Inter-individual differences in laboratory rats as revealed by three behavioural tasks.

Stable inter-individual differences in behaviour and personality have been studied for several decades now. The aim of this study was to test the repeatability of behaviour of the Long Evans strain of laboratory rats in order to assess their inter-individual differences. Male laboratory rats (n = 36) were tested in a series of tasks (Open field test, Elevated plus maze test, and modified T-maze test) repeated over time to assess their personality traits. To evaluate the temporal stability of the behaviour, we calculated repeatability estimates of the examined traits. We also checked for a link in behavioural traits across these experiments, which would suggest the existence of a behavioural syndrome. We found stable inter-individual differences in behaviour. Interestingly, no link emerged between the tasks we studied and therefore we did not find support for a behavioural syndrome. The lack of behavioural correlations between these experiments suggests that the results derived from these tasks should be interpreted carefully, as these experiments may measure various behavioural axes. Moreover, the animals habituate to the apparatus. Consequently, behaviour in the Open field test and Elevated plus maze test is not fully consistent and repeatable across subsequent trials.

Selective impairment of timing in a NMDA hypofunction animal model of psychosis.

Schizophrenia is severe neuropsychiatric disease, which is commonly accompanied not only by positive or negative symptoms, but also by cognitive impairment. To study neuronal mechanisms underlying cognitive distortions and mechanisms underlying schizophrenia, animal pharmacological models of cognitive symptoms are commonly used. Between various cognitive impairments in schizophrenia patients, disturbed time perception has often been reported. Here, we examined temporal and spatial cognition in a modified Carousel maze task in the animal model of schizophrenia induced by non-competitive NMDA-receptor antagonists MK-801. Male Long-Evans rats (n = 18) first learned to avoid the aversive sector on a rotating arena in both dark and light intervals. We verified that during dark, rats used temporal cues, while during light they relied predominantly on spatial cues. We demonstrated that the timing strategy depends on the stable rotation speed of the arena and on the repositioning clues such as aversive stimuli. During testing (both in light and dark intervals), half of the rats received MK-801 and the control half received saline solution. We observed dose-dependent disruptions of both temporal and spatial cognition. Namely, both doses of MK-801 (0.1 and 0.12 mg/kg) significantly impaired timing strategy in the dark and increased locomotor activity. MK-801 dose 0.1 mg/kg, but not 0.12, also impaired spatial avoidance strategy in light. We found that the timing strategy is more sensitive to NMDA antagonist MK-801 than the spatial strategy. To conclude, a modified version of the Carousel maze is a useful and sensitive tool for detecting timing impairments in the MK-801 induced rodent model of schizophrenia.

Is short-term memory capacity (7±2) really predicted by theta to gamma cycle length ratio?

Several studies suggest that EEG parameters, reflecting top-down processes in the brain, may predict cognitive performance, e.g. short-term memory (STM) capacity. According to Lisman and Idiart's model, STM capacity is predicted by theta and gamma EEG waves and their ratio. This model suggests that the more periods of gamma band waves fit into one period of theta band waves, the more information can be stored. We replicated the study by Kaminski et al. (2011), which recorded spontaneous EEG activity and measured verbal STM capacity with a modified digit span task from the Wechsler battery. Our study included more subjects and two EEG recording sessions. We discuss the possible limits of EEG correlates of STM capacity as EEG parameters were not stable across the two measurements and no correlation was found between the theta/gamma ratio and performance in the digit span task.

What is the future for immersive virtual reality in memory rehabilitation? A systematic review.

BACKGROUND: A growing interest in non-pharmacological approaches aimed at cognitive rehabilitation and cognitive enhancement pointed towards the application of new technologies. The complex virtual reality (VR) presented using immersive devices has been considered a promising approach. OBJECTIVE: The article provides a systematic review of studies aimed at the efficacy of VR-based rehabilitation. First, we shortly summarize literature relevant to the role of immersion in memory assessment and rehabilitation. METHODS: We searched Web of Science, ScienceDirect, and PubMed with the search terms "memory rehabilitation", "virtual reality", "memory deficit". Only original studies investigating the efficacy of complex three-dimensional VR in rehabilitation and reporting specific memory output measures were included. RESULTS: We identified 412 citations, of which 21 met our inclusion criteria. We calculated appropriate effect sizes for 10 studies including control groups and providing descriptive data. The effect sizes range from large to small, or no effect of memory rehabilitation was present, depending on the control condition applied. Summarized studies with missing control groups point out to potential positive effects of VR but do not allow any generalization. CONCLUSIONS: Even though there are some theoretical advantages of immersive VE over non-immersive technology, there is not enough evidence yet to draw any conclusions.

