Assessing Area-Level Deprivation as a Proxy for Individual-Level Social Risks.

INTRODUCTION: Concerns about the opportunity costs of social screening initiatives have led some healthcare organizations to consider using social deprivation indices (area-level social risks) as proxies for self-reported needs (individual-level social risks). Yet, little is known about the effectiveness of such substitutions across different populations. METHODS: This analysis explores how well the highest quartile (cold spot) of three different area-level social risk measures-the Social Deprivation Index, Area Deprivation Index, and Neighborhood Stress Score-corresponds with six individual-level social risks and three risk combinations among a national sample of Medicare Advantage members (N=77,503). Data were derived from area-level measures and cross-sectional survey data collected between October 2019 and February 2020. Agreement between individual and individual-level social risks, sensitivity values, specificity values, positive predictive values, and negative predictive values was calculated for all measures in summer/fall 2022. RESULTS: Agreement between area and individual-level social risks ranged from 53% to 77%. Sensitivity for each risk and risk category never exceeded 42%; specificity values ranged from 62% to 87%. Positive predictive values ranged from 8% to 70%, and negative predictive values ranged from 48% to 93%. There were modest performance discrepancies across area-level measures. CONCLUSIONS: These findings provide additional evidence that area-level deprivation indices may be inconsistent indicators of individual-level social risks, supporting policy efforts to promote individual-level social screening programs in healthcare settings.

Association of Health-Related Social Needs With Quality and Utilization Outcomes in a Medicare Advantage Population With Diabetes.

Importance: Recent research highlights the association of social determinants of health with health outcomes of patients with type 2 diabetes (T2D). Objective: To examine associations between health-related social needs (HRSNs) and health care quality and utilization outcomes in a Medicare Advantage population with T2D. Design, Setting, and Participants: This cross-sectional study used medical and pharmacy claims data from 2019. An HRSN survey was given between October 16, 2019, and February 29, 2020, to Medicare Advantage beneficiaries. Inclusion criteria were diagnosis of T2D, age of 20 to 89 years, continuous Medicare Advantage enrollment in 2019, and response to the HRSN survey. Data were analyzed between June 2021 and January 2022. Exposures: Enrollment in Medicare Advantage, diagnosis of T2D, and completion of a survey on HRSNs. Main Outcomes and Measures: Quality outcomes included diabetes medication adherence, statin adherence, completion of a glycated hemoglobin (HbA1c) laboratory test in the past 12 months, and controlled HbA1c. Utilization outcomes included all-cause hospitalization, potentially avoidable hospitalization, emergency department discharge, and readmission. Results: Of the 21 528 Medicare Advantage beneficiaries with T2D included in the study (mean [SD] age, 71.0 [8.3] years; 55.4% women), most (56.9%) had at least 1 HRSN. Among the population with T2D reporting HRSNs, the most prevalent were financial strain (73.6%), food insecurity (47.5%), and poor housing quality (39.1%). In adjusted models, loneliness (odds ratio [OR], 0.85; 95% CI, 0.73-0.99), lack of transportation (OR, 0.80; 95% CI, 0.69-0.92), utility insecurity (OR, 0.86; 95% CI, 0.76-0.98), and housing insecurity (OR, 0.78; 95% CI, 0.67-0.91) were each associated with lower diabetes medication adherence. Loneliness and lack of transportation were associated with increased emergency visits (marginal effects of 173.0 [95% CI, 74.2-271.9] and 244.6 [95% CI, 150.4-338.9] emergency visits per 1000 beneficiaries for loneliness and transportation, respectively). Food insecurity was the HRSN most consistently associated with higher acute care utilization (marginal effects of 84.6 [95% CI, 19.8-149.4] emergency visits, 30.4 [95% CI, 9.5-51.3] inpatient encounters, and 17.1 [95% CI, 4.7-29.5] avoidable hospitalizations per 1000 beneficiaries). Conclusions and Relevance: In this cross-sectional study of Medicare Advantage beneficiaries with T2D, some HRSNs were associated with care quality and utilization. The results of the study may be used to direct interventions to the social needs most associated with T2D health outcomes and inform policy decisions at the insurance plan and community level.

