Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been maintaining the behavior. There is close correspondence between fear and human anxiety, and therefore studies of extinction learning might provide insight into the biological nature of anxiety-related disorders such as post-traumatic stress disorder, and they might help to develop strategies to treat them. Preclinical research aims to aid extinction learning and to induce targeted plasticity in extinction circuits to consolidate the newly formed memory. Vagus nerve stimulation (VNS) is a powerful approach that provides tight temporal and circuit-specific release of neurotransmitters, resulting in modulation of neuronal networks engaged in an ongoing task. VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here, we provide a detailed protocol for the preparation of custom-made parts and the surgical procedures required for VNS in rats. Using this protocol we show how VNS can facilitate the extinction of conditioned fear responses in an auditory fear conditioning task. In addition, we provide evidence that VNS modulates synaptic plasticity in the pathway between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA), which is involved in the expression and modulation of extinction memory.     

Protocol for Studying Extinction of Conditioned Fear in Naturally Cycling Female Rats

Extinction of conditioned fear has been extensively studied in male rodents. Recently, there have been an increasing number of studies indicating that neural mechanisms for certain behavioral tasks and response behaviors are different in females and males. Using females in research studies can represent a challenge because of the variation of gonadal hormones during their estrous cycle. This protocol describes well-established procedures that are useful in investigating the role of estrogen in fear extinction memory consolidation in female rats. Phase of the estrous cycle and exogenous estrogen administration prior to extinction training can influence extinction recall 24 hr later. The vaginal swabbing technique for estrous phase identification described here aids the examination and manipulation of naturally cycling gonadal hormones. The use of this basic rodent model may further delineate the mechanisms by which estrogen can modulate fear extinction memory in females.     

Ingestion of Lactobacillus strain reduces anxiety and improves cognitive function in the hyperammonemia rat

Evidence suggests that the hyperammonemia(HA)-induced neuroinflammation and alterations in the serotonin(5-HT)system may contribute to cognitive decline and anxiety disorder during hepatic encephalopathy(HE).Probiotics that maintain immune system homeostasis and regulate the 5-HT system may be potential treatment for HA-mediated neurological disorders in HE.In this study,we tested the efficacy of probiotic Lactobacillus helveticus strain NS8 in preventing cognitive decline and anxiety-like behavior in HA rats.Chronic HA was induced by intraperitoneal injection of ammonium acetate for four weeks in male Sprague-Dawley rats.HA rats were then given Lactobacillus helveticus strain NS8(109 CFU mL?1)in drinking water as a daily supplementation.The Morris water maze task assessed cognitive function,and the elevated plus maze test evaluated anxiety-like behavior.Neuroinflammation was assessed by measuring the inflammatory markers:inducible nitric oxide synthase,prostaglandin E2,and interleukin-1βin the brain.5-HT system activity was evaluated by measuring 5-HT and its metabolite,5-HIAA,and the 5-HT precursor,tryptophan.Probiotic treatment of HA rats significantly reduced the level of inflammatory markers,decreased 5-HT metabolism,restored cognitive function and improved anxiety-like behavior.These results indicate that probiotic L.helveticus strain NS8 is beneficial for the treatment of cognitive decline and anxiety-like behavior in HA rats.     

Advantages and limitations of Internet‐based interventions for common mental disorders

Several Internet interventions have been developed and tested for common mental disorders, and the evidence to date shows that these treatments often result in similar outcomes as in face‐to‐face psychotherapy and that they are cost‐effective. In this paper, we first review the pros and cons of how participants in Internet treatment trials have been recruited. We then comment on the assessment procedures often involved in Internet interventions and conclude that, while online questionnaires yield robust results, diagnoses cannot be determined without any contact with the patient. We then review the role of the therapist and conclude that, although treatments including guidance seem to lead to better outcomes than unguided treatments, this guidance can be mainly practical and supportive rather than explicitly therapeutic in orientation. Then we briefly describe the advantages and disadvantages of treatments for mood and anxiety disorders and comment on ways to handle comorbidity often associated with these disorders. Finally we discuss challenges when disseminating Internet interventions. In conclusion, there is now a large body of evidence suggesting that Internet interventions work. Several research questions remain open, including how Internet interventions can be blended with traditional forms of care.     

The roles of DNA methylation of NR3C1 and 11β-HSD2 and exposure to maternal mood disorder in utero on newborn neurobehavior

Exposure to maternal mood disorder in utero may program infant neurobehavior via DNA methylation of the glucocorticoid receptor (NR3C1) and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), two placental genes that have been implicated in perturbations of the hypothalamic pituitary adrenocortical (HPA) axis. We tested the relations among prenatal exposure to maternal depression or anxiety, methylation of exon 1F of NR3C1 and 11β-HSD-2, and newborn neurobehavior. Controlling for relevant covariates, infants whose mothers reported depression during pregnancy and showed greater methylation of placental NR3C1 CpG2 had poorer self-regulation, more hypotonia, and more lethargy than infants whose mothers did not report depression. On the other hand, infants whose mothers reported anxiety during pregnancy and showed greater methylation of placental 11β-HSD-2 CpG4 were more hypotonic compared with infants of mothers who did not report anxiety during pregnancy. Our results support the fetal programming hypothesis and suggest that fetal adjustments to cues from the intrauterine environment, in this case an environment that could be characterized by increased exposure to maternal cortisol, may lead to poor neurodevelopmental outcomes.     

