Identification of conserved frontal neurophysiological markers of cognitive flexibility in humans and rats.

Cognitive flexibility broadly describes behavioral alterations made in response to environmental changes and is fundamental for survival. While human and non-human animal assessments of cognitive flexibility are available, a systematic cross-species comparison of behavioral, neurophysiological, and computational markers of cognitive flexibility has not been reported. Using versions of a probabilistic reversal learning task aligned between humans and rats, electroencephalogram recordings reveal a frontal reward positivity (RewP) associated with unexpected reward outcomes.

Error-related Alpha Suppression: Scalp Topography and (Lack of) Modulation by Modafinil.

Errors in performance trigger cognitive and neural changes that are implemented to adaptively adjust to fluctuating demands. Error-related alpha suppression (ERAS)-which refers to decreased power in the alpha frequency band after an incorrect response-is thought to reflect cognitive arousal after errors. Much of this work has been correlational, however, and there are no direct investigations into its pharmacological sensitivity.

Concurrent electrophysiological recording and cognitive testing in a rodent touchscreen environment.

Challenges in therapeutics development for neuropsychiatric disorders can be attributed, in part, to a paucity of translational models capable of capturing relevant phenotypes across clinical populations and laboratory animals. Touch-sensitive procedures are increasingly used to develop innovative animal models that better align with testing conditions used in human participants. In addition, advances in electrophysiological techniques have identified neurophysiological signatures associated with characteristics of neuropsychiatric illness.

Concordant neurophysiological signatures of cognitive control in humans and rats.

Progress towards understanding neural mechanisms in humans relevant to psychiatric conditions has been hindered by a lack of translationally-relevant cognitive tasks for laboratory animals. Accordingly, there is a critical need to develop parallel neurophysiological assessments of domains of cognition, such as cognitive control, in humans and laboratory animals. To address this, we developed a touchscreen-based cognitive (Eriksen Flanker) task in rats and used its key characteristics to construct a novel human version, with similar testing parameters and endpoints across species.

Nucleus Accumbens Medium Spiny Neuron Subtypes Differentially Regulate Stress-Associated Alterations in Sleep Architecture.

Background: Stress is implicated in the pathophysiology of major depression and posttraumatic stress disorder. These conditions share core features, including motivational deficits, heighted anxiety, and sleep dysregulation. Chronic stress produces these same features in rodents, with some individuals being susceptible or resilient, as seen in humans.

Differential Effects of Nicotine and Nicotine Withdrawal on Fear Conditioning in Male Rats.

Background: Tobacco use is prevalent in individuals who are routinely exposed to stress. However, little is known about how nicotine affects responses to trauma. We examined in rats how nicotine exposure affects fear conditioning, a procedure often used to study stress-related psychiatric illness.

Learned avoidance requires VTA KOR-mediated reductions in dopamine.

Proper learning from an aversive experience is essential for survival, yet it is an aberrant process in a wide range of mental disorders, as well as dopaminergic neurodegenerative disease. While the mesolimbic dopamine system is known to be essential for reward learning, the characterization of a potential pattern of dopamine signaling that guides avoidance remains unknown. Aversive stimuli may directly modulate dopamine signaling through the dynorphin/kappa opioid receptor (KOR) system, as kappa opioid receptors are expressed in this neural circuit and their activation is aversive in both rodents and humans.

Dopamine and Addiction.

Addiction is commonly identified with habitual nonmedical self-administration of drugs. It is usually defined by characteristics of intoxication or by characteristics of withdrawal symptoms. Such addictions can also be defined in terms of the brain mechanisms they activate; most addictive drugs cause elevations in extracellular levels of the neurotransmitter dopamine.

Drug predictive cues activate aversion-sensitive striatal neurons that encode drug seeking.

Drug-associated cues have profound effects on an addict's emotional state and drug-seeking behavior. Although this influence must involve the motivational neural system that initiates and encodes the drug-seeking act, surprisingly little is known about the nature of such physiological events and their motivational consequences. Three experiments investigated the effect of a cocaine-predictive stimulus on dopamine signaling, neuronal activity, and reinstatement of cocaine seeking.

Aversive stimuli drive drug seeking in a state of low dopamine tone.

Background: Stressors negatively impact emotional state and drive drug seeking, in part, by modulating the activity of the mesolimbic dopamine system. Unfortunately, the rapid regulation of dopamine signaling by the aversive stimuli that cause drug seeking is not well characterized. In a series of experiments, we scrutinized the subsecond regulation of dopamine signaling by the aversive stimulus, quinine, and tested its ability to cause cocaine seeking.

Corticosterone acts in the nucleus accumbens to enhance dopamine signaling and potentiate reinstatement of cocaine seeking.

Stressful life events are important contributors to relapse in recovering cocaine addicts, but the mechanisms by which they influence motivational systems are poorly understood. Studies suggest that stress may "set the stage" for relapse by increasing the sensitivity of brain reward circuits to drug-associated stimuli. We examined the effects of stress and corticosterone on behavioral and neurochemical responses of rats to a cocaine prime after cocaine self-administration and extinction.

Sensory reinforcement as a predictor of cocaine and water self-administration in rats.

Rationale: The ability of locomotor activity in a novel environment (Loco) and visual stimulus reinforcement (VSR) to predict acquisition of responding for cocaine and water reinforcers in the absence of explicit audiovisual signals was evaluated.

Methods: In Experiment 1 (Exp 1), rats (n = 60) were tested for VSR, followed by Loco, and finally acquisition of responding for cocaine (0.3 mg/kg/inf).

Association between locomotor response to novelty and light reinforcement: sensory reinforcement as a rodent model of sensation seeking.

Background: The human personality trait of sensation seeking (SS) indicates an attraction to novel sensations and experiences, and is associated with greater likelihood of drug abuse. In rodents, locomotor activity in a novel environment (Loco) has been found to predict drug self-administration (SA), and has been hypothesized to be a translational model of human SS. Previously, we reported (Gancarz et al.