Association Between Community-Level Social Risk and Spending Among Medicare Beneficiaries: Implications for Social Risk Adjustment and Health Equity.

Importance: Payers are increasingly using approaches to risk adjustment that incorporate community-level measures of social risk with the goal of better aligning value-based payment models with improvements in health equity. Objective: To examine the association between community-level social risk and health care spending and explore how incorporating community-level social risk influences risk adjustment for Medicare beneficiaries. Design, Setting, and Participants: Using data from a Medicare Advantage plan linked with survey data on self-reported social needs, this cross-sectional study estimated health care spending health care spending was estimated as a function of demographics and clinical characteristics, with and without the inclusion of Area Deprivation Index (ADI), a measure of community-level social risk. The study period was January to December 2019. All analyses were conducted from December 2021 to August 2022. Exposures: Census block group-level ADI. Main Outcomes and Measures: Regression models estimated total health care spending in 2019 and approximated different approaches to social risk adjustment. Model performance was assessed with overall model calibration (adjusted R2) and predictive accuracy (ratio of predicted to actual spending) for subgroups of potentially vulnerable beneficiaries. Results: Among a final study population of 61 469 beneficiaries (mean [SD] age, 70.7 [8.9] years; 35 801 [58.2%] female; 48 514 [78.9%] White; 6680 [10.9%] with Medicare-Medicaid dual eligibility; median [IQR] ADI, 61 [42-79]), ADI was weakly correlated with self-reported social needs (r = 0.16) and explained only 0.02% of the observed variation in spending. Conditional on demographic and clinical characteristics, every percentile increase in the ADI (ie, more disadvantage) was associated with a $11.08 decrease in annual spending. Directly incorporating ADI into a risk-adjustment model that used demographics and clinical characteristics did not meaningfully improve model calibration (adjusted R2 = 7.90% vs 7.93%) and did not significantly reduce payment inequities for rural beneficiaries and those with a high burden of self-reported social needs. A postestimation adjustment of predicted spending for dual-eligible beneficiaries residing in high ADI areas also did not significantly reduce payment inequities for rural beneficiaries or beneficiaries with self-reported social needs. Conclusions and Relevance: In this cross-sectional study of Medicare beneficiaries, the ADI explained little variation in health care spending, was negatively correlated with spending conditional on demographic and clinical characteristics, and was poorly correlated with self-reported social risk factors. This prompts caution and nuance when using community-level measures of social risk such as the ADI for social risk adjustment within Medicare value-based payment programs.

Association Between Self-reported Health-Related Social Needs and Acute Care Utilization Among Older Adults Enrolled in Medicare Advantage.

Importance: There is increased focus on identifying and addressing health-related social needs (HRSNs). Understanding how different HRSNs relate to different health outcomes can inform targeted, evidence-based policies, investments, and innovations to address HRSNs. Objective: To examine the association between self-reported HRSNs and acute care utilization among older adults enrolled in Medicare Advantage. Design Setting and Participants: This cross-sectional study used data from a large, national survey of Medicare Advantage beneficiaries to identify the presence of HRSNs. Survey data were linked to medical claims, and regression models were used to estimate the association between HRSNs and rates of acute care utilization from January 1, 2019, through December 31, 2019. Exposures: Self-reported HRSNs, including food insecurity, financial strain, loneliness, unreliable transportation, utility insecurity, housing insecurity, and poor housing quality. Main Outcomes and Measures: All-cause hospital stays (inpatient admissions and observation stays), avoidable hospital stays, all-cause emergency department (ED) visits, avoidable ED visits, and 30-day readmissions. Results: Among a final study population of 56 155 Medicare Advantage beneficiaries (mean [SD] age, 74.0 [5.8] years; 32 779 [58.4%] women; 44 278 [78.8%] White; and 7634 [13.6%] dual eligible for Medicaid), 27 676 (49.3%) reported 1 or more HRSNs. Health-related social needs were associated with statistically significantly higher rates of all utilization measures, with the largest association observed for avoidable hospital stays (incident rate ratio for any HRSN, 1.53; 95% CI, 1.35-1.74; P < .001). Compared with beneficiaries without HRSNs, beneficiaries with an HRSN had a 53.3% higher rate of avoidable hospitalization (incident rate ratio, 1.53; 95% CI, 1.35-1.74; P < .001). Financial strain and unreliable transportation were each independently associated with increased rates of hospital stays (marginal effects of 26.5 [95% CI, 14.2-38.9] and 51.2 [95% CI, 30.7-71.8] hospital stays per 1000 beneficiaries, respectively). All HRSNs, except for utility insecurity, were independently associated with increased rates of ED visits. Unreliable transportation had the largest association with increased hospital stays and ED visits, with marginal effects of 51.2 (95% CI, 30.7-71.8) and 95.5 (95% CI, 65.3-125.8) ED visits per 1000 beneficiaries, respectively. Only unreliable transportation and financial strain were associated with increased rates of 30-day readmissions, with marginal effects of 3.3% (95% CI, 2.0%-4.0%) and 0.4% (95% CI, 0.2%-0.6%), respectively. Conclusions and Relevance: In this cross-sectional study of older adults enrolled in Medicare Advantage, self-reported HRSNs were common and associated with statistically significantly increased rates of acute care utilization, with variation in which HRSNs were associated with different utilization measures. These findings provide evidence of the unique association between certain HRSNs and different types of acute care utilization, which could help refine the development and targeting of efforts to address HRSNs.

