Background: Veterans are disproportionately affected by cocaine use disorder (CUD), a condition without approved pharmacotherapies, marked by high return to use rates. Prize-Based Contingency Management (PBCM) is an effective behavioral intervention, but treatment response varies. Electrophysiological and cognitive measures may help identify who is likely to benefit from specific PBCM variants. This study evaluates whether neurocognitive profiles predict differential response to monetary versus tangible reward-based PBCM, with the goal of informing measurement-based, personalized treatment. Methods: Forty-five Veterans with CUD completed EEG and cognitive assessments before randomization to a 12-week treatment trial evaluating PBCM with either tangible or voucher rewards. Manipulation checks validated the measurement approach for candidate neurocognitive predictors. Treatment outcomes were analyzed using longitudinal logistic regression across 24 possible PBCM sessions. A forward selection approach guided model building, and generalizability was assessed using leave-one-out cross-validation. Results: Manipulation checks confirmed expected neurocognitive effects across tasks. Modeling identified greater anticipatory alpha suppression to tangible reward, larger ERN amplitudes, and lower craving as significant predictors of abstinence. Voucher PBCM, younger age, and earlier timepoints were also associated with better outcomes. Model 1 demonstrated good discrimination (AUC = 0.773), with no added benefit from predictor-by-treatment interactions. Conclusions: This study highlights the potential of neurocognitive markers associated with PBCM outcomes in Veterans with CUD to inform treatment development and personalization. Baseline features did not predict differential outcomes by reward type; instead, tangible rewards were generally linked to poorer outcomes. Findings therefore also support the broad utility of abstract, voucher-based rewards in PBCM treatment.
Objective: Contingency management (CM) is the gold standard treatment for stimulant use disorder but typically requires twice- to thrice -weekly in -person treatment visits to objectively verify abstinence and deliver therapeutic incentives. There has been growing interest in telehealth-based delivery of CM to support broad access to this essential intervention-a need that has been emphatically underscored by the COVID-19 pandemic. Herein, we present observations from initial efforts to develop and test a protocol for telehealth-based delivery of prize -based CM treatment incentivizing stimulant abstinence. Method: Four participants engaged in hybrid courses of CM, including one or more telehealth-based treatment sessions, involving self-administered oral fluid testing to confirm abstinence. Observations from initial participants informed iterative improvements to telehealth procedures, and a 12 -week course of telehealth-based CM was subsequently offered to two additional participants to further evaluate preliminary feasibility and acceptability. Results: In most cases, participants were able to successfully join telehealth treatment sessions, self-administer oral fluid testing, and share oral fluid test results to verify stimulant abstinence. However, further improvements in telehealth-based toxicology testing may be necessary to interpret test results accurately and reliably, especially when colorimetric immunoassay results reflect substance concentrations near the cutoff for point -of -care testing devices. Conclusions: Preliminary findings suggest that telehealth-based CM is sufficiently feasible and acceptable to support future development, in particular through improved methods for remote interpretation and verification of test results. This is especially important in CM, wherein accurate and reliable detection of both early and sustained abstinence is crucial for appropriate delivery of therapeutic incentives. ( J. Stud. Alcohol Drugs, 85, 26-31, 2024)
Research examining episodic future thinking (EFT; i.e., imagining oneself in future contexts) in community samples has demonstrated reduced discounting of delayed rewards when personalized event cues are included to prompt EFT related to reward latencies. While this EFT effect was recently demonstrated in individuals with substance use disorders, it is not yet known if it manifests similarly in individuals with and without a significant incarceration history-the latter being at elevated risk for negative outcomes including criminal recidivism. Individuals with cocaine use disorder (n = 35) identified personally-relevant future events and participated in a computerized delay discounting task, involving decisions between smaller immediate rewards or larger delayed rewards with and without EFT cues. Individuals with (n = 19) and without (n = 16) a significant history of incarceration were identified using the Addiction Severity Index-Lite. A significant reduction in discounting rates was observed when event cues were included to promote EFT (p = 0.02); however, there was no main effect of incarceration history on discounting behavior, or interaction between episodic future thinking condition and incarceration history. Results suggest personalized cues included to evoke EFT reduce discounting behavior in individuals with cocaine use disorder, regardless of incarceration history. EFT-based interventions may therefore have promise to reduce impulsive decision-making in individuals with cocaine use disorder with and without a significant history of incarceration, potentially supporting improved outcomes with respect to both substance use and future criminality.
