Tolerance of uncertainly as a key to resilience.

As a followup to the previous post on The Neurobiology of Stress I want to point to Maggie Jackson's opinion piece in the NYTimes titled  "How to Thrive in an Uncertain World."  A few clips:

...a wave of new scientific discoveries reveals that learning to lean into uncertainty in times of rapid change is a promising antidote to mental distress, not a royal road to angst, as many of us assume...Studies of the pandemic era offer a starting illustration of the links between uncertainty and flourishing. Ohio State researchers have found that adults who scored high on a measure of “intolerance of uncertainty” were more likely to struggle with stress and anxiety during the pandemic....a British study found. In contrast, those who struggle less with uncertainty were more likely to accept the realities of the situation.

Tolerating and even delighting in uncertainty doesn’t merely help us to accept life’s unpredictability; it also readies us to learn and adapt. Each day, the brain uses honed mental models about how the world works, which are used to process a shifting environment. When we meet something unexpected, a neural “prediction error” signals a mismatch between what we assumed would occur and what our senses tell us. Yet our uneasy sense of not knowing triggers a host of beneficial neural changes, including heightened attention, bolstered working memory and sensitivity to new information. The brain is preparing to update our knowledge of the world. Uncertainty offers the opportunity for life to go in different directions...and that is exciting..

The article continues to describe several experiments showing that generalized anxiety disorder can be relieved by therapy sessions that focus on reducing aversion to uncertainty by introducing it in small doses.

Does a "P-factor" underlie core attributes of mental health maladies?

I want to point to an open source "Core Concepts" article in PNAS by David Adam that presents "the views of some psychiatrists who argue that the same bit of biology—genetics gone awry or some misplaced brain circuitry—could underlie the vast majority of humanity’s mental health problems. Studies have shown, for example, that many of the same genes seem to drive increased risk for autism, attention-deficit hyperactivity disorder (ADHD), bipolar disorder, major depression, and schizophrenia. They call this as-yet-unidentified common cause the “psychopathology factor,” or “p-factor” for short."

Two promising post-traumatic stress disorder treatments

I want to pass on references to two new approaches to relieving the symptoms of post-traumatic stress disorder (PTSD). Nuwer describes a new study showing that MDMA (known as the party drug Ecstasy, or Molly) can bring relief to PTSD when used in conjunction with talk therapy. Ressler et al. address the problem that human patients cannot be directly re-exposed to trauma-cues of the sort that have been used in animal studies to induce and then disrupt reconsolidation of traumatic memories. They devise a procedure for covertly capturing and attenuating a hippocampu-dependent fear memory in male rats, a procedure that might prove to be useful in human therapy. Here is their abstract:

Reconsolidation may be a viable therapeutic target to inhibit pathological fear memories. In the clinic, incidental or imaginal reminders are used for safe retrieval of traumatic memories of experiences that occurred elsewhere. However, it is unknown whether indirectly retrieved traumatic memories are sensitive to disruption. Here we used a backward (BW) conditioning procedure to indirectly retrieve and manipulate a hippocampus (HPC)-dependent contextual fear engram in male rats. We show that conditioned freezing to a BW conditioned stimulus (CS) is mediated by fear to the conditioning context, activates HPC ensembles that can be covertly captured and chemogenetically activated to drive fear, and is impaired by post-retrieval protein synthesis inhibition. These results reveal that indirectly retrieved contextual fear memories reactivate HPC ensembles and undergo protein synthesis-dependent reconsolidation. Clinical interventions that rely on indirect retrieval of traumatic memories, such as imaginal exposure, may open a window for editing or erasure of neural representations that drive pathological fear.

The paradox of pleasurable fear.

A study by Anderson et al. finds an inverted U-shaped relationship between fear and enjoyment, consistent with the theory that the pursuit of pleasurable fear is a form of play. Fear and enjoyment can coexist in frightening leisure activities that become enjoyable when they offer forms of arousal dynamics that are “just right.”. Here is their abstract:

Haunted attractions are illustrative examples of recreational fear in which people voluntarily seek out frightening experiences in pursuit of enjoyment. We present findings from a field study at a haunted-house attraction where visitors between the ages of 12 and 57 years (N = 110) were equipped with heart rate monitors, video-recorded at peak scare points during the attraction, and asked to report on their experience. Our results show that enjoyment has an inverted-U-shaped relationship with fear across repeated self-reported measures. Moreover, results from physiological data demonstrate that the experience of being frightened is a linear function of large-scale heart rate fluctuations, whereas there is an inverted-U-shaped relationship between participant enjoyment and small-scale heart rate fluctuations. These results suggest that enjoyment is related to forms of arousal dynamics that are “just right.” These findings shed light on how fear and enjoyment can coexist in recreational horror.