术前抑郁和焦虑对腹部择期手术患者术后认知功能的影响

目的:探讨紧张和焦虑对手术患者术后认知功能的影响。方法:100例腹部择期手术病人术前1天用汉密顿焦虑量表(HAMA)、汉密顿抑郁量表(HAMD)、简易智能测试量表(MMSE)、数字广度对病人进行测试。术后7天分别用MMSE、数字广度进行神经心理学测试,术后MMSE结果低于术前一个标准差则视为术后认知障碍(POCD)。结果:术前焦虑、抑郁以及同时发生焦虑和抑郁的阳性率分别为30%、50%和10%。女性患者术后7天POCD的发生率为30%,男性患者术后7天POCD的发生率为20%;女性患者焦虑得分为7.2±4.0,高于男性患者4.5±3.3,P=0.05女性患者的抑郁得分为6.5±3.6,明显高于男性患者4.2±3.4(P=0.1),术前焦虑与POCD的相关性不显著,术前焦虑与MMSE、数字广度的Pearson’s相关系数分别为-0.50(P=0.2)和-0.20(P=0.1)。术前抑郁与POCD存在显著的相关性,其中术前抑郁与MMSE的Pearson’s相关系数为-0.61(P=0.01),术前抑郁与数字广度的Pearson’s相关系数为-0.72(P=0.03)。结论:术前抑郁的患者术后容易发生POCD;相对于男性患者,女性更容易出现POCD;而术前焦虑对POCD没有重要的影响。     

The Psychological and Physiological Effects of Using a Therapy Dog in Mindfulness Training

ABSTRACT

The present study was a randomized controlled trial examining the psychological and physiological effects of adding animal-assisted therapy (AAT) to a modified Mindfulness-Based Stress Reduction program (MBSR) for clients experiencing psychological distress. It was hypothesized that AAT would complement mindfulness-based interventions because the therapy dog will provide a focus for attention to the current experience and exemplify acceptance and “being,” enabling the understanding and practice of the main aspects of mindfulness. Participants (n=21) were randomly assigned to an MBSR or MBSR+AAT group and then completed an intervention consisting of six 50-minute individual therapy sessions. Each session included didactic and experiential components modified for delivery with or without a certified therapy dog. State and trait mindfulness, psychological distress measures, blood pressure, and heart rate were assessed at each session. Results indicate that all participants experienced fewer anxiety and depressive symptoms, decreased psychological distress, and increased mindfulness skills from preto post-treatment. Additionally, state anxiety, blood pressure, and heart rate decreased within sessions. No significant difference was found between the control and experimental groups, indicating that interaction with a therapy dog had no impact on symptom reduction, skill acquisition, or client satisfaction in the current study. However, moderate to large effect size estimates indicate clinically significant differences between groups, with higher ratings for the MBSR+AAT group on therapist efficacy, recommending the training, and participating in future treatment. Future studies need to increase methodological rigor by including multiple therapist/dog teams and increasing sample size. Moreover, researchers must more thoroughly examine the role the dog might have in altering the social environment, such as reducing stigma surrounding mental health services and enhancing the therapeutic alliance.     

Exploring Synchronicity in the Heart Rates of Familiar and Unfamiliar Pairs of Horses and Humans Undertaking an In-Hand Task

ABSTRACT

Physiological responses that occur in horses and humans during their interactions, on the ground and during ridden work, have been investigated in a number of studies with some conflicting results. These suggest that in some situations emotional state may be transferred from humans to horses and that there is the potential for the heart rates of horse–human pairs to become synchronized during ridden work. Here we explore the effect of familiarity on the physiological responses of horse–human pairs completing a task in-hand, using heart rate as an indicator for emotional state. We investigated differences in heart rate response between familiar and unfamiliar pairings and the possibility of heart rate synchronization within each pair. Complete sets of horse and human heart rate data were available for 17 horses. We found a significant order affect, with higher horse heart rates seen the first time around the course regardless of whether a familiar or unfamiliar handler was leading (Wilcoxon test: Z=–2.67, p<0.05). However, despite this, the horses’ mean heart rates for each course were significantly higher with the unfamiliar handler than with the familiar handler (Wilcoxon test: Z=–4.46, p<0.001). In contrast, human heart rates were higher when paired with a familiar horse compared with an unfamiliar horse (Mann-Whitney U test: Z=–5.08, p<0.001). Significant correlations between horse and human heart rates were seen in three familiar pairings and two unfamiliar pairings. Our findings indicate that the relationship between horse and human heart rates during interactions is not straightforward or consistent between horses and humans, and is likely to depend on a number of factors such as experience of the test situation. Although the lower heart rates seen in horses being led by their familiar handler suggest that they are more relaxed with someone they know, this could not be said for the human partner.