Reward-predictive stimuli augment instrumental reward-seeking in humans, an effect denoted Pavlovian-to-instrumental transfer (PIT), but the role of differential reward value of these stimuli and of emotional conditioned responses in PIT remains unknown. Fifty one participants experienced a Pavlovian phase that associated two stimuli with either 10p (CS10) or 50p (CS50). Next, participants underwent instrumental training for two responses reinforced with either 10p or 50p. Finally, the transfer phase continued as had instrumental training, now in the presence of the Pavlovian stimuli. Participants were dichotomised as aware/unaware according to their expectancy awareness of the CS→outcome associations. Only aware participants demonstrated PIT (increased choice and number of responses on the 10p and 50p response key in the presence of CS10 and CS50 respectively), yet both aware and unaware groups rated the 50p stimulus as more pleasant than the 10p stimulus. These findings suggest that expectancy of reward is necessary for PIT; however, emotional conditioned responses appear not sufficient to influence PIT. Future research should attempt to manipulate emotional conditioned responses in a PIT context, to test the sufficiency of reward expectancy in PIT.

At present, there is a considerable lack of human studies that investigated the impact of conditioned cues on instrumental responding although these processes are considered as core mechanisms contributing to the development and maintenance of addictive behaviours. No studies are available that assessed these processes with regard to Internet gaming or Internet shopping applications. We thus developed a Pavlovian-to-instrumental transfer (PIT)-Paradigm implementing appetitive stimuli related to Internet gaming and Internet shopping applications and investigated whether an outcome-specific PIT-Effect is observed. In addition, we assessed whether the problematic use of gaming or shopping applications, personality traits and stress would affect the acquisition of knowledge of the experimental contingencies during Pavlovian training and the impact of conditioned stimuli on instrumental responding. A PIT-Paradigm, screenings for Internet gaming disorder and Internet shopping disorder (s-IAT), and questionnaires on personality traits (NEO-FFI, BIS-15) and perceived stress (PSQ20) were administered to sixty-six participants. The PIT-Paradigm demonstrated the effects of stimuli conditioned to rewards related to Internet gaming and Internet shopping applications on instrumental responding to obtain such rewards. Findings also indicated that severity of problematic Internet gaming, but not Internet shopping, contributed to the acquisition of knowledge of the experimental contingencies. Stress, extraversion, neuroticism and gender emerged as further predictors. The strength of expectancy of the different reinforcers affected the 'gaming PIT'-Effect; however, none of the variables assessed in the present study showed any effect on the 'shopping PIT'-Effect. Future studies including participants with pathological use patterns that can be classified as internet use disorder are warranted to extend these findings.

Functional hemispheric asymmetries emerge as the left and the right hemisphere are dominant for different aspects of task processing. However, the hemispheres do not work independent of each other but share information through the corpus callosum. The integration of information across the corpus callosum is dependent on its structural integrity and functionality. Several hormones, like estradiol and progesterone, can influence this function. Since earlier work has demonstrated that long-term changes in stress hormone levels are accompanied by changes in hemispheric asymmetries in several mental disorders, the aim of the current study was to investigate whether acute stress and the associated changes in stress hormone levels also affect information transfer across the corpus callosum. For this purpose, we collected EEG data from 51 participants while completing a lexical decision task and a Poffenberger paradigm twice, once after stress induction with the Trier Social Stress Test and once after a control-condition. While there were no differences in interhemispheric transfer between the stress and the non-stress condition in the Poffenberger paradigm, we observed shorter latencies to stimuli in the left visual field in the left hemisphere at the CP3-CP4 electrode pair after stress. These results suggest that the transfer of lexical material from the right to the left hemisphere was quicker under stress. Stress may increase callosal excitability and lead to more efficient signal transfer across the corpus callosum between language related areas. Future studies using pharmacological intervention are needed to further examine cooperation of the hemispheres under stress in more detail.

We have previously shown that the ventromedial prefrontal cortex (vmPFC) is involved in spontaneous working memory and anxiety-related behaviour in CD-1 mice. Specifically, pretrial microinjection of the kappa(1) agonist, U-69,593, in the infralimbic (IL) area of the vmPFC produced a robust anxiolytic behavioural profile in the elevated plus-maze and enhanced spontaneous working memory in the Y-maze. In the present study we sought to determine whether these effects were specific to IL kappa receptors. We hypothesized that microinjection of the kappa antagonist, norBNI, in the IL cortex would influence anxiety and spontaneous memory in an opposite direction to the effects produced by the kappa(1) agonist. In week 1, transfer-latency reference memory and anxiety were tested in the elevated plus-maze in two separate trials with an intertrial interval of 24 h. In week 2, spontaneous working memory was tested in the Y-maze followed immediately by defensive/withdrawal anxiety in the open field for one half of the animals in each group, and the other half was tested in reverse order. Pretreatment with one injection of vehicle, 1, 5 or 10 nmol/0.5 microl norBNI in the IL cortex dose-dependently reduced transfer-latencies and produced an anxiogenic behavioural profile in the first elevated plus-maze trial. Following a 24 h delay, transfer-latency reference memory was not influenced, but a robust anxiogenic behavioural profile was observed in the second no-injection anxiety trial in the elevated plus-maze relative to control animals. In week 2, the same groups of mice were again pretreated with one injection of the same doses of norBNI in the IL cortex and tested in the open field and Y-maze. NorBNI pretreatment was anxiogenic in the defensive/withdrawal anxiety test and disrupted spontaneous working memory regardless of testing order. The present results show the influence of kappa receptor modulation on anxiety induction and spontaneous working memory. These results also support the hypothesis that immediate memory processing may modulate the induction of anxiety-related behaviours.

