Examination-related anticipatory levels of dehydroepiandrosterone and cortisol predict positive affect, examination marks and support-seeking in college students.

Dehydroepiandrosterone (DHEA) and cortisol release appear to have contrasting effects on stress perception during stressful tasks. This study aimed to investigate anticipatory examination stress in college students by considering DHEA, cortisol, psycho-emotional aspects and examination performance. Seventy-six students (66 females, 10 males; age range 18-25 years) provided saliva samples and completed questionnaires in two sessions 48 hours apart. During the second session, the students performed the examination. The questionnaires used were the State-Trait Anxiety Inventory, the Positive and Negative Affect Scale, and the Brief-Coping Orientation to Problems Experienced Inventory. DHEA, cortisol, anxiety and negative affect showed an anticipatory rise before the examination (all ps < 0.001). This rise of DHEA and cortisol was associated with lower positive affect (p = 0.001 and p = 0.043, respectively). However, only the DHEA anticipatory levels were linked to poorer examination marks (p = 0.020). Higher levels of the DHEA/cortisol ratio in anticipation of the examination were related to lower scores on the support-seeking strategy (p = 0.022). There was no association between DHEA and cortisol levels and anxiety, negative affect, active and avoidant coping strategies, or academic record. These results suggest that how DHEA and cortisol respond in anticipation of examination stress significantly impacts students' emotional well-being during examination periods and how they cope with stress. They also suggest that levels of DHEA in anticipation of an academic stressor have detrimental effects on stress management.

How people with brain injury run and evaluate a SLAM-based smartphone augmented reality application to assess object-location memory.

Augmented reality (AR) technology allows virtual objects to be superimposed on the real-world environment, offering significant potential for improving cognitive assessments and rehabilitation processes in the field of visuospatial learning. This study examines how patients with acquired brain injury (ABI) evaluate the functions and usability of a SLAM-based smartphone AR app to assess object-location skills. Ten ABI patients performed a task for the spatial recall of four objects using an AR app. The data collected from 10 healthy participants provided reference values for the best performance. Their perceptions of the AR app/technology and its usability were investigated. The results indicate lower effectiveness in solving the task in the patient group, as the time they needed to complete it was related to their level of impairment. The patients showed lower, yet positive, scores in factors related to app usability and acceptance (e.g., mental effort and satisfaction, respectively). There were more patients reported on entertainment as a positive aspect of the app. Patients' perceived enjoyment was related to concentration and calm, whereas usability was associated with perceived competence, expertise, and a lower level of physical effort. For patients, the sensory aspects of the objects were related to their presence, while for healthy participants, they were related to enjoyment and required effort. The results show that AR seems to be a promising tool to assess spatial orientation in the target patient population.

Female students' personality and stress response to an academic examination.

BACKGROUND: Women are vulnerable to stress-related disorders. Examinations are a source of stress, triggering emotional, cognitive, and hormonal responses. We examined women's psychological and hormonal stress responses and academic performance according to personality during a real-life examination. METHODS: Female students (N = 66) were divided into two groups based on hierarchical cluster analysis: one cluster characterized by high neuroticism and moderate extraversion (HN-ME; n = 42) and the other by low neuroticism and high extraversion (LN-HE; n = 24). Academic performance, perceived stress, and emotional dysregulation were analyzed. State anxiety, affect, and cortisol release were measured before and on the examination day. RESULTS: The HN-ME cluster was high in perceived stress, emotional dysregulation, and negative affect. This cluster also had higher state anxiety levels two days before and shortly after the examination compared to the LN-HE cluster. Students' cortisol levels were higher on the examination day, and there was a marginal significance of the Cluster factor in the cortisol release regardless of the day of measurement. CONCLUSIONS: Women with high neuroticism and moderate extraversion may be more vulnerable to psychological stress in academic settings but similar to other women in their cortisol response.

