Limited Consistency and Strength of Neural Oscillations During Sustained Visual Attention in Schizophrenia.

BACKGROUND: Neural oscillations support perception, attention, and higher-order decision making. Aberrations in the strength or consistency of these oscillations in response to stimuli may underlie impaired visual perception and attention in schizophrenia. Here, we examined the phase and power of alpha oscillations (8-12 Hz) as well as aspects of beta and theta frequency oscillations during a demanding visual sustained attention task. METHODS: Patients with schizophrenia (n = 74) and healthy control participants (n = 68) completed the degraded stimulus continuous performance task during electroencephalography. We used time-frequency analysis to evaluate the consistency (intertrial phase coherence) of the alpha cycle shortly after stimulus presentation (50-250 ms). For oscillation strength, we examined event-related desynchronization in a later window associated with decision making (360-700 ms). RESULTS: Alpha intertrial phase coherence was reduced in schizophrenia, and similar reductions were observed in theta (4-7 Hz) and beta (13-20 Hz), suggesting a lack of responsiveness in slower oscillations to visual stimuli. Alpha and beta event-related desynchronization were also reduced in schizophrenia and associated with worse task performance, increased symptoms, and poorer cognition, suggesting that limited responsiveness of oscillations is related to impairments in the disorder. Individuals with lower intertrial phase coherence had slower resting-state alpha rhythms consistent with dysfunctional oscillations persisting across default and task-related brain states. CONCLUSIONS: In schizophrenia, abnormalities in the phase consistency and strength of slower oscillations during visual perception are related to symptoms and cognitive functioning. Altered visual perception and impaired attention in the disorder may be the consequence of aberrant slower oscillations that fail to dynamically reset and modulate in response to stimuli.

Acquired Alterations in Nucleus Accumbens Responsiveness to a Cocaine-Paired Discriminative Stimulus Preceding Rats' Daily Cocaine Consumption.

Resumption of drug taking is a primary focus for substance use disorder research and can be triggered by drug-associated environmental stimuli. The Nucleus Accumbens (NAc) is a key brain region which guides motivated behavior and is implicated in resumption. There remains a pressing need to characterize NAc neurons' responsiveness to drug associated stimuli during withdrawal and abstinence. We recorded discriminative stimulus (DS) induced NAc activity via in vivo single-unit electrophysiology in rats that self-administered cocaine. Male and female rats implanted with a jugular catheter and a microwire array in NAc Core and Shell self-administered cocaine under control of a 30s auditory DS for 6 hours per session across 14 consecutive days. Rats acquired tone discrimination within 4 sessions. To exclude pharmacological effects of circulating cocaine from all neural analyses, we studied changes in DS-induced firing only for trials preceding the first infusion of cocaine in each of the 14 sessions, which were defined as "pre-drug trials." NAc neuron responses were assessed prior to tone-evoked movement onset. Responsiveness to the DS tone was exhibited throughout all sessions by the NAc Core population, but only during Early sessions by the NAc Shell population. Both Core and Shell responded selectively to the DS, i.e., more strongly on drug taking trials, or Hits, than on Missed opportunities. These findings suggest that NAc Core and Shell play distinct roles in initiating cocaine seeking prior to daily cocaine consumption, and align with reports suggesting that as drug use becomes chronic, cue-evoked activity shifts from NAc Shell to NAc Core.

Developmental trajectories of delay discounting from childhood to young adulthood: longitudinal associations and test-retest reliability.

Delay discounting (DD) indexes an individual's preference for smaller immediate rewards over larger delayed rewards, and is considered a form of cognitive impulsivity. Cross-sectional studies have demonstrated that DD peaks in adolescence; longitudinal studies are needed to validate this putative developmental trend, and to determine whether DD assesses a temporary state, or reflects a more stable behavioral trait. In this study, 140 individuals aged 9-23 completed a delay discounting (DD) task and cognitive battery at baseline and every-two years thereafter, yielding five assessments over approximately 10 years. Models fit with the inverse effect of age best approximated the longitudinal trajectory of two DD measures, hyperbolic discounting (log[k]) and area under the indifference-point curve (AUC). Discounting of future rewards increased rapidly from childhood to adolescence and appeared to plateau in late adolescence for both models of DD. Participants with greater verbal intelligence and working memory displayed reduced DD across the duration of the study, suggesting a functional interrelationship between these domains and DD from early adolescence to adulthood. Furthermore, AUC demonstrated good to excellent reliability across assessment points that was superior to log(k), with both measures demonstrating acceptable stability once participants reached late adolescence. The developmental trajectories of DD we observed from childhood through young adulthood suggest that DD may index cognitive control more than reward sensitivity, and that despite modest developmental changes with maturation, AUC may be conceptualized as a trait variable related to cognitive control vs impulsivity.

The Sensory Gating Inventory-Brief.

The Sensory Gating Inventory (SGI) is a 36-item measure used to assess an individual's subjective ability to modulate, filter, over-include, discriminate, attend to, and tolerate sensory stimuli. Due to its theoretical and empirical link with sensory processing deficits, this measure has been used extensively in studies of psychosis and other psychopathology. The current work fills a need within the field for a briefer measure of sensory gating aberrations that maintains the original measure's utility. For this purpose, large samples (total n = 1552) were recruited from 2 independent sites for item reduction/selection and brief measure validation, respectively. These samples reflected subgroups of individuals with a psychosis-spectrum disorder, at high risk for a psychosis-spectrum disorder, nonpsychiatric controls, and nonpsychosis psychiatric controls. Factor analyses and item-response models were used to create the SGI-Brief (SGI-B; 10 Likert-rated items), a unidimensional self-report measure that retains the original SGI's transdiagnostic (ie, present across disorders) utility and content breadth. Findings show that the SGI-B has excellent psychometric properties (alpha = 0.92) and demonstrates external validity through strong associations with measures of psychotic symptomatology, theoretically linked measures of personality (eg, perceptual dysregulation), and modest associations with laboratory-based sensory processing tasks in the auditory and visual domains on par with the original version. Accordingly, the SGI-B will be a valuable tool for dimensional and transdiagnostic examination of sensory gating abnormalities within clinical science research, while reducing administrator and participant burden.

