Disturbances In Social Behavior Research Articles

Study of the effect of phosphorylated carboxylic acids new derivatives on the main behavioral disorders in rats in the valproate model of autism

BACKGROUND: Due to the increasing frequency of autism in the population, the complexity of behavioral symptoms, and the need for long-term therapy, it is important to find new safe drugs for the correction of behavioral disorders.
 AIM: Studying the possibility of correcting behavioral changes characteristic of autism in rats in the valproate model of autism using new derivatives of phosphorylated carboxylic acids.
 MATERIAL AND METHODS: The possibility of correcting behavioral disorders in male and female rats in the valproate model of autism was studied with intraperitoneal administration (7 days) of new derivatives from the group of phosphorylated acetohydrazides (B2, C5) and thiosemicarbazide (T8) in doses of 1/100 LD50 on behavioral tests “Elevated Plus Maze”, “Burying Balls”, “Extended Open Field”. Statistical processing was carried out in the GraphPad prism 8.0.1 program using Student's t-test.
 RESULTS: It was found that the most pronounced anxiolytic effect on rats with autism was exerted by the compound 2-[(diphenylphosphoryl)acetyl]-N-phenylhydrazine-1-carbothioamide (T8), increasing by 4.8 times (p=0.033) in females and 4.4 times (p=0.036) in males, the time they spent in open arms in the “Elevated Plus Maze” test. The corrective effect on social behavior in rats with autism was most noted for T8 and B2 [2-ethoxy-2-oxoethanammonium salt (2-ethoxy-2-oxotyl) phenylphosphinic acid], which was characterized by an increase in the time spent with a social object (unfamiliar rat) 6.4 times (p=0.04) and 5.2 times (p=0.039), respectively, in the “Extended open field” method. When assessing the behavior of rats in the valproate model of autism in the “Burying Balls” test, it was found that the use of B2, T8 and C5 reduced the level of stereotypy, reducing the number of buried balls by 1.7 times (p=0.009), 1.5 times (p=0.046 ) and 1.7 times (p=0.011), respectively, compared to rats in the valproate model of autism without treatment.
 CONCLUSION: Derivatives of phosphorylated acetohydrazides and thiosemicarbazide have an anxiolytic effect, correct disturbances in social behavior and reduce the severity of stereotypic behavior in rats in the valproate model of autism.

Diagnostic approaches to assessing mild behavioral impairment in patients with mild cognitive impairment

To assess the prevalence of mild behavioral impairment (MBI ) in elderly individuals with mild cognitive impairment (MCI ), refine diagnostic criteria, and characterize the identified neuropsychiatric symptoms. Sixty-three individuals over 50 years of age (median 72 [68; 77]) with MCI underwent psychiatric and psychometric assessments using clinical and psychopathological methods and scales. Statistical analysis was conducted to evaluate intergroup differences, ROC-analysis with calculation of the area under the curve (AUC) was performed, and sensitivity, specificity, and accuracy of MBI diagnosis were determined for MBI-C. The prevalence of MBI using only ISTAART research criteria was 65%. An optimal diagnostic cut point for the MBI-C scale with the highest AUC (0.793), at 10 points, was identified. Upon a comprehensive assessment of MBI using criteria and optimal cut point values from the MBI-C scale, the prevalence was 33% (median 16 [14; 20]). Patients with MBI+MCI and MCI only did not significantly differ in MMSE and MoCA test results. Significant intergroup differences were observed in the severity of symptoms such as apathy (p<0.001), depression and anxiety (p<0.001), agitation and impulsivity (p<0.001), social behavioral disturbances (p=0.009), and subsyndromal psychotic symptoms (p<0.001). The most common symptoms were related to impulse control deficits, irritability, agitation, depression, anxiety, and apathy, while less common symptoms were associated with social behavioral disturbances and subsyndromal psychotic symptoms. Novel data on the diagnostic features of MBI in elderly patients with MCI in the Russian-speaking population are presented. An optimal diagnostic cut point for the MBI-C scale in a sample of patients from specialized clinics for comprehensive use with commonly accepted criteria was determined. Further research is needed to adapt and validate the MBI-C scale and provide prognostic evaluation of MBI in the context of MCI progression to dementia.