A variety of psychological and physical phenomena elicit variations in the diameter of pupil of the eye. Changes in pupil size are mediated by the relative activation of the sphincter pupillae muscle (decrease pupil diameter) and the dilator pupillae muscle (increase pupil diameter), innervated by the parasympathetic and sympathetic branches, respectively, of the autonomic nervous system. The current guidelines are intended to inform and guide psychophysiological research involving pupil measurement by (1) summarizing important aspects concerning the physiology of the pupil, (2) providing methodological and data-analytic guidelines and recommendations, and (3) briefly reviewing psychological phenomena that modulate pupillary reactivity. Because of the increased ease and tractability of pupil measurement, the goal of these guidelines is to promote accurate recording, analysis, and reporting of pupillary data in psychophysiological research.
Association between familial loading for alcohol use disorders (AUD) and event-related potentials (ERPs) suggests a genetic basis for these oscillations though much less is known about epigenetic pathways influenced by environmental variation. Early life adversity (ELA) influences negative outcomes much later in life. The stress-activated neuropeptide corticotropin-releasing hormone (CRH) contributes to the deleterious effects of ELA on brain structure and function in animals. Accordingly, we hypothesized that ELA would be related to cortical thickness and electrophysiological characteristics through an epigenetic effect on CRH receptor type-1 (CRHR1) methylation. A total of 217 adolescent and young adult participants from either multiplex alcohol dependence or control families were scanned using magnetic resonance imaging (MRI) at 3T and cortical thickness was determined. Longitudinal follow-up across childhood, adolescence, and young adulthood provided developmental ERP data and measures of adversity. Blood samples for genetic and epigenetic analyses were obtained in childhood. Cortical thickness and visual ERP components were analyzed for their association and tested for familial risk group differences. Visual P300 amplitude at Pz and cortical thickness of the left lateral orbitofrontal region (LOFC), were significantly related to risk group status. LOFC cortical thickness showed a negative correlation with CRHR1 methylation status and with childhood total stress scores from the Life Stressors and Social Resources Inventory (LISRES). Stress scores were also significantly related to P300 amplitude recorded in childhood. The present results suggest that early life adversity reflected in greater total LISRES stress scores in childhood can impact the methylation of the CRHR1 gene with implications for brain development as seen in cortical thickness and electrophysiological signals emanating from particular brain regions.
Objective: Long-acting injectable antipsychotics (LAI-As) are a crucial treatment option for individuals with serious mental illness. However, due to the necessity of in-person administration of LAI-As, pandemics pose unique challenges for continuity of care in the population prescribed these medications. This project investigated the impact of the coronavirus disease 2019 (COVID-19) pandemic on LAI-A adherence at a Veterans Health Administration medical facility in the United States, as well as changes in LAI-A prescribing and administration practices during this period. Methods: Electronic health records were evaluated for 101 patients prescribed LAI-As. A subset of 13 patients also participated in an interview and rated subjective concerns about pandemic-related barriers to medication adherence. Results: Pandemic-related barriers to LAI-A adherence and/or changes to LAI-A medications were documented in 33% of the patients. Within-subjects comparison of an adherence metric computed from electronic health record data further suggested a somewhat higher incidence of missed or delayed LAI-A doses during the pandemic compared with before the pandemic. In contrast, only 2 of the 13 patients interviewed anticipated that pandemic-related concerns would interfere with medication adherence. Conclusions: The results of this study suggest that LAI-A access and adherence can be disrupted by pandemics and other public health emergencies but this finding may not generalize to other sites. As patients may not foresee the potential for disruption, psychiatric service providers may need to assist in proactively problem-solving barriers to access. Improved preparedness and additional safeguards against pandemic-related disruptions to LAI-A access and adherence may help mitigate adverse outcomes in the future. Identifying patients at elevated risk for such disruptions may help support these efforts.