Positive association between neighborhood retail alcohol outlet access and hospital admissions for alcohol withdrawal syndrome in New Orleans.

Objectives: We used treatment for alcohol withdrawal syndrome as an objective surrogate marker to investigate the relationship between alcohol-related health outcomes and home neighborhood alcohol outlet density and alcohol advertising density.Methods: Mixed effects logistic regression examined whether alcohol outlet density or alcohol advertisement density within either one-quarter mile or one-half mile of individuals' home address was associated with treatment for alcohol withdrawal.Results: Adjusted models showed outlet and advertising density, particularly off-sale outlet density within one-quarter mile of the home, increased the risk of hospital admission for alcohol withdrawal syndrome (AOR = 1.15).Conclusion/impact: These data inform public policy initiatives to reduce the harmful effects of alcohol by regulating the neighborhood alcohol environment.

The Patient-Centered Outcomes Research Network Antibiotics and Childhood Growth Study: Implementing Patient Data Linkage.

PCORnet, the Patient-Centered Outcomes Research Network, is comprised of health systems and health plans that transform electronic health records (EHRs) and claims data to a common data model (CDM) to facilitate real-world clinical research. Because patients receive health care in multiple care delivery settings, linking health records across systems and health plan claims would provide a more comprehensive and accurate picture of health care for patients. The current study expanded on a PCORnet Antibiotics and Childhood Growth (ABX) study to (1) identify and implement a privacy-preserving patient linkage solution among a clinical data research network and a health plan network within the ABX Study, and (2) assess overlap in prescribed and dispensed antibiotics and additional data gained from claims among the linked patients. This manuscript describes the linkage process and resulting overlap analysis. The authors identified 549 patients from the EHR record study cohort who had claims records with the health plan. Sixty percent (n = 329) of patients had consistent antibiotic exposure data across the 2 sources, indicating antibiotic exposure (44.3%) or nonexposure (15.7%). Among total antibiotic prescribing records, 43.1% had a matched claims record for dispensing within 60 days. Among antibiotic dispense records 26.5% were not associated with a prescribing record in the linked health systems. These findings showcase the feasibility of linking health plan claims data to PCORnet CDM in a privacy-preserving manner while also demonstrating continued gaps in data that may occur. The study highlights the importance of combining multiple health data sources for comprehensive clinical research.

Cortical substrates of cue-reactivity in multiple substance dependent populations: transdiagnostic relevance of the medial prefrontal cortex.

