N2 and P3 modulation during partial inhibition in a modified go/nogo task.

The neural response following the partial inhibition of responses can provide insight into the processes underlying response inhibition. We examined the N2 and P3 on trials where participants correctly responded to go stimuli, successfully inhibited their response to nogo stimuli, and nogo trials where they initiated but did not complete their response (partial inhibitions) in an adult sample (N=24, M(age)=21.17, SD(age)=3.52). An enhanced and delayed N2 was observed on partially inhibited compared to successfully inhibited nogo trials. Further analysis showed that this modulation was error-related. An enhanced central P3 was observed following successful inhibitions compared to correct go trials, but not following partial inhibitions. The results suggest that the central P3 enhancement is specific to the complete and successful inhibition of responses. Therefore, the absence of a central P3 on partial inhibitions could reflect insufficient inhibition or a monitored failure in inhibiting the response. Although, our findings provide support for the role of P3 in response inhibition, it raises questions about the processes involved in the subsequent inhibition or correction of the erroneous response. Further research examining the neural response following both partial and unsuccessful inhibitions could provide insight regarding these processes.

Time-based prospective memory predicts engagement in risk behaviors among substance users: results from clinical and nonclinical samples.

Deficits in prospective memory (PM; i.e., enacting previously learned actions at the right occasion) and risky decision-making (i.e., making choices with a high chance of undesirable/dangerous outcomes) are both common among individuals with substance use disorders (SUD). Previous research has raised the possibility of a specific relationship between PM and risk-taking, and the present study aimed to systematically study if PM provides unique variance in the prediction of risky decision-making. Two samples were included: (1) a group of 45 individuals with SUD currently in treatment, and (2) a nonclinical group of 59 university students with high-risk drinking and/or substance use. Regression analyses indicated that time-based, but not event-based, PM predicted increased risky behavior (e.g., risky sexual practices and criminal behaviors) in both groups after controlling for demographic, psychiatric, and substance use variables, as well as other neuropsychological functions. The current findings contribute to the growing literature supporting the role of PM as a predictor of everyday functioning, and suggest that cognitive rehabilitation may be an important avenue of research as an adjunct to traditional substance use treatment, particularly in addressing the potential adverse effects of PM deficits in the implementation of treatment-related homework activities and risk management strategies.

Prospective memory in substance abusers at treatment entry: associations with education, neuropsychological functioning, and everyday memory lapses.

Individuals with substance use disorders (SUDs) commonly report lapses in prospective memory (PM) in their daily lives; however, our understanding of the profile and predictors of laboratory-based PM deficits in SUDs and their associations with everyday PM failures is still very preliminary. The current study examined these important questions using well-validated measures of self-report and laboratory-based PM in a mixed cohort of 53 SUD individuals at treatment entry and 44 healthy adults. Consistent with prior research, the SUD group endorsed significantly more self-cued and environmentally based PM failures in their daily lives. Moreover, the SUD group demonstrated significantly lower time-based PM performance, driven largely by cue detection errors. The effect of SUDs on PM was particularly strong among participants with fewer years of education. Within the SUD cohort, time-based PM was correlated with clinical measures assessing executive functions, retrospective memory, and psychomotor speed. Importantly, time-based PM was uniquely associated with elevated PM failures in daily lives of the SUD participants, independent of current affective distress and other neurocognitive deficits. Findings suggest that individuals with SUD are vulnerable to deficits in PM, which may in turn increase their risk for poorer everyday functioning outcomes (e.g., treatment non-compliance).

The Audio Recorded Cognitive Screen (ARCS): a flexible hybrid cognitive test instrument.

