and staff who are not knowledgeable about gender-affirming services and the transition journey. Finding an affirming physician can be a trial-and-error process, causing concern and uncertainty. In 2021, Kaiser Permanente Mid-Atlantic States (KPMAS) researchers published a study examining the gaps in care and experience for transgender and nonbinary patients within the KPMAS healthcare system. KPMAS realized an opportunity to both close the gaps in care identified by transgender and nonbinary patients and enhance services for the broader LGBTQ+ patient community by creating Pride Medical at Capitol Hill-an additional and optional care site for individuals who identify as LGBTQ+. During the analysis timeframe of 30 June 2021 through 30 November 2022, 586 patients accessed care through 763 visits. A total of 675 visits (88%) were for primary care and 88 (12%) for OB/GYN. Over 50% (n = 384) of total visits were conducted virtually. The plurality of patients seen identified as a man (35%; n = 204) and gay (30%; n = 176). Postvisit survey results showed that 92% of survey respondents strongly agreed that the physician treated them with courtesy and respect, and 72% of survey respondents rated their overall care as excellent. Survey results show high acceptability of this program among the patients served. Pride Medical does not carve out care. The program offers patients access to a more specialized team of physicians-a similar model to other specialties-that is easily found by the division name Pride Medical. Layering additional specialty divisions on top of existing care, for interested patients, could be an option for other medical groups and health systems seeking to offer additional options of care for interested LGBTQ+ patients.

Cerebro-Cerebellar Response to Sequence Violation in a Cognitive Task: an fMRI Study.

The phonological loop is part of Baddeley's verbal working memory (VWM) model that stores phonological information and refreshes its contents through an articulatory process. Many studies have reported the cerebellum's involvement during VWM tasks. In the motor literature, the cerebellum is thought to support smooth and rapid movement sequences through internal models that simulate the action of motor commands, then use the error signals generating from the discrepancy between the predicted and actual sensory consequences to adjust the motor system. Here, we hypothesize that a similar monitoring and error-driven adjustment process can be extended to VWM; specifically, the cerebellum checks for discrepancies between the predicted and actual articulatory process to ensure the accuracy and fluency of articulatory rehearsal. During neuroimaging, participants rehearsed a sequence of letters in sync with the presentation of a visual pacing stimulus (#) that was terminated by the occurrence of a probe letter. Participants judged whether the probe was the correct letter in the sequence (i.e., match trial), or deviated from the sequence (i.e., mismatch trial). Detection of sequence violation was not only associated with prolonged reaction time but also an increased activation in a left executive control network. Psychophysiological interaction was used to investigate whether the cerebellum interacts with the cerebral cortex for error monitoring and adjustments. We found increased functional connectivity between the right cerebellum and the cerebral cortex during mismatch relative to match probes, indicating sequence violation resulting in greater cerebellar connectivity with areas in the cerebral cortex involved in phonological sequencing.

Changes in Hemodynamic Response Function Resulting From Chronic Alcohol Consumption.

BACKGROUND: Functional MRI (fMRI) task-related analyses rely on an estimate of the brain's hemodynamic response function (HRF) to model the brain's response to events. Although changes in the HRF have been found after acute alcohol administration, the effects of heavy chronic alcohol consumption on the HRF have not been explored, and the potential benefits or pitfalls of estimating each individual's HRF on fMRI analyses of chronic alcohol use disorder (AUD) are not known. METHODS: Participants with AUD and controls (CTL) received structural, functional, and vascular scans. During fMRI, participants were cued to tap their fingers, and averaged responses were extracted from the motor cortex. Curve fitting on these HRFs modeled them as a difference between 2 gamma distributions, and the temporal occurrence of the main peak and undershoot of the HRF was computed from the mean of the first and second gamma distributions, respectively. RESULTS: ANOVA and regression analyses found that the timing of the HRF undershoot increased significantly as a function of total lifetime drinking. Although gray matter volume in the motor cortex decreased with lifetime drinking, this was not sufficient to explain undershoot timing shifts, and vascular factors measured in the motor cortex did not differ among groups. Comparison of random-effects analyses using custom-fitted and canonical HRFs for CTL and AUD groups showed better results throughout the brain for custom-fitted versus canonical HRFs for CTL subjects. For AUD subjects, the same was true except for the basal ganglia. CONCLUSIONS: These findings suggest that excessive alcohol consumption is associated with changes in the HRF undershoot. HRF changes could provide a possible biomarker for the effects of lifetime drinking on brain function. Changes in HRF topography affect fMRI activation measures, and subject-specific HRFs generally improve fMRI activation results.