Oxytocin can increase or decrease anxiety-related behaviors.

Duque-Wilckens et al. report experiments in mice showing that oxytocin, usually regarding as reducing anxious behaviors, enables stress-induced social anxiety behaviors if it is produced outside of its normal source in the hypothalmus.  

Significance

The neuropeptide oxytocin is an important regulator of social behavior and is widely considered to reduce anxiety-related behaviors. However, growing evidence suggests that sometimes oxytocin increases anxiety. How can the same molecule have such different effects on behavior? Here we provide evidence that oxytocin produced outside of the hypothalamus is necessary and sufficient for stress-induced social anxiety behaviors. This suggests that the diverse effects of oxytocin on anxiety-related behaviors are mediated by circuit-specific oxytocin action.

Abstract

Oxytocin increases the salience of both positive and negative social contexts and it is thought that these diverse actions on behavior are mediated in part through circuit-specific action. This hypothesis is based primarily on manipulations of oxytocin receptor function, leaving open the question of whether different populations of oxytocin neurons mediate different effects on behavior. Here we inhibited oxytocin synthesis in a stress-sensitive population of oxytocin neurons specifically within the medioventral bed nucleus of the stria terminalis (BNSTmv). Oxytocin knockdown prevented social stress-induced increases in social vigilance and decreases in social approach. Viral tracing of BNSTmv oxytocin neurons revealed fibers in regions controlling defensive behaviors, including lateral hypothalamus, anterior hypothalamus, and anteromedial BNST (BNSTam). Oxytocin infusion into BNSTam in stress naïve mice increased social vigilance and reduced social approach. These results show that a population of extrahypothalamic oxytocin neurons plays a key role in controlling stress-induced social anxiety behaviors.

Training internal resilience

I want to point to an interesting article by Eva Holland on relieving trauma, which is very relevant to the potential mental0health fallout from living through our current pandemic. Some clips describing a therapy called E.M.D.R., eye movement desensitization and reprocessing:

E.M.D.R. was developed in the late 1980s and greeted with much skepticism at first. “It sounded like yet another of the crazes that have always plagued psychiatry,” Bessel van der Kolk, a trauma expert, wrote in “The Body Keeps The Score.” But clinical trials and peer-reviewed studies that spoke to its efficacy piled up over the three decades since its invention, and Dr. van der Kolk and many others eventually adopted it as part of their therapeutic practice.

It works like this: A therapist prompts the patient to move their eyes back and forth, rhythmically, behind their eyelids. (Devices that beep or buzz help to encourage and regulate the eye movements.) At the same time, the therapist talks the patient through the traumatic event or events at issue, leading them through a series of questions about how their body is reacting to the discussion. It is a strange, and strangely physical, experience. The precise mechanisms at play are not fully understood, but the theory is that something about the eye motion, combined with the focused discussion, can lay the intrusive memories to rest.

E.M.D.R. taught me an important lesson: that internal resilience can be deliberately cultivated...I had never before thought of resilience as a muscle I could train and strengthen. The idea felt empowering.

In a reversal of this therapy, the therapist asks the client to recall four resources from their memories: a places where they have left safest and happiest, a nurturing figure, a protector, and a source of wisdom. The author reports:

As I held a vibrating pod in each hand, and as my eyes rolled back and forth behind my eyelids in time to their pulsing, following the vibrations from left to right and back again, I thought about my grandmother — my nurturing figure, who had died when I was 18. I pictured her at the open kitchen window of her suburban bungalow....The pods pulsed. My eyes moved from side to side. I felt loved and safe. To my surprise, I felt stronger, too. In the time since, I have sometimes called up those sensory memories of my grandmother when I’m upset, or when I feel in need of support. It always helps.