Elevated drug-cue elicited brain activity is one of the most widely cited, transdiagnostically relevant traits of substance dependent populations. These populations, however, are typically studied in isolation. The goal of this study was to prospectively investigate the spatial topography of drug-cue reactivity in a large set of individuals dependent on either cocaine, alcohol, or nicotine. Functional MRI data was acquired from 156 substance dependent individuals (55 cocaine, 53 alcohol, and 48 nicotine) as they performed a standardized drug-cue exposure task. Clusters of significant activation to drug-cues relative to neutral cues ('hot spots') were isolated for each individual. K-means clustering was used to classify the spatial topography of the hotspots in the data set. The percentage of hotspots that would be reached at several distances (2-5 cm) of transcranial magnetic stimulation (TMS) were calculated. One hundred and three participants had at least one cluster of significant frontal cortex activity (66%). K-means revealed 3 distinct clusters within the medial prefrontal cortex (MPFC), left inferior frontal gyrus/insula, right premotor cortex. For the group as a whole (and for alcohol users and nicotine users independently), medial prefrontal cortex (BA 10) was the location of the greatest number of hotspots. The frontal pole was cortical location closest to the largest percentage of hotspots. While there is individual variability in the location of the cue-elicited 'hot spot' these data demonstrate that elevated BOLD signal to drug cues in the MPFC may be a transdiagnostic endophenotype of addiction which may also be a fruitful neuromodulation target.

School Lunch Consumption Among 3 Food Service Providers in New Orleans.

BACKGROUND: Louisiana has one of the highest rates of overweight and obese children in the United States. The Healthy School Food Collaborative (HSFC) was created to allow New Orleans's schools to select their own healthy school Food Service Provider (FSP) with requirements for higher nutritional standards than traditional options. The goal of this cross-sectional study was to examine whether HSFC membership was associated with lunch consumption rates in elementary school children. METHODS: An 8-week plate waste study examining 18,070 trays of food among fourth and fifth graders was conducted. Participants included 7 schools and the 3 FSPs (2 HSFC and 1 non-HSFC member) that serviced them. Mixed models analysis examined whether consumption rates of food items differed among FSPs. RESULTS: On average, students consumed 307 cal during lunch. Analyses showed significant differences in consumption rates of entrée, vegetables, fruit, and milk between the 3 FSPs (p < .01). The highest consumption rate was among entrées at 65%. One HSFC provider had consumption levels consistent with the non-HSFC FSP. CONCLUSIONS: Overall, students consumed less than 60% of the US Department of Agriculture recommended calories for school lunch. While overall caloric consumption was higher among the non-HSFC schools, interventions to increase lunch consumption across all schools are needed.

Factors Associated with School Lunch Consumption: Reverse Recess and School "Brunch".

BACKGROUND: While school foods have become healthier under the Healthy, Hunger Free Kids Act, research suggests there is still substantial food waste in cafeterias. It is therefore necessary to study factors that can impact food consumption, including holding recess before lunch ("reverse recess") and starting lunch periods very early or very late. OBJECTIVE: This study examined the association between the timing of recess (pre-lunch vs post-lunch recess), the timing of the lunch period, and food consumed by students at lunch. DESIGN: We conducted a secondary data analysis from a repeated cross-sectional design. PARTICIPANTS/SETTING: An 8-week plate waste study examining 20,183 trays of food was conducted in New Orleans, LA, in 2014. The study involved 1,036 fourth- and fifth-grade students from eight public schools. MAIN OUTCOME MEASURES: We measured percent of entrées, fruit, vegetables, and milk consumed by students at lunch. STATISTICAL ANALYSES PERFORMED: We used mixed-model analyses, controlling for student sex, grade, and the timing of the lunch period, and examined the association between reverse recess and student lunch consumption. Mixed-model analyses controlling for student sex, grade, and recess status examined whether the timing of the lunch period was associated with student lunch consumption. RESULTS: On average, students with reverse recess consumed 5.1% more of their fruit than students with post-lunch recess (P=0.009), but there were no significant differences in entrées, vegetables, or milk intake. Compared to students with "midday" lunch periods, on average students with "early" lunch periods consumed 5.8% less of their entrées (P<0.001) and 4.5% less of their milk (P=0.047). Students with "late" lunch periods consumed 13.8% less of their entrées (P<0.001) and 15.9% less of their fruit (P<0.001). CONCLUSIONS: Reverse recess was associated with increased fruit consumption. "Early" lunch periods were associated with decreased entrée and milk consumption, and "late" lunch periods were associated with decreased entrée and fruit consumption. Additional research is recommended to determine whether these associations are causal.