58 Right Anterior Temporal Lobe Atrophy is Associated with Informant-Reported Socioemotional Dysfunction in Patients with Frontotemporal and Early Onset Alzheimer's Dementia

Objective:Abnormalities in social and emotional behavior are the major diagnostic criteria for behavioral variant frontotemporal dementia (bvFTD). Investigators have attributed their behavioral disturbances to disease in mesial prefrontal and related networks, such as the salience network. This study examined the main neural correlates of informant-reported socioemotional dysfunction among patients with bvFTD compared to those with early-onset (before age 65) Alzheimer's Disease (EOAD).Participants and Methods:Participants included 13 patients with bvFTD and their caregivers and 18 patients with EOAD and their caregivers. The caregivers consisted of a spouse, family member, or other informant who resided with the patient. They completed the informant-based Socioemotional Dysfunction Scale (SDS), a 40-item scale which rates common disturbances in social and emotional behavior on a five-point Likert scale (1-5). The patients underwent magnetic resonance imaging (MRI) with tensor-based morphometry (TBM) analysis of the 3D T1-weighted MRI scans. Computations of mean Jacobian values within select regions of interest (ROIs) in frontal and temporal lobes generated numerical summaries of regional volumes, and voxel-wise regressions created 3D statistical maps of the association between tissue volume and SDS total scores. Statistical analyses included independent samples t-tests group differences in ROIs and SDS scores, Pearson correlations between SDS scores and brain volumes, and multiple regression of ROIs with SDS scores and group as predictor variables.Results:Compared to the EOAD group, the bvFTD group had significantly higher SDS scores (p &lt; .001; d = 2.24), smaller frontal lobe volumes (specifically dorsolateral-prefrontal cortex, p = .003; d = 1.24), and larger temporal lobe volumes (specifically hippocampus, p = .014; d = 0.979). Within the bvFTD group, higher SDS scores were associated with a smaller right anterior temporal lobe (ATL; p = .005; r = -.729), especially the lateral ATLs (p = .002; r = -.776), and a smaller bilateral orbitofrontal cortex (OFC; p = .016; r = -.650). In contrast, within the EOAD group, higher SDS scores were associated with a smaller right parietal cortex (p = .030; r = .542). In the entire sample (both bvFTD and EOAD), higher SDS scores was associated with a smaller lateral ATL volumes (p = .019; r = -.431). Regression analyses confirmed that SDS score predicted lateral ATL volume (p = .041; b = -.262) after controlling for diagnosis (p &lt; .001; b = -.692).Conclusions:These findings are consistent with greater socioemotional dysfunction, smaller frontal, and larger mesial temporal regions in bvFTD, when compared to EOAD. The findings, however, suggest that positively disturbed socioemotional behavior in bvFTD, as reported by caregivers, results from involvement of the right temporal lobe and the lateral temporal region, with further contribution from disease in OFC. The association of SDS scores and ATL volume across diagnostic groups suggests that this region is instrumental in socioemotional functioning and that the SDS may have diagnostic value in distinguishing the "right-temporal variant" of bvFTD.

Post-weaning social isolation in male mice leads to abnormal aggression and disrupted network organization in the prefrontal cortex: Contribution of parvalbumin interneurons with or without perineuronal nets

