Medicaid Coverage Disruptions Among Children Enrolled in North Carolina Medicaid From 2016 to 2018.

Importance: Brief disruptions in insurance coverage among eligible participants are associated with poorer health outcomes for children. Objective: To describe factors associated with coverage disruptions among children enrolled in North Carolina Medicaid from 2016 to 2018 and estimate the outcome of preventing such disruptions on medical expenditures. Design Setting and Participants: This was a retrospective cohort study using North Carolina Medicaid claims data. All enrolled individuals were aged 1 to 20 years on January 1, 2016, and with 30 days of prior continuous enrollment. Children were observed from January 1, 2016, until December 31, 2018. Analyses were conducted from June 2020 through December 2020. Main Outcomes and Measures: Risk of Medicaid coverage disruptions of 1 to less than 12 months was assessed. Among children who disenrolled from Medicaid for 30 or more days, the risk of reenrollment within 1 to 6 months and 7 to 11 months was assessed. An inverse probability of censoring weights method was then used to estimate the outcome of an intervention to reduce coverage disruptions through preventing disenrollment on per member per month (PMPM) cost. Results: The study population included 831 173 Medicaid beneficiaries aged 1 to 5 years (23%), 6 to 17 years (68%), and 18 to 20 years (9%); 35% were Black, 44% were White, and 14% were Hispanic/Latinx. Among those with a first disenrollment (n = 214 401, 26%), the risk of reenrollment within 6 months and 7 to 11 months was 19% and 7%, respectively. Risk of coverage disruption was higher for Black children (hazard ratio [HR], 1.21; 95% CI, 1.18-1.24), children of other races (Asian, American Indian, Hawaiian or Pacific Islander, multiple races, or unreported; HR, 1.37; 95% CI, 1.33-1.40), and Latinx children (HR, 1.65; 95% CI, 1.60-1.70) compared with White children. Risk of coverage disruption was also higher for children with higher medical complexity (HR, 1.15; 95% CI, 1.12-1.19). The risk of coverage disruption was lower for children living in counties with the highest unemployment rates (HR, 0.89; 95% CI, 0.85-0.94), and comparisons between county-level measures of child poverty and graduation rates showed little or no difference. The estimated PMPM cost for the full population under a scenario in which all medical costs were included was $125.73. Estimated PMPM cost for the full cohort in a counterfactual scenario in which disenrollment was prevented was slightly lower ($122.14). Across all subgroups, estimated PMPM costs were modestly lower ($2-$8) in the scenario in which disenrollment was prevented. Conclusions and Relevance: In this cohort study, the risk of Medicaid coverage disruption was high, with many eligible children in historically marginalized communities continuing to experience unstable enrollment. In addition to improving health outcomes, preventing coverage gaps through policies that decrease disenrollment may also reduce Medicaid costs.

Experimental Pain Sensitivity in Subjects with Temporomandibular Disorders and Multiple Other Chronic Pain Conditions: The OPPERA Prospective Cohort Study.

AIMS: To investigate associations between experimental pain sensitivity and five chronic pain conditions among 655 participants in the OPPERA study. METHODS: Quantitative sensory tests were used to measure sensitivity to three modalities of nociception: blunt pressure pain, mechanical pinprick pain, and thermal heat pain. Participants were also classified according to the presence or absence of five chronic pain conditions: temporomandibular disorders, headache, low back pain, irritable bowel syndrome, and fibromyalgia. RESULTS: Univariate analyses found each modality to be significantly associated with at least one pain condition, most consistently for pressure pain sensitivity (8 of 15 instances) and least consistently for heat pain sensitivity (5 of 35 instances). Yet, multivariable analyses that evaluated the independent contributions of all five pain conditions found few significant associations (12 of 75 instances). Instead, pain sensitivity consistently varied according to the total number of pain conditions a person experienced, implying that the combination of pain conditions influences each nociceptive modality. CONCLUSION: When evaluating nociceptive sensitivity in a chronic pain patient, comorbid pain conditions should be considered, as the more salient feature underlying sensitivity is likely the number rather than the type(s) of pain conditions.

Attributes Germane to Temporomandibular Disorders and Their Associations with Five Chronic Overlapping Pain Conditions.