Assessing the Relationship Between Mental Distress and Tobacco Use in Post-Katrina and Rita Louisiana.

BACKGROUND: The relationship between mental health status and smoking is complicated and often confounded by bi-directionality, yet most research on this relationship assumes exogeneity. OBJECTIVES: The goal of this article is to implement an instrumental variable approach to (1) test the exogeneity assumption and (2) report on the association between mental health status and smoking post-disaster. METHODS: This analysis utilizes the 2006 and 2007 Louisiana Behavioral Risk Factor Surveillance Survey to examine the link between mental distress and smoking in areas affected by Hurricanes Katrina and Rita. Residence in a hurricane-affected parish (county) was used as an instrumental variable for mental distress. RESULTS: Just over 22% of the sample resided in a hurricane-affected parish. Residents of hurricane-affected parishes were significantly more likely to report occasional and frequent mental distress. Residence in a hurricane-affected parish was not significantly associated with smoking status. With residence established as a salient instrumental variable for mental distress, the exogeneity assumption was tested and confirmed in this sample. A dose-response relationship existed between mental distress and smoking, with smoking prevalence increasing directly (and non-linearly) with mental distress. CONCLUSIONS: In this sample, the relationship between mental distress and smoking status was exogenous and followed a dose-response relationship, suggesting that the disasters did not result in an uptake of smoking initiation, but that the higher amounts of mental distress may lead to increased use among smokers. The findings suggest that tobacco control programs should devise unique strategies to address mentally distressed populations.

Developing Repetitive Transcranial Magnetic Stimulation (rTMS) as a Treatment Tool for Cocaine Use Disorder: a Series of Six Translational Studies.

PURPOSE OF THE REVIEW: Cocaine dependence is a chronic and relapsing disorder which is particularly resistant to behavioral or pharmacologic treatment, and likely involves multiple dysfunctional frontal-striatal circuits. Through advances in preclinical research in the last decade, we now have an unprecedented understanding of the neural control of drug-taking behavior. In both rodent models and human clinical neuroimaging studies, it is apparent that medial frontal-striatal limbic circuits regulate drug cue-triggered behavior. While non-human preclinical studies can use invasive stimulation techniques to inhibit drug cue-evoked behavior, in human clinical neuroscience, we are pursuing non-invasive theta burst stimulation (TBS) as a novel therapeutic tool to inhibit drug cue-associated behavior. RECENT FINDINGS: Our laboratory and others have spent the last 7 years systematically and empirically developing a non-invasive, neural circuit-based intervention for cocaine use disorder. Utilizing a multimodal approach of functional brain imaging and brain stimulation, we have attempted to design and optimize a repetitive transcranial magnetic stimulation treatment protocol for cocaine use disorder. This manuscript will briefly review the data largely from our own lab that motivated our selection of candidate neural circuits, and then summarize the results of six studies, culminating in the first double-blinded, sham-controlled clinical trial of TMS as a treatment adjuvant for treatment-engaged cocaine users (10 sessions, medial prefrontal cortex, 110% resting motor threshold, continuous theta burst stimulation, 3600 pulses/session). SUMMARY: The intent of this review is to highlight one example of a systematic path for TMS treatment development in patients. This path is not necessarily optimal, exclusive, or appropriate for every neurologic or psychiatric disease. Rather, it is one example of a reasoned, empirically derived pathway which we hope will serve as scaffolding for future investigators seeking to develop TMS treatment protocols.

Measuring the Effect of Environmental Tobacco Smoke on Lung Function: Results From a Small Observational Investigation of Acute Exposure.

OBJECTIVE: Exposure to environmental tobacco smoke (ETS) in smoky venues puts patrons and employees at risk for immediate respiratory symptoms. Although much literature focuses on outcomes associated with chronic ETS exposure, the current study assesses changes in lung function after acute exposure. METHODS: Ninety-six nonsmoking, healthy adults were exposed to ETS at a bar. Lung function [eg, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1)] was assessed at baseline, immediately after 3 hours of ETS exposure, and 2 hours after exiting the bar. PM2.5 recordings were also measured. RESULTS: Repeated-measures analysis of variance found significant decreases in FEV1, FVC and FEF25-75%, and peak expiratory flow after ETS exposure compared with baseline that remained significantly decreased after a 2-hour recovery period. CONCLUSIONS: Acute exposure to ETS in a natural environment significantly attenuates lung function. A subgroup experienced heightened reductions in lung function.