Neural Substrates Underlying Eyeblink Classical Conditioning in Adults With Alcohol Use Disorders.

BACKGROUND: Excessive alcohol consumption produces changes in the brain that often lead to cognitive impairments. One fundamental form of learning, eyeblink classical conditioning (EBC), has been widely used to study the neurobiology of learning and memory. Participants with alcohol use disorders (AUD) have consistently shown a behavioral deficit in EBC. The present functional magnetic resonance imaging (fMRI) study is the first to examine brain function during conditioning in abstinent AUD participants and healthy participants. METHODS: AUD participants met DSM-IV criteria for alcohol dependence, had at least a 10-year history of heavy drinking, and were abstinent from alcohol for at least 30 days. During fMRI, participants received auditory tones that predicted the occurrence of corneal airpuffs. Anticipatory eyeblink responses to these tones were monitored during the experiment to assess learning-related changes. RESULTS: Behavioral results indicate that AUD participants showed significant conditioning deficits and that their history of lifetime drinks corresponded to these deficits. Despite this learning impairment, AUD participants showed hyperactivation in several key cerebellar structures (including lobule VI) during conditioning. For all participants, history of lifetime drinks corresponded with their lobule VI activity. CONCLUSIONS: These findings suggest that excessive alcohol consumption is associated with abnormal cerebellar hyperactivation and conditioning impairments.

Disruption of Cerebellar Prediction in Verbal Working Memory.

Mounting evidence suggests that the right cerebellum contributes to verbal working memory, but the functional role of this contribution remains unclear. In an established theory of motor control, the cerebellum is thought to predict sensory consequences of movements through an internal "forward model." Here, we hypothesize a similar predictive process can generalize to cerebellar non-motor function, and that the right cerebellum plays a predictive role that is beneficial for rapidly engaging the phonological loop in verbal working memory. To test this hypothesis, double-pulse transcranial magnetic stimulation (TMS) was administered over either the right cerebellum or right occipital lobe (control site), on half the trials, to interrupt the rehearsal of a 6-letter sequence. We found that cerebellar stimulation resulted in greater errors in participants' report of the letter in the current position. Additional analyses revealed that immediately after cerebellar TMS, participants were more likely to use out of date information to predict the next letter in the sequence. This pattern of errors is consistent with TMS causing a temporary disruption of state estimation and cerebellar forward model function, leading to prediction errors in the phonological loop.

Cerebellar contributions to sequence prediction in verbal working memory.

Verbal working memory is one of the most studied non-motor functions with robust cerebellar involvement. While the superior cerebellum (lobule VI) has been associated with articulatory control, the inferior cerebellum (lobule VIIIa) has been linked to phonological storage. The present study was aimed to elucidate the differential roles of these regions by investigating whether the cerebellum might contribute to verbal working memory via predictions based on sequence learning/detection. 19 healthy adult subjects completed an fMRI-based Sternberg task which included repeating and novel letter sequences that were phonologically similar or dissimilar. It was hypothesized that learning a repeating sequence of study letters would reduce phonological storage demand and associated right inferior cerebellar activations and that this effect would be modulated by phonological similarity of the study letters. Specifically, while increased phonological storage demand due to high phonological similarity was expected to be reflected in increased right inferior cerebellar activations for similar relative to dissimilar study letters, the reduction in activation for repeating relative to novel sequences was expected to be more profound for phonologically similar than for dissimilar study letters, especially at higher memory load. Results confirmed the typical effects of cognitive load (5 vs. 2 study letters) and phonological similarity in several cerebellar and neocortical brain regions as well as in behavioral data (accuracy and response time). Importantly, activations in superior and inferior cerebellar regions were differentially modulated as a function of similarity and sequence novelty, indicating that particularly lobule VIIIa may contribute to verbal working memory by generating predictions of letter sequences that reduce the likelihood of phonological loop failure before stored items need to be retrieved. The present study is consistent with other investigations that support prediction, which can be based on sequence learning or detection, as an overarching cerebellar function.

A neural mechanism of cognitive control for resolving conflict between abstract task rules.