Mapping the Scene and Object Processing Networks by Intracranial EEG.

Human perception and cognition are based predominantly on visual information processing. Much of the information regarding neuronal correlates of visual processing has been derived from functional imaging studies, which have identified a variety of brain areas contributing to visual analysis, recognition, and processing of objects and scenes. However, only two of these areas, namely the parahippocampal place area (PPA) and the lateral occipital complex (LOC), were verified and further characterized by intracranial electroencephalogram (iEEG). iEEG is a unique measurement technique that samples a local neuronal population with high temporal and anatomical resolution. In the present study, we aimed to expand on previous reports and examine brain activity for selectivity of scenes and objects in the broadband high-gamma frequency range (50-150 Hz). We collected iEEG data from 27 epileptic patients while they watched a series of images, containing objects and scenes, and we identified 375 bipolar channels responding to at least one of these two categories. Using K-means clustering, we delineated their brain localization. In addition to the two areas described previously, we detected significant responses in two other scene-selective areas, not yet reported by any electrophysiological studies; namely the occipital place area (OPA) and the retrosplenial complex. Moreover, using iEEG we revealed a much broader network underlying visual processing than that described to date, using specialized functional imaging experimental designs. Here, we report the selective brain areas for scene processing include the posterior collateral sulcus and the anterior temporal region, which were already shown to be related to scene novelty and landmark naming. The object-selective responses appeared in the parietal, frontal, and temporal regions connected with tool use and object recognition. The temporal analyses specified the time course of the category selectivity through the dorsal and ventral visual streams. The receiver operating characteristic analyses identified the PPA and the fusiform portion of the LOC as being the most selective for scenes and objects, respectively. Our findings represent a valuable overview of visual processing selectivity for scenes and objects based on iEEG analyses and thus, contribute to a better understanding of visual processing in the human brain.

Fusiform Activity Distinguishes Between Subjects With Low and High Xenophobic Attitudes Toward Refugees.

This study analyzes how people's attitudes to the European refugee crisis (ERC) correspond to selected psychological state and trait measures and impact the neural processing of media images of refugees. From a large pool of respondents, who filled in an online xenophobia questionnaire, we selected two groups (total N = 38) with the same socio-demographic background, but with opposite attitudes toward refugees. We found that a negative attitude toward refugees (high xenophobia - HX) was associated with a significantly higher conscientiousness score and with a higher trait aggression and hostility, but there was no group effect connected with empathy, fear, and anxiety measures. At the neural level we found that brain activity during the presentation of ERC stimuli is affected by xenophobic attitudes-with more xenophobic subjects exhibiting a higher BOLD response in the left fusiform gyrus. However, while the fMRI results demonstrate increased attention and vigilance toward ERC-related stimuli in the HX group, they do not show differentiated patterns of brain activity associated with perception of dehumanized outgroup.

Validation of the Human-Animal Interaction Scale (HAIS) in Czech Language.

Human-Animal interaction (HAI) refers to any contact between humans and animals. Despite the lack of standardized measures of evaluation, one possible tool is the Human Animal Interaction Scale (HAIS). This study aimed to evaluate it in Czech language and to verify its use in clinical settings. One group of participants included 85 non-clinical volunteers; the second included 22 clinical participants, who were hospitalized in a long-term inpatient department All participants filled out the HAIS, the Companion Animal Bonding Scale (CABS) and the Companion Animal Semantic Differential (CASD). The Czech HAIS achieved similarly good psychometric properties as the original scale. The Cronbach's alpha showed strong internal consistency (α = 0.920) in the sample of volunteers, but low internal consistency (α = 0.656) in the group of clinical participants. In non-clinical volunteers, all scales and subscales correlated mutually at the p < 0.01 level. In the group of clinical participants, the CABS did not show significant correlations with other scales and subscales, nor was there a correlation of total HAIS score with the perceived rapport with animals. The findings of this study suggest that the Czech HAIS may be an effective tool for evaluating HAI with non-clinical contingents, however careful modification is suggested before clinical use. One reason for this is the difficulty in conducting some activities assessed by the scale in a clinical practice or hospital setting.