Adverse social experiences during childhood increase the risk of developing aggression-related psychopathologies. The prefrontal cortex (PFC) is a key regulator of social behavior, where experience-dependent network development is tied to the maturation of parvalbumin-positive (PV+) interneurons. Maltreatment in childhood could impact PFC development and lead to disturbances in social behavior during later life. However, our knowledge regarding the impact of early-life social stress on PFC operation and PV+ cell function is still scarce. Here, we used post-weaning social isolation (PWSI) to model early-life social neglect in mice and to study the associated neuronal changes in the PFC, additionally distinguishing between the two main subpopulations of PV+ interneurons, i.e. those without or those enwrapped by perineuronal nets (PNN). For the first time to such detailed extent in mice, we show that PWSI induced disturbances in social behavior, including abnormal aggression, excessive vigilance and fragmented behavioral organization. PWSI mice showed altered resting-state and fighting-induced co-activation patterns between orbitofrontal and medial PFC (mPFC) subregions, with a particularly highly elevated activity in the mPFC. Surprisingly, aggressive interaction was associated with a higher recruitment of mPFC PV+ neurons that were surrounded by PNN in PWSI mice that seemed to mediate the emergence of social deficits. PWSI did not affect the number of PV+ neurons and PNN density, but enhanced PV and PNN intensity as well as cortical and subcortical glutamatergic drive onto mPFC PV+ neurons. Our results suggest that the increased excitatory input of PV+ cells could emerge as a compensatory mechanism for the PV+ neuron-mediated impaired inhibition of mPFC layer 5 pyramidal neurons, since we found lower numbers of GABAergic PV+ puncta on the perisomatic region of these cells. In conclusion, PWSI leads to altered PV-PNN activity and impaired excitatory/inhibitory balance in the mPFC, which possibly contributes to social behavioral disruptions seen in PWSI mice. Our data advances our understanding on how early-life social stress can impact the maturing PFC and lead to the development of social abnormalities in adulthood.

Sex Differences in Rats with the Valproate Model of Autism: Disturbances in Social Behavior and Changes in Drd1 Gene Expression in Various Brain Structures

Sex Differences in Rats with the Valproate Model of Autism: Disturbances in Social Behavior and Changes in Drd1 Gene Expression in Various Brain Structures

Second-generation antipsychotic olanzapine attenuates behavioral and prefrontal cortex synaptic plasticity deficits in a neurodevelopmental schizophrenia-related rat model

Second-generation antipsychotics are the drugs of choice for the treatment of neurodevelopmental-related mental diseases such as schizophrenia. Despite the effectiveness of these drugs to ameliorate some of the symptoms of schizophrenia, specifically the positive ones, the mechanisms beyond their antipsychotic effect are still poorly understood. Second-generation antipsychotics are reported to have anti-inflammatory, antioxidant and neuroplastic properties. Using the neonatal ventral hippocampus lesion (nVHL) in the rat, an accepted schizophrenia-related model, we evaluated the effect of the second-generation antipsychotic olanzapine (OLZ) in the behavioral, neuroplastic, and neuroinflammatory alterations exhibited in the nVHL animals. OLZ corrected the hyperlocomotion and impaired working memory of the nVHL rats but failed to enhance social behavior disturbances of these animals. In the prefrontal cortex (PFC), OLZ restored the pyramidal cell structural plasticity in the nVHL rats, enhancing the dendritic arbor length, the spinogenesis and the proportion of mature spines. Moreover, OLZ attenuated astrogliosis as well as some pro-inflammatory, oxidative stress, and apoptosis-related molecules in the PFC. These findings reinforce the evidence of anti-inflammatory, antioxidant, and neurotrophic mechanisms of second-generation antipsychotics in the nVHL schizophrenia-related model, which allows for the possibility of developing more specific drugs for this disorder and thus avoiding the side effects of current schizophrenia treatments.

The Ntan1 gene is expressed in perineural glia and neurons of adult Drosophila

The Drosophila Ntan1 gene encodes an N-terminal asparagine amidohydrolase that we show is highly conserved throughout evolution. Protein isoforms share more than 72% of similarity with their human counterparts. At the cellular level, this gene regulates the type of glial cell growth in Drosophila larvae by its different expression levels. The Drosophila Ntan1 gene has 4 transcripts that encode 2 protein isoforms. Here we describe that although this gene is expressed at all developmental stages and adult organs tested (eye, antennae and brain) there are some transcript-dependent specificities. Therefore, both quantitative and qualitative cues could account for gene function. However, widespread developmental stage and organ-dependent expression could be masking cell-specific constraints that can be explored in Drosophila by using Gal4 drivers. We report a new genetic driver within this gene, Mz317-Gal4, that recapitulates the Ntan1 gene expression pattern in adults. It shows specific expression for perineural glia in the olfactory organs but mixed expression with some neurons in the adult brain. Memory and social behavior disturbances in mice and cancer and schizophrenia in humans have been linked to the Ntan1 gene. Therefore, these new tools in Drosophila may contribute to our understanding of the cellular basis of these alterations.