Development and Validation of the Self-efficacy for Writing and Defending Academic Texts Scale1 / El desarrollo y la validación de la escala de autoeficacia para escribir y defender textos académicos

Writing and defending a thesis is a requirement to earn a university degree. Previous findings indicate that self-efficacy is related to academic performance. However, no existing tools register students’ perception of efficacy towards writing and defining academic texts. Our purpose was to develop and validate such a scale. Scale scores content, structural, convergent, and criterion-related validity as well as the measurement invariance across sex was evaluated using data from 418 students from 23 Spanish universities. Our findings showed that the scale holds a unidimensional structure that is invariant across sex. Data also supported the convergent validity, with correlations with self-efficacy and anxiety measures. The scale could track the effect of an educational intervention designed to improve students’ writing and defending academic texts skills, and the scores were related to performance on a writing task. Norms are provided to facilitate the interpretation of the scale scores.(AU)

Redactar y defender una tesina es un requisito para obtener un título universitario. La investigación previa indica que la autoeficacia está relacionada con el rendimiento académico. Sin embargo, no existen instrumentos que registren la percepción de la eficacia de los estudiantes para escribir y definir textos académicos. Nuestro objetivo fue desarrollar y validar una escala de este tipo. Se recopilaron pruebas de validez de contenido, estructural, convergente y de criterio y de invarianza de medida entre sexos, utilizando datos de 418 estudiantes de 23 universidades españolas. La escala presenta una estructura unidimensional invariante en cuanto al sexo. También se encontraron correlaciones con medidas de autoeficacia y ansiedad. La escala pudo seguir el efecto de una intervención educativa diseñada para mejorar las habilidades de escritura y defensa de textos académicos, y se encontró relación con el rendimiento en una tarea de escritura. Se proporcionan baremos para interpretar las puntuaciones.(AU)

Anosmia in COVID-19 could be associated with long-term deficits in the consolidation of procedural and verbal declarative memories.

Background and purpose: Long-COVID describes the long-term effects of the coronavirus disease 2019 (COVID-19). In long-COVID patients, neuropsychological alterations are frequently reported symptoms. Research points to medial temporal lobe dysfunction and its association with anosmia in long-COVID patients. This study aims to investigate the acquisition and consolidation of declarative and procedural memory in long-COVID patients and to explore whether anosmia is related to these dissociated memory functions. Methods: Forty-two long-COVID participants and 30 controls (C) were recruited. The sample of long-COVID patients was divided into two groups based on the presence or absence of anosmia, group A and group NA, respectively. Objective performance in verbal declarative memory (Paired-Associate Learning, PAL), procedural memory (Mirror Tracing Test, MTT), general cognitive function (Montreal Cognitive Assessment scale), psychomotor speed, and incidental learning (Digit Symbol Substitution Test) were assessed and compared among the A, NA, and C groups. Long-term retention of PAL and MTT were assessed 24 h after acquisition. Results: Lower scores in general cognition, psychomotor speed, and sustained attention were found in A and NA compared with C. However, incidental learning, both cue-guided and free-recalled, was diminished in group A compared with C, with no differences with group NA. General cognition and incidental learning were related to declarative memory function exclusively in long-COVID groups. Long-COVID groups presented lower long-term retention of verbal declarative memory than controls in recall tests but no differences in recognition tests. No group differences were found in the acquisition of procedural memory. However, long-term retention of this memory was worse in group A as compared to the NA and C groups, respectively, when errors and time of execution were considered. Conclusion: Findings support that consolidation of both procedural and declarative memories is more affected than the acquisition of these memories in long-COVID patients, who are also more vulnerable to deficits in delayed recall than in recognition of declarative memories. Deficits in the consolidation of procedural memory and immediate recall of declarative information are especially relevant in long-COVID participants with anosmia. This indicates that anosmia in COVID-19 could be associated with a long-term dysfunction of the limbic system.

Functional near-infrared spectroscopy in the neuropsychological assessment of spatial memory: A systematic review.