Conflict between multiple sensory stimuli or potential motor responses is thought to be resolved via bias signals from prefrontal cortex (PFC). However, population codes in the PFC also represent abstract information, such as task rules. How is conflict between active abstract representations resolved? We used functional neuroimaging to investigate the mechanism responsible for resolving conflict between abstract representations of task rules. Participants performed two different tasks based on a cue. We manipulated the degree of conflict at the task-rule level by training participants to associate the color and shape dimensions of the cue with either the same task rule (congruent cues) or different ones (incongruent cues). Phonological and semantic tasks were used in which performance depended on learned, abstract representations of information, rather than sensory features of the target stimulus or on any habituated stimulus-response associations. In addition, these tasks activate distinct regions that allowed us to measure magnitude of conflict between tasks. We found that incongruent cues were associated with increased activity in several cognitive control areas, including the inferior frontal gyrus, inferior parietal lobule, insula, and subcortical regions. Conflict between abstract representations appears to be resolved by rule-specific activity in the inferior frontal gyrus that is correlated with enhanced activity related to the relevant information. Furthermore, multi-voxel pattern analysis of the activity in the inferior frontal gyrus was shown to carry information about both the currently relevant rule (semantic/phonological) and the currently relevant cue context (color/shape). Similar to models of attentional selection of conflicting sensory or motor representations, the current findings indicate part of the frontal cortex provides a bias signal, representing task rules, that enhances task-relevant information. However, the frontal cortex can also be the target of these bias signals in order to enhance abstract representations that are independent of particular stimuli or motor responses.

Exposure to parental verbal abuse is associated with increased gray matter volume in superior temporal gyrus.

OBJECTIVE: Exposure to parental verbal aggression (PVA) during childhood increases risk for the development of psychopathology, particularly mood and anxiety disorders. Other forms of childhood abuse have been found to be associated with alterations in brain structure. The aim of this study was to ascertain whether exposure to PVA was associated with discernible effects on brain morphology. METHODS: Optimized voxel-based morphometry was performed on 21 unmedicated, right-handed subjects (18-25 years) with histories of PVA and 19 psychiatrically healthy controls of comparable age and gender. Group differences in gray matter volume (GMV)--covaried by age, gender, parental education, financial stress, and total GMV--were assessed using high-resolution, T1-weighted, volumetric MRI data sets (Siemens 3T trio scanner). RESULTS: GMV was increased by 14.1% in the left superior temporal gyrus (STG, BA 22) (P=0.004, corrected cluster level). GMV in this cluster was associated most strongly with levels of maternal (ß=0.544, P<0.0001) and paternal (ß=0.300, P<0.02) verbal aggression and inversely associated with parental education (ß=-0.577, P<0.0001). CONCLUSION: Previous studies have demonstrated an increase in STG GMV in children with abuse histories, and found a reduction in fractional anisotropy in the arcuate fasciculus connecting Wernicke's and frontal areas in young adults exposed to PVA. These findings and the present results suggest that the development of auditory association cortex involved in language processing may be affected by exposure to early stress and/or emotionally abusive language.

Object working memory performance depends on microstructure of the frontal-occipital fasciculus.

Re-entrant circuits involving communication between the frontal cortex and other brain areas have been hypothesized to be necessary for maintaining the sustained patterns of neural activity that represent information in working memory, but evidence has so far been indirect. If working memory maintenance indeed depends on such temporally precise and robust long-distance communication, then performance on a delayed recognition task should be highly dependent on the microstructural integrity of white-matter tracts connecting sensory areas with prefrontal cortex. This study explored the effect of variations in white-matter microstructure on working memory performance in two separate groups of participants: patients with multiple sclerosis and age- and sex-matched healthy adults. Functional magnetic resonance imaging was performed to reveal cortical regions involved in spatial and object working memory, which, in turn, were used to define specific frontal to extrastriate white-matter tracts of interest via diffusion tensor tractography. After factoring out variance due to age and the microstructure of a control tract (the corticospinal tract), the number of errors produced in the object working memory task was specifically related to the microstructure of the inferior frontal-occipital fasciculus. This result held for both groups, independently, providing a within-study replication with two different types of white-matter structural variability: multiple sclerosis-related damage and normal variation. The results demonstrate the importance of interactions between specific regions of the prefrontal cortex and sensory cortices for a nonspatial working memory task that preferentially activates those regions.

Harsh corporal punishment is associated with increased T2 relaxation time in dopamine-rich regions.

