Classical conditioning and conditioning-specific reflex modification of rabbit heart rate as a function of unconditioned stimulus location.

Heart rate conditioning is used as an index of conditioned fear and is important for understanding disorders of anxiety and stress, including post traumatic stress disorder (PTSD). One important feature of PTSD is that patients generalize conditioned fear from danger signals to safety signals especially when the two signals have overlapping features. What has not been determined is whether generalization occurs between unconditioned stimuli with overlapping features. In the current experiment, heart rate conditioning and conditioning-specific reflex modification of rabbit heart rate were examined as a function of two different unconditioned stimulus locations. Heart rate conditioning occurred at identical terminal levels whether electrical stimulation was presented near the eye or on the back. Despite different heart rate response topographies to electrical stimulation at the two locations, conditioning-specific reflex modification was detected near the eye and on the back and appeared to generalize between the locations. Interestingly, only conditioning-specific reflex modification detected on the back persisted for a week after heart rate conditioning. This persistence may be a model for some features of post traumatic stress disorder. Overgeneralization of unconditioned responses to unconditioned stimuli similar to the trauma may also be an important aspect of PTSD modeled here. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Cognitive impact of traumatic events

The impact of traumatic experiences on cognitive processes, especially memory, is reviewed. The major psychological sequelae of trauma (reexperiencing, avoidance, hypervigilance) and posttraumatic stress disorder (PTSD) are noted and related to traditional views of fear conditioning. Evidence indicating enhanced memory for the gist of emotional events is reviewed as are psychological and neurophysiological mechanisms underlying this enhancement. This view is updated by introducing the distinction between explicit and implicit memory and its relevance to traumatic memory and PTSD. The central role of "the experiencing ego" in the storage and retrieval of episodic memories is postulated. This leads into discussion of dissociative experiences during traumas and the occasional amnesia for voluntary recall of the trauma accompanied by involuntary, uncontrollable flashbacks of it. The relationship of dissociative experiences to hypnotizability and to pathological reactions to traumas is discussed, although the interpretation of those correlations is questioned. The article concludes by noting that beyond conditioning of fear, traumas often violate and shake the victims' basic assumptions about the benevolence, justice, and meaningfulness of their physical and social worlds. Psychotherapy with trauma victims then needs to attend not only to extinguishing the victims' fear and feelings of extreme vulnerability, but also to rebuilding their basic beliefs about the relative benevolence of the world.     

Pretraining NMDA receptor blockade in the basolateral complex, but not the central nucleus, of the amygdala prevents savings of the conditional fear.

The acquisition of conditional freezing is abolished by N-methyl-D-aspartate (NMDA) receptor antagonism in the basolateral complex of the amygdala (BLA) during fear conditioning, suggesting that memory formation is prevented. The present study examined whether there is residual memory, or "savings," for fear conditioning in rats trained under amygdaloid NMDA receptor blockade. Rats infused with D,L-2-amino-5-phosphonovalerate (APV) into the BLA or central nucleus of the amygdala (CEA) during fear conditioning did not acquire either auditory or contextual fear conditioning. However, savings of conditional fear was exhibited by rats infused with APV into the CEA but not the BLA. These results suggest that both the BLA and CEA play a critical role in the acquisition of conditional fear but that the BLA is able to process and retain some aspects of aversive memories in the absence of the CEA. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attention and memory dysfunction in posttraumatic stress disorder.

Attention and memory performances were studied in Persian Gulf War veterans with and without posttraumatic stress disorder (PTSD) diagnoses. Veterans diagnosed with PTSD showed relative performance deficiencies on tasks of sustained attention, mental manipulation, initial acquisition of information, and retroactive interference. Their performances were also characterized by errors of commission and intrusion. The tendency toward response disinhibition and intrusion on cognitive tasks was correlated positively with re-experiencing symptoms and negatively with avoidance-numbing symptoms. These cognitive deficit patterns are consistent with models of PTSD that emphasize the role of hyperarousal and implicate dysfunction of frontal-subcortical systems. Results suggest that intrusion of traumatic memories in PTSD may not be limited to trauma-related cognitions but instead reflects a more general pattern of disinhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Central and basolateral amygdala neurons crash the aversive conditioning party: Theoretical comment on Rorick-Kehn and Steinmetz (2005).