The article proceeds to discuss further techniques for cultivating resilience that do not involve paying a therapist.

Feeling bad is not bad.

MindBlog is passing on the link to each of Arthur Brooks' biweekly articles in his series "How to Build a Life". This latest installment deals with negative emotions, using them to grow and develop resilience rather than pushing them away. It is more difficult to summarize in a tidy way as I have some previous installments in the series. I suggest you read the whole piece. I will note the last two paragraphs:

One last thought: In 2019, the comedian Stephen Colbert was asked in an interview by CNN’s Anderson Cooper about a plane crash that killed Colbert’s father and two of his brothers when he was 10 years old. Cooper quoted a previous statement by Colbert that he had learned to “love the thing that I most wish had not happened.” He asked Colbert to clarify this extraordinary remark. “It’s a gift to exist, and with existence comes suffering,” Colbert replied. “I don’t want it to have happened … but if you are grateful for your life … then you have to be grateful for all of it. You can’t pick and choose what you’re grateful for.”

Colbert’s words resonated deeply with me, and perhaps they do with you, too. No normal person skips merrily into a tragic loss, nor usually seeks out even minor discomfort. But those things find us, over and over again in life. This is especially true today, in the era of COVID-19. The meaning from this pain, and the benefits it can bring to our lives and society, comes from how we choose to use it.

Anxiolytic actions of oxytocin, unlike those of benzodiazepines, involve brain regions outside the amygdala

From Kreuder et al.:

Significance

A potential new target for anxiolytic drug development is the oxytocin (OXT) neuropeptide system. An emerging question is whether OXT has similar effects on the neural microcircuitry of fear compared with clinically established compounds such as benzodiazepines. The present functional MRI study showed that both OXT and its benzodiazepine comparator lorazepam (LZP) reduced centromedial amygdala responses to fear signals. OXT, but not LZP, increased extra-amygdalar connectivity between the centromedial amygdala and frontoparietal regions. Thus, while both compounds inhibited the centromedial amygdala, OXT, but not LZP, elicited large-scale connectivity changes of potential therapeutic relevance.

Abstract

Benzodiazepines (BZDs) represent the gold standard of anxiolytic pharmacotherapy; however, their clinical benefit is limited by side effects and addictive potential. Consequently, there is an urgent need to develop novel and safe anxiolytics. The peptide hormone oxytocin (OXT) exhibits anxiolytic-like properties in animals and humans, but whether OXT and BZDs share similar effects on the neural circuitry of fear is unclear. Therefore, the rationale of this ultra-high-field functional MRI (fMRI) study was to test OXT against the clinical comparator lorazepam (LZP) with regard to their neuromodulatory effects on local and network responses to fear-related stimuli. One hundred twenty-eight healthy male participants volunteered in this randomized double-blind, placebo-controlled, between-group study. Before scanning using an emotional face-matching paradigm, participants were randomly administered a single dose of OXT (24 IU), LZP (1 mg), or placebo. On the behavioral level, LZP, but not OXT, caused mild sedation, as evidenced by a 19% increase in reaction times. On the neural level, both OXT and LZP inhibited responses to fearful faces vs. neutral faces within the centromedial amygdala (cmA). In contrast, they had different effects on intra-amygdalar connectivity; OXT strengthened the coupling between the cmA and basolateral amygdala, whereas LZP increased the interplay between the cmA and superficial amygdala. Furthermore, OXT, but not LZP, enhanced the coupling between the cmA and the precuneus and dorsomedial prefrontal cortex. These data implicate inhibition of the cmA as a common denominator of anxiolytic action, with only OXT inducing large-scale connectivity changes of potential therapeutic relevance.

One mechanism of a basic life choice - to ‘go for it’ or to ‘scram’

Miller et al. use a variety of methods to find subpopulations of dopamine sensitive neurons in the amygdala of mice, projecting to different brain areas, that become active either either during explorative approach or threat-avoiding behaviors:

Avoidance of innate threats is often in conflict with motivations to engage in exploratory approach behavior. The neural pathways that mediate this approach–avoidance conflict are not well resolved. Here we isolated a population of dopamine D1 receptor (D1R)-expressing neurons within the posteroventral region of the medial amygdala (MeApv) in mice that are activated either during approach or during avoidance of an innate threat stimulus. Distinct subpopulations of MeApv-D1R neurons differentially innervate the ventromedial hypothalamus and bed nucleus of the stria terminalis, and these projections have opposing effects on investigation or avoidance of threatening stimuli. These projections are potently modulated through opposite actions of D1R signaling that bias approach behavior. These data demonstrate divergent pathways in the MeApv that can be differentially weighted toward exploration or evasion of threats.