Harsh corporal punishment (HCP) was defined as frequent parental administration of corporal punishment (CP) for discipline, with occasional use of objects such as straps, or paddles. CP is linked to increased risk for depression and substance abuse. We examine whether long-term exposure to HCP acts as sub-traumatic stressor that contributes to brain alterations, particularly in dopaminergic pathways, which may mediate their increased vulnerability to drug and alcohol abuse. Nineteen young adults who experienced early HCP but no other forms of maltreatment and twenty-three comparable controls were studied. T2 relaxation time (T2-RT) measurements were performed with an echo planar imaging TE stepping technique and T2 maps were calculated and analyzed voxel-by-voxel to locate regional T2-RT differences between groups. Previous studies indicated that T2-RT provides an indirect index of resting cerebral blood volume. Region of interest (ROI) analyses were also conducted in caudate, putamen, nucleus accumbens, anterior cingulate cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus and cerebellar hemispheres. Voxel-based relaxometry showed that HCP was associated with increased T2-RT in right caudate and putamen. ROI analyses also revealed increased T2-RT in dorsolateral prefrontal cortex, substantia nigra, thalamus and accumbens but not globus pallidus or cerebellum. There were significant associations between T2-RT measures in dopamine target regions and use of drugs and alcohol, and memory performance. Alteration in the paramagnetic or hemodynamic properties of dopaminergic cell body and projection regions were observed in subjects with HCP, and these findings may relate to their increased risk for drug and alcohol abuse.

Hurtful words: association of exposure to peer verbal abuse with elevated psychiatric symptom scores and corpus callosum abnormalities.

OBJECTIVE: Previous studies have shown that exposure to parental verbal abuse in childhood is associated with higher rates of adult psychopathology and alterations in brain structure. In this study the authors sought to examine the symptomatic and neuroanatomic effects, in young adulthood, of exposure to peer verbal abuse during childhood. METHOD: A total of 848 young adults (ages 18-25 years) with no history of exposure to domestic violence, sexual abuse, or parental physical abuse rated their childhood exposure to parental and peer verbal abuse and completed a self-report packet that included the Kellner Symptom Questionnaire, the Limbic Symptom Checklist-33, and the Dissociative Experiences Scale. Diffusion tensor images were collected for a subset of 63 young adults with no history of abuse or exposure to parental verbal abuse selected for varying degrees of exposure to peer verbal abuse. Images were analyzed using tract-based spatial statistics. RESULTS: Analysis of covariance revealed dose-dependent effects of peer verbal abuse on anxiety, depression, anger-hostility, dissociation, "limbic irritability," and drug use. Peer and parental verbal abuse were essentially equivalent in effect size on these ratings. Path analysis indicated that peer verbal abuse during the middle school years had the most significant effect on symptom scores. Degree of exposure to peer verbal abuse correlated with increased mean and radial diffusivity and decreased fractional anisotropy in the corpus callosum and the corona radiata. CONCLUSIONS: These findings parallel results of previous reports of psychopathology associated with childhood exposure to parental verbal abuse and support the hypothesis that exposure to peer verbal abuse is an aversive stimulus associated with greater symptom ratings and meaningful alterations in brain structure.

Reduced prefrontal cortical gray matter volume in young adults exposed to harsh corporal punishment.

OBJECTIVE: Harsh corporal punishment (HCP) during childhood is a chronic, developmental stressor associated with depression, aggression and addictive behaviors. Exposure to traumatic stressors, such as sexual abuse, is associated with alteration in brain structure, but nothing is known about the potential neurobiological consequences of HCP. The aim of this study was to investigate whether HCP was associated with discernible alterations in gray matter volume (GMV) using voxel-based morphometry (VBM). METHODS: 1455 young adults (18-25 years) were screened to identify 23 with exposure to HCP (minimum 3 years duration, 12 episodes per year, frequently involving objects) and 22 healthy controls. High-resolution T1-weighted MRI datasets were obtained using Siemens 3 T trio scanner. RESULTS: GMV was reduced by 19.1% in the right medial frontal gyrus (medial prefrontal cortex; MPFC, BA10) (P=0.037, corrected cluster level), by 14.5% in the left medial frontal gyrus (dorsolateral prefrontal cortex; DLPFC, BA9) (P=0.015, uncorrected cluster level) and by 16.9% in the right anterior cingulate gyrus (BA24) (P<0.001, uncorrected cluster level) of HCP subjects. There were significant correlations between GMV in these identified regions and performance IQ on the WAIS-III. CONCLUSIONS: Exposing children to harsh HCP may have detrimental effects on trajectories of brain development. However, it is also conceivable that differences in prefrontal cortical development may increase risk of exposure to HCP.