Enhancement of spatial learning by predator odor in mice: Involvement of amygdala and hippocampus

Olfaction has particular links with learning and memory compared with other sensory cues, due to the interrelations between their neural circuitry. The present study deals with the effects of a putative stressor (i.e. a predator odor) on visuo-spatial learning in mice. Firstly, the results show that a predator odor spread during the Morris water maze task led to learning enhancement. In addition, a stereotaxic approach was used to investigate the involvement of the amygdala in this hippocampus-dependent type of learning. Thus, the performance of mice in visuo-spatial learning under predator odor conditions was dramatically reduced by an ibotenate bilateral amygdala lesion. The involvement of the amygdala was confirmed by a reduced expression of c-fos in the CA1 hippocampus of amygdala-lesioned mice at the end of the learning procedure.Mild exposure to a predator odor during hippocampus-dependent learning therefore leads to an enhancement of performance through the co-activation of the amygdala, probably by a stress mediated mechanism.     

The effect of odors on human newborn infants under stress

Five-day-old human infants' responses to heelstick stress were assessed with behavioral and physiological indices. The subjects were divided randomly into three groups: the LAV group, who were presented with artificial odor of lavender during the heelstick; the MILK group, who were presented with artificial odor of milk during the heelstick; and the CONT group, who were presented with no special odors. The CONT group showed more adrenocortisol release in saliva than the other groups, but there were no differences between the two odors.     

Successful Treatment of Olfactory Reference Syndrome With Cognitive Behavioral Therapy: A Case Study

Olfactory reference syndrome (ORS) is characterized by a preoccupation with the belief that one's body emits a foul odor. Cognitive behavioral therapy (CBT) was used to treat a woman in her 50s who presented in our outpatient anxiety disorders specialty clinic with ORS, accompanied by embarrassment, shame, distress, avoidance behavior, and social isolation. Monitoring and systematic reduction of safety behaviors, combined with exposure to anxiety-provoking situations, resulted in elimination of the perceived body odor over the course of ten treatment sessions. Scores on the Overvalued Ideas Scale indicated improvements in the client's insight over the course of treatment, and there was an 82.6% reduction in her preoccupation and compulsive behaviors as measured by the Body Dysmorphic Disorder Yale-Brown Obsessive Compulsive Scale. Indices of depression, anxiety, and stress as measured by the 21-item version of the Depression Anxiety Stress Scales were also reduced from the extremely severe to normal range. These findings suggest further investigation of CBT in the treatment of ORS is warranted.     

Role of stress, corticotrophin releasing factor (CRF) and amygdala plasticity in chronic anxiety

Stress initiates a series of neuronal responses that prepare an organism to adapt to new environmental challenges. However, chronic stress may lead to maladaptive responses that can result in psychiatric syndromes such as anxiety and depressive disorders. Corticotropin-releasing factor (CRF) has been identified as a key neuropeptide responsible for initiating many of the endocrine, autonomic and behavioral responses to stress. The amygdala expresses high concentrations of CRF receptors and is itself a major extrahypothalamic source of CRF containing neurons. Within the amygdala, the basolateral nucleus (BLA) has an important role in regulating anxiety and affective responses. During periods of stress, CRF is released into the amygdala and local CRF receptor activation has been postulated as a substrate for stress-induced alterations in affective behavior. Previous studies have suggested that synaptic plasticity in the BLA contributes to mechanisms underlying long-term changes in the regulation of affective behaviors. Several studies have shown that acute glutamate receptor-mediated activation, by either GABA-mediated disinhibition or CRF-mediated excitation, induces long-term synaptic plasticity and increases the excitability of BLA neurons. This review summarizes some of the data supporting the hypotheses that stress induced plasticity within the amygdala may be a critical step in the pathophysiology of the development of chronic anxiety states. It is further proposed that such a change in the limbic neural circuitry is involved in the transition from normal vigilance responses to pathological anxiety, leading to syndromes such as panic and post-traumatic stress disorders.     