Novel probiotic treatment of autism spectrum disorder associated social behavioral symptoms in two rodent models

The prevalence of autism spectrum disorder (ASD) has rapidly increased in the past decades, and several studies report about the escalating use of antibiotics and the consequent disruption of the gastrointestinal microbiome leading to the development of neurobehavioral symptoms resembling to those of ASD. The primary purpose of this study was to investigate whether depletion of the gastrointestinal microbiome via antibiotics treatment could induce ASD-like behavioral symptoms in adulthood. To reliably evaluate that, validated valproic acid (VPA) ASD animal model was introduced. At last, we intended to demonstrate the assessed potential benefits of a probiotic mixture (PM) developed by our research team. Male Wistar rats were used to create antibiotics treated; antibiotics and PM treated; PM treated, VPA treated; VPA and PM treated; and control groups. In all investigations we focused on social behavioral disturbances. Antibiotics-induced microbiome alterations during adulthood triggered severe deficits in social behavior similar to those observed in the VPA model. Furthermore, it is highlighted that our PM proved to attenuate both the antibiotics- and the VPA-generated antisocial behavioral symptoms. The present findings underline potential capacity of our PM to improve social behavioral alterations thus, indicate its promising therapeutic power to attenuate the social-affective disturbances of ASD.

A Selective Review of the Excitatory-Inhibitory Imbalance in Schizophrenia: Underlying Biology, Genetics, Microcircuits, and Symptoms.

Schizophrenia is a chronic disorder characterized by specific positive and negative primary symptoms, social behavior disturbances and cognitive deficits (e.g., impairment in working memory and cognitive flexibility). Mounting evidence suggests that altered excitability and inhibition at the molecular, cellular, circuit and network level might be the basis for the pathophysiology of neurodevelopmental and neuropsychiatric disorders such as schizophrenia. In the past decades, human and animal studies have identified that glutamate and gamma-aminobutyric acid (GABA) neurotransmissions are critically involved in several cognitive progresses, including learning and memory. The purpose of this review is, by analyzing emerging findings relating to the balance of excitatory and inhibitory, ranging from animal models of schizophrenia to clinical studies in patients with early onset, first-episode or chronic schizophrenia, to discuss how the excitatory-inhibitory imbalance may relate to the pathophysiology of disease phenotypes such as cognitive deficits and negative symptoms, and highlight directions for appropriate therapeutic strategies.

Stress-induced alterations of social behavior are reversible by antagonism of steroid hormones in C57/BL6 mice

Various disturbances of social behavior, such as autism, depression, or posttraumatic stress disorder, have been associated with an altered steroid hormone homeostasis and a dysregulation of the hypothalamus–pituitary–adrenal axis. A link between steroid hormone antagonists and the treatment of stress-related conditions has been suggested. We evaluated the effects of stress induction on social behavior in the three chambers and its potential reversibility upon specific steroid hormone antagonism in mice. C57BL/6 mice were stressed twice daily for 8 days by chronic swim testing. Social behavior was evaluated by measuring, first, the preference for sociability and, second, the preference for social novelty in the three-chamber approach before and after the chronic swim test. The reversibility of behavior upon stress induction was analyzed after applying steroid hormone antagonists targeting glucocorticoids with etomidate, mineralocorticoids with potassium canrenoate, and androgens with cyproterone acetate and metformin. In the chronic swim test, increased floating time from 0.8 ± 0.2 min up to 4.8 ± 0.25 min was detected (p < 0.01). In the three-chamber approach, increased preference for sociability and decreased preference for social novelty was detected pre- versus post-stress induction. These alterations of social behavior were barely affected by etomidate and potassium canrenoate, whereas the two androgen antagonists metformin and cyproterone acetate restored social behavior even beyond baseline conditions. The alteration of social behavior was better reversed by the androgen as compared with the glucocorticoid and mineralocorticoid antagonists. This suggests that social behavior is primarily controlled by androgen rather than by glucocorticoid or mineralocorticoid action. The stress-induced changes in preference for sociability are incompletely explained by steroid hormone action alone. As the best response was related to metformin, an effect via glucose levels might confound the results and should be subject to future research.