Spontaneous color preferences in rhesus monkeys: What is the advantage of primate trichromacy?

Color perception and color signaling play an important role in various aspects of animal behavior. However, in mammals, trichromatic vision characterized by three retinal photopigments tuned to peak short, middle and long wavelengths is limited only to some primate species. In Old and New World primates a second photopigment has appeared repeatedly during phylogeny, allowing red colors to be distinguished from yellows and greens. Several hypotheses aspire to explain the adaptive benefits of trichromatic vision for primates. The predominant one is foraging adaptation for facilitation visual detection of fruits or young leaves. Alternative explanations are based on the function of red color in aposematic signaling or its role in socio-sexual communication. We tested spontaneous color preference in macaque monkeys (Macaca mulatta) for both food and non-food objects in a laboratory environment. We hypothesized that preference for or avoidance of red color together with the context of such behavior may help us to understand what the adaptive advantage leading to a rapid expansion of a gene for a second pigment in the long-wavelength region was. We found neither preference nor avoidance toward red color in non-food objects, but we found a significant preference for red color in food; therefore, we suggest that the results support the foraging hypothesis in macaque monkeys.

Reactions to novel objects in monkeys: what does it mean to be neophobic?

Animals' reactions to novel objects vary not only with zoological taxa and their ecology but also in the types of presented stimuli, the context, and individual characteristics. Behavioral reactions can vary from extremely neophobic (avoiding novel objects) to extremely neophilic (intense exploration of novel objects); most often, a mixture of these behavioral patterns appears. In primates, reactions toward novel objects vary according to species, age, sex, population, and the types of objects. Most experiments in this field have used a free exploration design with food or non-food objects. Here, we tested the reactions of captive male rhesus macaques using various stimuli, motivation levels, rewards, and time limits. We found that the monkeys explored and manipulated novel objects in various contexts, with little evidence of a neophobic response; however, environment, types of stimuli, and other parameters of the test can significantly affect monkeys' reactions.

Could Prolonged Usage of GPS Navigation Implemented in Augmented Reality Smart Glasses Affect Hippocampal Functional Connectivity?

BACKGROUND: Augmented reality (AR) glasses with GPS navigation represent the rapidly evolving technology which spares (and externalizes) navigational capacities. Regarding the expected everyday usage of this device, its impact on neuroplastic brain changes and navigation abilities should be evaluated. AIMS: This study aimed to assess possible changes in functional connectivity (FC) of hippocampus and other brain regions involved in spatial navigation. METHODS: Thirty-three healthy participants completed two resting state functional magnetic resonance imaging (rsfMRI) measurements at the baseline and after 3 months. For this period, the experimental group (n = 17) has had used AR device (Vuzix M100) with incorporated GPS guidance system during navigation in real world. Participants from the control group (n = 16) have not used any GPS device while navigating during walking. The rsfMRI FC of right and left hippocampi was analyzed using a seed-driven approach. Virtual city task was used to test navigational abilities both before and after the usage of AR device. RESULTS: We identified strong functional coupling of right and left hippocampi at the baseline (p < 0.05, FDR corrected). Mild changes in bilateral hippocampal FC (p < 0.05, FDR uncorrected) were observed in both assessed groups mainly between the bilateral hippocampi and between each hippocampus and temporal regions and cerebellum. However, the experimental group showed FC decrease after three months of using GPS navigation implemented in AR glasses in contrast to FC increase in the control group without such intervention. Importantly, no effect of intervention on navigational abilities was observed. DISCUSSION: Our observation supports the assumption that externalization of spatial navigation to technological device (GPS in AR glasses) can decrease the functional coupling between hippocampus and associated brain regions. Considering some limitations of the present study, further studies should elucidate the mechanism of the observed changes and their impact on cognitive abilities.