Olfactory preferences resulting from mere exposure in human neonates

Twenty-four (12 males, 12 females) healthy, full-term neonates were exposed to an artificial odorant within the first day after birth for approximately 24 hrs to determine if mere exposure would lead to a subsequent preference for that odor. In choice tests following the treatment period, female infants displayed preferential orientation to the exposure odor. Males, in contrast, displayed no evidence of preference for the exposure odor; rather, they demonstrated a right turning bias regardless of odor location. These data suggest that familiarization with an odor shortly after birth is sufficient for female infants to develop preferential responsiveness to that odor.     

Maternal odor shapes rapid face categorization in the infant brain

To successfully interact with a rich and ambiguous visual environment, the human brain learns to differentiate visual stimuli and to produce the same response to subsets of these stimuli despite their physical difference. Although this visual categorization function is traditionally investigated from a unisensory perspective, its early development is inherently constrained by multisensory inputs. In particular, an early‐maturing sensory system such as olfaction is ideally suited to support the immature visual system in infancy by providing stability and familiarity to a rapidly changing visual environment. Here, we test the hypothesis that rapid visual categorization of salient visual signals for the young infant brain, human faces, is shaped by another highly relevant human‐related input from the olfactory system, the mother's body odor. We observe that a right‐hemispheric neural signature of single‐glance face categorization from natural images is significantly enhanced in the maternal versus a control odor context in individual 4‐month‐old infant brains. A lack of difference between odor conditions for the common brain response elicited by both face and non‐face images rules out a mere enhancement of arousal or visual attention in the maternal odor context. These observations show that face‐selective neural activity in infancy is mediated by the presence of a (maternal) body odor, providing strong support for multisensory inputs driving category acquisition in the developing human brain and having important implications for our understanding of human perceptual development.     

Paradoxical olfactory function in combat Veterans: The role of PTSD and odor factors

Stress- and trauma-related disorders, including posttraumatic stress disorder (PTSD), are characterized by an increased sensitivity to threat cues. Given that threat detection is a critical function of olfaction and that combat trauma is commonly associated with burning odors, we sought a better understanding of general olfactory function as well as response to specific trauma-related (i.e. burning) odors in combat-related PTSD. Trauma-exposed combat Veterans with (n = 22) and without (n = 25) PTSD were assessed for general and specific odor sensitivities using a variety of tools. Both groups had similar general odor detection thresholds. However, the combat Veterans with PTSD, compared to combat Veterans with comparable trauma exposure but without PTSD, had increased ratings of odor intensity, negative valence, and odor-triggered PTSD symptoms, along with a blunted heart rate in response to burning rubber odor. These findings are discussed within the context of healthy versus pathological changes in olfactory processing that occur over time after psychological trauma.     

Unique characteristics of neonatal classical conditioning: The role of the amygdala and locus coeruleus

The central nervous system of altricial infants is specialized for optimizing attachments to their caregiver. During the first postnatal days, infant rats show a sensitive period for learning and particularly susceptible to learning an attraction to their mother’s odor. Classical conditioning appears to underlie this learning that is expressed behaviorally as anincreased ability to acquire odor preferences and a decreased ability to acquire odor aversions. Specifically, in neonatal rats, pairing an odor with moderately painful shock (0.5mA) or milk produces a subsequent relativepreference for that odor. The neural circuitry supporting theincreased ability to acquire odor preferences appears to be the heightened functioning of the noradrenergic pontine nucleus locus coeruleus. Indeed, norepinephrine from the locus coeruleus appears to be both necessary and sufficient for learning during the sensitive period. On the other hand, thedecreased ability to acquire odor aversions seems to be due to the lack of participation of the amygdala in at least some aversive learning situations. The site of plasticity in the pup’s brain appears to be limited to the olfactory bulb. This neonatal sensitive period for learning ends around postnatal day 9–10, at which time pups make the transition from crawling to walking and classical conditioning becomes “adultlike”. The neonatal behavioral and neural induced changes are retained into adulthood where it modifies sexual behavior.     