Background: Electrophysiological measures can predict and reflect substance use treatment response. Veterans are disproportionately affected by disorders of addiction; cocaine use disorder (CUD) being particularly problematic due to high relapse rates and the absence of approved pharmacotherapies. Prize-based Contingency Management (PBCM) is an evidence-based behavioral intervention for CUD, involving incentives for cocaine abstinence but treatment response is variable. Measurement-based adaptation of PBCM has promise to improve effectiveness but remains to be usefully developed. Methods: This trial aims to determine if individuals with distinct neurocognitive profiles differentially benefit from one of two existing versions of PBCM. CUD patients will be randomized into treatment-as-usual or 12-weeks of PBCM using either monetary or tangible prize incentives. Prior to randomization, EEG will be used to assess response to monetary versus tangible reward; EEG and cognitive-behavioral measures of working memory, cognitive control, and episodic future thinking will also be acquired. Substance use and treatment engagement will be monitored throughout the treatment interval and assessments will be repeated at post-treatment. Discussion: Results of this trial may elucidate individual differences contributing to PBCM treatment response and reveal predictors of differential benefits from existing treatment variants. The design also affords the opportunity to evaluate treatment-related changes in neurocognitive functioning over the course of PBCM. Our model posits that PBCM scaffolds future-oriented goal representation and self-control to support abstinence. Individuals with poorer functioning may be less responsive to abstract monetary reward and will therefore achieve better outcomes with respect to abstinence and treatment engagement when tangible incentives are utilized.
Background: Episodic future thinking (EFT; i.e., envisioning oneself in future contexts) has been demonstrated to reduce discounting of future reward in healthy adults. While this approach has the potential to support future-oriented decision-making in substance use recovery, the impact of EFT on discounting behavior in illicit stimulant users has not yet been evaluated.Objectives: This pilot study aimed to (1) assess the feasibility of utilizing EFT methods in individuals with cocaine use disorder (CUD) and (2) conduct preliminary measurement of the EFT effect on discounting behavior in this population.Methods: Eighteen treatment-seeking individuals with CUD (17 males) were interviewed about positive and neutral events expected to occur at a range of future latencies. Future event information identified by participants was subsequently included on a subset of trials in an intertemporal choice task to promote EFT; within-subject differences in discounting between standard and EFT conditions were evaluated.Results: Participants identified relevant events and demonstrated decreased discounting of future reward when event descriptors were included (relative to discounting without event descriptors; p = .039). It was further noted that most events identified by participants were goals, rather than plans or significant dates.Conclusion: While methods previously used to study the effect of EFT on discounting behavior in healthy individuals are also effective in individuals with CUD, methodological factors - including types of events identified - should be carefully considered in future work. These preliminary findings suggest that EFT can reduce impulsive decision-making in cocaine use disorder and may therefore have therapeutic value.
The number of research groups studying the pupil is increasing, as is the number of publications. Consequently, new standards in pupillography are needed to formalize the methodology including recording conditions, stimulus characteristics, as well as suitable parameters of evaluation. Since the description of intrinsically photosensitive retinal ganglion cells (ipRGCs) there has been an increased interest and broader application of pupillography in ophthalmology as well as other fields including psychology and chronobiology. Color pupillography plays an important role not only in research but also in clinical observational and therapy studies like gene therapy of hereditary retinal degenerations and psychopathology. Stimuli can vary in size, brightness, duration, and wavelength. Stimulus paradigms determine whether rhodopsin-driven rod responses, opsin-driven cone responses, or melanopsin-driven ipRGC responses are primarily elicited. Background illumination, adaptation state, and instruction for the participants will furthermore influence the results. This standard recommends a minimum set of variables to be used for pupillography and specified in the publication methodologies. Initiated at the 32nd International Pupil Colloquium 2017 in Morges, Switzerland, the aim of this manuscript is to outline standards in pupillography based on current knowledge and experience of pupil experts in order to achieve greater comparability of pupillographic studies. Such standards will particularly facilitate the proper application of pupillography by researchers new to the field. First we describe general standards, followed by specific suggestions concerning the demands of different targets of pupil research: the afferent and efferent reflex arc, pharmacology, psychology, sleepiness-related research and animal studies.