The role of the hippocampus in object discrimination based on visual features.

The role of rodent hippocampus has been intensively studied in different cognitive tasks. However, its role in discrimination of objects remains controversial due to conflicting findings. We tested whether the number and type of features available for the identification of objects might affect the strategy (hippocampal-independent vs. hippocampal-dependent) that rats adopt to solve object discrimination tasks. We trained rats to discriminate 2D visual objects presented on a computer screen. The objects were defined either by their shape only or by multiple-features (a combination of filling pattern and brightness in addition to the shape). Our data showed that objects displayed as simple geometric shapes are not discriminated by trained rats after their hippocampi had been bilaterally inactivated by the GABAA-agonist muscimol. On the other hand, objects containing a specific combination of non-geometric features in addition to the shape are discriminated even without the hippocampus. Our results suggest that the involvement of the hippocampus in visual object discrimination depends on the abundance of object's features.

Perception of direct vs. averted gaze in portrait paintings: An fMRI and eye-tracking study.

In this study, we use separate eye-tracking measurements and functional magnetic resonance imaging to investigate the neuronal and behavioral response to painted portraits with direct versus averted gaze. We further explored modulatory effects of several painting characteristics (premodern vs modern period, influence of style and pictorial context). In the fMRI experiment, we show that the direct versus averted gaze elicited increased activation in lingual and inferior occipital and the fusiform face area, as well as in several areas involved in attentional and social cognitive processes, especially the theory of mind: angular gyrus/temporo-parietal junction, inferior frontal gyrus and dorsolateral prefrontal cortex. The additional eye-tracking experiment showed that participants spent more time viewing the portrait's eyes and mouth when the portrait's gaze was directed towards the observer. These results suggest that static and, in some cases, highly stylized depictions of human beings in artistic portraits elicit brain activation commensurate with the experience of being observed by a watchful intelligent being. They thus involve observers in implicit inferences of the painted subject's mental states and emotions. We further confirm the substantial influence of representational medium on brain activity.

Scopolamine disrupts place navigation in rats and humans: a translational validation of the Hidden Goal Task in the Morris water maze and a real maze for humans.

RATIONALE: Development of new drugs for treatment of Alzheimer's disease (AD) requires valid paradigms for testing their efficacy and sensitive tests validated in translational research. OBJECTIVES: We present validation of a place-navigation task, a Hidden Goal Task (HGT) based on the Morris water maze (MWM), in comparable animal and human protocols. METHODS: We used scopolamine to model cognitive dysfunction similar to that seen in AD and donepezil, a symptomatic medication for AD, to assess its potential reversible effect on this scopolamine-induced cognitive dysfunction. We tested the effects of scopolamine and the combination of scopolamine and donepezil on place navigation and compared their effects in human and rat versions of the HGT. Place navigation testing consisted of 4 sessions of HGT performed at baseline, 2, 4, and 8 h after dosing in humans or 1, 2.5, and 5 h in rats. RESULTS: Scopolamine worsened performance in both animals and humans. In the animal experiment, co-administration of donepezil alleviated the negative effect of scopolamine. In the human experiment, subjects co-administered with scopolamine and donepezil performed similarly to subjects on placebo and scopolamine, indicating a partial ameliorative effect of donepezil. CONCLUSIONS: In the task based on the MWM, scopolamine impaired place navigation, while co-administration of donepezil alleviated this effect in comparable animal and human protocols. Using scopolamine and donepezil to challenge place navigation testing can be studied concurrently in animals and humans and may be a valid and reliable model for translational research, as well as for preclinical and clinical phases of drug trials.