Effects of novel odors on intermale attack behavior in mice

Offensive, defensive, and nonagonistic social behaviors of resident male mice toward unfamiliar intruders were examined during exposure to the novel odors of chocolate or sheep's wool. Both novel odors reduced lateral attacks and boxing when compared to familiar sawdust odor. Chocolate, but not sheep's wool, also reliably increased flight behavior by residents. Neither social behaviors nor self-grooming were affected by these odors. The novel odors had no effect upon, or actually decreased, the defensive responses of intruders towards residents. The equivalent effectiveness of both predator and nonpredator odors in elevating risk assessment and suppressing attack during firsttime exposure, and the decreased potency of cat odors following repeated exposure, suggests that novelty contributes to the enhanced defensiveness seen among subjects during initial exposure to predator odors. © 1995 Wiley-Liss, Inc.     

Safety behaviours preserve threat beliefs: Protection from extinction of human fear conditioning by an avoidance response

A laboratory autonomic conditioning procedure was used to establish fear conditioning in human participants by pairing neutral stimuli with electric shock. Participants were also trained to make a button-press response to avoid shock. A target fear stimulus was then extinguished by presenting it without shock. The experimental group was given the opportunity to make the avoidance response during extinction whereas the control group was not. When the fear stimulus was tested without the response available, the control group showed normal extinction of both shock expectancy ratings and skin conductance responses, but the experimental group showed “protection from extinction”: they continued to give high expectancy ratings and strong skin conductance responses. We interpret this effect as analogous to the role of within-situation safety behaviours in preserving threat beliefs during exposure therapy for anxiety disorders. The results support a cognitive account of learning and anxiety. The procedure provides a potential laboratory model for further examination of the cognitive and neural mechanisms underlying anxiety and its reduction.     

Interactions between perinatal and neonatal associative learning defined by contiguous olfactory and tactile stimulation

Tactile stimulation of the neonate, as performed by the mother during and after delivery, has been described as an effective unconditioned stimulus during early ontogeny (Leon, 1987; Ronca & Alberts, 1994). The present experiments examined the interaction between perinatal and neonatal learning determined by the explicit association between alcohol odor and vigorous body stimulation of the perinatal organism. In Experiment 1, rat fetuses were exposed to either alcohol or saline 10 min prior to cesarean delivery. The alcohol administration procedure here employed was sufficient to provide sensory contamination of the amniotic fluid but avoid fetal alcohol intoxication. Pups in the two prenatal treatments later experienced the smell of alcohol, tactile stimulation, or both stimuli explicitly paired or unpaired. Other postnatal groups were composed of pups that had no explicit experience with either experimental stimulus. Pups subjected to alcohol odor in utero displayed more overall motor activity in response to that odor than saline controls. The increased motor responses were further potentiated in pups that experienced additional postnatal alcohol odor paired with tactile stimulation. In Experiment 2, pups were exposed to alcohol in the amniotic fluid 10 or 30 min prior to birth. As previously demonstrated the memory acquired in utero appears highly dependent upon contingency between exposure to this particular scent and delivery procedures. Pups in both prenatal treatment groups were then exposed to alcohol odor paired or unpaired with tactile stimulation. Some control animals received no further experience with either stimuli. Those pups exposed to alcohol odor paired with tactile stimulation both pre- and postnatally later showed maximum motor activity elicited by the odor of alcohol. The results support the notion of fetal associative learning comprising alcohol's chemosensory cues and behaviorally activating stimuli. Furthermore, the conditioned response under analysis is potentiated whenever neonates are reexposed to contingent presentations of the elements that defined the original associative memory.     

Olfactory predator recognition in predator-naïve gray mouse lemurs (Microcebus murinus)

Olfactory cues of predators, such as feces, are known to elicit antipredator responses in animals (e.g., avoidance, activity). To date, however, there is little information on olfactory predator recognition in primates. We tested whether the odor of feces of different predator categories (historical Malagasy predators and introduced predators) and of Malagasy nonpredators (control) induces antipredator behavior in captive born, predator-na?ve gray mouse lemurs. In an olfactory predator experiment a mouse lemur was exposed to a particular odor, fixed at a preferred location, where the animal was trained to get a reward. The behavior of the mouse lemur toward the respective stimulus category was videotaped and quantified. Results showed that mouse lemurs avoided the place of odor presentation when the odor belonged to a predator. They reacted with a significantly enhanced activity when exposed to odors of carnivores compared to those of nonpredatory controls. These findings are in favor of a genetic predisposition of olfactory predator recognition that might be based on the perception of metabolites from meat digestion.     

