Evaluating effects of episodic future thinking on valuation of delayed reward in cocaine use disorder: a pilot study.

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.

Longitudinal predictors of cannabis use and dependence in offspring from families at ultra high risk for alcohol dependence and in control families.

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.

Telehealth-Based Contingency Management Targeting Stimulant Abstinence: A Case Series From the COVID-19 Pandemic.

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.

Patients with cocaine use disorder exhibit reductions in delay discounting with episodic future thinking cues regardless of incarceration history.

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.

Publication guidelines and recommendations for pupillary measurement in psychophysiological studies.

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.

Epigenetic Effects in HPA Axis Genes Associated with Cortical Thickness, ERP Components and SUD Outcome.

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.

Barriers to Long-acting Injectable Antipsychotic Adherence During the COVID-19 Pandemic: Observations From One Site.

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.

Pupillary unrest correlates with arousal symptoms and motor signs in Parkinson disease.

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. © 2011 Movement Disorder Society.

Electrophysiological predictors and indicators of contingency management treatment response: Rationale and design for the ways of rewarding abstinence project (WRAP).

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.

Timing matters in elaborative processing of positive stimuli: Gamma band reactivity in schizophrenia compared to depression and healthy adults.

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.

Standards in Pupillography.

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.

Semantic memory in schizophrenia: association with cell membrane essential fatty acids.

INTRODUCTION: Semantic memory and language deficits are associated with schizophrenia. Understanding how these systems operate in this disorder will likely require a multi-factorial model that explains their linkages with cognition and modulation by dopamine. A biological factor that may provide causal convergence for these connections is cell membrane composition and dynamics. METHODS: N400 is an electrophysiological measure of semantic memory and language that is sensitive to deficits in schizophrenia. Relationships among N400, cognition, dopamine, and cell membrane polyunsaturated fatty acids (PUFAs) were examined for patients tested under medicated (haloperidol only) and unmedicated (placebo) conditions. Relationships between these factors and clinical symptoms were also evaluated. The sample included 37 male schizophrenia inpatients and 34 male normal controls. The N400 priming effect was measured from visual event-related potentials recorded during a semantic priming-lexical decision task, in which semantic association (related versus unrelated words) and presentation rate (Stimulus Onset Asynchrony/SOAs: 350 and 950 ms) were varied. RESULTS: N400 was associated with cognition (speed, visuoperception, attention) in patients and controls. These relationships were influenced by SOA in both groups, and by pharmacological condition in patients. Levels of total PUFAs and arachidonic acid were associated with N400 in unmedicated patients. Clinical symptoms (paranoia, thought disturbance) were associated with N400, but not with cognition or PUFAs. CONCLUSIONS: Results suggest cell membrane fatty acids are associated with semantic memory and language in schizophrenia. Findings also suggest a series of linkages that are modulated by dopamine: cell membrane fatty acids are associated with N400 semantic priming; N400 semantic priming is associated with clinical symptoms.

Cerebellar volume in offspring from multiplex alcohol dependence families.

BACKGROUND: Increased susceptibility for developing alcohol dependence (AD) might be related to structural differences in brain circuits that influence the salience of rewards and/or modify the efficiency of information processing. The role of the cerebellum in regulating cognitive functions is being increasingly recognized along with its well-known influence on motor performance. Additionally, developmental changes in cerebellar volume during adolescence have been reported. METHODS: Magnetic resonance imaging was used to measure the cerebellum in 17 high-risk adolescent and young adult offspring from multiplex alcohol dependence families and 16 control subjects matched for gender, age, and IQ. RESULTS: High-risk (HR) adolescents/young adults showed increased total cerebellum volume and total grey in comparison with control subjects. Age-related decreases in total grey volume were seen with age, a pattern that was not seen in HR offspring. CONCLUSIONS: Offspring from multiplex families for AD manifest genetic susceptibility by having larger cerebellar volume, which seems to be related to lesser grey matter pruning for age. Larger cerebellar volumes in adult obsessive compulsive disorder (OCD) patients have been reported. This suggests a possible similarity in structural underpinnings for alcohol dependence and OCD.

Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features.

BACKGROUND: Major depressive disorder is characterized by increased and sustained emotional reactivity, which has been linked to sustained amygdala activity. It is also characterized by disruptions in executive control, linked to abnormal dorsolateral prefrontal cortex (DLPFC) function. These mechanisms have been hypothesized to interact in depression. This study explored relationships between amygdala and DLPFC activity during emotional and cognitive information processing in unipolar depression. METHOD: Twenty-seven unmedicated patients with DSM-IV unipolar major depressive disorder and 25 never-depressed healthy control subjects completed tasks requiring executive control (digit sorting) and emotional information processing (personal relevance rating of words) during event-related functional magnetic resonance imaging (fMRI) assessment. RESULTS: Relative to control subjects, depressed subjects displayed sustained amygdala reactivity on the emotional tasks and decreased DLPFC activity on the digit-sorting task. Decreased relationships between the time-series of amygdala and DLPFC activity were observed within tasks in depression, but different depressed individuals showed each type of bias. CONCLUSIONS: Depression is associated with increased limbic activity in response to emotional information processing and decreased DLPFC activity in response to cognitive tasks though these may reflect separate mechanisms. Depressed individuals also display decreased relationships between amygdala and DLPFC activity, potentially signifying decreased functional relationships among these structures.

Event-related potentials reflect impaired temporal interval learning following haloperidol administration.