Social threat learning transfers to our decision making.

Lindström et al. (open source) demonstrate that threat associations acquired both by social observation (e.g., through video) and by instruction (e.g., through spoken language) strongly transfer to decision making. This transfer leads to maladaptive decisions when socially acquired associations are outdated rather than valid. The full text describes the three different experimental paradigms noted in the abstract below:

Significance

In today’s world, indirect exposure to threatening situations is more common than ever, as illustrated by footage of terror and disaster in social media. How do such social threat learning experiences shape our decisions? We found that learning about threats from both observation and verbal information strongly influenced decision making. As with learning from our own experience, this influence could be either adaptive or maladaptive depending on whether the social information provided accurate expectations about the environment. Our findings can help explain both adaptive and pathological behaviors resulting from the indirect exposure to threatening events.

Abstract

In today’s world, mass-media and online social networks present us with unprecedented exposure to second-hand, vicarious experiences and thereby the chance of forming associations between previously innocuous events (e.g., being in a subway station) and aversive outcomes (e.g., footage or verbal reports from a violent terrorist attack) without direct experience. Such social threat, or fear, learning can have dramatic consequences, as manifested in acute stress symptoms and maladaptive fears. However, most research has so far focused on socially acquired threat responses that are expressed as increased arousal rather than active behavior. In three experiments (n = 120), we examined the effect of indirect experiences on behaviors by establishing a link between social threat learning and instrumental decision making. We contrasted learning from direct experience (i.e., Pavlovian conditioning) (experiment 1) against two common forms of social threat learning—social observation (experiment 2) and verbal instruction (experiment 3)—and how this learning transferred to subsequent instrumental decision making using behavioral experiments and computational modeling. We found that both types of social threat learning transfer to decision making in a strong and surprisingly inflexible manner. Notably, computational modeling indicated that the transfer of observational and instructed threat learning involved different computational mechanisms. Our results demonstrate the strong influence of others’ expressions of fear on one’s own decisions and have important implications for understanding both healthy and pathological human behaviors resulting from the indirect exposure to threatening events.

Control of OCD behavior by amygdala to prefrontal input.

Sun et al. find a brain circuit in mice regulating OCD behavior that in humans might be susceptible to non drug manipulations such as transcranial magnetic stimulation.

Significance

The pathophysiology underlying obsessive-compulsive disorder (OCD) remains unclear, leading to major challenges in the treatment of OCD patients. Here, we defined a projection from the basolateral amygdala glutamate neurons to the medial prefrontal cortex glutamate and GABA neurons and described the putative importance of this circuit in manifesting the checking symptoms of OCD in mice. In addition, the above major findings were further verified in an fMRI mouse study. These findings raise the possibility of developing optimal treatments for OCD that involve the use of nondrug approaches, such as transcranial magnetic stimulation, that target the converging pathways.

Abstract

Obsessive-compulsive disorder (OCD) affects ∼1 to 3% of the world’s population. However, the neural mechanisms underlying the excessive checking symptoms in OCD are not fully understood. Using viral neuronal tracing in mice, we found that glutamatergic neurons from the basolateral amygdala (BLA^Glu) project onto both medial prefrontal cortex glutamate (mPFC^Glu) and GABA (mPFC^GABA) neurons that locally innervate mPFC^Glu neurons. Next, we developed an OCD checking mouse model with quinpirole-induced repetitive checking behaviors. This model demonstrated decreased glutamatergic mPFC microcircuit activity regulated by enhanced BLA^Glu inputs. Optical or chemogenetic manipulations of this maladaptive circuitry restored the behavioral response. These findings were verified in a mouse functional magnetic resonance imaging (fMRI) study, in which the BLA–mPFC functional connectivity was increased in OCD mice. Together, these findings define a unique BLA^Glu→mPFC^GABA→Glu circuit that controls the checking symptoms of OCD.