Co-expression of glutamatergic and autism-related genes in the hippocampus of male mice with disturbances of social behavior

В настоящее время существует представление о вовлеченности глутаматергической системы (ГГ) в механизмы развития аутизма. В предыдущих исследованиях нами было показано, что негативный социальный опыт, приобретенный в ежедневных межсамцовых конфронтациях, приводит к нарушениям в социальном поведении: снижению коммуникативности, нарушению социализации, появлению стереотипных форм поведения, которые могут рассматриваться как симптомы аутистического спектра. В связи с этим целью нашей работы было изучение с помощью транскриптомного анализа изменений экспрессии генов, кодирующих белки, вовлеченные в функционирование глутаматергической системы, и генов, связанных с патологией аутизма (ГА), в гиппокампе. В эксперименте использовали животных с нарушениями социального поведения, вызванными повторным опытом социальных побед или поражений в ежедневных агонистических взаимодействиях. Для формирования групп животных с контрастными типами поведения использовали модель сенсорного контакта (хронического социального стресса). Полученные образцы мозга были секвенированы в ЗАО «Геноаналитика» (http://genoanalytica.ru/, Россия, Москва). Транскриптомный анализ показал, что у агрессивных животных снижается экспрессия генов Shank3, Auts2, Ctnnd2, Nrxn2, для которых показано участие в развитии аутизма, а также глутаматергического гена Grm4. В то же время у животных с негативным социальным опытом экспрессия ГА Shank2, Nlgn2, Ptcdh10, Reln, Arx возрастает. При этом ГГ (Grik3, Grm2, Grm4, Slc17a7, Slc1a4, Slc25a22), за исключением гена Grin2a, повышают свою экспрессию. Корреляционный анализ выявил статистически значимую взаимосвязь из- мененной экспрессии ГГ и ГА. Полученные результаты, с одной стороны, могут служить подтверждением участия ГГ в патофизиологии развития симптомов аутистического спектра, с другой – свидетельствовать о коэкспрессии ГГ и ГА в гиппокампе, развивающейся под влиянием социальной среды. Так как большинство ГА, изменивших экспрессию в настоящем исследовании, являются генами, связанными с клеточным скелетом и внеклеточным матриксом, в частности участвующими в формировании синапсов, а ГГ, изменившие свою экспрессию, – генами, кодирующими субъединицы рецепторов, то можно предположить, что вовлечение ГГ в патофизиологию аутизма происходит на уровне рецепторов.

Dietary phytoestrogens modulate aggression and activity in social behavior circuits of male mice

Phytoestrogens comprise biologically active constituents of human and animal diet that can impact on systemic and local estrogen functions in the brain. Here we report on the importance of dietary phytoestrogens for maintaining activity in a brain circuit controlling aggressive and social behavior of male mice. After six weeks of low-phytoestrogen chronic diet (diadzein plus genistein <20 μg/g) a reduction of intermale aggression and altered territorial marking behavior could be observed, compared to littermates on a standard soy-bean based diet (300 μg/g). Further, mice on low-phyto diet displayed a decrease in sociability and a reduced preference for social odors, indicating a general disturbance of social behavior. Underlying circuits were investigated by analysing the induction of the activity marker c-Fos upon social encounter. Low-phyto diet led to a markedly reduced c-Fos induction in the medial as well as the cortical amygdala, the lateral septum, medial preoptic area and bed nucleus of the stria terminalis. No difference between groups was observed in the olfactory bulb. Together our data suggest that dietary phytoestrogens critically modulate social behavior circuits in the male mouse brain.