Functional near-infrared spectroscopy (fNIRS) is a non-invasive optical imaging technique that employs near-infrared light to measure cortical brain oxygenation. The use of fNIRS has increased exponentially in recent years. Spatial memory is defined as the ability to learn and use spatial information. This neuropsychological process is constantly used in our daily lives and can be measured by fNIRS but no research has reviewed whether this technique can be useful in the neuropsychological assessment of spatial memory. This study aimed to review empirical work on the use of fNIRS in the neuropsychological assessment of human spatial memory. We used four databases: PubMed, PsycINFO, Scopus and Web of Science, and a total of 18 articles were found to be eligible. Most of the articles assessed spatial or visuospatial working memory with a predominance in computer-based tasks, used fNIRS equipment of 16 channels and mainly measured the prefrontal cortex (PFC). The studies analysed found linear or quadratic relationships between working memory load and PFC activity, greater activation of PFC activity and worse behavioural results in healthy older people in comparison with healthy adults, and hyperactivation of PFC as a form of compensation in clinical samples. We conclude that fNIRS is compatible with the standard neuropsychological assessment of spatial memory, making it possible to complement behavioural results with data of cortical functional activity.

Evaluation of an Augmented Reality Application for Learning Neuroanatomy in Psychology.

Neuroanatomy is difficult for psychology students because of spatial visualization and the relationship among brain structures. Some technologies have been implemented to facilitate the learning of anatomy using three-dimensional (3D) visualization of anatomy contents. Augmented reality (AR) is a promising technology in this field. A mobile AR application to provide the visualization of morphological and functional information of the brain was developed. A sample of 67 students of neuropsychology completed tests for visuospatial ability, anatomical knowledge, learning goals, and experience with technologies. Subsequently, they performed a learning activity using one of the visualization methods considered: a 3D method using the AR application and a two-dimensional (2D) method using a textbook to color, followed by questions concerning their satisfaction and knowledge. After using the alternative method, the students expressed their preference. The two methods improved knowledge equally, but the 3D method obtained higher satisfaction scores and was more preferred by students. The 3D method was also more preferred by the students who used this method during the activity. After controlling for the method used in the activity, associations were found between the preference of the 3D method because of its usability and experience with technologies. These results found that the AR application was highly valued by students to learn and was as effective as the textbook for this purpose.

SLAM-based augmented reality for the assessment of short-term spatial memory. A comparative study of visual versus tactile stimuli.

The assessment of human spatial short-term memory has mainly been performed using visual stimuli and less frequently using auditory stimuli. This paper presents a framework for the development of SLAM-based Augmented Reality applications for the assessment of spatial memory. An AR mobile application was developed for this type of assessment involving visual and tactile stimuli by using our framework. The task to be carried out with the AR application is divided into two phases: 1) a learning phase, in which participants physically walk around a room and have to remember the location of simple geometrical shapes; and 2) an evaluation phase, in which the participants are asked to recall the location of the shapes. A study for comparing the performance outcomes using visual and tactile stimuli was carried out. Fifty-three participants performed the task using the two conditions (Tactile vs Visual), but with more than two months of difference (within-subject design). The number of shapes placed correctly was similar for both conditions. However, the group that used the tactile stimulus spent significantly more time completing the task and required significantly more attempts. The performance outcomes were independent of gender. Some significant correlations among variables related to the performance outcomes and other tests were found. The following significant correlations among variables related to the performance outcomes using visual stimuli and the participants' subjective variables were also found: 1) the greater the number of correctly placed shapes, the greater the perceived competence; 2) the more attempts required, the less the perceived competence. We also found that perceived enjoyment was higher when a higher sense of presence was induced. Our results suggest that tactile stimuli are valid stimuli to exploit for the assessment of the ability to memorize spatial-tactile associations, but that the ability to memorize spatial-visual associations is dominant. Our results also show that gender does not affect these types of memory tasks.