Validity of Quinpirole Sensitization Rat Model of OCD: Linking Evidence from Animal and Clinical Studies.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with 1-3% prevalence. OCD is characterized by recurrent thoughts (obsessions) and repetitive behaviors (compulsions). The pathophysiology of OCD remains unclear, stressing the importance of pre-clinical studies. The aim of this article is to critically review a proposed animal model of OCD that is characterized by the induction of compulsive checking and behavioral sensitization to the D2/D3 dopamine agonist quinpirole. Changes in this model have been reported at the level of brain structures, neurotransmitter systems and other neurophysiological aspects. In this review, we consider these alterations in relation to the clinical manifestations in OCD, with the aim to discuss and evaluate axes of validity of this model. Our analysis shows that some axes of validity of quinpirole sensitization model (QSM) are strongly supported by clinical findings, such as behavioral phenomenology or roles of brain structures. Evidence on predictive validity is contradictory and ambiguous. It is concluded that this model is useful in the context of searching for the underlying pathophysiological basis of the disorder because of the relatively strong biological similarities with OCD.

MK-801 and memantine act differently on short-term memory tested with different time-intervals in the Morris water maze test.

N-methyl-d-aspartate receptors (NMDARs) play a crucial role in spatial memory formation. In neuropharmacological studies their functioning strongly depends on testing conditions and the dosage of NMDAR antagonists. The aim of this study was to assess the immediate effects of NMDAR block by (+)MK-801 or memantine on short-term allothetic memory. Memory was tested in a working memory version of the Morris water maze test. In our version of the test, rats underwent one day of training with 8 trials, and then three experimental days when rats were injected intraperitoneally with low- 5 (MeL), high - 20 (MeH) mg/kg memantine, 0.1mg/kg MK-801 or 1ml/kg saline (SAL) 30min before testing, for three consecutive days. On each experimental day there was just one acquisition and one test trial, with an inter-trial interval of 5 or 15min. During training the hidden platform was relocated after each trial and during the experiment after each day. The follow-up effect was assessed on day 9. Intact rats improved their spatial memory across the one training day. With a 5min interval MeH rats had longer latency then all rats during retrieval. With a 15min interval the MeH rats presented worse working memory measured as retrieval minus acquisition trial for path than SAL and MeL and for latency than MeL rats. MK-801 rats had longer latency than SAL during retrieval. Thus, the high dose of memantine, contrary to low dose of MK-801 disrupts short-term memory independent on the time interval between acquisition and retrieval. This shows that short-term memory tested in a working memory version of water maze is sensitive to several parameters: i.e., NMDA receptor antagonist type, dosage and the time interval between learning and testing.

The effect of prolonged simvastatin application on serotonin uptake, membrane microviscosity and behavioral changes in the animal model.

Simvastatin and other statins (HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors) are extensively used in clinical practices and are very effective in decreasing serum low-density lipoprotein cholesterol. However, their effect on cholesterol synthesis in central nervous system and its behavioral consequences have not been fully understood yet. We have studied selected biologic traits potentially affected by statin treatment - serotonin (5-HT) uptake in platelets, membrane microviscosity in erythrocytes, cholesterol level in the brain (amygdala; hippocampus and prefrontal cortex), as well as behavioral changes in an elevated plus maze and open field test in male Long-Evans rats, which were treated by simvastatin (30mg/kg per day) for 2 or 4weeks. We demonstrated: 1) a decrease in both serotonin transporter (SERT) activity and membrane microviscosity after treatment with simvastatin, 2) lower cholesterol content in all tested brain regions in animals from the simvastatin treated group, and 3) longer time spent in the open arms and a higher number of entrances to the closed arms in the elevated plus maze by animals from the simvastatin group compared to animals from the control group, but no differences in behavior in the open field test. Taken together, our results confirmed complex alterations, including behavioral changes, after the cholesterol lowering treatment. Furthermore, we discuss the possibility that the behavioral changes, traditionally interpreted as an anxiolytic effect, may be interpreted as increased impulsivity. We also confirmed that such behavioral changes may be attributed to changes in serotonergic neurotransmission.

Bridging disparate symptoms of schizophrenia: a triple network dysfunction theory.