Details of how a fear response is unlearned.

Learning requires the formation of new nerve connections. When that learning is extinguished are those connections inhibited or lost? Wan Lai et al. provide evidence for the latter:

Significance

Whether learning-induced changes in neuronal circuits are inhibited or erased during the process of unlearning remains unclear. In this study, we examined the impact of auditory-cued fear conditioning and extinction on the remodeling of synaptic connections in the living mouse auditory cortex. We found that fear conditioning leads to cue-specific formation of new postsynaptic dendritic spines, whereas fear extinction preferentially eliminates these new spines in a cue-specific manner. Our findings suggest that learning-related changes of synaptic connections in the cortex are at least partially reversed after unlearning.

Abstract

Fear conditioning-induced behavioral responses can be extinguished after fear extinction. While fear extinction is generally thought to be a form of new learning, several lines of evidence suggest that neuronal changes associated with fear conditioning could be reversed after fear extinction. To better understand how fear conditioning and extinction modify synaptic circuits, we examined changes of postsynaptic dendritic spines of layer V pyramidal neurons in the mouse auditory cortex over time using transcranial two-photon microscopy. We found that auditory-cued fear conditioning induced the formation of new dendritic spines within 2 days. The survived new spines induced by fear conditioning with one auditory cue were clustered within dendritic branch segments and spatially segregated from new spines induced by fear conditioning with a different auditory cue. Importantly, fear extinction preferentially caused the elimination of newly formed spines induced by fear conditioning in an auditory cue-specific manner. Furthermore, after fear extinction, fear reconditioning induced reformation of new dendritic spines in close proximity to the sites of new spine formation induced by previous fear conditioning. These results show that fear conditioning, extinction, and reconditioning induce cue- and location-specific dendritic spine remodeling in the auditory cortex. They also suggest that changes of synaptic connections induced by fear conditioning are reversed after fear extinction.

Brain-heart dialogue shows how racism hijacks perception

Tsakiris does a nice summary of his work that shows a biological basis for why you’re more than twice as likely as a white person to be unarmed if you’re killed in an encounter with the police. Here is the core text:

At my lab at Royal Holloway, University of London, we decided to test whether the cardiac cycle made a difference to the expression of racial prejudice. The heart is constantly informing the brain about the body’s overall level of ‘arousal’, the extent to which it is attuned to what is happening around it. On a heartbeat, sensors known as ‘arterial baroreceptors’ pick up pressure changes in the heart wall, and fire off a message to the brain; between heartbeats, they are quiescent. Such visceral information is initially encoded in the brainstem, before reaching the parts implicated in emotional and motivational behaviour. The brain, in turn, responds by trying to help the organism stabilise itself. If it receives signals of a raised heart-rate, the brain will generate predictions about the potential causes, and consider what the organism should do to bring itself down from this heightened state. This ongoing heart-brain dialogue, then, forms the basis of how the brain represents the body to itself, and creates awareness of the external environment.

In our experiment, we used what’s known as the ‘first-person shooter’s task’, which simulates the snap judgments police officers make. Participants see a white or black man holding a gun or phone, and have to decide whether to shoot depending on the perceived level of threat. In prior studies, participants were significantly more likely to shoot an unarmed black individual than a white one.

But we timed the stimuli to occur either between or on a heartbeat. Remarkably, the majority of misidentifications occurred when black individuals appeared at the same time as a heartbeat. Here, the number of false positives in which phones were perceived as weapons rose by 10 per cent compared with the average. In a different version of the test, we used what’s known as the ‘weapons identification task’, where participants see a white or black face, followed by an image of a gun or tool, and must classify the object as quickly as possible. When the innocuous items were presented following a black face, and on a heartbeat, errors rose by 20 per cent.

Yet in both instances, when the judgment happened between heartbeats, we observed no differences in people’s accuracy, irrespective of whether they were responding to white or black faces. It seems that the combination of the firing of signals from the heart to the brain, along with the presentation of a stereotypical threat, increased the chances that even something benign will be perceived as dangerous.