Methylene blue and photobiomodulation recover cognitive impairment in hepatic encephalopathy through different effects on cytochrome c-oxidase.

Mitochondrial dysfunction plays a central role in hepatic encephalopathy (HE), due to changes in enzyme cytochrome c-oxidase (CCO), causing a decline in brain metabolism. We used an HE animal model and applied intracranial administration of methylene blue (MB) and transcranial photobiomodulation (PBM), both targeting CCO, to determine their differential effects on recovering cognition. Five groups of rats were used: sham-operated group + saline (SHAM + SAL, n = 6), hepatic encephalopathy + SAL (HE + SAL, n = 7), SHAM + methylene blue (SHAM + MB, n = 7), HE + MB (n = 7), HE + PBM (n = 7). PBM animals were exposed transcranially to 670 +/- 10 nm LED light at a dose of 9 J/cm2 once a day for 7 days, and the MB and SAL groups were injected with 2.2 µg/0.5 µL in the accumbens. Cognitive dysfunction was evaluated on a striatal stimulus-response task using the Morris water maze. Our results showed cognitive improvement in the HE group when treated with MB. This improvement was accompanied by a decrease in CCO activity in the prefrontal cortex, dorsal striatum, and dorsal hippocampus. When comparing MB and PBM, we found that, although both treatments effectively improved the HE-memory deficit, there was a differential effect on CCO. A general decrease in CCO activity was found in the prefrontal and entorhinal cortices, dorsal striatum, and hippocampus when PBM, compared to MB, was applied. Our results suggest that mitochondrial dysfunction and brain metabolic decline in HE might involve CCO alteration and can be improved by administering MB and PBM.

Wayfinding Strategy and Gender - Testing the Mediating Effects of Wayfinding Experience, Personality and Emotions.

BACKGROUND: Individual differences have been seen to play a key role in spatial orientation. Gender implications have been previously described but little is known about how other variables, such as wayfinding anxiety, emotional difficulties and wayfinding experience can mediate this relationship. METHODS: A group of 269 participants were involved in this study and completed questionnaires on their self-reported allocentric orientation strategy, wayfinding experience and satisfaction with the ability for wayfinding. Emotional outcomes were also investigated: spatial and trait anxiety, neuroticism, difficulties in emotion regulation, and personal safety. First, a principal component analysis was conducted and the studied variables were grouped into four components: outdoor wayfinding experience, wayfinding-related fear, emotional difficulties, and effective wayfinding skill. Afterwards, structural equation modelling was performed, using the MPLUS statistical program. RESULTS: The results showed that gender constitutes a predictor for using an effective wayfinding skill and for feeling wayfinding-related fear. However, outdoor wayfinding experience, wayfinding-related fear and emotional difficulties did not mediate the relationship between effective wayfinding skill and gender. CONCLUSION: These results highlight the differential contribution of gender in the emotions that are experienced during spatial orientation and emotions that are related to other types of situations. The limitations, strengths and theoretical implications of the proposed model are discussed. Further investigation is needed in order to understand the role of emotions in spatial orientation.

Memory for Object Location in Augmented Reality: The Role of Gender and the Relationship Among Spatial and Anxiety Outcomes.

The potential of augmented reality (AR) technology for the study of spatial memory and orientation is a new research field. AR defines systems that attempt to enhance the user's experience with the physical world. In our app, we enhance the sense of sight by adding interactive 3D elements to the real environment. Our app can be used in any real environment so that the experimental conditions during the tasks and the way in which an individual navigates are similar to those used in real life. With AR, the experimenter has a high level of control of the task and can store the participant's responses accurately. The classical factors that influence an individual's performance on virtual spatial tasks are gender and cognitive factors. The influence of emotional factors on spatial performance has been studied more recently. Since AR tasks for the study of spatial memory and spatial orientation are new developments, little is known about the factors that are related to performance on tasks of this type. In our study, we tested 46 young adults (26 women) in an AR object-location task that was performed in a building. The participants had to memorize the position of eight virtual objects while they were walking through the environment. We also assessed the participants' performance on an object-recall task, a map-pointing task, and a paper-and-pencil spatial orientation task. The self-reported importance of different spatial strategies for wayfinding and the levels of trait anxiety and wayfinding anxiety were also evaluated. Our findings indicate that men performed better on the spatial paper-and-pencil test and spent more time completing the learning phase of the AR task. The spatial memory for the location of the objects in AR and on the map correlated positively. Anxiety was related to individual differences in the self-reported use of a spatial orientation strategy, but the association among them was weak. Trait anxiety was positively related to the time employed by the participants during the learning phase of the AR task, whereas wayfinding anxiety correlated negatively with the preference for an orientation strategy. Our results highlight the importance of anxiety in spatial orientation.