AIMS: To investigate whether TMD-related characteristics are indeed specific to TMD or whether they are also associated with other chronic overlapping pain conditions (COPCs). METHODS: In this cross-sectional study, 22 characteristics related broadly to TMD (eg, jaw kinesiophobia, overuse behaviors, and functional limitation) were measured in 178 painful TMD cases who were also classified according to four COPCs: headache, low back pain, irritable bowel syndrome, and fibromyalgia. Differences in mean subscale scores were compared according to individual chronic pain conditions and according to number of COPCs. RESULTS: Headache, low back pain, irritable bowel syndrome, and fibromyalgia were each associated (P < .05) with higher values of at least one TMD-relevant characteristic. In the multivariable analysis, TMD was independently associated with 20 of the 22 characteristics (P < .01), and other COPCs were associated variably. A critical threshold existed between the number of COPCs and TMD characteristics: all characteristics were elevated for subjects with ≥ 3 COPCs (P ≤ .01). CONCLUSION: The overlap between COPCs and characteristics typically regarded as specific to painful TMD has implications for treatment targeted at both the local TMD condition and the broader pain disorder underlying the COPC(s). In TMD patients, the overall burden of pain from COPCs may create a shift in the pain-processing systems that underlie these TMD-relevant characteristics.

Associations of Sleep Disturbance, Atopy, and Other Health Measures with Chronic Overlapping Pain Conditions.

AIMS: To quantify the contributions of atopic disorders, sleep disturbance, and other health conditions to five common pain conditions. METHODS: This cross-sectional analysis used data from 655 participants in the OPPERA study. The authors investigated the individual and collective associations of five chronic overlapping pain conditions (COPCs) with medically diagnosed atopic disorders and self-reported sleep disturbance, fatigue, and symptoms of obstructive sleep apnea. Atopic disorders were allergies, allergic rhinitis, atopic dermatitis, allergic asthma, urticaria, allergic conjunctivitis, and food allergy. Logistic regression models estimated odds ratios as measures of association with temporomandibular disorders, headache, irritable bowel syndrome, low back pain, and fibromyalgia. Measures of sleep and atopy disorders were standardized to z scores to determine the relative strength of their associations with each COPC. Sociodemographic characteristics and body mass index were covariates. Random forest regression analyzed all variables simultaneously, computing importance metrics to determine which variables best differentiated pain cases from controls. RESULTS: Fatigue and sleep disturbance were strongly associated with each COPC and with the total number of COPCs. An increase of one standard deviation in fatigue or sleep disturbance score was associated with approximately two-fold greater odds of having a COPC. In random forest models, atopic disorders contributed more than other health measures to differentiating between cases and controls of headache, whereas other COPCs were best differentiated by measures of fatigue or sleep. CONCLUSION: Atopic disorders, previously recognized as predictors of poor sleep, are associated with COPCs after accounting for sleep problems.

Associations of Psychologic Factors with Multiple Chronic Overlapping Pain Conditions.

AIMS: To characterize psychologic functioning across five chronic overlapping pain conditions (COPCs)-temporomandibular disorders, fibromyalgia, low back pain, headache, and irritable bowel syndrome-and their overlaps. METHODS: Participants were 655 adults in the OPPERA study. Psychologic variables were standardized in separate logistic regression models to compare their relative strength of association with each COPC. Random forest regression was used to explore the association of all psychologic measures with COPCs simultaneously. Linear regression analyses examined whether the count of COPCs was associated with psychologic measures. RESULTS: In univariate and multivariable analyses, measures of somatic symptom burden showed the strongest associations with individual COPCs and with the number of COPCs. Additional psychologic variables that showed significant associations with individual COPCs and their overlap included negative mood, perceived stress, and pain catastrophizing. CONCLUSION: These findings highlight the importance of psychologic functioning in the assessment and management of these overlapping pain conditions.

Premorbid and concurrent predictors of TMD onset and persistence.