Emotion recognition and social cognition in juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsy. Disease onset is typically in puberty and poor social adjustment and behavioral disturbances, which resemble frontal lobe dysfunction, are often observed. In recent advanced brain imaging studies on JME patients, emotional and behavioral problems have been associated to subtle structural and functional alterations mainly in frontal cortex and thalamus. There is emerging evidence that patients with abnormal emotion processing and regulation, such as those with bipolar disorder, show disrupted connectivity between limbic structures and frontal cortices. There are no neuroimaging or neuropsychological studies related to emotion processing in patients with JME with a focus on limbic structures. We aimed to address the problem of emotional disturbances and social adjustment in JME patients from multiple aspects through thorough functional and structural assessment, which would potentially enable elaboration of a unifying concept explaining neurobiological background of disturbances in emotional processing and social adjustment in JME patients. Results of this study may potentially enable the development of psychological and pharmacological interventional strategies for managing behavioral disturbances in patients with JME.

Impairments in cognitive functions and emotional and social behaviors in a rat lithium-pilocarpine model of temporal lobe epilepsy

The aim of this study was to evaluate in detail behavioral patterns and comorbid disturbances in rats using the lithium-pilocarpine model. A comprehensive set of behavioral tests was used to investigate behavioral patterns, including the open field test, Morris water maze, Y-maze, fear conditioning, the elevated plus maze, the forced swimming test, and the resident-intruder paradigm. Motor and explorative activity, learning and memory, anxiety and depressive-like behavior, aggression, and communication were evaluated 8–15 d after pilocarpine-induced status epilepticus (SE) (latent phase of the model) and 41–53 d (chronic phase) after pilocarpine-induced SE. Increased motor activity and impaired memory function were the most noticeable behavioral modifications in the epileptic rats. Both the movement speed and distance traveled increased in the open field test in both the latent and chronic phases. Significant impairments were detected in short-and long-term spatial memory in the Morris water maze during the latent phase. Besides the alterations in spatial memory, behaviors indicative of short- and long-term fear-associated memory disturbances were observed in the fear conditioning test during the chronic phase of the model. In the resident-intruder paradigm, epileptic rats exhibited disturbed communicative behavior, with impaired social behaviors. In contrast, emotional disturbances were less prominent, with the rats exhibiting decreased anxiety. There were no changes in depressive-like behavior. The data suggest that the lithium-pilocarpine model of TLE in rodents is more useful for studies of comorbid disturbances in memory, hyperactivity, and social behavior than for research on psychoemotional impairments, such as anxiety and depression.

Yoga: Balancing the excitation-inhibition equilibrium in psychiatric disorders.

Social behavioral disturbances are central to most psychiatric disorders. A disequilibrium within the cortical excitatory and inhibitory neurotransmitter systems underlies these deficits. Gamma-aminobutyric acid (GABA) and glutamate are the most abundant excitatory and inhibitory neurotransmitters in the brain that contribute to this equilibrium. Several contemporary therapies used in treating psychiatric disorders, regulate this GABA-glutamate balance. Yoga has been studied as an adjuvant treatment across a broad range of psychiatric disorders and is shown to have short-term therapeutic gains. Emerging evidence from recent clinical in vivo experiments suggests that yoga improves GABA-mediated cortical-inhibitory tone and enhances peripheral oxytocin levels. This is likely to have a more controlled downstream response of the hypothalamo-pituitary-adrenal system by means of reduced cortisol release and hence a blunted sympathetic response to stress. Animal and early fetal developmental studies suggest an inter-dependent role of oxytocin and GABA in regulating social behaviors. In keeping with these observations, we propose an integrated neurobiological model to study the mechanisms of therapeutic benefits with yoga. Apart from providing a neuroscientific basis for applying a traditional system of practice in the clinical setting, this model can be used as a framework for studying yoga mechanisms in future clinical trials.