Rorick-Kehn and Steinmetz (2005) (see record 2005-13804-012) report that neurons in the central and basolateral nuclei of the amygdala exhibit learning-related spike firing to conditional stimuli associated with shock in 3 different aversive conditioning paradigms: eyeblink conditioning, fear conditioning, and signaled avoidance conditioning. Central nucleus neurons responded in all 3 tasks, whereas basolateral nucleus neurons were more activated by fear and avoidance conditioning. These results reveal that amygdala neurons are differentially engaged by aversive conditioning, but questions remain concerning the associative basis and functional role for these unit responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The body keeps the score: memory and the evolving psychobiology of posttraumatic stress

Ever since people's responses to overwhelming experiences have been systematically explored, researchers have noted that a trauma is stored in somatic memory and expressed as changes in the biological stress response. Intense emotions at the time of the trauma initiate the long-term conditional responses to reminders of the event, which are associated both with chronic alterations in the physiological stress response and with the amnesias and hypermnesias characteristic of posttraumatic stress disorder (PTSD). Continued physiological hyperarousal and altered stress hormone secretion affect the ongoing evaluation of sensory stimuli as well. Although memory is ordinarily an active and constructive process, in PTSD failure of declarative memory may lead to organization of the trauma on a somatosensory level (as visual images or physical sensations) that is relatively impervious to change. The inability of people with PTSD to integrate traumatic experiences and their tendency, instead, to continuously relieve the past are mirrored physiologically and hormonally in the misinterpretation of innocuous stimuli as potential threats. Animal research suggests that intense emotional memories are processed outside of the hippocampally mediated memory system and are difficult to extinguish. Cortical activity can inhibit the expression of these subcortically based emotional memories. The effectiveness of this inhibition depends, in part, on physiological arousal and neurohormonal activity. These formulations have implications for both the psychotherapy and the pharmacotherapy of PTSD.     

Meal patterns in the SENECA study of nutrition and the elderly in Europe: assessment method and preliminary results on the role of the midday meal

This study compared the acute stress disorder and post-traumatic stress disorder (PTSD) symptom profiles in motor vehicle accident survivors who sustained a mild traumatic brain injury (MTBI) or no TBI. Consecutive adult patients who sustained a MTBI (n = 79) and no TBI (n = 92) were assessed for acute stress disorder within 1 month of their trauma and reassessed for PTSD (MTBI: n = 63; non-TBI; n = 72) 6-months post-trauma. Comparable rates of acute stress disorder and PTSD were reported in MTBI and non-TBI patients. Intrusive memories and fear and helplessness in response to the trauma were reported less frequently by MTBI than non-TBI patients at the acute phase. Six-months post-trauma fewer MTBI patients than non-TBI reported fear and helplessness in response to the trauma. These findings suggest that, whereas impaired consciousness at the time of a trauma may reduce the frequency of traumatic memories in the initial month post-trauma, MTBI does not result in a different profile of longer-term PTSD.     

Intrusive memories in perpetrators of violent crime: Emotions and cognitions.

The authors investigated factors that may determine whether perpetrators of violent crime develop intrusive memories of their offense. Of 105 young offenders who were convicted of killing or seriously harming others, 46% reported distressing intrusive memories, and 6% had posttraumatic stress disorder. Intrusions were associated with lower antisocial beliefs before the assault, greater helplessness, fear, dissociation, data-driven processing and lack of self-referent processing during the assault, more disorganized assault narratives, and greater negative view of the self, negative interpretations of intrusive memories, perceived permanent change, and self-blame. In a logistic regression analysis, the cognitive and emotional variables explained substantial variance over and above demographic factors. The results suggest that cognitive factors that predict reexperiencing symptoms in victims of crime generalize to perpetrators. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Opioid receptors regulate retrieval of infant fear memories: Effects of naloxone on infantile amnesia.