BACKGROUND: Multiple risk factors predict temporomandibular disorders (TMD) onset, but temporal changes in risk factors and their contribution to risk of TMD have not been evaluated. The study aims were to (a) describe changes occurring in premorbid TMD risk factors when re-measured at TMD onset and 6 months later, and (b) determine if measures of change improve accuracy in predicting TMD incidence compared to premorbid measures alone. METHODS: In this observational prospective cohort study at four university research clinics, 3,258 community-based, 18- to 44-year-olds without TMD were enrolled. During the 3-year median follow-up, 260 incident cases of first-onset TMD were identified, and 196 TMD-free subjects were selected as matched controls. Six-months later, 147 of 260 incident cases (56.6%) were re-examined revealing 72 (49%) with 'persistent TMD' and 75 (51%) whose condition had resolved ('transient TMD'). Virtually all (126) of the 127 re-examined controls remained without TMD. Questionnaires and clinical measurements evaluated risk factors from clinical, health, psychological and behavioural and neurosensory domains. RESULTS: Most risk factors across all four domains increased with TMD onset, remained elevated in the persistent group and declined in the transient group (i.e., significant ANOVA interactions, p < .05). Accuracy in predicting first-onset TMD, quantified as area under the receiver operating characteristic curve was 0.71 (95% CL 0.68, 0.73) using only premorbid measures of risk factors, which increased to 0.91 (95% CL 0.89, 0.94) after addition of change measures. CONCLUSIONS: TMD pain onset and persistence appear to be determined by enduring characteristics of the person as well as mutually interactive with temporally evolving variables. SIGNIFICANCE: TMD is known to be a complex disorder, in which onset and persistence are associated with disease-related variables in multiple domains, including environmental exposure, clinical, psychological, health status, and pain processing variables. Using a more dynamic approach in order to capture change across time, many aspects of those domains were found to worsen prior to the reporting of pain, with bidirectional influences between domains and pain emergence likely. TMD onset appears to represent the cumulative effect of multiple system dysregulation.

Clinical predictors of persistent temporomandibular disorder in people with first-onset temporomandibular disorder: A prospective case-control study.

BACKGROUND: When patients first develop a painful temporomandibular disorder (TMD) and seek care, 1 priority for clinicians is to assess prognosis. The authors aimed to develop a predictive model by using biopsychosocial measures from the Diagnostic Criteria for Temporomandibular Disorders (DC-TMD) to predict risk of developing TMD symptom persistence. METHODS: At baseline, trained examiners identified 260 participants with first-onset TMD classified by using DC-TMD-compliant protocols. After follow-up at least 6 months later, 72 (49%) had examiner-classified TMD (persistent cases), and 75 (51%) no longer had examiner-classified TMD (transient cases). For multivariable logistic regression analysis, the authors used blocks of variables selected using minimum redundancy maximum relevance to construct a model to predict the odds of TMD persistence. RESULTS: At onset, persistent cases had multiple worse TMD clinical measures and, among Axis II measures, only greater baseline pain intensity (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.04 to 2.2; P = .030) and more physical symptoms (OR, 1.8; 95% CI, 1.2 to 2.9; P = .004) than did transient cases. A multivariable model using TMD clinical measures showed greater discriminative capacity (area under the receiver operating characteristic curve, 0.74; 95% CI, 0.73 to 0.75) than did a model involving psychosocial measures (area under the receiver operating characteristic curve, 0.63; 95% CI, 0.62 to 0.64). CONCLUSIONS: Clinical measures that clinicians can assess readily when TMD first develops are useful in predicting the risk of developing persistent TMD. Psychosocial measures are important predictors of onset but do not add meaningfully to the predictive capacity of clinical measures. PRACTICAL IMPLICATIONS: When TMD first develops, clinicians usefully can identify patients at higher risk of developing persistence by using clinical measures that they logically also could use in treatment planning and for monitoring outcomes of intervention.

Distress Tolerance: Associations With Posttraumatic Stress Disorder Symptoms Among Trauma-Exposed, Cocaine-Dependent Adults.

The present investigation examined associations between distress tolerance and posttraumatic stress disorder (PTSD) symptoms in a cocaine-dependent sample. Participants were comprised of 138 cocaine-dependent adults (Mage = 45.4, SD = 9.9; 81% male; 76.3% African American) who endorsed trauma exposure, defined according to Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) PTSD Criterion A. Participants were administered interview-based measures and completed a series of self-report questionnaires. Results indicated that distress tolerance was significantly, incrementally (negatively) associated with PTSD symptom severity, contributing 6.8% of unique variance to the model (p < .001); notably, the overall model explained 44.8% of variance in PTSD symptomatology. Distress tolerance also contributed between 2.7% and 6.8% of unique variance across each of the PTSD symptom clusters (ps < .05). Incremental effects were documented, after accounting for the variance explained by theoretically relevant covariates (i.e., gender, cocaine-use severity, depressive symptoms, trauma-exposure severity). Theoretical and clinical implications are discussed.

Bradycardia as a Marker of Chronic Cocaine Use: A Novel Cardiovascular Finding.

