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EEG reveals that dextroamphetamine improves cognitive control through multiple processes in healthy participants.

ABSTRACT: The poor translatability between preclinical and clinical drug trials has limited pro-cognitive therapeutic development. Future pro-cognitive drug trials should use translatable cross-species cognitive tasks with biomarkers (1) relevant to specific cognitive constructs, and (2) sensitive to drug treatment. Here, we used a difficulty-modulated variant of a cross-species cognitive control task with simultaneous electroencephalography (EEG) to identify neurophysiological biomarkers sensitive to the pro-cognitive effects of dextroamphetamine (d-amp) (10 or 20 mg) in healthy adults (n = 23), in a randomized, placebo-controlled, counterbalanced, double blind, within-subject study, conducted across three test days each separated by one week. D-amp boosted d-prime, sped reaction time, and increased frontal P3a amplitude to non-target correct rejections independent of task difficulty. Task difficulty did however, moderate d-amp effects on EEG during target performance. D-amp suppressed frontal theta power during easy target responses which negatively correlated with drug-induced improvement in hit rate while d-amp-induced changes in P3b amplitude during hard target trials strongly correlated with drug-induced improvement in hit rate. In summary, d-amp affected both behavioral and neurophysiological measures of cognitive control elements. Under low-demand, d-amp diminished cognitive control by suppressing theta, yet under high-demand it boosted control in concert with higher P3b amplitudes. These findings thus appear to reflect a gain-sharpening effect of d-amp: during high-demand processes were boosted while during low-demand processes were neglected. Future studies will use these neurophysiological measures of cognitive control as biomarkers to predict d-amp sensitivity in people with cognitive control deficits, including schizophrenia.

SUBMITTER: Bhakta SG

PROVIDER: S-EPMC8938448 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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EEG reveals that dextroamphetamine improves cognitive control through multiple processes in healthy participants.

Bhakta Savita G SG Cavanagh James F JF Talledo Jo A JA Kotz Juliana E JE Benster Lindsay L Roberts Benjamin Z BZ Nungaray John A JA Brigman Jonathan L JL Light Gregory A GA Swerdlow Neal R NR Young Jared W JW

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20220118 5

The poor translatability between preclinical and clinical drug trials has limited pro-cognitive therapeutic development. Future pro-cognitive drug trials should use translatable cross-species cognitive tasks with biomarkers (1) relevant to specific cognitive constructs, and (2) sensitive to drug treatment. Here, we used a difficulty-modulated variant of a cross-species cognitive control task with simultaneous electroencephalography (EEG) to identify neurophysiological biomarkers sensitive to the ...[more]

PMID: 35042948

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Project description:Working memory performance can be influenced by motivational factors, which may be associated with specific brain activities, including suppression of alpha oscillations. We investigated whether providing individuals online feedback about their ongoing oscillations (EEG-neurofeedback) can improve working memory under high and low reward expectancies. We combined working memory training with neurofeedback to enhance alpha suppression in a monetary-rewarded delayed match-to-sample task for visual objects. Along with alpha, we considered the neighbouring theta and beta bands. In a double-blind experiment, individuals were trained over 5 days to suppress alpha power by receiving real-time neurofeedback or control neurofeedback (placebo) in reward and no-reward trials. We investigated (i) whether neurofeedback enhances alpha suppression, (ii) whether monetary reward enhances alpha suppression and working memory, and (iii) whether any performance benefits of neurofeedback-training would transfer to unrelated cognitive tasks. With the same experimental design, we conducted two studies with differing instructions given at the maintenance, yielding together 300 EEG recording sessions. In Study I, participants were engaged in a mental calculation task during maintenance. In Study II, they were instructed to visually rehearse the sample image. Results from Study I demonstrated a significant training and reward-anticipation effect on working memory accuracy and reaction times over 5 days. Neurofeedback and reward anticipation showed effects on theta suppression but not on alpha suppression. Moreover, a cognitive training effect was observed on beta suppression. Thus, neurofeedback-training of alpha was unrelated to working memory performance. Study II replicated the training and reward-anticipation effect on working memory but without any effects of neurofeedback-training on oscillations or working memory. Neither study showed transfer effects of either working memory or neurofeedback-training. A linear mixed-effect model analysis of neurofeedback-independent training-related improvement of working memory combining both studies showed that improved working memory performance was related to oscillatory changes over training days in the encoding and maintenance phases. Improvements in accuracy were related to increasing beta amplitude in reward trials over right parietal electrodes. Improvements in reaction times were related to increases in right parietal theta amplitude during encoding and increased right parietal and decreased left parietal beta amplitudes during maintenance. Thus, while our study provided no evidence that neurofeedback targeting alpha improved the efficacy of working memory training or evidence for transfer, it showed a relationship between training-related changes in parietal beta oscillations during encoding and improvements in accuracy. Right parietal beta oscillations could be an intervention target for improving working memory accuracy.

Project description:BackgroundSchizophrenia spectrum disorders (SSDs) feature social cognitive deficits, although their neural basis remains unclear. Social cognitive performance may relate to neural circuit activation patterns more than to diagnosis, which would have important prognostic and therapeutic implications. The current study aimed to determine how functional connectivity within and between social cognitive networks relates to social cognitive performance across individuals with SSDs and healthy control participants.MethodsParticipants with SSDs (n = 164) and healthy control participants (n = 117) completed the Empathic Accuracy task during functional magnetic resonance imaging as well as lower-level (e.g., emotion recognition) and higher-level (e.g., theory of mind) social cognitive measures outside the scanner. Functional connectivity during the Empathic Accuracy task was analyzed using background connectivity and graph theory. Data-driven social cognitive networks were identified across participants. Regression analyses were used to examine network connectivity-performance relationships across individuals. Positive and negative within- and between-network connectivity strengths were also compared in poor versus good social cognitive performers and in SSD versus control groups.ResultsThree social cognitive networks were identified: motor resonance, affect sharing, and mentalizing. Regression and group-based analyses demonstrated reduced between-network negative connectivity, or segregation, and greater within- and between-network positive connectivity in worse social cognitive performers. There were no significant effects of diagnostic group on within- or between-network connectivity.ConclusionsThese findings suggest that the neural circuitry of social cognitive performance may exist dimensionally. Across participants, better social cognitive performance was associated with greater segregation between social cognitive networks, whereas poor versus good performers may compensate via hyperconnectivity within and between social cognitive networks.

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EEG reveals that dextroamphetamine improves cognitive control through multiple processes in healthy participants.

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EEG reveals that dextroamphetamine improves cognitive control through multiple processes in healthy participants.

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