BACKGROUND: 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. METHODS: ERN and FRN were recorded during a temporal interval learning task (TILT) following randomized, double-blind administration of haloperidol (3 mg; n = 18), diphenhydramine (an active control for haloperidol; 25 mg; n = 20), or placebo (n = 21) to healthy controls. Centroparietal positivities, the Pe and feedback-locked P300, were also measured and correlations between ERP measures and behavioral indices of learning, overall accuracy, and post-error compensatory behavior were evaluated. We hypothesized that haloperidol would reduce ERN and FRN, but that ERN would uniquely track automatic, error-related performance adjustments, while FRN would be associated with learning and overall accuracy. RESULTS: As predicted, ERN was reduced by haloperidol and in those exhibiting less adaptive post-error performance; however, these effects were limited to ERNs following fast timing errors. In contrast, the FRN was not affected by drug condition, although increased FRN amplitude was associated with improved accuracy. Significant drug effects on centroparietal positivities were also absent. CONCLUSIONS: Our results support a functional and neurobiological dissociation between the ERN and FRN.

Indicators of genetic liability to schizophrenia: a sibling study of neuropsychological performance.

Despite clear evidence of important genetic influences on schizophrenia, identifying the genes involved has been difficult because of the genetic complexity of the phenotype. The use of additional phenotypic measures that are more sensitive to the genetic liability than is the clinical diagnosis should enhance the power to detect small individual genetic effects. The present study assessed the neuropsychological performance of 30 male schizophrenia probands, 30 of their unaffected male siblings, and 20 well controls matched on age, sex, and education in order to identify measures that may be particularly sensitive to the genetic liability to schizophrenia and thus may be useful in gene mapping studies. Siblings showed impaired neuropsychological performance compared to controls on four out of the five measures used. Additional results suggested that Trails B was especially effective at discriminating index siblings from controls, thus supporting its potential utility as a candidate quantitative phenotype to aid in gene mapping studies of the disorder.

Reduced electrodermal activity in psychopathy-prone adolescents.

This study tests the hypothesis that psychopathy-prone adolescents show reduced anticipatory skin conductance responding. Electrodermal activity was recorded while participants anticipated and responded to a 105 dB signaled or unsignaled white-noise burst. Using an extreme groups design, the authors used Child Psychopathy Scale (D. R. Lynam, 1997) scores from a community sample of 335 male adolescents (age 16) to form control (n = 65) and psychopathy-prone (n = 65) groups. Significantly more psychopathy-prone participants were nonresponders in the signaled anticipatory (p = .014), signaled responsivity (p = .037), and unsignaled responsivity (p = .003) conditions compared with controls. Anticipatory hyporesponsivity of psychopathy-prone adolescents similar to the electrodermal hyporesponsivity found in psychopathic adults suggests that this autonomic impairment is present by adolescence and may predispose individuals to adult psychopathy.

Pharmacological Isolation of Cognitive Components Influencing the Pupillary Light Reflex.

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.

Can't shake that feeling: event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals.

BACKGROUND: Previous research suggests that depressed individuals engage in prolonged elaborative processing of emotional information. A computational neural network model of emotional information processing suggests this process involves sustained amygdala activity in response to processing negative features of information. This study examined whether brain activity in response to emotional stimuli was sustained in depressed individuals, even following subsequent distracting stimuli. METHODS: Seven depressed and 10 never-depressed individuals were studied using event-related functional magnetic resonance imaging during alternating 15-sec emotional processing (valence identification) and non-emotional processing (Sternberg memory) trials. Amygdala regions were traced on high-resolution structural scans and co-registered to the functional data. The time course of activity in these areas during emotional and non-emotional processing trials was examined. RESULTS: During emotional processing trials, never-depressed individuals displayed amygdalar responses to all stimuli, which decayed within 10 sec. In contrast, depressed individuals displayed sustained amygdala responses to negative words that lasted throughout the following non-emotional processing trials (25 sec later). The difference in sustained amygdala activity to negative and positive words was moderately related to self-reported rumination. CONCLUSIONS: Results suggest that depression is associated with sustained activity in brain areas responsible for coding emotional features.

Automatic activation of the semantic network in schizophrenia: evidence from event-related brain potentials.

BACKGROUND: Language disorder associated with schizophrenia might be due to disturbances in both automatic activation and mechanisms of controlled attention. The contribution of each process to semantic memory dysfunction has not been determined for schizophrenia, and the semantic priming paradigm is well-suited for addressing this question. In the present report, event-related potentials (ERPs) elicited under conditions assumed to reveal automatic activation (short prime-target interval and low proportion of related words) are compared directly with ERPs elicited under conditions associated with controlled processing (long prime-target interval and high proportion of related words). METHODS: Visual ERPs were recorded during a lexical decision task, in which semantic relationship (associated and unassociated words), expectancy (relatedness proportions), and prime-target interval (250- and 850-msec inter-stimulus intervals [ISIs]) were varied. Diagnosis and expectancy were between-subjects factors; semantic relationship and ISI were repeated measures. The N400 priming effect (enhanced negativity to unassociated words) was compared between 34 male normal control subjects tested once and 37 male schizophrenia inpatients evaluated during their participation in a double-blind haloperidol maintenance therapy and placebo replacement protocol. RESULTS: The N400 priming effect for patients was significantly reduced during both pharmacologic phases, compared with controls. During haloperidol treatment, however, patients showed a significant N400 priming effect over the anterior scalp region and additionally under the automatic activation condition. The N400 priming effect was enhanced under the controlled processing condition for control subjects; this effect was not observed for patients. N400 amplitude elicited under the rapid presentation rate (250-msec ISI) differed between medicated patients and controls; groups did not differ for the 850-msec ISI. CONCLUSIONS: Findings suggest that automatic activation and mechanisms of controlled attention are both disrupted during semantic memory access for schizophrenia patients. Pharmacologic agents, such as haloperidol, might enhance automatic activation of the semantic network in this patient population, as indexed by the N400 component of the ERP.