Implicit and explicit tests of odor memory reveal different outcomes following interference

Experiencing two odors as a mixture can later increase their perceived similarity when presented separately. Such an increase in similarity can be used as an implicit measure of how well participants remember the mixture. Three experiments tested the resistance to interference of this effect by first giving participants exposure to two 2-odor mixtures and then presenting each odor from one mixture (interfered pair) separately many times. After the latter interference phase, participants rated the similarity of the two odors in each pair. The experiments varied in terms of the number of initial exposures to the mixtures, the number of odor presentations in the interference phase, and the control conditions employed. No difference in similarity ratings for the interfered and non-interfered pair was found in any experiment. In contrast to the lack of interference with this implicit measure, an explicit measure of memory based on participants’ ratings of odor frequency revealed that they could recall to some degree that the interfered odors had been presented alone in the second phase. These results suggest that implicit memory for odor mixtures is highly resistant to interference and is consistent with a configural encoding account of this effect.     

Recalling safety: cooperative functions of the ventromedial prefrontal cortex and the hippocampus in extinction

Anxiety disorders are commonly treated with exposure-based therapies that rely on extinction of conditioned fear. Persistent fear and anxiety following exposure therapy could reflect a deficit in the recall of extinction learning. Animal models of fear learning have elucidated a neural circuit for extinction learning and recall that includes the amygdala, ventromedial prefrontal cortex (vmPFC), and hippocampus. Whereas the amygdala is important for extinction learning, the vmPFC is a site of neural plasticity that allows for the inhibition of fear during extinction recall. We suggest that the vmPFC receives convergent information from other brain regions, such as contextual information from the hippocampus, to determine the circumstances under which extinction or fear will be recalled. Imaging studies of human fear conditioning and extinction lend credence to this extinction network. Understanding the neural circuitry underlying extinction recall will lead to more effective therapies for disorders of fear and anxiety.     

Anxiety Disorders in Late Life: Considerations for Assessment and Cognitive-Behavioral Treatment

Anxiety disorders are among the most frequently diagnosed mental disorders in late life. As older adults comprise a growing segment of the population, evidence-based treatments for anxiety disorders in late life have come into sharper focus. Cognitive-behavioral therapy (CBT) for anxiety disorders in late life has received less empirical attention and widespread dissemination relative to other age groups. Increasing older adults’ access to timely assessment and effective treatment can help reduce the personal and societal costs of anxiety disorders. The purpose of this review paper is to discuss important considerations for the assessment of anxiety disorders in older adults and offer adaptations to CBT treatment for this population. As part of assessment considerations, we discuss how physical health conditions, cognitive impairment, and functional limitations can impact anxiety disorder diagnoses with older adults. We also outline validated self-report measures of anxiety disorder symptoms for older adults and highlight the importance of assessing older adults’ suitability for CBT. Several recommendations for adapting CBT protocols for older adults with anxiety disorders are described, such as extending psychoeducation, altered treatment pacing, use of content aids, and medical contraindications for interoceptive exposure. A case study is included that illustrates helpful assessment and treatment adaptions for an older woman with panic disorder. We highlight the pressing need to increase research and dissemination of CBT for anxiety disorders for older adults to meet the needs of an increasing segment of the population worldwide.     