BDNF over-expression induces striatal serotonin fiber sprouting and increases the susceptibility to l-DOPA-induced dyskinesia in 6-OHDA-lesioned rats.

In addition to its role in neuronal survival, the brain neurotrophic factor (BDNF) has been shown to influence serotonin transmission and synaptic plasticity, events strongly implicated in the appearance of l-DOPA-induced dyskinesia (LID), a motor complication occurring in parkinsonian patients after long-term treatment with the dopamine precursor. In order to evaluate a possible influence of BDNF in the appearance of LID, 6-OHDA-lesioned rats received a striatal injection of different concentrations of an adeno-associated viral (AAV) vector over-expressing either BDNF or GFP, as control vector. Eight weeks later, animals started to receive a daily treatment with l-DOPA (4-6mg/kg plus benserazide 4-6mg/kg, s.c.) or saline, and dyskinesias, as well as l-DOPA-induced rotations, were evaluated at several time-points. Moreover, molecular changes in striatal D1 receptor-dependent cAMP/PKA and ERK/mTORC signaling pathways, as well as, sprouting of striatal serotonin axons, were measured. Results showed that the AAV-BDNF vector injection induced striatal over-expression of BDNF, as well as striatal and pallidal serotonin axon hyperinnervation. Moreover, rats that over-expressed BDNF were more prone to develop LID and l-DOPA-induced rotations, compared to the GFP-treated control group. Finally, rats that over-expressed BDNF showed increased levels of striatal D1R-dependent signaling phospho-proteins in response to l-DOPA administration. This study suggests that BDNF over-expression, by inducing changes in pre-synaptic serotonin axonal trophism, is able to exacerbate maladaptive responses to l-DOPA administration.

The 5-alpha reductase inhibitor finasteride reduces dyskinesia in a rat model of Parkinson's disease.

Levodopa-induced dyskinesia (LID) is a disabling motor complication occurring in Parkinson's disease patients (PD) after long-term l-DOPA treatment. Although its etiology remains unclear, there is accumulating evidence that LID relies on an excessive dopamine receptor transmission, particularly at the downstream signaling of D1 receptors. We previously reported that the pharmacological blockade of 5-alpha reductase (5AR), the rate limiting enzyme in neurosteroids synthesis, rescued a number of behavioral aberrations induced by D1 receptor-selective and non-selective agonists, without inducing extrapyramidal symptoms. Thus, the present study was designed to verify whether the 5AR inhibitor finasteride (FIN) may counteract the dyskinesias induced by dopaminergic agonists in 6-hydroxydopamine (6-OHDA)-lesioned rats. First, we assessed the acute and chronic effect of different doses of FIN (30-60mg/kg) on LID, in male 6-OHDA-lesioned dyskinetic rats. Thereafter, to fully characterize the therapeutic potential of FIN on LID and its impact on l-DOPA efficacy, we assessed abnormal involuntary movements and forelimb use in hemiparkinsonian male rats chronically injected with FIN (30-60mg/kg/24days) either prior to- or concomitant with l-DOPA administration. In addition, to investigate whether the impact of FIN on LID may be ascribed to a modulation of the D1- or D2/D3-receptor function, dyskinesias were assessed in l-DOPA-primed 6-OHDA-lesioned rats that received FIN in combination with selective direct dopaminergic agonists. Finally, we set to investigate whether FIN may produce similar effect in female hemiparkinsonian rats, as seen in males. The results indicated that FIN administrations significantly dampened LID in all tested treatment regimens, without interfering with the ability of l-DOPA to ameliorate forelimb use in the stepping test. The antidyskinetic effect appears to be due to modulation of both D1- and D2/D3-receptor function, as FIN also reduced abnormal involuntary movements induced by the selective D1 receptor agonist SKF-82958 and the D2/D3 receptor agonist ropinirole. Significant dampening of LID was also observed in female rats, although only at the higher tested dose. Clinical investigations are warranted to assess whether similar protection from dyskinesia is seen in PD patients.