Attenuated neural response to emotional cues in cocaine-dependence: a preliminary analysis of gender differences.

BACKGROUND: Cocaine users often report a loss of arousal for nondrug-related stimuli, which may contribute to their response to drug-related rewards. However, little is known about users' neural reactivity to emotional nondrug-related stimuli and the potential influence of gender. OBJECTIVES: Test the hypotheses that cocaine-dependent individuals have an attenuated neural response to arousing stimuli relative to controls and that this difference is amplified in women. METHODS: The brain response to typically arousing positive and negative images as well as neutral images from the International Affective Picture System was measured in 40 individuals (20 non-treatment seeking cocaine-dependent and 20 age- and gender-matched control participants; 50% of whom were women). Images were displayed for 4 s each in blocks of five across two 270-second runs. General linear models assessed within and between group activation differences for the emotional images. RESULTS: Cocaine-dependent individuals had a significantly lower response to typically arousing positive and negative images than controls, with attenuated neural activity present in the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). Analyses by gender revealed less mPFC/ACC activation among female users, but not males, for both positive and negative images. CONCLUSION: The dampened neural response to typically arousing stimuli among cocaine-dependent polydrug users suggests decreased salience processing for nondrug stimuli, particularly among female users. This decreased responding is consistent with data from other substance using populations and suggests that this may be a general feature of addiction. Amplifying the neural response to naturally arousing nondrug-related reinforcers may present an opportunity for unique behavioral and brain stimulation therapies.

Mobilization of Medial and Lateral Frontal-Striatal Circuits in Cocaine Users and Controls: An Interleaved TMS/BOLD Functional Connectivity Study.

The integrity of frontal-striatal circuits is an area of great interest in substance dependence literature, particularly as the field begins to develop neural circuit-specific brain stimulation treatments for these individuals. Prior research indicates that frontal-striatal connectivity is disrupted in chronic cocaine users in a baseline (resting) state. It is unclear, however, if this is also true when these circuits are mobilized by an external source. In this study, we measured the functional and structural integrity of frontal-striatal circuitry involved in limbic arousal and executive control in 36 individuals-18 cocaine-dependent individuals with a history of failed quit attempts and 18 age-matched controls. This was achieved by applying a transcranial magnetic stimulation to the medial prefrontal cortex (Brodmann area 10) and the dorsolateral prefrontal cortex (lateral Brodmann 9) while participants rested in the MRI scanner (TMS/BOLD imaging). Relative to the controls, cocaine users had a lower ventral striatal BOLD response to MPFC stimulation. The dorsal striatal BOLD response to DLPFC stimulation however was not significantly different between the groups. Among controls, DLPFC stimulation led to a reciprocal attenuation of MPFC activity (BA 10), but this pattern did not exist in cocaine users. No relationship was found between regional diffusion metrics and functional activity. Considered together these data suggest that, when engaged, cocaine users can mobilize their executive control system similar to controls, but that the 'set point' for mobilizing their limbic arousal system has been elevated-an interpretation consistent with opponent process theories of addiction.

Individualized real-time fMRI neurofeedback to attenuate craving in nicotine-dependent smokers.