It’s surprising to think of racial bias as not just a state or habit of mind, nor even a widespread cultural norm, but as a process that’s also part of the ebbs and flows of the body’s physiology. The heart-brain dialogue plays a crucial role in regulating blood pressure and heart rate, as well as motivating and supporting adaptive behaviour in response to external events. So, in fight-or-flight responses, changes in cardiovascular function prepare the organism for subsequent action. But while the brain might be predictive, those predictions can be inaccurate. What our findings illustrate is the extent to which racial and possibly other stereotypes are hijacking bodily mechanisms that have evolved to deal with actual threats.

The psychologist Lisa Barrett Feldman at Northeastern University in Boston coined the term ‘affective realism’ to describe how the brain perceives the world through the body. On the one hand, this is a reason for optimism: if we can better understand the neurological mechanisms behind racial bias, then perhaps we’ll be in a better position to correct it. But there is a grim side to the analysis, too. The structures of oppression that shape who we are also shape our bodies, and perhaps our most fundamental perceptions. Maybe we do not ‘misread’ the phone as a gun; we might we actually see a gun, rather than a phone. Racism might not be something that societies can simply overcome with fresh narratives and progressive political messages. It might require a more radical form of physiological retraining, to bring our embodied realities into line with our stated beliefs.

Reducing future fears by suppressing episodic simulation in the brain.

Benoit et al. offer some findings relevant to understanding the heightened anxiety many are feeling in the Age of Trump.

An edited summary that starts the discussion section of their paper:

Recurrently imagining dreaded future situations potentiates fears and can even support the development and maintenance of anxiety disorders. We tested the hypothesis that such simulations can be suppressed with the opposite effect of down-regulating apprehensiveness. Our data indicate that future suppression is based on a brain mechanism that is remarkably similar to a system implicated in the voluntary suppression of past experiences. This mechanism recruits right dorsolateral prefrontal cortex, which originates an inhibitory signal that down-regulates activation in brain regions supporting both retrieval and episode-construction processes. Paralleling the suppression of recently acquired memories, the regions targeted by future suppression included the hippocampus, a structure that is fundamental for the retrieval of past episodes and the construction of coherent future and fictitious events. Critically, the suppression of recurring fears of the future differs from suppressing past events in that it also involved modulating the vmPFC (ventromedial prefrontal cortex). The mPFC fosters the integration of overlapping memories into a common representation.

A clip describing their procedure:

To examine future suppression, we adapted the “Think/No-Think” procedure, used to study the suppression of past events, to create the new “Imagine/No-Imagine” paradigm. The procedure first asked participants to describe their fears. Importantly, they only provided recurrent future fears—that is, those that they had already worried might happen before entering the experiment. Participants then gave one key detail for each fear that was typical to their recurring imaginings of it. (These typical event details served as a dependent measure; see below.) Afterward, they entered the critical Imagine/No-Imagine phase, which was composed of trials that presented reminders to these fears. For some trials, participants were asked to imagine the feared event as vividly as possible in response to the reminder (Imagine condition); for others, participants were asked to suppress their imagining of the event, upon seeing the reminder (Suppress condition). (A third of the originally provided episodes, the Baseline items, were set aside and were not cued during this phase.) Over the course of the Imagine/No-Imagine phase, participants either imagined or suppressed a feared event 12 times. Following this phase, we gave participants each reminder again and asked them to recall the typical feature of its corresponding fear. Once all typical details were tested, participants were then asked to freely imagine each episode aloud in detail for 2 min. Finally, we assessed the impact of suppression on participants’ apprehensiveness toward these future events.

Here are the significance and abstract section of their paper:

Significance 

Humans possess the remarkable ability to recombine details of divergent memories into imaginings of future events. Such imaginings are useful, for example, because they foster planning and motivate farsighted decisions. Importantly, recurrently imagining feared situations can also undermine our well-being and may even contribute to the development of anxiety. Here, we demonstrate that fearful imaginings about the future can be inhibited by neural mechanisms that help to suppress the past. Importantly, suppression reduces later apprehensiveness about the feared events, a benefit that was diminished in individuals with greater trait anxiety. This pattern suggests that the observed inhibition mechanism serves to control people’s future fears and its disruption may foster psychological disorders characterized by intrusive prospective thoughts. 