Some individuals with schizophrenia report similar feelings of positive affect "in the moment" compared to control participants but report decreased trait positive affect overall. One possible explanation for this disconnection between state and trait positive affect is the extent to which individuals with schizophrenia engage in elaborative processing of positive stimuli. To assess this, we examined evoked gamma band activity in response to positive words over several seconds in a group with schizophrenia, a group with major depressive disorder, and a healthy control group. From a pre-stimulus baseline to 2000 ms after onset of the stimulus (henceforth, "early period"), the schizophrenia group showed a reliable increase in gamma activity compared to both the control and depressed groups, who did not differ from each other. In contrast, the depressed group showed a reliable increase in gamma activity from 2001 to 8000 ms (henceforth, "late period") compared to the other groups, who did not differ from each other. At the same time, the schizophrenia group showed a reliable decrease from the early to late period while the depressed group showed the opposite pattern. In addition, self-reported depression and social anhedonia in the schizophrenia group were related to decreased gamma band activity over the entire processing window. Overall, these results suggest that schizophrenia is associated with increased initial reactivity but decreased sustained elaborative processing over time, which could be related to decreased trait positive affect. The results also highlight the importance of considering depressive symptomology and anhedonia when examining emotional abnormalities in schizophrenia.
Signals carried by the mesencephalic dopamine system and conveyed to anterior cingulate cortex are critically implicated in probabilistic reward learning and performance monitoring. A common evaluative mechanism purportedly subserves both functions, giving rise to homologous medial frontal negativities in feedback- and response-locked event-related brain potentials (the feedback-related negativity (FRN) and the error-related negativity (ERN), respectively), reflecting dopamine-dependent prediction error signals to unexpectedly negative events. Consistent with this model, the dopamine receptor antagonist, haloperidol, attenuates the ERN, but effects on FRN have not yet been evaluated.
Cannabis use is common among adolescents. Identification of the factors associated with continued heavy use into young adulthood and development of cannabis abuse and dependence is of considerable importance. The role of familial risk for addiction and an associated endophenotype, P300 amplitude, has not previously been related to cannabis use and dependence. A prospective longitudinal study spanning childhood and young adulthood provided the opportunity for exploring these factors, along with genetic variation, in the cannabis use behaviors of 338 young adult offspring from high and low familial risk for alcohol dependence families (ages 19–30). P300 data were collected multiple times in childhood. The association between young adult patterns of cannabis use or cannabis abuse/dependence was tested with genetic variation in the cannabinoid gene, CNR1, the ANKK1‐DRD2 gene, and childhood developmental trajectories of P300. Young adult patterns of cannabis use was characterized by three patterns: (i) no use throughout; (ii) declining use from adolescence through young adulthood; and (iii) frequent use throughout. Following the low P300 trajectory in childhood predicted cannabis abuse and dependence by young adulthood. A four SNP ANKK1‐DRD2 haplotype (G‐G‐G‐C) was found to be significantly associated with the frequency of use patterns ( P = 0.0008). Although CNR1 variation overall was not significantly associated with these patterns, among individuals with cannabis abuse/dependence the presence of one or both copies of the rs806368 A > G minor allele conferred a 5.4‐fold increase ( P = 0.003) in the likelihood that they would be in the frequent and persistent use group rather than the declining use group. © 2016 Wiley Periodicals, Inc.
Cognitive operations can be detected by reduction of the pupillary light response. Neurophysiological pathways mediating this reduction have not been distinguished. We utilized selective blockade of pupillary sphincter or dilator muscles to isolate parasympathetic or sympathetic activity during cognition, without modifying central processes. Pupil diameter was measured during the light reaction in 29 normal adults under three processing levels: No Task, during an easy task (Add 1), or a difficult task (Subtract 7). At three separate sessions, the pupil was treated with placebo, tropicamide (blocking the muscarinic sphincter receptor), or dapiprazole (blocking the adrenergic dilator receptor). With placebo, pupil diameter increased with increasing task difficulty. The light reaction was reduced only in the Subtract 7 condition. Dapiprazole (which decreased overall diameter) showed similar task-related changes in diameter and light reflex as for placebo. Following tropicamide (which increased overall diameter), there was a further increase in diameter only in the difficult task. Findings suggest two separate inhibitory components at the parasympathetic oculomotor center. Changes in baseline diameter are likely related to reticular activation. Inhibition of the light reaction in the difficult task is likely associated with cortical afferents. Sustained sympathetic activity also was present during the difficult task.