BACKGROUND: Cue-induced craving plays an important role in relapse, and the neural correlates of cue-induced craving have been elucidated using fMRI. This study examined the utility of real-time fMRI (rtfMRI) neurofeedback to strengthen self-regulation of craving-related neural activation and cue-reactivity in cigarette smokers. METHODS: Nicotine-dependent smokers were randomized to rtfMRI neurofeedback or to a no-feedback control group. Participants completed 3 neuroimaging visits. Within each visit, an initial run during which smoking-related cues were used to provoke craving, an individualized craving-related region of interest (ROI) in the prefrontal cortex or anterior cingulate cortex was identified. In the rtfMRI group, activity from the ROI was fed back via a visual display during 3 subsequent runs while participants were instructed to reduce craving during cue exposure. The control group had an identical experience with no feedback provided. RESULTS: Forty-four nicotine-dependent smokers were recruited to participate in our study; data from the 33 participants who completed a 1-week follow-up visit were included in the analysis. Subjective craving ratings and cue-induced brain activation were lower in the rtfMRI group than in the control group. LIMITATIONS: As participants were not seeking treatment, clinical outcomes are lacking. CONCLUSION: Nicotine-dependent smokers receiving rtfMRI feedback from an individualized ROI attenuated smoking cue-elicited neural activation and craving, relative to a control group. Further studies are needed in treatment-seeking smokers to determine if this intervention can translate into a clinically meaningful treatment modality.

Right anterior insula connectivity is important for cue-induced craving in nicotine-dependent smokers.

The insula has been implicated in cue-induced craving and relapse in nicotine-dependent tobacco cigarette smokers. The aims of the present study were to identify brain regions that exhibit greater functional connectivity with the right anterior insula in response to smoking cues than to neutral cues and the role of functional connectivity between these regions in mediating cue-induced craving in healthy (free of axis I psychiatric disorders) nicotine-dependent tobacco cigarette smokers. Functional magnetic resonance imaging data were collected from 63 healthy nicotine-dependent smokers viewing blocks of smoking and neutral cues. Craving ratings were obtained after each block. A psychophysiologic interaction approach was used to identify regions that exhibited significantly greater functional connectivity with the right anterior insula (seed) during the smoking cues than during the neutral (corrected cluster thresholding, Z > 2.3, P = 0.05). Parameter estimates of the interaction effects from each region were regressed against the mean cue-induced craving scores. Significant task by seed interactions were observed in two clusters centered in the bilateral precuneus and left angular gyrus. The strength of connectivity between the right anterior insula and the precuneus, which is involved interoceptive processing and self-awareness, was positively correlated with the magnitude of the craving response to the smoking cues (r(2) = 0.15; P < 0.01). These data suggest that among smokers, cue-induced craving may be a function of connectivity between two regions involved in interoception and self-awareness. Moreover, treatment strategies that incorporate mindful attention may be effective in attenuating cue-induced craving and relapse in nicotine-dependent smokers.

Visual cortex activation to drug cues: a meta-analysis of functional neuroimaging papers in addiction and substance abuse literature.

BACKGROUND: Although the visual cortex does not typically receive much attention in addiction literature, neuroimaging studies often report significant activity in visual areas when drug users are exposed to drug cues. The purpose of this meta-analysis was to investigate the frequency with which occipital cortex activity is observed during drug cue exposure and to determine its spatial distribution. METHODS: A comprehensive literature search was performed of human functional neuroimaging studies of drug cue-reactivity. Fifty-five studies were used to determine the frequency with which clusters of significant visual cortex activity during visual drug cues versus non-drug cues were reported. The spatial distribution of visual cortex activations was determined via activation likelihood estimation (ALE; FDR corrected, p<0.01) in a subset of these studies (n=24). RESULTS: Eighty-six percent of studies that reported fMRI results for drug versus neutral visual cues within a substance-dependent group showed significant drug-elicited activity in the visual cortex. ALE revealed clusters in the left secondary visual cortex (BA 19) and clusters in the primary visual cortex (BA 17) that were consistently activated by drug cues. CONCLUSIONS: These data demonstrate that the visual cortex, often overlooked in our discussions of the neural circuitry of addiction, consistently discriminates drug cues from neutral cues in substance dependent populations. While it remains unclear whether drug cue-elicited activation in occipital cortex is related to the rewarding properties of the drug and/or attentional mechanisms, these data support further exploration.

Executive control circuitry differentiates degree of success in weight loss following gastric-bypass surgery.

