Olga Rass

Temporal Discounting of Rewards in Patients With Bipolar Disorder and Schizophrenia

Patients with bipolar disorder (BD) and schizophrenia (SZ) often show decision-making deficits in everyday circumstances. A failure to appropriately weigh immediate versus future consequences of choices may contribute to these deficits. We used the delay discounting task in individuals with BD or SZ to investigate their temporal decision making. Twenty-two individuals with BD, 21 individuals with SZ, and 30 healthy individuals completed the delay discounting task along with neuropsychological measures of working memory and cognitive function. Both BD and SZ groups discounted delayed rewards more steeply than did the healthy group even after controlling for current substance use, age, gender, and employment. Hierarchical multiple regression analyses showed that discounting rate was associated with both diagnostic group and working memory or intelligence scores. In each group, working memory or intelligence scores negatively correlated with discounting rate. The results suggest that (a) both BD and SZ groups value smaller, immediate rewards more than larger, delayed rewards compared with the healthy group and (b) working memory or intelligence is related to temporal decision making in individuals with BD or SZ as well as in healthy individuals.

Disturbed resting state EEG synchronization in bipolar disorder: A graph-theoretic analysis.

Disruption of functional connectivity may be a key feature of bipolar disorder (BD) which reflects disturbances of synchronization and oscillations within brain networks. We investigated whether the resting electroencephalogram (EEG) in patients with BD showed altered synchronization or network properties. Resting-state EEG was recorded in 57 BD type-I patients and 87 healthy control subjects. Functional connectivity between pairs of EEG channels was measured using synchronization likelihood (SL) for 5 frequency bands (δ, θ, α, β, and γ). Graph-theoretic analysis was applied to SL over the electrode array to assess network properties. BD patients showed a decrease of mean synchronization in the alpha band, and the decreases were greatest in fronto-central and centro-parietal connections. In addition, the clustering coefficient and global efficiency were decreased in BD patients, whereas the characteristic path length increased. We also found that the normalized characteristic path length and small-worldness were significantly correlated with depression scores in BD patients. These results suggest that BD patients show impaired neural synchronization at rest and a disruption of resting-state functional connectivity.

Auditory Steady State Response in the Schizophrenia, First-Degree Relatives, and Schizotypal Personality Disorder

The power and phase synchronization of the auditory steady state response (ASSR) at 40 Hz stimulation is usually reduced in schizophrenia (SZ). The sensitivity of the 40 Hz ASSR to schizophrenia spectrum phenotypes, such as schizotypal personality disorder (SPD), or to familial risk has been less well characterized. We compared the ASSR of patients with SZ, persons with schizotypal personality disorder, first degree relatives of patients with SZ, and healthy control participants. ASSRs were obtained to 20, 30, 40 and 50 Hz click trains, and assessed using measures of power (mean trial power or MTP) and phase consistency (phase locking factor or PLF). The MTP to 40 Hz stimulation was reduced in relatives, and there was a trend for MTP reduction in SZ. The 40 Hz ASSR was not reduced in SPD participants. PLF did not differ among groups. These data suggest the 40 Hz ASSR is sensitive to familial risk factors associated with schizophrenia.

The auditory steady-state response (ASSR): a translational biomarker for schizophrenia.

Electrophysiological methods have demonstrated disturbances of neural synchrony and oscillations in schizophrenia which affect a broad range of sensory and cognitive processes. These disturbances may account for a loss of neural integration and effective connectivity in the disorder. The mechanisms responsible for alterations in synchrony are not well delineated, but may reflect disturbed interactions within GABAergic and glutamatergic circuits, particularly in the gamma range. Auditory steady-state responses (ASSRs) provide a non-invasive technique used to assess neural synchrony in schizophrenia and in animal models at specific response frequencies. ASSRs are electrophysiological responses entrained to the frequency and phase of a periodic auditory stimulus generated by auditory pathway and auditory cortex activity. Patients with schizophrenia show reduced ASSR power and phase locking to gamma range stimulation. We review alterations of ASSRs in schizophrenia, schizotypal personality disorder, and first-degree relatives of patients with schizophrenia. In vitro and in vivo approaches have been used to test cellular mechanisms for this pattern of findings. This translational, cross-species approach provides support for the role of N-methyl-D-aspartate and GABAergic dysregulation in the genesis of perturbed ASSRs in schizophrenia and persons at risk.