P300 amplitude in childhood predicts substance use disorders by young adulthood. Trajectories of visual P300 amplitude show an association between low amplitude P300 and familial risk for alcohol dependence (AD). Variation in the cholinergic muscarinic receptor gene (CHRM2) has previously been associated with P300 amplitude and AD. The present study used group based trajectory modeling of auditory P300 data collected longitudinally from offspring in families with and without familial loading for AD to determine if specific trajectories would be associated with familial risk and CHRM2 variation. Trajectory modeling confirms previous reports of an association between the low visual P300 trajectory with high familial risk in male offspring. This association was detected in offspring in the 8-12 age range, but not in 13-18 or 19-29 year olds or in high-risk female offspring. CHRM2 association analysis with P300 finds 8-12 year olds who are homozygous for the T allele of rs1824024 are 2.6 times more likely to follow a P300 trajectory characterized by lower and slower change regardless of familial loading. Combining the odds for being male and having a TT genotype results in odds of 6.5 that individuals will follow the low P300 trajectory.
We discovered that an error was made in the onset times plotted significant at multiple time windows across the 1 s epoch and over when the waveformswere created for our recent report (International Journal of Psychophysiology 75, 2010, 141–156). Waveforms for initial Prime words rather than the intended subsequent Target words were presented. This error did not affect any of the results based on themain analyses of the values for Target words. Corrected waveforms and the corresponding tables are presented in the following figures and tables, which replace Figs. 1–6 and Tables 4 and 5 in the original paper.
A growing number of studies have reported altered functional connectivity in schizophrenia during putatively “task-free” states and during the performance of cognitive tasks. However, there have been few systematic examinations of functional connectivity in schizophrenia across rest and different task states to assess the degree to which altered functional connectivity reflects a stable characteristic or whether connectivity changes vary as a function of task demands. We assessed functional connectivity during rest and during three working memory loads of an N-back task (0-back, 1-back, 2-back) among: (1) individuals with schizophrenia (N = 19); (2) the siblings of individuals with schizophrenia (N = 28); (3) healthy controls (N = 10); and (4) the siblings of healthy controls (N = 17). We examined connectivity within and between four brain networks: (1) frontal–parietal (FP); (2) cingulo-opercular (CO); (3) cerebellar (CER); and (4) default mode (DMN). In terms of within-network connectivity, we found that connectivity within the DMN and FP increased significantly between resting state and 0-back, while connectivity within the CO and CER decreased significantly between resting state and 0-back. Additionally, we found that connectivity within both the DMN and FP was further modulated by memory load. In terms of between network connectivity, we found that the DMN became significantly more “anticorrelated” with the FP, CO, and CER networks during 0-back as compared to rest, and that connectivity between the FP and both CO and CER networks increased with memory load. Individuals with schizophrenia and their siblings showed consistent reductions in connectivity between both the FP and CO networks with the CER network, a finding that was similar in magnitude across rest and all levels of working memory load. These findings are consistent with the hypothesis that altered functional connectivity in schizophrenia reflects a stable characteristic that is present across cognitive states.
Background: Arousal symptoms (e. g., sleepiness) are common in Parkinson's disease, and pupillary unrest (spontaneous changes in pupil diameter) is positively associated with sleepiness. We explored pupillary unrest in Parkinson's disease.Methods: Arousal symptoms (Epworth sleepiness scale and sleep/fatigue domain of the nonmotor symptoms scale for Parkinson's disease) and pupillary unrest were assessed in 31 participants (14 patients with Parkinson's disease, 17 controls). Effect sizes and t tests compared patients with Parkinson's disease with control participants. Correlation coefficients were calculated among arousal symptoms, pupillary unrest, and Unified Parkinson Disease Rating Scale Part III. Linear regression was performed with arousal symptoms or pupillary unrest as outcome.Results: Participants with Parkinson's disease reported more arousal symptoms than controls. Pupillary unrest, arousal symptoms, and Unified Parkinson Disease Rating Scale Part III were positively correlated. The association between nonmotor symptoms scale-sleep score and pupillary unrest was higher in participants with Parkinson's disease than controls and higher in those with more Parkinsonian motor signs. Unified Parkinson Disease Rating Scale Part III was positively associated with pupillary unrest.Conclusions: Pupillary unrest correlates with motor and nonmotor features associated with Lewy-related pathology, suggesting it may be a nonmotor marker of progression in Parkinson's disease. (C) 2011 Movement Disorder Society