OBJECTIVE: While overall success rates of bariatric surgery are high, approximately 20% of patients either regain or never lose the expected amount of weight. The purpose of this study was to determine whether, after gastric-bypass surgery, the degree of weight loss can be differentiated based on the neural response to food cues. DESIGN AND METHODS: In this functional MRI study, 31 post-surgical patients viewed food and neutral images in two counterbalanced runs during which they were either instructed to "crave" or to "resist" craving. The neural response to food cues was assessed within and between runs for all participants, and further analyzed between more successful (n = 24) and less successful (n = 7) groups. More successful was defined by meeting 50% excess weight loss. RESULTS: Overall, instructions to "crave" elicited significant activity in the dorsomedial prefrontal cortex (PFC) whereas "resist" elicited significant activity in the dorsolateral PFC (DLPFC). Between groups there was no brain difference when instructed to "crave." The more successful participants however had significantly more activity in the DLPFC when instructed to "resist." CONCLUSIONS: These findings suggest that the ability to mobilize neural circuits involved in executive control post-gastric-bypass surgery may be a unique component of successful outcome post-surgery.

Sustained reduction of nicotine craving with real-time neurofeedback: exploring the role of severity of dependence.

BACKGROUND: Neurofeedback delivered via real-time functional magnetic resonance imaging (rtfMRI) is a promising therapeutic technique being explored to facilitate self-regulation of craving in nicotine-dependent cigarette smokers. The current study examined the role of nicotine-dependence severity and the efficacy of multiple visits of neurofeedback from a single region of interest (ROI) in the anterior cingulate cortex (ACC) on craving reduction. METHODS: Nine nicotine-dependent cigarette smokers participated in three rtfMRI visits that examined cue-induced craving and brain activation. Severity of nicotine dependence was assessed with the Fagerström Test for Nicotine Dependence. When viewing smoking-related images with instructions to "crave," patient-tailored ROIs were generated in the vicinity of the ACC. Activity levels from the ROI were fed back while participants viewed smoking cues with the instruction to reduce craving. RESULTS: Neurofeedback from a single ROI in the ACC led to consistent decreases in self-reported craving and activation in the ACC across the three visits. Dependence severity predicted response to neurofeedback at Visit 3. CONCLUSIONS: This study builds upon previous rtfMRI studies on the regulation of nicotine craving in demonstrating that feedback from the ACC can reduce activation to smoking cues across three separate visits. Individuals with lower nicotine-dependence severity were more successful in reducing ACC activation over time. These data highlight the need to consider dependence severity in developing more individualized neurofeedback methods.

Probing the frontostriatal loops involved in executive and limbic processing via interleaved TMS and functional MRI at two prefrontal locations: a pilot study.

BACKGROUND: The prefrontal cortex (PFC) is an anatomically and functionally heterogeneous area which influences cognitive and limbic processing through connectivity to subcortical targets. As proposed by Alexander et al. (1986) the lateral and medial aspects of the PFC project to distinct areas of the striatum in parallel but functionally distinct circuits. The purpose of this preliminary study was to determine if we could differentially and consistently activate these lateral and medial cortical-subcortical circuits involved in executive and limbic processing though interleaved transcranial magnetic stimulation (TMS) in the MR environment. METHODS: Seventeen healthy individuals received interleaved TMS-BOLD imaging with the coil positioned over the dorsolateral (EEG: F3) and ventromedial PFC (EEG: FP1). BOLD signal change was calculated in the areas directly stimulated by the coil and in subcortical regions with afferent and efferent connectivity to the TMS target areas. Additionally, five individuals were tested on two occasions to determine test-retest reliability. RESULTS: Region of interest analysis revealed that TMS at both prefrontal sites led to significant BOLD signal increases in the cortex under the coil, in the striatum, and the thalamus, but not in the visual cortex (negative control region). There was a significantly larger BOLD signal change in the caudate following medial PFC TMS, relative to lateral TMS. The hippocampus in contrast was significantly more activated by lateral TMS. Post-hoc voxel-based analysis revealed that within the caudate the location of peak activity was in the ventral caudate following medial TMS and the dorsal caudate following lateral TMS. Test-retest reliability data revealed consistent BOLD responses to TMS within each individual but a large variation between individuals. CONCLUSION: These data demonstrate that, through an optimized TMS/BOLD sequence over two unique prefrontal targets, it is possible to selectively interrogate the patency of these established cortical-subcortical networks in healthy individuals, and potentially patient populations.