OBJECTIVE: To describe and characterise the Audio Recorded Cognitive Screen (ARCS), a novel instrument that uses an audio device to administer selected neuropsychological tests to unsupervised individuals who write their responses in a special booklet for later scoring. METHODS: The ARCS was administered to 733 individuals, comprising 550 from a normative community sample (mean age=59.14, range 18-84 years), 101 clinic patients and a separate validation sample of 82 community controls, who, together with the patients, underwent detailed neuropsychological assessments. These data were examined for the influence of demographic variables on ARCS performance, to establish normal performance and develop scoring routines, and to characterise the structure, reliability and validity of the instrument. RESULTS: Age, gender and education influenced ARCS performance. ARCS tests were generally reliable and correlated well with corresponding conventional neuropsychological tests. Factor analyses indicated that the ARCS measures executive functioning/attention, memory, language, verbal fluency and visuospatial functioning. The ARCS discriminated well between normal (n=82), impaired (n=33) and demented (n=25) individuals, and significantly better than did the Mini Mental State Examination (MMSE), including on a single, demographically adjusted, global QuickARCS score obtainable in about 3 min of the clinician's time. Receiver Operating Characteristic analyses confirmed the superiority of the ARCS over MMSE as a screen for mild dementia (AUC 0.98, 99% CI 0.95 to 1.00) or cognitive impairment (AUC 0.90, 99% CI 0.83 to 0.97). CONCLUSIONS: The ARCS has good validity and reliability, has a sound normative base and measures functioning in multiple cognitive domains while imposing minimal time demands upon the clinician.

Integrating objective gene-brain-behavior markers of psychiatric disorders.

There is little consensus about which objective markers should be used to assess major psychiatric disorders, and predict/evaluate treatment response for these disorders. Clinical practice relies instead on subjective signs and symptoms, such that there is a "translational gap" between research findings and clinical practice. This gap arises from: a) a lack of integrative theoretical models which provide a basis for understanding links between gene-brain-behavior mechanisms and clinical entities; b) the reliance on studying one measure at a time so that linkages between markers are their specificity are not established; and c) the lack of a definitive understanding of what constitutes normative function. Here, we draw on a standardized methodology for acquiring multiple sources of genomic, brain and behavioral data in the same subjects, to propose candidate markers of selected psychiatric disorders: depression, post-traumatic stress disorder, schizophrenia, attention-deficit/hyperactivity disorder and dementia disorders. This methodology has been used to establish a standardized international database which provides a comprehensive framework and the basis for testing hypotheses derived from an integrative theoretical model of the brain. Using this normative base, we present preliminary findings for a number of disorders in relation to the proposed markers. Establishing these objective markers will be the first step towards determining their sensitivity, specificity and treatment prediction in individual patients.

Rates of decline distinguish Alzheimer's disease and mild cognitive impairment relative to normal aging: integrating cognition and brain function.

AIMS: Increasing age is the strongest risk factor for Alzheimer's disease (AD). Yet, departure from normal age-related decline for established markers of AD including memory, cognitive decline and brain function deficits, has not been quantified. METHODS: We examined the cross-sectional estimates of the "rate of decline" in cognitive performance and psychophysiological measures of brain function over age in AD, preclinical (subjective memory complaint-SMC, Mild Cognitive Impairment-MCI) and healthy groups. Correlations between memory performance and indices of brain function were also conducted. RESULTS: The rate of cognitive decline increased between groups: AD showed advanced decline, and SMC/MCI groups represented intermediate stages of decline relative to normal aging expectations. In AD, advanced EEG alterations (excessive slow-wave/reduced fast-wave EEG, decreased working memory P450 component) were observed over age, which were coupled with memory decline. By contrast, MCI group showed less severe cognitive changes but specific decreases in the working memory N300 component and slow-wave (delta) EEG, associated with decline in memory. DISCUSSION AND INTEGRATIVE SIGNIFICANCE: While the cognitive data suggests a continuum of deterioration associated with increasing symptom severity across groups, integration with brain function measures points to possible distinct compensatory strategies in MCI and AD groups. An integrative approach offers the potential for objective markers of the critical turning point, with age as a potential factor, from mild memory problems to disease.