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Erase Bad Memories and Enhance Good Ones with Manipulation of Specific Neurons

Erase Bad Memories and Enhance Good Ones with Manipulation of Specific Neurons

Stony Brook researchers discover a method to change emotionally charged memory patterns.

Imagine if memory could be tuned in such a way where good memories are enhanced for those suffering from dementia or bad memories are wiped away for individuals with post-traumatic stress disorder. A Stony Brook University research team has taken a step toward the possibility of tuning the strength of memory by manipulating one of the brain’s natural mechanisms for signaling involved in memory, a neurotransmitter called acetylcholine. Their findings are published in the journal Neuron.

Brain mechanisms underlying memory are not well understood, but most scientists believe that the region of the brain most involved in emotional memory is the amygdala. Acetylcholine is delivered to the amygdala by cholinergic neurons that reside in the base of the brain. These same neurons appear to be affected early in cognitive decline. Previous research has suggested that cholinergic input to the amygdala appears to strengthen emotional memories.

“Memories of emotionally charged experiences are particularly strong, whether positive or negative experiences, and the goal of our research is to determine the mechanisms underlying the strengthening of memory,” said Lorna Role, PhD, Professor and Chair of the Department of Neurobiology and Behavior and Co-Director of the Neurosciences Institute at Stony Brook Medicine.

In the paper, titled “Cholinergic Signaling Controls Conditioned Fear Behaviors and Enhances Plasticity of Cortical-Amygdala Circuits,” Dr. Role and colleagues used a fear-based memory model in mice to test the underlying mechanism of memory because fear is a strong and emotionally charged experience.

Brain mechanisms underlying memory are not well understood, but most scientists believe that the region of the brain most involved in emotional memory is the amygdala. Image is for illustrative purposes only.

The team used optogenetics, a newer research method using light to control cells in living tissue, to stimulate specific populations of cholinergic neurons during the experiments.

Two of the team’s findings stand out. First, when they increased acetylcholine release in the amygdala during the formation of a traumatic memory, it greatly strengthened memory making the memory last more than twice as long as normal. Then, when they decreased acetylcholine signaling in the amygdala during a traumatic experience, one that normally produces a fear response, they could actually wipe out memory.

“This second finding was particularly surprising, as we essentially created fearless mice by manipulating acetylcholine circuits in the brain,” explained Dr. Role. “The findings provide the basis for research examining novel approaches to reverse post-traumatic stress disorder.”
The challenge of continued research is that cholinergic neurons remain difficult to study because they are intermingled with other types of neurons and are few in number compared to other types of neurons in the brain.

Because acetylcholine is a natural signaling mechanism and seemingly essential for memory, additional research will center on non-pharmacologic ways to manipulate or fine-tune memory.

“The long-term goal of our research is that we would like to find ways – potentially independent of drug administration – to enhance or diminish the strength of specific memories, the good ones, and diminish the bad ones,” summarized Dr. Role.

ABOUT THIS MEMORY RESEARCH

The research involves faculty and students from the Stony Brook University Departments of Neurobiology and Behavior, and Pharmacological Sciences, as well as the CNS Disorders Center, the Neurosciences Institute, and the Program in Neurosciences. Co-authors include Li Jiang, Srikanya Kunda, James D. Lederman, Gretchen Y. Lopez-Hernandez, Elizabeth C. Ballinger, Shaohua Wang, and David A. Talmage.

Source: Gregory Filiano – Stony Brook University
Image Source: The image is in the public domain.
Original Research: Abstract for “Cholinergic Signaling Controls Conditioned Fear Behaviors and Enhances Plasticity of Cortical-Amygdala Circuits” by Li Jiang, Srikanya Kundu, James D. Lederman, Gretchen Y. López-Hernández, Elizabeth C. Ballinger, Shaohua Wang, David A. Talmage, Lorna W. Role in Neuron. Published online May 5 2016 doi:10.1016/j.neuron.2016.04.028


Abstract

Cholinergic Signaling Controls Conditioned Fear Behaviors and Enhances Plasticity of Cortical-Amygdala Circuits

Highlights
•Photostimulation of ACh in BLA during cue-fear training makes memory more durable
•Stimulating ACh input to BLA in vivo and ex vivo increases neuronal excitability
•Stimulating ACh input to BLA can elicit LTP
•All of the above effects are dependent on acetylcholine receptors (AChRs)

Summary

We examined the contribution of endogenous cholinergic signaling to the acquisition and extinction of fear- related memory by optogenetic regulation of cholinergic input to the basal lateral amygdala (BLA). Stimulation of cholinergic terminal fields within the BLA in awake-behaving mice during training in a cued fear-conditioning paradigm slowed the extinction of learned fear as assayed by multi-day retention of extinction learning. Inhibition of cholinergic activity during training reduced the acquisition of learned fear behaviors. Circuit mechanisms underlying the behavioral effects of cholinergic signaling in the BLA were assessed by in vivo and ex vivo electrophysiological recording. Photostimulation of endogenous cholinergic input (1) enhances firing of putative BLA principal neurons through activation of acetylcholine receptors (AChRs), (2) enhances glutamatergic synaptic transmission in the BLA, and (3) induces LTP of cortical-amygdala circuits. These studies support an essential role of cholinergic modulation of BLA circuits in the inscription and retention of fear memories.

“Cholinergic Signaling Controls Conditioned Fear Behaviors and Enhances Plasticity of Cortical-Amygdala Circuits” by Li Jiang, Srikanya Kundu, James D. Lederman, