Joseph H. R. Maes

Auditory event-related potentials in humans and rats: Effects of task manipulation

The purpose of this study was to compare components of the rat and human auditory event-related potential (ERP) as generated in active oddball and passive single-stimulus tasks. The rats were trained to discriminate between target and standard stimuli in an oddball task, whereas the human subjects received instructions. Task effects on various ERP components were found in both species. Interestingly, effects on the P3 component were similar in the species with regard to amplitude: Target stimuli elicited a higher amplitude in the oddball task than did standard stimuli. This might indicate that the P3 shares the same characteristics between species. However, the first four components occurred 1.82 times earlier in rats than in humans, expecting a P3 of about 200 ms in rats. The P3 in rats appeared at 380 ms. We conclude that either the relation between human and rat peak latencies is not linear, or the P3 in rats is not the equivalent of the human P3.

Attentional set shifting in autism spectrum disorder: differentiating between the role of perseveration, learned irrelevance, and novelty processing.

Autism spectrum disorders (ASD) are associated with impaired attentional set shifting, which may reflect enhanced perseverative responding, enhanced learned irrelevance, and/or reduced novelty processing. We assessed the contribution of these potential error sources in ASD adults. A total of 17 ASD and 19 matched comparison individuals first solved a discrimination learning task. Thereafter, the participants faced three types of attentional shift, specifically designed to isolate the effect of the three possible error sources. ASD participants made more errors than comparison individuals in a shift implying a choice between a novel relevant stimulus attribute and a familiar attribute that was previously relevant but now irrelevant. However, they made fewer errors in a shift involving a choice between a novel irrelevant attribute and a familiar, previously irrelevant but now relevant attribute. The results in combination suggest that the performance difference, at least in the present shift task, is caused by reduced novelty processing in ASD participants.

Orbitofrontal cortex and amygdalar over-activity is associated with an inability to use the value of expected outcomes to guide behaviour in serotonin transporter knockout rats

A disturbance in 5-HT signalling can lead to maladaptive and disruptive behavioural changes seen in neuropsychiatric disorders, potentially by 5-HTs role in cognitive control over behaviour. 5-HT levels are tightly controlled by the serotonin transporter (5-HTT). We and others have observed that 5-HTT availability affects reversal learning. Here we investigated the role of 5-HT in another type of cognitive control, which is the ability to use the value of expected outcomes to guide behaviour. 5-HTT knockout (5-HTT(-/-)) rats and wild-type (5-HTT(+/+)) controls were subjected to a Pavlovian reinforcer devaluation paradigm, which assesses the ability of an appetitive conditioned stimulus (CS) to gain access to the motivational properties of an upcoming aversive unconditioned stimulus (US). Neural correlates were evaluated using c-Fos immunohistochemistry, in brains of animals sacrificed 90min following the start of the probe test. Results show that conditioned responding was decreased in 5-HTT(+/+), but not 5-HTT(-/-), rats after US devaluation. In addition, OFC and basolateral amygdala (BLA) c-Fos immunoreactivity was increased in non-devalued 5-HTT(-/-) rats compared to non-devalued 5-HTT(+/+) rats. Whereas US devaluation increased c-Fos immunoreactivity in the OFC and BLA of 5-HTT(+/+) rats, there was no further increase in c-Fos immunoreactivity in the OFC and BLA of 5-HTT(-/-) rats. Taken together, 5-HTT(-/-) rats are unable to use the value of expected outcomes to guide behaviour, potentially due to over-activity of the OFC and BLA. Our findings suggest a new modulatory role of 5-HT in cognitive control over behaviour, which may have important implications for psychopathologies, like anxiety disorders and addiction.

Improved cognitive flexibility in serotonin transporter knockout rats is unchanged following chronic cocaine self-administration

Cocaine dependence is associated with orbitofrontal cortex (OFC)‐dependent cognitive inflexibility in both humans and laboratory animals. A critical question is whether cocaine self‐administration affects pre‐existing individual differences in cognitive flexibility. Serotonin transporter knockout (5‐HTT−/−) mice show improved cognitive flexibility in a visual reversal learning task, whereas 5‐HTT−/− rats self‐administer increased amounts of cocaine. Here we assessed: (1) whether 5‐HTT−/− rats also show improved cognitive flexibility (next to mice); and (2) whether this is affected by cocaine self‐administration, which is increased in these animals. Results confirmed that naïve 5‐HTT−/− rats (n = 8) exhibit improved cognitive flexibility, as measured in a sucrose reinforced reversal learning task. A separate group of rats was subsequently trained to intravenously self‐administer cocaine (0.5 mg/kg/infusion), and we observed that the 5‐HTT−/− rats (n = 10) self‐administered twice as much cocaine [632.7 mg/kg (±26.3)] compared with 5‐HTT+/+ rats (n = 6) [352.3 mg/kg (±62.0)] over 50 1‐hour sessions. Five weeks into withdrawal the cocaine‐exposed animals were tested in the sucrose‐reinforced reversal learning paradigm. Interestingly, like the naïve 5‐HTT−/− rats, the cocaine exposed 5‐HTT−/− rats displayed improved cognitive flexibility. In conclusion, we show that improved reversal learning in 5‐HTT−/− rats reflects a pre‐existing trait that is preserved during cocaine‐withdrawal. As 5‐HTT−/− rodents model the low activity s‐allele of the human serotonin transporter‐linked polymorphic region, these findings may have heuristic value in the treatment of s‐allele cocaine addicts.

Cognitive performance in both clinical and non-clinical burnout.

Abstract Relatively little is known about cognitive performance in burnout. The aim of the present study was to further our knowledge on this topic by examining, in one study, cognitive performance in both clinical and non-clinical burnout while focusing on three interrelated aspects of cognitive performance, namely, self-reported cognitive problems, cognitive test performance, and subjective costs associated with cognitive test performance. To this aim, a clinical burnout patient group (n = 33), a non-clinical burnout group (n = 29), and a healthy control group (n = 30) were compared on self-reported cognitive problems, assessed by a questionnaire, as well as on cognitive test performance, assessed with a cognitive test battery measuring both executive functioning and more general cognitive processing. Self-reported fatigue, motivation, effort and demands were assessed to compare the different groups on subjective costs associated with cognitive test performance. The results indicated that the clinical burnout patients reported more cognitive problems than the individuals with non-clinical burnout, who in turn reported more cognitive problems relative to the healthy controls. Evidence for impaired cognitive test performance was only found in the clinical burnout patients. Relative to the healthy controls, these patients displayed some evidence of impaired general cognitive processing, reflected in slower reaction times, but no impaired executive functioning. However, cognitive test performance of the clinical burnout patients was related to larger reported subjective costs. In conclusion, although both the clinical and the non-clinical burnout group reported cognitive problems, evidence for a relatively mild impaired cognitive test performance and larger reported subjective cost associated with cognitive test performance was only found for the clinical burnout group.

Serotonin transporter knockout rats show improved strategy set-shifting and reduced latent inhibition

Behavioral flexibility is a cognitive process depending on prefrontal areas allowing adaptive responses to environmental changes. Serotonin transporter knockout (5-HTT(-/-)) rodents show improved reversal learning in addition to orbitofrontal cortex changes. Another form of behavioral flexibility, extradimensional strategy set-shifting (EDSS), heavily depends on the medial prefrontal cortex. This region shows functional changes in 5-HTT(-/-) rodents as well. Here we subjected 5-HTT(-/-) rats and their wild-type counterparts to an EDSS paradigm and a supplementary latent inhibition task. Results indicate that 5-HTT(-/-) rats also show improved EDSS, and indicate that reduced latent inhibition may contribute as an underlying mechanism.

