The contextual brain: implications for fear conditioning, extinction and psychop


FOTCM Member
The following are some excerpts from a Review just published in Nature Reviews Neuroscience 14, 417–428 (2013).

And doing Eiriu Eolas provides the greatest context of all ;) As far as research goes, it pretty much shows that it is the best aid for emotional integration and for maximizing the brain's capacity to contextualize information.

The contextual brain: implications for fear conditioning, extinction and psychopathology

Stephen Maren, K. Luan Phan & Israel Liberzon

Contexts surround and imbue meaning to events; they are essential for recollecting the past, interpreting the present and anticipating the future. Indeed, the brain's capacity to contextualize information permits enormous cognitive and behavioural flexibility. Studies of Pavlovian fear conditioning and extinction in rodents and humans suggest that a neural circuit including the hippocampus, amygdala and medial prefrontal cortex is involved in the learning and memory processes that enable context-dependent behaviour. Dysfunction in this network may be involved in several forms of psychopathology, including post-traumatic stress disorder, schizophrenia and substance abuse disorders.

Contexts serve a psychological function — they are essential for abstracting situationally informed meaning from the world. Contexts shape and define the perception of sensory traces, memories of episodes past, the content of thought, the meaning of words and the goals of purposive behaviour. Contexts are routinely encoded without awareness1. But what is a context? Here, we take a very broad view of context (Box 1) and define it as the internal (cognitive and hormonal) and external (environmental and social) backdrop against which psychological processes operate2. It assigns contingencies, spatial locations, necessary conditions and special circumstances to salient cues and memory traces. Context includes perceptions of time, thereby framing the memory of an experience (for recollection, recognition and familiarity) and shaping future expectations of similar experiences (for anticipation, foresight and planning). As such, contexts enable the flexible representation and retrieval of information and have a central role in resolving ambiguity, all of which are necessary for adaptive behaviour. Importantly, contexts can be distinguished from the discrete cues, such as Pavlovian conditional stimuli (CSs) and unconditional stimuli (USs), that they inform3. This very broad view of context that we adopt here might be criticized as being too general, especially by those investigators who study it in a well-controlled experimental environment in animals. However, the concept of context has been extensively used in the human and clinical literature to refer to general cognitive, semantic or 'emotional' backgrounds. As the aim of this Review is to highlight the common brain circuitry underlying context processing across different species, we opted for a definition of context that is broader, albeit less discriminating.

Given the essential role of context in emotion and cognition, a major scientific challenge is to understand how the brain processes contextual information. Indeed, an inability to appropriately contextualize information may lead to psychological dysfunction characterized by inaccurate percepts or inappropriate responses that contribute to specific psychopathologies. In the past two decades, considerable research in animals has explored how contexts are encoded in the brain. More recent studies have explored the neural mechanisms by which context modulates memory retrieval induced by ambiguous cues. This research in animals has provided a foundation for studies in humans, which have begun to explore the neuroanatomy of context processing in both healthy subjects and patients with psychiatric disorders. The goal of this Review is to synthesize this work and to propose an integrated circuit model of context processing in the brain. We will focus on the neurocircuitry that mediates the processing of environmental contexts in emotional learning and memory tasks, particularly fear conditioning.

{I skipped a lot of details which can be synthesized with two words: transmarginal inhibition.}

[...] Context conditioning occurs with either a signalled shock, in which a conditional stimulus (CS), for example, a sound, is paired with the shock (the unconditional stimulus (US)) [...]

Contextual processing in psychopathology

Considering the central role of context in the flexible representation and retrieval of information and in resolving ambiguity regarding the meaning of stimuli, deficits in contextual processing often lead to inflexible, rigid and inappropriate behavioural responses. In humans, these can in turn lead to various symptoms — from paranoid beliefs or intrusive thoughts to compulsive behaviours — that are seen in multiple psychiatric disorders, including schizophrenia, PTSD, depression and drug addiction. Among these disorders, PTSD may be most representative of context processing pathology, given that the core features of PTSD involve intrusive thoughts, memories and perceptions (flashbacks) that are experienced outside the current context — as if the person was re-experiencing the traumatic event. Deficits in the extinction of fear memory have been hypothesized to contribute to PTSD and have been identified as therapeutic targets for extinction-based behavioural therapies109, 110, 111. These deficits may reflect a loss of contextual control of extinction, causing extinguished fear to inappropriately renew in any context.