The authors examined the role of the endogenous opioid system in infantile amnesia for contextual fear conditioning. Rats that were 18 days of age received an aversive footshock in a novel context. Rats displayed conditioned fear when tested 1 min after training but not 24 hr after training. Systemic injection of the opioid receptor antagonist naloxone prior to test, but not immediately after training, alleviated infantile amnesia. Naloxone also alleviated infantile amnesia when injected prior to test 7 days after training. These effects of naloxone were due to actions on central rather than peripheral opioid receptors and were not due to any tendency of the drug to produce fear or freezing. These results show that central opioid receptors regulate retrieval of fear memories in infant rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.

The contribution of the amygdala and hippocampus to the acquisition of conditioned fear responses to a cue (a tone paired with footshock) and to context (background stimuli continuously present in the apparatus in which tone–shock pairings occurred) was examined in rats. In unoperated controls, responses to the cue conditioned faster and were more resistant to extinction than were responses to contextual stimuli. Lesions of the amygdala interfered with the conditioning of fear responses to both the cue and the context, whereas lesions of the hippocampus interfered with conditioning to the context but not to the cue. The amygdala is thus involved in the conditioning of fear responses to simple, modality-specific conditioned stimuli (CS) as well as to complex, polymodal stimuli, whereas the hippocampus is only involved in fear conditioning situations involving complex, polymodal events. Findings suggest an associative role for the amygdala and a sensory relay role for the hippocampus in fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fear-potentiated startle conditioning to explicit and contextual cues in Gulf War veterans with posttraumatic stress disorder.

Aversive conditioning to explicit and contextual cues was examined in Gulf War veterans with and without posttraumatic stress disorder (PTSD) by use of the startle reflex methodology. Veterans participated in a differential aversive conditioning experiment consisting of 2 sessions separated by 4 or 5 days. Each session comprised two startle habituation periods, a preconditioning phase, a conditioning phase, and a postconditioning extinction test. In contrast to the non-PTSD group, the PTSD group showed a lack of differential startle response in the presence of a conditioned stimulus with or without an unconditioned stimulus in Session 1 and an increase in the baseline startle response during Session 2. The PTSD group also exhibited normal differential conditioning following reconditioning in Session 2. These data suggest that individuals with PTSD tend to generalize fear across stimuli and are sensitized by stress. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Associative structure of fear memory after basolateral amygdala lesions in rats.

The authors have recently demonstrated that rats with basolateral amygdala (BLA) lesions acquire Pavlovian fear conditioning after overtraining. However, it is not known whether the associative basis of Pavlovian fear memory acquired by rats with BLA lesions is similar to that of intact rats. Associations are typically formed between the conditional (CS) and unconditional (US) stimuli (stimulus-stimulus; S-S), although it is possible for stimuli to enter into association with the responses they produce (stimulus-response; S-R). Indeed, the central nucleus of the amygdala, which is essential for fear conditioning in rats with BLA lesions, may mediate S-R associations in some Pavlovian tasks. The authors therefore used a postconditioning US inflation procedure (i.e., exposure to intense footshock USs) to assess the contribution of S-S associations to fear conditioning after overtraining in rats with BLA lesions. In Experiment 1, intact rats that were overtrained and later inflated displayed elevated freezing levels when tested, indicating that S-S associations contribute to overtrained fear memories. Interestingly, neither neurotoxic BLA lesions nor temporary inactivation of the BLA during overtraining prevented the inflation effect (Experiment 2 and 3, respectively). These results reveal that S-S associations support Pavlovian fear memories after overtraining in both intact rats and rats with BLA lesions, and imply that the central nucleus of the amygdala encodes CS-US associations during fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning with masked stimuli affects the timecourse of skin conductance responses.