Perceptual Mechanisms of Visual Hallucinations and Illusions in Psychosis.

Psychosis has been associated with neural anomalies across a number of brain regions and cortical networks. Nevertheless, the exact pathophysiology of the disorder remains unclear. Aberrant visual perceptions such as hallucinations are evident in psychosis, while the occurrence of visual distortions is elevated in individuals with genetic liability for psychosis. The overall goals of this project are to: (1) use psychophysical tasks and neuroimaging to characterize deficits in visual perception; (2) acquire a mechanistic understanding of these deficits through development and validation of a computational model; and (3) determine if said mechanisms mark genetic liability for psychosis. Visual tasks tapping both low- and high-level visual processing are being completed as individuals with psychotic disorders (IPD), first-degree biological siblings of IPDs (SibIPDs) and healthy controls (HCs) undergo 248-channel magneto-encephalography (MEG) recordings followed by 7 Tesla functional magnetic resonance imaging (MRI). By deriving cortical source signals from MEG and MRI data, we will characterize the timing, location and coordination of neural processes. We hypothesize that IPDs prone to visual hallucinations will exhibit deviant functions within early visual cortex, and that aberrant contextual influences on visual perception will involve higher-level visual cortical regions and be associated with visual hallucinations. SibIPDs who experience visual distortions-but not hallucinations-are hypothesized to exhibit deficits in higher-order visual processing reflected in abnormal inter-regional neural synchronization. We hope the results lead to the development of targeted interventions for psychotic disorders, as well as identify useful biomarkers for aberrant neural functions that give rise to psychosis.

Neural anomalies during vigilance in schizophrenia: Diagnostic specificity and genetic associations.

Impaired vigilance is a core cognitive deficit in schizophrenia and may serve as an endophenotype (i.e., mark genetic liability). We used a continuous performance task with perceptually degraded stimuli in schizophrenia patients (N = 48), bipolar disorder patients (N = 26), first-degree biological relatives of schizophrenia patients (N = 55) and bipolar disorder patients (N = 28), as well as healthy controls (N = 68) to clarify whether previously reported vigilance deficits and abnormal neural functions were indicative of genetic liability for schizophrenia as opposed to a generalized liability for severe psychopathology. We also examined variation in the Catechol-O-methyltransferase gene to evaluate whether brain responses were related to genetic variation associated with higher-order cognition. Relatives of schizophrenia patients had an increased rate of misidentification of nontarget stimuli as targets when they were perceptually similar, suggestive of difficulties with contour perception. Larger early visual responses (i.e., N1) were associated with better task performance in patients with schizophrenia consistent with enhanced N1 responses reflecting beneficial neural compensation. Additionally, reduced N2 augmentation to target stimuli was specific to schizophrenia. Both patients with schizophrenia and first-degree relatives displayed reduced late cognitive responses (P3b) that predicted worse performance. First-degree relatives of bipolar patients exhibited performance deficits, and displayed aberrant neural responses that were milder than individuals with liability for schizophrenia and dependent on sex. Variation in the Catechol-O-methyltransferase gene was differentially associated with P3b in schizophrenia and bipolar groups. Poor vigilance in schizophrenia is specifically predicted by a failure to enhance early visual responses, weak augmentation of mid-latency brain responses to targets, and limited engagement of late cognitive responses that may be tied to genetic variation associated with prefrontal dopaminergic availability. Experimental results illustrate specific neural functions that distinguish schizophrenia from bipolar disorder and provides evidence for a putative endophenotype that differentiates genetic liability for schizophrenia from severe mental illness more broadly.

Emergence of negative affect as motivation for drug taking in rats chronically self-administering cocaine.

RATIONALE: The role of negative affect as a motivational factor in animal models of drug addiction has been underexplored in the context of cocaine self-administration. OBJECTIVES: The present investigation studied the relationship between magnitude of affective response and quantity of cocaine consumed in order to clarify the affective components that drive drug use in a preclinical model. METHODS: Rats self-administered (SA) cocaine 6 h/day for 14 consecutive days while their ultrasonic vocalizations (USVs) were recorded. RESULTS: Animals displayed an increase in 50-kHz call rates (indicating positive affect) when their drug levels were rapidly rising and an increase in 22-kHz call rates (indicating negative affect) when forced to abstain. The rate of 50-kHz calls predicted drug consumption during the 1st week of SA, but not week two. Contrarily, there was a strongly predictive positive association between rate of 22-kHz calls and amount of drug consumed during the 2nd week of SA. CONCLUSIONS: Experimental results indicate that after chronic cocaine self-administration, negative affect emerges when animals are deprived of expected drug during withdrawal. Moreover, the increase in USVs indicating negative affect when deprived of drug was directly related to drug intake, concurrent with a decay in the direct relationship between USVs indicating positive affect and drug intake. The present preclinical support for the widely hypothesized shift from positive to negative affect as a salient motivational factor in human drug abuse adds to growing evidence of the unique value of rat USVs for understanding the role of emotion in drug addiction.