Few studies have examined the effects of chronic cocaine use on the resting surface electrocardiogram (ECG) between exposures to cocaine. Researchers compared 12-lead ECGs from 97 treatment-seeking cocaine-dependent patients, with ECG parameters from 8,513 non-cocaine-using control patients from the Atherosclerosis Risk in Communities study. After matching and adjusting for relevant covariates, cocaine use demonstrated large and statistically reliable effects on early repolarization, bradycardia, severe bradycardia, and heart rate. Current cocaine dependence corresponds to an increased odds of demonstrating early repolarization by a factor of 4.92 and increased odds of bradycardia and severe bradycardia by factors 3.02 and 5.11, respectively. This study demonstrates the novel finding that long-lasting effects of cocaine use on both the cardiac conduction and the autonomic nervous system pose a risk of adverse cardiovascular events between episodes of cocaine use, and that bradycardia is a marker of chronic cocaine use.

Anti-saccade error rates as a measure of attentional bias in cocaine dependent subjects.

Cocaine-dependent (CD) subjects show attentional bias toward cocaine-related cues, and this form of cue-reactivity may be predictive of craving and relapse. Attentional bias has previously been assessed by models that present drug-relevant stimuli and measure physiological and behavioral reactivity (often reaction time). Studies of several CNS diseases outside of substance use disorders consistently report anti-saccade deficits, suggesting a compromise in the interplay between higher-order cortical processes in voluntary eye control (i.e., anti-saccades) and reflexive saccades driven more by involuntary midbrain perceptual input (i.e., pro-saccades). Here, we describe a novel attentional-bias task developed by using measurements of saccadic eye movements in the presence of cocaine-specific stimuli, combining previously unique research domains to capitalize on their respective experimental and conceptual strengths. CD subjects (N = 46) and healthy controls (N = 41) were tested on blocks of pro-saccade and anti-saccade trials featuring cocaine and neutral stimuli (pictures). Analyses of eye-movement data indicated (1) greater overall anti-saccade errors in the CD group; (2) greater attentional bias in CD subjects as measured by anti-saccade errors to cocaine-specific (relative to neutral) stimuli; and (3) no differences in pro-saccade error rates. Attentional bias was correlated with scores on the obsessive-compulsive cocaine scale. The results demonstrate increased saliency and differential attentional to cocaine cues by the CD group. The assay provides a sensitive index of saccadic (visual inhibitory) control, a specific index of attentional bias to drug-relevant cues, and preliminary insight into the visual circuitry that may contribute to drug-specific cue reactivity.

Demographic and psychological factors associated with lifetime cocaine use: An exploratory factor analysis of baseline questionnaires.

OBJECTIVES: Underlying heterogeneity among individuals with cocaine dependence is widely postulated in the literature, however, identification of a group of factors that explain risk of cocaine use severity has yet to be confirmed. METHODS: Latent mixture modeling evaluated 338 cocaine-dependent individuals recruited from the community to assess the evidence for the presence of distinct subgroups. Variables included 5 baseline questionnaires measuring cognitive function (Shipley), impulsivity (BIS), mood (BDI), affective lability (ALS), and addiction severity (ASI). Results failed to suggest multiple subgroups. Given a lack of evidence for discrete latent classes, an exploratory factor analysis (EFA) followed by exploratory structural equation modeling (ESEM) was implemented to identify functional dimensions to enhance interpretation of these variables. RESULTS: Findings from the EFA indicated a 3-factor model as the best fit, and the subsequent ESEM solution resulted in associations with lifetime cocaine use. Factor 1, best characterized by demographic factors (gender, age), is associated with less lifetime cocaine use. Psychological problems best characterize factor 2, which is associated with higher lifetime cocaine use. Finally, factor 3 is characterized by other substance use (alcohol and marijuana). Although this factor did not demonstrate a statistically reliable relation with self-reported, lifetime cocaine use, it did indicate a potentially meaningful positive association. CONCLUSIONS: These 3 factors delineate dimensions of functioning that likewise help characterize the variability found in previously established associations with self-reported cocaine use.

Effects of Intranasal Oxytocin on Aggressive Responding in Antisocial Personality Disorder.