The Visually Mediated Social Preference Test: A Novel Technique to Measure Social Behavior and Behavioral Disturbances in Zebrafish.

Zebrafish are an emerging model in behavioral neuroscience. They display a wide range of measurable behaviors such as locomotion, aggression, anxiety, learning and memory, and social behavior. In addition, the relative ease of genetic manipulation and the increasing availability of disease models mean that zebrafish have gained in popularity as an animal model for various neurological and psychiatric diseases including autism spectrum disorder (ASD). In order to better characterize social behavior and behavioral abnormalities in zebrafish, we have developed the visually mediated social preference (VMSP) test, a novel assay to measure social preference and social novelty in two consecutive 5-min sessions. Using recording and video tracking, the time spent in different areas of the tank, the time spent immobile, swimming speed, and distance moved can be easily measured and analyzed. Untreated experimentally naive AB WT zebrafish typically show a strong preference for spending time near and interacting with a compartment containing unfamiliar conspecifics over the empty compartments during session 1 and a stronger preference for a group of unfamiliar zebrafish over familiar conspecifics from session 1, during session 2 of the test. Research in our lab has shown that the VMSP is suitable to measure the social behavior of individual zebrafish, to uncover social phenotypes of mutant strains, and to better understand animal models of disease that include impaired sociability such as ASD. The current paper provides a step-by-step guide on how to implement and perform this test and highlights important considerations for data acquisition, analysis, and interpretation.

The effects of high environmental ammonia on the structure of rainbow trout hierarchies and the physiology of the individuals therein

Our goals were: (i) to determine whether sublethal concentrations of water-borne ammonia would prevent the formation of a dominance hierarchy, or alter its structure, in groups of 4 juvenile trout; (ii) to investigate the behavioral and physiological responses of individuals of different social rank exposed to a concentration of ammonia that still allowed hierarchy formation. Social hierarchies were created by using a technique in which a food delivery system that created competition also served to isolate individual fish for respirometry. Groups of 4 fish were exposed to elevated ammonia (NH4HCO3) 12 h before first feeding; aggression was recorded by video camera during morning feedings. Experimental ammonia concentrations were 700, 1200 and 1500 μmol L−1 at pH 7.3, 12 °C (9.8, 16.8, and 21.0 mg L−1 as total ammonia-N, or 0.0515, 0.0884, and 0.1105 mg L−1 as NH3-N). Aggression was severely reduced by 1200 and abolished by 1500 μmol L−1 total ammonia, such that hierarchies did not form. However, groups exposed to 700 μmol L−1 total ammonia still formed stable hierarchies but displayed lower levels of aggression in comparison to control hierarchies. Exposure continued for 11 days. Physiological parameters were recorded on day 5 (end of period 1) and day 10 (end of period 2), while feeding and plasma cortisol were measured on day 11. In control hierarchies, dominant (rank 1) trout generally exhibited higher growth rates, greater increases in condition factor, higher food consumption, and lower cortisol levels than did fish of ranks 2, 3, and 4. In comparison to controls, the 700 μmol L−1 total ammonia hierarchies generally displayed lower growth, lower condition factor increases, lower O2 consumption, lower cortisol levels, but similar feeding patterns, with smaller physiological differences amongst ranks during period 1. Effects attenuated during period 2, as aggression and physiological measures returned towards control levels, indicating both behavioral and physiological acclimation to ammonia. These disturbances in social behavior and associated physiology occurred at an ammonia concentration in the range of regulatory significance and relevance to aquaculture.