Abstract 

Imagining future events conveys adaptive benefits, yet recurrent simulations of feared situations may help to maintain anxiety. In two studies, we tested the hypothesis that people can attenuate future fears by suppressing anticipatory simulations of dreaded events. Participants repeatedly imagined upsetting episodes that they feared might happen to them and suppressed imaginings of other such events. Suppressing imagination engaged the right dorsolateral prefrontal cortex, which modulated activation in the hippocampus and in the ventromedial prefrontal cortex (vmPFC). Consistent with the role of the vmPFC in providing access to details that are typical for an event, stronger inhibition of this region was associated with greater forgetting of such details. Suppression further hindered participants’ ability to later freely envision suppressed episodes. Critically, it also reduced feelings of apprehensiveness about the feared scenario, and individuals who were particularly successful at down-regulating fears were also less trait-anxious. Attenuating apprehensiveness by suppressing simulations of feared events may thus be an effective coping strategy, suggesting that a deficiency in this mechanism could contribute to the development of anxiety.

Mapping discrete and dimensional emotions onto the brain.

Here I am passing on the abstract and one summary figure from a useful recent review article by Stephan Hamann:

A longstanding controversy in the field of emotion research has concerned whether emotions are better conceptualized in terms of discrete categories, such as fear and anger, or underlying dimensions, such as arousal and valence. In the domain of neuroimaging studies of emotion, the debate has centered on whether neuroimaging findings support characteristic and discriminable neural signatures for basic emotions or whether they favor competing dimensional and psychological construction accounts. This review highlights recent neuroimaging findings in this controversy, assesses what they have contributed to this debate, and offers some preliminary conclusions. Namely, although neuroimaging studies have identified consistent neural correlates associated with basic emotions and other emotion models, they have ruled out simple one-to-one mappings between emotions and brain regions, pointing to the need for more complex, network-based representations of emotion.

Figure - Levels of mapping between emotion models and the brain. The left panel illustrates the most commonly proposed one-to-one mappings between elements of emotion theories and individual brain regions. For example, amygdala activation typically correlates with emotional arousal, whereas activation in the orbitofrontal cortex correlates with emotional valence. As noted in the text, these one-to-one mappings run afoul of numerous experimental findings that show that, for example, fear consistently activates regions other than the amygdala, and the amygdala in turn is associated with several emotion processes. Such difficulties with one-to-one mappings have motivated a shift to more complex interrelationships, such as functional networks. For example, in the right panel, network mappings may involve individual brain regions (small rectangles) participating in networks that carry out the processing mediating different emotions. An individual region, such as the amygdala (red rectangle) can participate in multiple networks and that region's role can be modulated according to the currently active network configuration. These network dynamics have important implications for evaluating the neuroimaging evidence for different emotion theories.

Half a heartbeat can chill out our response to threat.

Whether we are breathing in or breathing out can have a pronounced effect on our threat detection threshold. Meditation regimes and stress performance training (as for Navy Seals) emphasize prolongation of exhalation as a calming technique. During exhalation, measurements have shown a relative increase in parasympathetic and vagal activity, a relative decrease in amygdala reactivity, and lower reactivity to possible threats. Now work of Garfinkel and colleagues, reported at the recent meeting on the Assoc. for the Scientific Study of Consciousness in Brighton, U.K. (meeting abstracts here, 4.7 MB download) shows that the cardiac cycle can influence our emotional response to scary stimuli. Here is a clip from the writeup in The New Scientist:

In one experiment...people were asked to look at a stream of flashing images and highlight when they spotted a face. Some of the faces looked fearful, others looked neutral...Unbeknown to the volunteers, images were time-locked to appear in sync with their heart-beat. Sometimes the images were synced with the systole phase - the part of the cardiac cycle where the heart muscle contracts to squeeze blood out of the heart, at other times they were linked to the diastole phase - the stage where the heart relaxes and fills after contracting...people were better at spotting fearful faces compared with neutral faces, but only when the pictures were timed to appear at the systole phase.