Auditory steady state response in bipolar disorder: relation to clinical state, cognitive performance, medication status, and substance disorders

OBJECTIVES   Abnormalities in auditory steady state response (ASSR) at gamma range frequencies have been found in bipolar disorder, but the relationship of these neurophysiological disturbances to clinical factors has not been well characterized. We therefore evaluated the ASSR in bipolar disorder and examined its sensitivity to clinical symptoms, cognitive function, and pharmacological treatment. METHODS   A total of 68 patients with bipolar disorder and 77 control participants were evaluated. Click trains presented at 20, 30, 40, and 50 Hz evoked ASSRs. Mean trial power (MTP) and phase locking factor (PLF) measured response magnitude and phase synchronization of the ASSR at each stimulation frequency. Clinical state, pharmacological treatment, and neuropsychological performance were assessed, and their respective relationships with ASSR measures were evaluated. RESULTS   Patients with bipolar disorder showed reduced MTP and PLF compared to control participants. Bipolar disorder patients taking psychotropic medications had decreased PLF relative to patients withdrawn from medications. Control participants performed better on neuropsychological tests than bipolar disorder patients; however, test scores did not correlate with ASSR measures. CONCLUSIONS   Deficits in the generation and maintenance of ASSR are present in bipolar disorder, implicating disturbances in auditory pathways. ASSR may be sensitive to medication status. Other clinical features, including mood state, psychotic features, cognitive performance, smoking, or history of substance use disorder, were unrelated to MTP or PLF.

Computer-assisted cognitive remediation for schizophrenia: A randomized single-blind pilot study

Cognitive impairment is a core symptom in schizophrenia that has a significant impact on psychosocial function, but shows a weak response to pharmacological treatment. Consequently, a variety of cognitive remediation strategies have been evaluated to improve cognitive function in schizophrenia. The efficacy of computer-based cognitive remediation as a stand-alone intervention on general measures of neuropsychological function remains unclear. We tested the effectiveness of biweekly training using computerized cognitive remediation programs on neuropsychological and event-related potential outcome measures. Schizophrenia patients were randomly assigned to cognitive remediation training (N=17), active control (TV-watching; N=17), or treatment-as-usual (N=10) groups for ten weeks and run in parallel. Cognitive and ERP measures revealed no differential improvement over time in the cognitive remediation group. Practice effects might explain change over time on several cognitive measures for all groups, consistent with studies indicating task-specific improvement. Computer-assisted cognitive remediation alone may not be sufficient for robust or generalized effects on cognitive and electrophysiological measures in schizophrenia patients.

A randomized controlled trial of the effects of working memory training in methadone maintenance patients

OBJECTIVE Working memory impairment in individuals with chronic opioid dependence can play a major role in cognitive and treatment outcomes. Cognitive training targeting working memory shows promise for improved function in substance use disorders. To date, cognitive training has not been incorporated as an adjunctive treatment for opioid dependence. METHODS Methadone maintenance patients were randomly assigned to experimental (n=28) or active control (n=28) 25-session computerized training and run in parallel. Cognitive and drug use outcomes were assessed before and after training. RESULTS Participants in the experimental condition showed performance improvements on two of four working memory measures, and both groups improved on a third measure of working memory performance. Less frequent drug use was found in the experimental group than in the control group post-training. In contrast to previous findings with stimulant users, no significant effect of working memory training on delay discounting was found using either hypothetical or real rewards. There were no group differences on working memory outcome measures that were dissimilar from the training tasks, suggesting that another mechanism (e.g., increased distress tolerance) may have driven drug use results. CONCLUSIONS Working memory training improves performance on some measures of working memory in methadone maintenance patients, and may impact drug use outcomes. Working memory training shows promise in patients with substance use disorders; however, further research is needed to understand the mechanisms through which performance is improved and drug use outcomes are impacted.