Antidyskinetic effect of A2A and 5HT1A/1B receptor ligands in two animal models of Parkinson's disease.

BACKGROUND: The serotonin 5-HT1A/1B receptor agonist eltoprazine suppressed dyskinetic-like behavior in animal models of Parkinson's disease (PD) but simultaneously reduced levodopa (l-dopa)-induced motility. Moreover, adenosine A2A receptor antagonists, such as preladenant, significantly increased l-dopa efficacy in PD without exacerbating dyskinetic-like behavior. OBJECTIVES: We evaluated whether a combination of eltoprazine and preladenant may prevent or suppress l-dopa-induced dyskinesia, without impairing l-dopa's efficacy in relieving motor signs, in 2 PD models: unilateral 6-hydroxydopamine-lesioned rats and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. METHODS: Rotational behavior and abnormal involuntary movements, or disability and l-dopa-induced dyskinesia were evaluated in 6-hydroxydopamine-lesioned rats and MPTP-treated monkeys, respectively. Moreover, in the rodent striatum, induction of immediate-early gene zif-268, an index of long-term changes, was correlated with dyskinesia. RESULTS: In 6-hydroxydopamine-lesioned rats, combined administration of l-dopa (4 mg/kg) plus eltoprazine (0.6 mg/kg) plus preladenant (0.3 mg/kg) significantly prevented or reduced dyskinetic-like behavior without impairing motor activity. Zif-268 was increased in the striatum of rats treated with l-dopa and l-dopa plus preladenant compared with vehicle. In contrast, rats treated with eltoprazine (with or without preladenant) had lower zif-268 activation after chronic treatment in both the dyskinetic and l-dopa-non-primed groups. Moreover, acute l-dopa plus eltoprazine plus preladenant prevented worsening of motor performance (adjusting step) and sensorimotor integration deficit. Similar results were obtained in MPTP-treated monkeys, where a combination of preladenant with eltoprazine was found to counteract dyskinesia and maintain the full therapeutic effects of a low dose of l-dopa. CONCLUSIONS: Our results suggest a promising nondopaminergic pharmacological strategy for the treatment of dyskinesia in PD. © 2016 International Parkinson and Movement Disorder Society.

Modulation of serotonergic transmission by eltoprazine in L-DOPA-induced dyskinesia: Behavioral, molecular, and synaptic mechanisms.

L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesias (LIDs) represent the main side effect of Parkinson's Disease (PD) therapy. Among the various pharmacological targets for novel therapeutic approaches, the serotonergic system represents a promising one. In experimental models of PD and in PD patients the development of abnormal involuntary movements (AIMs) and LIDs, respectively, is accompanied by the impairment of bidirectional synaptic plasticity in key structures such as striatum. Recently, it has been shown that the 5-HT1A/1B receptor agonist, eltoprazine, significantly decreased LIDs in experimental PD and human patients. Despite the fact that several papers have tested this and other serotonergic drugs, nothing is known about the electrophysiological consequences on this combined serotonin receptors modulation at striatal neurons. The present study demonstrates that activation of 5-HT1A/1B receptors reduces AIMs via the restoration of Long-Term Potentiation (LTP) and synaptic depotentiation in a sub-set of striatal spiny projection neurons (SPNs). This recovery is associated with the normalization of D1 receptor-dependent cAMP/PKA and ERK/mTORC signaling pathways, and the recovery of NMDA receptor subunits balance, indicating these events as key elements in AIMs induction. Moreover, we analyzed whether the manipulation of the serotonergic system might affect motor behavior and cognitive performances. We found that a defect in locomotor activity in parkinsonian and L-DOPA-treated rats was reversed by eltoprazine treatment. Conversely, the impairment in the striatal-dependent learning was found exacerbated in L-DOPA-treated rats and eltoprazine failed to recover it.