Burnout and cortisol: Evidence for a lower cortisol awakening response in both clinical and non-clinical burnout

OBJECTIVE Although the relationship between burnout and cortisol levels has been examined in previous studies, the results are mixed. By adopting a design in which we attempted to overcome important limitations of earlier research, the purpose of the present study was to improve the understanding of the biological underpinnings of burnout and to further the knowledge about the relationship between burnout and cortisol. METHODS A clinical burnout patient group (n =32), a non-clinical burnout group (n =29), and a healthy control group (n =30) were compared on burnout symptoms, physical and psychological complaints, and on cortisol levels. In order to examine a broad range of cortisol indices, including different measures of the cortisol awakening response (CAR) and several day-curve measures, salivary cortisol was collected six times a day during two consecutive non-workdays. RESULTS As expected, the clinical burnout group reported more burnout symptoms, and physical and psychological complaints than the non-clinical burnout group, which in turn reported more burnout symptoms and physical and psychological complaints than the healthy control group. With regard to cortisol levels, we found that until 30 min after awakening, the CAR of both the clinical and the non-clinical burnout group was lower compared with the healthy control group. Furthermore, there was some evidence that the decline of cortisol during the day was smaller in the non-clinical burnout group than in the healthy control group. CONCLUSION The results of the present study provide support for lowered cortisol in both clinical and non-clinical burnout.

Enhanced re-habituation of the orienting response of the human event-related potential

Previous studies found the amplitude of the orienting response (OR) of the human event-related potential to decrease with repeated stimulus presentations. This decrease has been suggested to reflect short-term habituation and/or long-term habituation, both of which are learning processes. However, this earlier research failed to provide direct evidence supporting this claim. The present study attempted to show that the OR pattern shares one important feature of habituation: an enhanced response decrement across stimulus-presentation blocks (enhanced re-habituation). Participants received four blocks of 25 auditory stimulus presentations and showed an OR decrement both within (short-term habituation) and across (long-term habituation) blocks. Importantly, the OR decreased more rapidly during later than initial trial blocks, suggesting enhanced re-habituation. The latter result supports the notion that the amplitude decrement reflects an elementary learning process.

Reversal deficits in individuals with psychopathy in explicit but not implicit learning conditions

BACKGROUND Psychopathy is a severe personality disorder that has been linked to impaired behavioural adaptation during reinforcement learning. Recent electrophysiological studies have suggested that psychopathy is related to impairments in intentionally using information relevant for adapting behaviour, whereas these impairments remain absent for behaviour relying on automatic use of information. We sought to investigate whether previously found impairments in response reversal in individuals with psychopathy also follow this dichotomy. We expected response reversal to be intact when the automatic use of information was facilitated. In contrast, we expected impaired response reversal when intentional use of information was required. METHODS We included offenders with psychopathy and matched healthy controls in 2 experiments with a probabilistic cued go/no-go reaction time task. The task implicated the learning and reversal of 2 predictive contingencies. In experiment 1, participants were not informed about the inclusion of a learning component, thus making cue-dependent learning automatic/incidental. In experiment 2, the instructions required participants to actively monitor and learn predictive relationships, giving learning a controlled/intentional nature. RESULTS While there were no significant group differences in acquisition learning in either experiment, the results revealed impaired response reversal in offenders with psychopathy when controlled learning was facilitated. Interestingly, this impairment was absent when automatic learning was predominant. LIMITATIONS Possible limitations are the use of a nonforensic control group and of self-report measures for drug use. CONCLUSION Response reversal deficits in individuals with psychopathy are modulated by the context provided by the instructions, according to the distinction between automatic and controlled processing in these individuals.

Conditional control by midazolam and amphetamine in a rapid appetitive discrimination procedure

The present two experiments examined conditional control by midazolam and amphetamine cues in an appetitive discrimination procedure. In each of two experiments, male Wistar rats were subjected to a small number of two types of training sessions in a conditioning box. During one type of session, a stimulus was consistently followed by food in a magazine, whereas during the other type of session, this very same stimulus was followed by nothing. Groups of rats were injected with either midazolam (0.1 mg/kg, s.c.) or amphetamine (0.5 mg/kg, s.c.), prior to each food-reinforced session, and with saline prior to each food non-reinforced session. Other groups received the reverse treatment. Subsequent non-reinforced test session showed that, in both experiments, only the rats that had been food reinforced in a drug state displayed shorter magazine-response latencies in their previously reinforced than in their previously non-reinforced state, both prior to and during the stimulus. This finding was interpreted as reflecting the joint operation of unconditioned and conditioned drug effects, with the latter being based on occasion setting by the drug cues that was induced by the relatively short discrimination training procedure. The present results parallel those of previous aversive drug-discrimination experiments adopting a similar short discrimination procedure.