The attribution of animacy and agency in frontotemporal dementia versus Alzheimer's disease

Impaired attribution of animacy (state of living or being sentient) and of agency (capability of intrinsically-driven action) may underlie social behavior disturbances in behavioral variant frontotemporal dementia (bvFTD). We presented the Heider and Simmel film of moving geometric shapes to 11 bvFTD patients, 11 Alzheimer's disease (AD) patients, and 12 healthy controls (HCs) and rated their recorded verbal responses for animacy attribution and agency attribution. All participants had skin conductance (SC) continuously recorded while viewing the film, and all dementia participants underwent magnetic resonance imaging (MRI) for regions of interest. The bvFTD patients, but not the AD patients, were impaired in animacy attribution, compared to the HCs. In contrast, both bvFTD and AD groups were impaired in agency attribution, compared to the HCs, and only the HCs had increasing SC responsiveness during viewing of the film. On MRI analysis of cortical thicknesses, animacy scores significantly correlated across groups with the right pars orbitalis and opercularis; agency scores with the left inferior and superior parietal cortices and the supramarginal gyrus; and both scores with the left cingulate isthmus involved in visuospatial context. These findings suggest that bvFTD is specifically associated with impaired animacy attribution from right inferior frontal atrophy. In contrast, both dementias may have impaired agency attribution from left parietal cortical atrophy and absent SC increases during the film, a sympathetic indicator of attribution of a social “story” to the moving shapes. These findings clarify disease-related changes in social attribution and corroborate the neuroanatomical origins of animacy and agency.

Genetic control of social behavior: Lessons from mutant mice

Social behavior is evolutionary conserved, and is thought to be evolved since it increased reproductive and survival fitness of living species. In humans, disturbances of social behavior are a peculiar pathological trait of neurodevelopmental disorders, namely autism spectrum disorder (ASD). ASD is defined by deficits in two core domains (social interaction/communication and repetitive/restrictive behaviors), which emerge during early postnatal development. ASD has a strong genetic component: copy number variations, de novo and familial mutations, as well as epigenetic modifications have been reported in a huge number of genes. Recent studies in mice demonstrate that mutations in a wide variety of ASD-associated genes can cause neurodevelopmental defects, which subsequently result in social behavior disturbances during early postnatal age and adulthood. From these studies, it clearly emerges that functionally interrelated cellular mechanisms underlie social behavior and its disturbances in ASD. Indeed, most of ASD-associated genes control neuronal differentiation and migration, growth of neuronal connections and synaptic function. Here we will present the recent advances in understanding the genetic determinants of social behavior, as they emerge from the study of ASD mouse models, and discuss the importance of these studies for the development of novel therapeutic approaches to overcome social disturbances in ASD.

Epidemiology of cephalalgia in population of central part of India

Introduction: Headache is a major and common neurological problem in worldwide and is a main reason of morbidity, incapacity, absenteeism at work place, interrupted social interaction mood and behavioral disturbances. Yet they are under-recognized, under-diagnosed and under-treated worldwide, only minorities of people with headache disorders are professionally diagnosed. Aim: Given the population load, and the fact that most headaches seen in practice are under diagnosed and undertreated, the burden of headache is significant. The present study was aimed to assess the Epidemiology of chronic headache in population of south eastern Rajasthan India. Materials and Methods: This study was conducted in department of neurosurgery Jhalawar medical college Jhalawar Rajasthan from 15th January 2015 to 15 july2016. Clinical and radiological details of Two thousand Patients of south east Rajasthan and west part of Madhya Pradesh were noted. The data obtained was statistically analyzed using SPSS version 22 and descriptive statistics was used to compare the results obtained. Results: Out of two thousand patients 900(45%) patients were male and 1100(55%) were female. 1760(88%) patients were between 16-60 year age group, there were 1320(66%) patients residing in rural areas and 880(44%) patients were residing in urban areas. Socioeconomic status occupation / income were low in 680(34%) patient’s medium in 1200(60%) patients. Tension type headache occur in1200 (60%), migraine in 400 (20%), cluster headache in 60 (3%), medication overuse headache present in100 (5%) patients. Other cause of headache noted in 240 (12%) as sinusitis, stroke, decrease vision, atypical pain like trigeminal neuralgia brain tumor and abscess. Conclusion: Headache prevalence in central part of India is more in female, adult between 16-60 years age groups, and rural areas with low socioeconomic status / income. Most common cause of headache is tension type headache. Keywords: Cephalalgia, headache, Tens