Schizophrenia is a complex neuropsychiatric disorder with variable symptomatology, traditionally divided into positive and negative symptoms, and cognitive deficits. However, the etiology of this disorder has yet to be fully understood. Recent findings suggest that alteration of the basic sense of self-awareness may be an essential distortion of schizophrenia spectrum disorders. In addition, extensive research of social and mentalizing abilities has stressed the role of distortion of social skills in schizophrenia.This article aims to propose and support a concept of a triple brain network model of the dysfunctional switching between default mode and central executive network (CEN) related to the aberrant activity of the salience network. This model could represent a unitary mechanism of a wide array of symptom domains present in schizophrenia including the deficit of self (self-awareness and self-representation) and theory of mind (ToM) dysfunctions along with the traditional positive, negative and cognitive domains. We review previous studies which document the dysfunctions of self and ToM in schizophrenia together with neuroimaging data that support the triple brain network model as a common neuronal substrate of this dysfunction.

Pregnanolone Glutamate, a Novel Use-Dependent NMDA Receptor Inhibitor, Exerts Antidepressant-Like Properties in Animal Models.

UNLABELLED: A number of studies demonstrated a rapid onset of an antidepressant effect of non-competitive N-methyl-d-aspartic acid receptor (NMDAR) antagonists. Nonetheless, its therapeutic potential is rather limited, due to a high coincidence of negative side-effects. Therefore, the challenge seems to be in the development of NMDAR antagonists displaying antidepressant properties, and at the same time maintaining regular physiological function of the NMDAR. Previous results demonstrated that naturally occurring neurosteroid 3α5ß-pregnanolone sulfate shows pronounced inhibitory action by a use-dependent mechanism on the tonically active NMDAR. The aim of the present experiments is to find out whether the treatment with pregnanolone 3αC derivatives affects behavioral response to chronic and acute stress in an animal model of depression. Adult male mice were used throughout the study. Repeated social defeat and forced swimming tests were used as animal models of depression. The effect of the drugs on the locomotor/exploratory activity in the open-field test was also tested together with an effect on anxiety in the elevated plus maze. Results showed that pregnanolone glutamate (PG) did not induce hyperlocomotion, whereas both dizocilpine and ketamine significantly increased spontaneous locomotor activity in the open field. In the elevated plus maze, PG displayed anxiolytic-like properties. In forced swimming, PG prolonged time to the first floating. Acute treatment of PG disinhibited suppressed locomotor activity in the repeatedly defeated group-housed mice. Aggressive behavior of isolated mice was reduced after the chronic 30-day administration of PG. PG showed antidepressant-like and anxiolytic-like properties in the used tests, with minimal side-effects. Since PG combines GABAA receptor potentiation and use-dependent NMDAR inhibition, synthetic derivatives of neuroactive steroids present a promising strategy for the treatment of mood disorders. HIGHLIGHTS: -3α5ß-pregnanolone glutamate (PG) is a use-dependent antagonist of NMDA receptors.-We demonstrated that PG did not induce significant hyperlocomotion.-We showed that PG displayed anxiolytic-like and antidepressant-like properties.

Common mechanisms of pain and depression: are antidepressants also analgesics?

Neither pain, nor depression exist as independent phenomena per se, they are highly subjective inner states, formed by our brain and built on the bases of our experiences, cognition and emotions. Chronic pain is associated with changes in brain physiology and anatomy. It has been suggested that the neuronal activity underlying subjective perception of chronic pain may be divergent from the activity associated with acute pain. We will discuss the possible common pathophysiological mechanism of chronic pain and depression with respect to the default mode network of the brain, neuroplasticity and the effect of antidepressants on these two pathological conditions. The default mode network of the brain has an important role in the representation of introspective mental activities and therefore can be considered as a nodal point, common for both chronic pain and depression. Neuroplasticity which involves molecular, cellular and synaptic processes modifying connectivity between neurons and neuronal circuits can also be affected by pathological states such as chronic pain or depression. We suppose that pathogenesis of depression and chronic pain shares common negative neuroplastic changes in the central nervous system (CNS). The positive impact of antidepressants would result in a reduction of these pathological cellular/molecular processes and in the amelioration of symptoms, but it may also increase survival times and quality of life of patients with chronic cancer pain.