Eliminating the memory blocking effect.

Six experiments investigated the memory blocking effect (MBE) in which exposure to orthographically similar words (e.g., BALLOON) impairs ones ability to complete a similar fragment (e.g., BAL_ON_, solution is BALCONY). Experiments 1 and 2 demonstrated that blocking is not observed after a 72-hour delay; however, repetition priming was observed after the same delay. Experiments 3 and 4 showed that presenting unrelated semantic information during the fragment completion test eliminates blocking. Experiment 5 demonstrated that the MBE persists despite directed-forgetting instructions, and Experiments 5 and 6 demonstrated that activating both the solutions and blocking words for a particular fragment at study eliminates blocking. Collectively, the data demonstrate that reading orthographically similar primes automatically triggers retrieval of the blocking word and an executive control process works to manage this interference. A working framework that describes how an executive control mechanism could govern memory retrieval in the memory-blocking paradigm is presented to stimulate development of more advanced theoretical models that can explain blocking.

Cognitive performance in methadone maintenance patients: effects of time relative to dosing and maintenance dose level.

Given the long-term nature of methadone maintenance treatment, it is important to assess the extent of cognitive side effects. This study investigated cognitive and psychomotor performance in 51 methadone maintenance patients (MMP) as a function of time since last methadone dose and maintenance dose level. MMP maintained on doses ranging from 40 to 200 mg (mean = 97 mg) completed a battery of psychomotor and cognitive measures across 2 sessions, during peak and trough states, in a double-blind crossover design. Peak sessions were associated with worse performance on measures of sensory processing, psychomotor speed, divided attention, and working memory, compared with trough sessions. The effects of maintenance dose were mixed, with higher dose resulting in worse performance on aspects of attention and working memory, improved performance on executive function, and no effects on several measures. Longer treatment duration was associated with better performance on some measures, but was also associated with increased sensitivity to time since last dose (i.e., worse performance at peak vs. trough) on some measures. The results suggest that cognitive functioning can fluctuate as a function of time since last dose even in MMP who have been maintained on stable doses for an extended time (mean duration in treatment = 4 years), but worsened performance at peak is limited to a subset of functions and may not be clinically significant at these modest levels of behavioral effect. For patients on stable methadone maintenance doses, maintenance at higher doses may not significantly increase the risk of performance impairment.

Neural correlates of performance monitoring in daily and intermittent smokers

OBJECTIVES Despite efforts that have increased smoking regulation, cigarette taxation, and social stigma, cigarette smoking remains the leading cause of preventable death worldwide, and a significant personal and public economic burden. In the U.S., intermittent smokers comprise approximately 22% of all smokers and represent a stable, non-dependent group that may possess protective factors that prevent the transition to dependence. One possibility is that intermittent smokers have intact CNS frontal regulatory and control mechanisms that enable resistance to nicotine-induced changes. METHODS The present study measured inhibitory control using a flanker task and a go-nogo continuous performance tasks in daily dependent smokers, intermittent non-dependent smokers, and nonsmokers. Event-related potential (ERP) measures of were concurrently recorded to measure performance monitoring via Event-Related Negativity (ERN) and error positivity (Pe) components during error trials for each task. RESULTS In both tasks, behavioral and ERN measures did not differ between groups; however, amplitude of the Pe component was largest among intermittent smokers. CONCLUSIONS Thus, intermittent smokers differed from both daily smokers and nonsmokers on error processing, potentially revealing neuroprotective cognitive processes in nicotine dependence. SIGNIFICANCE A better understanding of factors that mediate behavioral regulation may provide novel treatment approaches that help individuals achieve controlled smoking or cessation.