This investigation aims to further our understanding of the brain mechanisms underlying the awareness of one's erroneous actions. While all errors are registered as such in the rostral cingulate zone, errors enter awareness only when the anterior insula cortex is activated. Aware but not unaware errors elicit autonomic nervous system reactivity. Our aim is to investigate the hypothesis that activation in the insula during error awareness is related to autonomic arousal and to inter-regional interactions with other areas of the brain. To examine the role of the anterior insula in error awareness, we assessed its functional connectivity to other brain regions along with autonomic nervous system reactivity in young healthy participants who underwent simultaneous pupil-diameter and functional magnetic resonance imaging measurements while performing a complex and error-prone task. Error blindness was associated with failures to engage sufficient autonomic reactivity. During aware errors increased pupil-diameter along with increased task-related activation within, and increased connectivity between anterior insula and task-related networks suggested an increased capacity for action-control information transfer. Increased pupil-diameter during aware errors was furthermore associated with decreased activation of the default-mode network along with decreased insular connectivity with regions of the default mode system, possibly reflecting decreased task-irrelevant information processing. This shifting mechanism may be relevant to a better understanding of how the brain and the autonomic nervous system interact to enable efficient adaptive behavior during cognitive challenge.

Entorhinal cortex neuropathology begins very early in Alzheimer's disease (AD), a disorder characterized by severe memory disruption. Indeed, loss of entorhinal volume is predictive of AD and two of the hallmark neuroanatomical markers of AD, amyloid plaques and neurofibrillary tangles (NFTs), are particularly prevalent in the entorhinal area of AD-afflicted brains. Gene transfer techniques were used to create a model neurofibrillary tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the entorhinal cortex of adult rats. The objective of the present investigation was to determine whether adult onset, spatially restricted tauopathy could be sufficient to reproduce progressive deficits in mnemonic function. Spatial memory on a Y-maze was tested for approximately 3 months post-surgery. Upon completion of behavioral testing the brains were assessed for expression of human tau and evidence of tauopathy. Rats injected with the tau vector became persistently impaired on the task after about 6 weeks of postoperative testing, whereas the control rats injected with a green fluorescent protein vector performed at criterion levels during that period. Histological analysis confirmed the presence of hyperphosphorylated tau and NFTs in the entorhinal cortex and neighboring retrohippocampal areas as well as limited synaptic degeneration of the perforant path. Thus, highly restricted vector-induced tauopathy in retrohippocampal areas is sufficient for producing progressive impairment in mnemonic ability in rats, successfully mimicking a key aspect of tauopathies such as AD.

Tauopathy in the hippocampus is one of the earliest cardinal features of Alzheimer's disease (AD), a condition characterized by progressive memory impairments. In fact, density of tau neurofibrillary tangles (NFTs) in the hippocampus strongly correlates with severity of cognitive impairments in AD. In the present study, we employed a somatic cell gene transfer technique to create a rodent model of tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the hippocampus of adult rats. The P301L mutation is causal for frontotemporal dementia with parkinsonism-17 (FTDP-17), but it has been used for studying memory effects characteristic of AD in transgenic mice. To ascertain if P301L-induced mnemonic deficits are persistent, animals were tested for 6 months. It was hypothesized that adult-onset, spatially restricted tau expression in the hippocampus would produce progressive spatial working memory deficits on a learned alternation task. Rats injected with the tau vector exhibited persistent impairments on the hippocampal-dependent task beginning at about 6 weeks post-transduction compared to rats injected with a green fluorescent protein vector. Histological analysis of brains for expression of human tau revealed hyperphosphorylated human tau and NFTs in the hippocampus in experimental animals only. Thus, adult-onset, vector-induced tauopathy spatially restricted to the hippocampus progressively impaired spatial working memory in rats. We conclude that the model faithfully reproduces histological and behavioral findings characteristic of dementing tauopathies. The rapid onset of sustained memory impairment establishes a preclinical model particularly suited to the development of potential tauopathy therapeutics.