In Pavlovian fear conditioning, an aversive unconditional stimulus (UCS) is repeatedly paired with a neutral conditional stimulus (CS). As a consequence, the subject begins to show conditional responses (CRs) to the CS that indicate expectation and fear. There are currently two general models competing to explain the role of subjective awareness in fear conditioning. Proponents of the single-process model assert that a single propositional learning process mediates CR expression and UCS expectancy. Proponents of a dual-process model assert that these behavioral responses are expressions of two independent learning processes. We used backward masking to block perception of our visual CSs and measured the effect of this training on subsequent unmasked performance. In two separate experiments we show a dissociation between CR expression and UCS expectancy following differential delay conditioning with masked CSs. In Experiment I, we show that masked training facilitates CR expression when the same CSs are presented during a subsequent unmasked reacquisition task. In Experiment II we show that masked training retards learning when the CS+ is presented as part of a compound CS during a subsequent unmasked blocking task. Our results suggest that multiple memory systems operate in a parallel, independent manner to encode emotional memories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intrusive memories and depression in cancer patients

Matched samples of depressed and nondepressed cancer patients were interviewed about past life events, particularly experiences of death and illness. They identified and described any spontaneous intrusive visual memories they had experienced in the past week corresponding to these events. About one quarter reported such memories and, as predicted, the majority of intrusive memories concerned illness, injury and death. The mean levels of intrusion and avoidance were equivalent to patients with post-traumatic stress disorder. Consistent with prediction, depressed patients reported significantly more intrusive memories than controls, and described the memories as typically beginning with or being exacerbated by the onset of depression. Greater numbers of intrusive memories were associated with more maladaptive coping, and greater avoidance with deficits in autobiographical memory functioning.     

The spectrum of accuracy in memories of childhood trauma

In the context of public outcry about "false memories" of childhood sexual abuse, many persons with posttraumatic stress disorder are dismayed by their confusion about the historical basis of their intrusive memories. Numerous interacting factors impinge on memory of trauma to yield a broad spectrum of accuracy. In their endeavors to reconstruct coherent narratives of traumatic experience, clinicians and their patients will benefit from thinking in shades of gray rather than in terms of "true" versus "false" memories.     

Psychobiologic research in post-traumatic stress disorder

PTSD can be a chronic, devastating disorder for which treatment is only partially effective. For some, this disorder progressively worsens over time and appears to affect nearly every aspect of life, including work, interpersonal relationships, physical health, and view of self. Although generally understood as a psychological disorder, PTSD also may be viewed from a biologic perspective. There is now accumulating evidence to suggest that severe psychological trauma can cause alterations in the organism's neurobiologic response to stress even years after the original insult. Long-standing alterations in the biologic response to stress may contribute to a number of complaints commonly expressed by patients with PTSD. For example, increased sensitivity and sensitization of the noradrenergic system may leave the individual in a hyperaroused, vigilant, sleep-deprived, and, at times, explosive state that worsens over time. Being irritable and on edge makes it difficult to interact with family members, friends, coworkers, and employers. To quiet these symptoms of hyperarousal, PTSD patients often withdraw and use substances, particularly central nervous system depressants, that suppress peripheral and central catecholamine function. Alterations in other neurobiologic systems may further contribute to multiple symptoms, such as intrusive memories, dissociation phenomena, and even numbing. Characterization of the biologic underpinnings of PTSD relies to a large degree on available neurobiologic technology. Much of what has been discussed in this article has grown out of advances in physiologic, hormone, and receptor assay methodology. With further advances in neurobiologic technology, in areas such as brain imaging, it soon will be possible to better delineate acute and long-term stress-induced changes in central and peripheral nervous system functioning. Undoubtedly a far richer, more complex understanding of neurobiologic responses and alterations will emerge in the near future. It is believed that an improved neurobiologic understanding will facilitate the development of more specific, effective treatments for individuals who have been severely traumatized.     