The oxytocin receptor is important in several domains of social behavior, and administration of oxytocin modulates social responding in several mammalian species, including humans. Oxytocin has both therapeutic and scientific potential for elucidating the neural and behavioral mechanisms governing social behavior. In the present study, operationally-defined aggressive behavior of six males with Antisocial Personality Disorder (ASPD) was measured following acute intranasal oxytocin dosing (12, 24, and 48 international units) and placebo, using a well-validated laboratory task of human aggression (Point-Subtraction Aggression Paradigm, or PSAP). The PSAP provides participants with concurrently available monetary-earning and operationally-defined aggressive response options, maintained by fixed ratio schedules of consequences. Shifts in response rates and inter-response time (IRT) distributions were observed on the aggressive response option following oxytocin doses, relative to placebo. Few changes were observed in monetary-reinforced responding. However, across participants the direction and magnitude of changes in aggressive responding were not systematically related to dose. No trends were observed between psychometric or physiological data and oxytocin dosing or aggressive behavior. While this report is to our knowledge the first to examine the acute effects of oxytocin in this population at high risk for violence and other forms of antisocial behavior, several limitations in the experimental design and the results cast the study as a preliminary report. Strategies for more extensive future projects are discussed.

Examination of the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) Factor Structure in a Sample of Pregnant Smokers.

INTRODUCTION: Smoking during pregnancy poses known risks to fetal and infant development. Women who continue to smoke during pregnancy exhibit higher levels of nicotine dependence than women who quit. Increased understanding of the construct of nicotine dependence in pregnant smokers may aid in the development of effective treatments. Research has suggested that nicotine dependence is a multifaceted construct, driven not only by withdrawal and tolerance processes, but also by reinforcement, sensory, and contextual processes. The Wisconsin inventory of smoking dependence motives (WISDM-68) assesses 13 varied smoking motives in order to assess processes that may lead to nicotine dependence. METHODS: The factor structure of the WISDM-68 was explored using an ethnically diverse sample of 294 pregnant women who had been screened and/or enrolled in a smoking cessation treatment study. Confirmatory analyses were conducted with previously published models. An exploratory factor analysis and exploratory structural equation modeling (ESEM) were conducted to develop and validate a measurement model for the WISDM-68 in this sample. RESULTS: Previously established models were not a good fit for the present data. Using ESEM, a 9-factor model exhibiting both predictive and concurrent validity emerged. Two factors predicted abstinence 6 months posttreatment. Several factors were associated with smoking heaviness, the Fagerström test for cigarette dependence and time to first cigarette. CONCLUSIONS: In contrast to previously published studies, a 9-factor model best characterizes the WISDM in the present sample. These findings may reflect smoking motivations unique to young, pregnant women who continue to smoke during pregnancy.

Comparison of Caffeine and d-amphetamine in Cocaine-Dependent Subjects: Differential Outcomes on Subjective and Cardiovascular Effects, Reward Learning, and Salivary Paraxanthine.

Due to indirect modulation of dopamine transmission, adenosine receptor antagonists may be useful in either treating cocaine use or improving disrupted cognitive-behavioral functions associated with chronic cocaine use. To compare and contrast the stimulant effects of adenosine antagonism to direct dopamine stimulation, we administered 150 mg and 300 mg caffeine, 20 mg amphetamine, and placebo to cocaine-dependent vs. healthy control subjects, matched on moderate caffeine use. Data were obtained on measures of cardiovascular effects, subjective drug effects (ARCI, VAS, DEQ), and a probabilistic reward-learning task sensitive to dopamine modulation. Levels of salivary caffeine and the primary caffeine metabolite paraxanthine were obtained on placebo and caffeine dosing days. Cardiovascular results revealed main effects of dose for diastolic blood pressure and heart rate; follow up tests showed that controls were most sensitive to 300 mg caffeine and 20 mg amphetamine; cocaine-dependent subjects were sensitive only to 300 mg caffeine. Subjective effects results revealed dose × time and dose × group interactions on the ARCI A, ARCI LSD, and VAS 'elated' scales; follow up tests did not show systematic differences between groups with regard to caffeine or d-amphetamine. Large between-group differences in salivary paraxanthine (but not salivary caffeine) levels were obtained under both caffeine doses. The cocaine-dependent group expressed significantly higher paraxanthine levels than controls under 150 mg and 3-4 fold greater levels under 300 mg at 90 min and 150 min post caffeine dose. However, these differences also covaried with cigarette smoking status (not balanced between groups), and nicotine smoking is known to alter caffeine/paraxanthine metabolism via cytochrome P450 enzymes. These preliminary data raise the possibility that adenosine antagonists may affect cocaine-dependent and non-dependent subjects differently. In conjunction with previous preclinical and human studies, the data suggest that adenosine modulating drugs may have value in the treatment of stimulant use disorders.