In another study, people saw the same pictures while having their brain scanned using MRI. People had a stronger response in the hippocampus and amygdala - areas of the brain associated with fear - when they were shown fearful faces at systole than when they saw them at diastole. In other words, half a heartbeat was all it took for a person to experience a significantly different response to the same scary stimulus...The finding seems to be mediated by barorecepors - stretch and pressure sensitive receptors in the heart and surrounding arteries which help initiate systole. "When barroreceptors are activated at systole, a flurry of activity is transferred to the brain at that moment," Garfinkel says, which could explain the difference in the brain scans.

It is not at all clear whether this is a functional adaptation, but other studies show heartbeat can mediate other emotional functions, such as empathy and overt fear responses.

Childhood maltreatment reduces brain volume.

Shortly after putting up this post on maternal nurturing correlating with larger hippocampal volumes, I can across the flip side of the story from Teicher et al. Comparing 193 subjects of average age 22 who showed high vs. low scores on the Childhood Trauma Questionnaire and Adverse Childhood Experience study showed volume reductions in several areas of the hippocampus:

Childhood maltreatment or abuse is a major risk factor for mood, anxiety, substance abuse, psychotic, and personality disorders, and it is associated with reduced adult hippocampal volume, particularly on the left side. Translational studies show that the key consequences of stress exposure on the hippocampus are suppression of neurogenesis in the dentate gyrus (DG) and dendritic remodeling in the cornu ammonis (CA), particularly the CA3 subfield... The sample consisted of 193 unmedicated right-handed subjects (38% male, 21.9 ± 2.1 y of age) selected from the community. Maltreatment was quantified using the Adverse Childhood Experience study and Childhood Trauma Questionnaire scores. The strongest associations between maltreatment and volume were observed in the left CA2-CA3 and CA4-DG subfields, and were not mediated by histories of major depression or posttraumatic stress disorder. Comparing subjects with high vs. low scores on the Childhood Trauma Questionnaire and Adverse Childhood Experience study showed an average volume reduction of 6.3% and 6.1% in the left CA2-CA3 and CA4-DG, respectively. Volume reductions in the CA1 and fimbria were 44% and 60% smaller than in the CA2-CA3. Interestingly, maltreatment was associated with 4.2% and 4.3% reductions in the left presubiculum and subiculum, respectively. These findings support the hypothesis that exposure to early stress in humans, as in other animals, affects hippocampal subfield development.

Added note: Relevant to the subject of this post, I just got an email from a children's metal health advocacy group, The Child Mind Institute, that is sponsoring an annual public education campaign called "Speak Up For Kids".

An App for your anxiety...

Continuing in the thread of yesterdays post about a science App, I should mention the blip of interest (and controversy) over the putative appearance of an array of 'therapists in your iPhone or Android phone." Benedict Carey offers a recent review. My first reaction is one of complete aversion, thinking that therapy is best cast in a social web of narrative, but as Carey notes:

The upside is that well-designed apps could reach millions of people who lack the means or interest to engage in traditional therapy and need more than the pop mysticism, soothing thoughts or confidence boosters now in use.

It is a fact that some cognitive missteps are of a very mechanical nature, reflecting glitches in stimulus-response matching. Here is a nice example of the app approach:

..cognitive bias modification...seeks to break some of the brain’s bad habits...and is straightforward. Consider people with social anxiety, a kind of extreme shyness that can leave people breathless with dread...many who struggle with such anxiety fixate subconsciously on hostile faces in a crowd of people with mostly relaxed expressions, as if they see only the bad apples in a bushel of mostly good ones...Modifying that bias — that is, reducing it — can interrupt the cascade of thoughts and feelings that normally follow, short-circuiting anxiety, lab studies suggest. In one commonly used program, for instance, people see two faces on the screen, one with a neutral expression and one looking hostile. The faces are stacked one atop the other, and a split-second later they disappear, and a single letter flashes on the screen, in either the top half or the bottom....Users push a button to identify the letter, but this is meaningless; the object is to snap the eyes away from the part of the screen that showed the hostile face, conditioning the brain to ignore those bad apples. That’s all there is to it. Repeated practice, the researchers say, may train the eyes to automatically look away, or the frontal areas of the brain to exercise more top-down control.

Some studies claim positive results with these simple games equivalent to normal therapy, other find no effect. There are the usual issues of whether positive outcomes are a placebo effort or undue attention is being paid to positive data, while negative results are rationalized or downplayed. The strongest claims seem to be for anxiety disorders, not depression.