However, few studies have directly and specifically implicated impaired contextual processing in PTSD pathophysiology112. In one study in which participants underwent a fear-conditioning–extinction protocol, patients with PTSD exhibited a robust conditioned fear response (an increase in skin conductance) to the previously extinguished CS, indicating impaired retention of extinction113. This was associated with impaired activation of the hippocampus and vmPFC [ ventromedial prefrontal cortex ] and exaggerated dorsal ACC [anterior cingulate cortex] responses during extinction recall compared with control subjects113. In another experiment, subjects were shown an image of an indoor scene (that is, an office containing desk and a lamp) in which illumination of the lamp (the CS) was paired with an aversive event (the US). During extinction, the subjects were shown a different indoor scene (that is, a library containing a shelf and a lamp), and illumination of the lamp was not followed by the US. In this task, contextual information (the room) provides information about whether the lamp will be followed by the US. Compared with controls, patients with PTSD exhibited lower activity in the vmPFC in response to the contextual stimuli during both late extinction training and extinction recall113, 114. This suggests that patients with PTSD may not be able to use contexts to limit fear responses to a CS that no longer yields an aversive outcome or to learn new relationships that define when formerly dangerous cues are safe112. This, in turn, may give rise to maladaptive behavioural responses to both trauma-relevant cues and other salient stimuli, including inappropriate fear responses (for example, exaggerated startle) to cues that resemble the trauma event (for example, a seemingly innocuous loud noise). These considerations raise the possibility that contextual processing deficits are at the core of PTSD pathophysiology, although further testing of this hypothesis is required.

Deficits in contextual processing have also been implicated in responses to drugs of abuse115, 116, 117, 118, 119 and in the enhancement of the incentive properties of amphetamines120. The role of abnormal contextual processing in the development of substance abuse in humans has received little attention relative to many studies that have examined responses to drugs and drug-associated cues121, 122. However, it is well documented in animal models that context plays a crucial part in the propensity of animals to self-administer drugs and in modulating the expression of drug-induced neuroplasticity and drug tolerance116. Given the important role of the setting in determining the quantity and even the type of drug that is consumed, it stands to reason that dysregulation in contextual processing would influence drug-taking behaviour. For instance, a loss of context-specific tolerance so that tolerance is experienced in any context might cause drug use to escalate in any context in which it has previously been taken. Similarly, the expression of drug sensitization, which is normally limited to the context of drug-taking, can be generalized if contextual processing is altered.

Abnormal contextual processing has also been associated with schizophrenia, insofar as individuals with this disorder have deficits in the so-called AX-continuous performance test, in which one cue (the letter A) sets the occasion for when subjects should respond (for example, by pressing a response key to another cue (the letter X)123, 124. Interestingly, fMRI studies have implicated the dorsolateral PFC, a key working memory region, in this task123, 124, but there is little evidence for hippocampal involvement, which may not be surprising given that discrete cues, rather than contexts, inform behavioural responses in this task. Nonetheless, a substantial body of literature implicates mPFC and hippocampus abnormalities in schizophrenia125, suggesting that dysfunction in contextual processing may account for some of the symptoms associated with this disorder. In addition, deficits in eliciting appropriate emotional responses or suppressing inappropriate ones (as the case may be in paranoid ideation) might reflect a failure to modulate thoughts and actions in response to environmental stimuli based on contextual information; examination of mPFC–hippocampal neurocircuitry using context-focused designs could yield important new information regarding the pathophysiology of schizophrenia.

Conclusions and future directions

The studies reviewed above indicate that convergent evidence from animal and human studies implicates the hippocampus and mPFC in the processing of spatial contextual information. The experimental manipulations used in animal studies allow firmer inferences regarding the causal relationships and the specific roles of the brain regions involved. However, the differences in the complexity of behaviour and of different kinds of context in humans versus animals, not to mention the difficulty in delineating homologies between rat and human cortical regions, clearly require further studies of the neurocircuitry underlying context processing in humans in vivo.

Nevertheless, converging findings from animal and human studies suggest a key, although not exclusive, role for the hippocampus in spatial context encoding, and of hippocampal and prefrontal cortical regions (mainly of the medial wall of the frontal cortex, including the medial prefrontal regions and the ACC, in humans and of the infralimbic and prelimbic cortices in rats) in spatial context retrieval. The pattern of functional connectivity between the hippocampus, mPFC and amygdala in rats and humans is consistent with a role of the hippocampus in encoding context memories and suggests that hippocampal–mPFC–amygdala circuits mediate contextual retrieval of fear memories after extinction.

A better understanding of the neural circuits involved in context processing in normal subjects is needed to identify the abnormalities in this circuitry that may accompany various psychiatric disorders. Indeed, fascinating early findings have advanced our understanding of PTSD, and novel avenues of future research should include studies of context processing in schizophrenia and substance abuse disorders. Without question, a comprehensive view of the brain circuits that mediate contextual processing and modulation will greatly enrich the future understanding of flexible, adaptive responses to environmental stimuli, and of pathophysiological processes that interfere with this flexibility.


The Living Force
Thank you for sharing this Psyche. Re: cognitive & behavioural flexibility, is inflexibility comparable with black-&-white or rigid/narrow thinking?

Mr. Premise said:
Not only EE, but also reading Sott helps with providing contexts.

Both are aids in seeing the bigger picture, seeing the forest for the trees per se.
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