Foetal Cell Transplantation for Parkinson's Disease: Focus on Graft-Induced Dyskinesia.

Transplantation of dopamine- (DA-) rich foetal ventral mesencephalic cells emerged as a promising therapy for Parkinson's disease (PD), as it allowed significant improvement of motor symptoms in several PD patients in open-label studies. However, double-blind clinical trials have been largely disappointing. The general agreement in the field is that the lack of standardization of tissue collection and preparation, together with the absence of postsurgical immunosuppression, played a key role in the failure of these studies. Moreover, a further complication that emerged in previous studies is the appearance of the so-called graft-induced dyskinesia (GID), in a subset of grafted patients, which resembles dyskinesia induced by L-DOPA but in the absence of medication. Preclinical evidence pointed to the serotonin neurons as possible players in the appearance of GID. In agreement, clinical investigations have shown that grafted tissue may contain a large number of serotonin neurons, in the order of half of the DA cells; moreover, the serotonin 5-HT1A receptor agonist buspirone has been found to produce significant dampening of GID in grafted patients. In this paper, we will review the recent preclinical and clinical studies focusing on cell transplantation for PD and on the mechanisms underlying GID.

Dynamic functional brain networks involved in simple visual discrimination learning.

Visual discrimination tasks have been widely used to evaluate many types of learning and memory processes. However, little is known about the brain regions involved at different stages of visual discrimination learning. We used cytochrome c oxidase histochemistry to evaluate changes in regional brain oxidative metabolism during visual discrimination learning in a water-T maze at different time points during training. As compared with control groups, the results of the present study reveal the gradual activation of cortical (prefrontal and temporal cortices) and subcortical brain regions (including the striatum and the hippocampus) associated to the mastery of a simple visual discrimination task. On the other hand, the brain regions involved and their functional interactions changed progressively over days of training. Regions associated with novelty, emotion, visuo-spatial orientation and motor aspects of the behavioral task seem to be relevant during the earlier phase of training, whereas a brain network comprising the prefrontal cortex was found along the whole learning process. This study highlights the relevance of functional interactions among brain regions to investigate learning and memory processes.

Brain network function during shifts in learning strategies in portal hypertension animals.

Patients with minimal hepatic encephalopathy exhibit early impairments in their ability to shift attentional set. We employed a task-switching protocol to evaluate brain network changes. Strategy switching requires the modification of both the relevant stimulus dimension and the required memory system. Rats were trained in an allocentric (A) and a cue-guided (C) task using a four-arm maze. To examine priming, we changed the order in which the tasks were presented. Five groups of animals were used: a SHAM (sham-operated) A-C group (n=10), a SHAM C-A group (n=8), a PH (portal hypertension) A-C group (n=8), PH C-A group (n=8), and a naïve group (n=10). The triple portal vein ligation method was used to create an animal model of the early evolutive phase of PH. The animals were tested in the four-arm radial water maze in a single 10-trial session each day for six days (three days for the allocentric task and three days for the cue-guided task). The metabolic activities of the brains were studied with cytochrome oxidase histochemistry, and brain network changes were assessed with principal component analysis. The behavioural results revealed significant increases in the numbers of correct choices across training days in all groups studied, and facilitation of the acquisition of the second task was present in the C-A groups. Moreover, different brain network activities were found; in the experimental groups, the performance of A-C switch involved the prefrontal cortex, and the key structures involved in the C-A switch in the other groups were the dentate gyrus of the dorsal hippocampus and the basolateral and central amygdala. These networks have a common nucleus of structures (i.e., the parietal cortex and the dorsal and ventral striatum), whereas other structures were specifically involved in each type of strategy, suggesting that these regions are part of both circuits and may interact with one another during learning.