Effect of naloxone on conditioned suppression in rats.

Painful stimuli are known to engage an endorphin analgesic system that can be reversed by the opiate antagonist, naloxone. Naloxone, then, should increase the effectiveness of aversive unconditioned stimulus/stimuli (UCS) in Pavlovian fear conditioning. Consistent with this hypothesis, naloxone administered during the acquisition of conditioned suppression in rats enhanced posttrial suppression and preconditioned stimulus (pre-CS; context-controlled) suppression. Furthermore, it enhanced CS-elicited suppression during extinction when administered during acquisition but not when administered only during extinction. Thus naloxone does not enhance an already existing fear nor enhance the memory of previous conditioning; instead, it enhances the conditioning of fear presumably by making the aversive UCS more painful. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Venous thromboembolism

Many symptoms of PTSD represent conditioned responses to stimuli associated with a traumatic experiences. In this review, we propose that the anterior cingulate--a brain region that appears to be involved in fear-conditioning--is dysfunctional in PTSD, thus facilitating exaggerated emotional and behavioral responses (hyperarousal) to conditioned stimuli. Preclinical studies suggest that the anterior cingulate may serve a critical gating function in modulating conditioned fear responses. As such, this region would be a key component of a neural circuit involved in the pathophysiology of PTSD. An amygdala-locus coeruleus-anterior cingulate circuit may be consistent with evidence for chronic noradrenergic activation documented in PTSD patients. According to this model, efferent noradrenergic projections from the locus coeruleus may dampen anterior cingulate function. This in turn would allow myriad external or internally driven stimuli to produce the exaggerated emotional and behavioral responses characteristic of PTSD. If confirmed in future research, cingulate dysfunction would have important theoretical and treatment implications.     

Impaired specific autobiographical memory as a risk factor for posttraumatic stress after trauma.

This study tested the proposal that impaired retrieval of specific autobiographical memories is a risk factor for psychological disturbance after trauma exposure. Trainee firefighters (N = 60) were assessed during training (before trauma exposure) on the Autobiographical Memory Test, Clinician Administered PTSD Scale, Beck Depression Inventory (BDI-II), and Traumatic Events Questionnaire. Participants were reassessed 4 years later (N = 46) on the Posttraumatic Diagnostic Scale and BDI-II. All participants had been exposed to multiple traumatic events, and 15% met criteria for posttraumatic stress disorder. Impaired retrieval of specific memories in response to positive cues prior to trauma exposure significantly predicted posttraumatic stress severity after trauma exposure. These findings provide initial evidence that impaired specific retrieval of memories may be a risk factor for posttraumatic stress. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning-specific reflex modification of the rabbit's nictitating membrane response and heart rate: Behavioral rules, neural substrates, and potential applications to posttraumatic stress disorder.

Interest in classical conditioning is usually focused on anticipatory responses to a stimulus associated with a significant event, and it is assumed that responses to the event itself are reflexive, involuntary, and relatively invariant. However, there is compelling evidence that both the rabbit nictitating membrane response (NMR) and heart rate response (HR), well-known reflexive reactions to aversive events, can change quite dramatically as a function of learning when measured in the absence of the conditioned stimulus. In the case of NMR conditioning, a simple blink is transformed into a larger and more complex response. For HR conditioning, reflexive heart rate acceleration can actually change to heart rate deceleration. In both cases, the reflex comes to resemble the conditioned response and follows some of the same behavioral laws. This change in response to the aversive event itself or weaker forms of that event is called conditioning-specific reflex modification (CRM). CRM may force us to reevaluate the behavioral and neural consequences of classical conditioning and may have important consequences for the treatment of conditions such as posttraumatic stress disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)