A two-phased screening paradigm for evaluating candidate medications for cocaine cessation or relapse prevention: modafinil, levodopa-carbidopa, naltrexone.

BACKGROUND: Cocaine pharmacotherapy trials are often confounded by considerable variability in baseline cocaine-use levels, obscuring possible medication efficacy. Testing the feasibility of using a prerandomization, abstinence-induction protocol, we screened three candidate medications to explore treatment response in patients who did, or did not, achieve abstinence during an extended baseline phase. METHOD: Eligible treatment-seeking, cocaine-dependent subjects entered a 4-week baseline period (Phase I) with high-value abstinence contingent vouchers and two motivational interviewing sessions, followed by a 12-week medication trial (Phase II) with random assignment stratified on Phase I abstinence status to (1) modafinil (400mg/d), (2) levodopa/carbidopa (800/200mg/d), (3) naltrexone (50mg/d), or (4) placebo. Treatment consisted of thrice-weekly clinic visits for urine benzoylecgonine testing and weekly cognitive behavioral therapy with contingency management targeting medication compliance. RESULTS: Of the 118 subjects enrolled, 81 (80%) completed Phase I, with 33 (41%) achieving abstinence, defined a priori as 6 consecutive cocaine-negative urines. Tests of the interaction of each medication (active versus placebo) by baseline status (abstinent versus nonabstinent) permitted moderator effect analysis. Overall, baseline abstinence predicted better outcome. Cocaine-use outcomes for levodopa and naltrexone treatment differed as a function of Phase I abstinence status, with both medications producing benefit in nonabstinent but not baseline-abstinent subjects. There was no evidence of a moderator effect for modafinil. CONCLUSIONS: The two-phase screening trial demonstrated that subgrouping of patients with respect to baseline abstinence status is feasible and clinically useful for exploring cocaine cessation and relapse-prevention effects of candidate medications.

Combination of Modafinil and d-amphetamine for the Treatment of Cocaine Dependence: A Preliminary Investigation.

BACKGROUND: Two stimulant medications, modafinil and d-amphetamine, when tested individually, have shown safety and efficacy for treatment of cocaine addiction. We hypothesized that the combination of modafinil and d-amphetamine, at low doses, would show equivalent or greater benefit in reducing cocaine use compared to higher doses of each individual medication or placebo. METHODS: Sixteen week, randomized, parallel-group design with four treatment arms comparing placebo to modafinil 400 mg; d-amphetamine 60 mg; modafinil 200 mg plus d-amphetamine 30 mg. Primary outcome variables, retention and cocaine use, were analyzed on the sample of 73 participants who received the first dose of the study medication. RESULTS: Retention rates did not differ between groups and were generally low, with 40% remaining in treatment at week 12 and 20% at week 16. Participants receiving the combination of modafinil and d-amphetamine showed a trend of increased cocaine use over time with a corresponding low Bayesian probability of benefit (33%). Relatively better cocaine outcomes were observed in the placebo and d-amphetamine only groups. The study medications were generally well-tolerated with few adverse effects, yet rates of adherence were suboptimal (≤80%). CONCLUSION: Data from this preliminary investigation fail to provide evidential support for conducting a larger study of this dual-agonist medication combination for treatment of cocaine dependence.

Working memory fMRI activation in cocaine-dependent subjects: association with treatment response.

Functional magnetic resonance imaging (fMRI) studies of early abstinence cocaine users offer information about the state of the brain when most cocaine users seek treatment. This study examined the relationship between pretreatment brain function and subsequent treatment response in 19 treatment-seeking early abstinence cocaine-dependent (CD) subjects. These subjects and 14 non-drug-using control subjects underwent fMRI while performing a working memory task with three levels of difficulty. CD subjects were then randomized to treatment studies. Results showed CD subjects had significantly lower (random effects, corrected for multiple comparisons) brain activation in caudate, putamen, cingulate gyrus, middle and superior frontal gyri, inferior frontal gyrus pars triangularis and pars opercularis, precentral gyrus, and thalamus compared with non-drug-using controls. Within CD subjects, thalamic activation significantly correlated with treatment response. This study shows CD subjects in early abstinence have alterations of brain function in frontal, striatal, and thalamic brain regions known to be part of a circuit associated with motor control, reward, and cognition. Subjects with pretreatment thalamic deactivation showed the poorest treatment response, possibly related to thalamic involvement in mesocortical and mesolimbic dopamine projections.