Killing Two Birds With One Stone: Exposure Simultaneously Addressing Panic Disorder and Obsessive-Compulsive Disorder

Massed exposure has gained acceptance as an effective method to treat anxiety disorders. When using this intervention in patients presenting with more than one anxiety disorder, specific treatment options need to be discussed. Should exposure be applied in sequential order for each of the comorbid disorders? Or can exposure sessions also be designed to simultaneously target both problem areas? We report on the cognitive-behavioral treatment of a 28-year-old woman with obsessive-compulsive disorder (OCD) and severe panic disorder with agoraphobia (PDA). A series of behavioral experiments based on prolonged exposure was planned. Due to the fact that avoided situations elicited both agoraphobic and contamination fears, we decided to combine exposure for PDA and OCD to optimize therapeutic transfer. Twelve sessions of this exposure resulted in a long-term reduction of both PDA and OCD symptoms. The case illustrates that two comorbid conditions can be effectively combined under one therapeutic rationale. Capabilities and limitations of the method and implications for current theoretical debates on exposure therapy are discussed.     

状态焦虑对条件性恐惧泛化的影响

恐惧的过度泛化是焦虑障碍患者重要的潜在病因,探索焦虑对恐惧泛化的影响具有重要意义。本研究在恐惧习得后,通过恐惧创伤电影范式诱发状态焦虑组被试的焦虑水平,采用主观预期值和皮电反应值作为指标,考察状态焦虑对条件性恐惧泛化的影响。结果表明,恐惧创伤电影范式显著提高了状态焦虑组被试的焦虑水平。在泛化阶段,状态焦虑组被试表现出更强的恐惧泛化,对与条件刺激相似的泛化刺激表现出更强烈的恐惧以及更高的预期。状态焦虑使得被试恐惧泛化的消退更慢,持续时间更长。研究同时发现,在状态焦虑下,被试对条件刺激的辨识出现增强趋势。研究结果提示在对经历负性事件个体进行临床干预时,可通过降低其焦虑水平来减少过度泛化。     

Enhancing the Efficacy of Cognitive Bias Modification for Social Anxiety

Cognitive bias modification for interpretation (CBM-I) is a promising treatment modality for social anxiety disorder, but effect sizes are relatively small across investigations (Hallion & Ruscio, 2011). Additionally, the extent to which CBM-I impacts other cognitive, emotional, and behavioral outcomes is unclear. This study investigated whether two empirically supported treatment components for anxiety disorders, imaginal exposure (IE) and relaxation, augment the effects of CBM-I and increase the extent to which the effects of CBM-I generalize to behavioral and affective outcomes. We randomly assigned 111 undergraduate students with social anxiety to undergo IE, relaxation, or neutral thinking prior to CBM-I, then measured their interpretation biases, as well as their speaking time, anxiety, and subjective evaluations of performance during a speech task. Results indicated that individuals who received IE prior to CBM-I evidenced more adaptive interpretation biases and less behavioral avoidance during the speech task than did individuals who engaged in relaxation or neutral thinking. However, they did not report differential anxiety, habituation, or evaluations of their performance on the speech task. These findings suggest that the combination of CBM-I with adjunct components that target behavioral, rather than cognitive, mechanisms can facilitate transfer of the effects of CBM-I to reducing behavioral avoidance.     

Putting the client in control: The perception of control in the behavioral treatment of anxiety

Traditional explanations of anxiety reduction through behavioral interventions such as extinction, habituation, reciprocal inhibition, and counterconditioning do not adequately account for all instances and aspects of anxiety reduction and clinical methods employed in contemporary behavior therapy. This article examines the role of an additional process — the alterations of perceptions of control — believed to be operative in anxiety reduction. We discuss three targets for establishing control in behavioral treatments of anxiety: (1) control over one's physiological responding while in an anxiety-producing situation, (2) control over the anxiety-producing stimulus or situation itself, and (3) control over the conduct of exposure. These three types of control perceptions are differentially important for different types of anxiety disorders. Implications for the conduct of behavioral treatments and possibilities for increasing client perceptions of control in anxiety treatment programs are outlined. We also recommend that client perceptions of control should be systematically assessed in order to relate them to treatment successes and failures.     

Effects of a Synthetic Predator Odor (TMT) on Freezing,Analgesia, Stereotypy,and Spatial Memory

The Psychological Record - Exposing rats to the predator odor of trimethylthiazoline (TMT), obtained from the red fox, was compared to exposure to the novel control odor of citronella. In...