The effects of hyperammonemia in learning and brain metabolic activity.

Ammonia is thought to be central in the development of hepatic encephalopathy. However, the specific relation of ammonia with brain energy depletions and learning has not been studied. Our work attempts to reproduce an increase in rat cerebral ammonia level, study the hyperamonemic animals' performance of two learning tasks, an allocentric (ALLO) and a cue guided (CG) task, and elucidate the contribution of hyperammonemia to the differential energy requirements of the brain limbic system regions involved in these tasks. To assess these goals, four groups of animals were used: a control (CHA) CG group (n = 10), a CHA ALLO group (n = 9), a hyperammonemia (HA) CG group (n = 7), and HA ALLO group (n = 8). Oxidative metabolism of the target brain regions were assessed by histochemical labelling of cytochrome oxidase (C.O.). The behavioural results revealed that the hyperammonemic rats were not able to reach the behavioural criterion in either of the two tasks, in contrast to the CHA groups. The metabolic brain consumption revealed increased C.O. activity in the anterodorsal thalamus when comparing the HA ALLO group with the CHA ALLO group. Significant differences between animals trained in the CG task were observed in the prelimbic, infralimbic, parietal, entorhinal and perirhinal cortices, the anterolateral and anteromedial striatum, and the basolateral and central amygdala. Our findings may provide fresh insights to reveal how the differential damage to the brain limbic structures involved in these tasks differs according to the degree of task difficulty.

The anti-dyskinetic effect of dopamine receptor blockade is enhanced in parkinsonian rats following dopamine neuron transplantation.

Graft-induced dyskinesia (GID) is a serious complication induced by dopamine (DA) cell transplantation in parkinsonian patients. We have recently shown that DA D2 receptor blockade produces striking blockade of dyskinesia induced by amphetamine in grafted 6-OHDA-lesioned rats, a model of GID. This study was designed to investigate whether blockade of DA D1 receptors could produce similar outcome, and to see whether the effect of these treatments in grafted rats was specific for dyskinesia induced by amphetamine, or could also influence L-DOPA-induced dyskinesia (LID). L-DOPA-primed rats received transplants of fetal DA neurons into the DA-denervated striatum. Beginning at 20weeks after transplantation rats were subjected to pharmacological treatments with either L-DOPA (6mg/kg) or amphetamine (1.5mg/kg) alone, or in combination with the D1 receptor antagonist SCH23390, the D2 receptor antagonist eticlopride, and the 5-HT1A agonist/D2 receptor antagonist buspirone. Grafted rats developed severe GID, while LID was reduced. Both eticlopride and SCH23390 produced near-complete suppression of GID already at very low doses (0.015 and 0.1mg/kg, respectively). Buspirone induced similar suppression at a dose as low as 0.3mg/kg, which is far lower than the dose known to affect LID in non-grafted dyskinetic rats. In agreement with our previous results, the effect of buspirone was independent from 5-HT1A receptor activation, as it was not counteracted by the selective 5-HT1A antagonist WAY100635, but likely due to D2 receptor blockade. Most interestingly, the same doses of eticlopride, SCH23390 and buspirone were found to suppress LID in grafted but not in control dyskinetic rats. Taken together, these data demonstrate that the DA cell grafts strikingly exacerbate the effect of DA D1 and D2 receptor blockade against both GID and LID, and suggest that the anti-GID effect of buspirone seen in patients may also be due to blockade of DA D2 receptors.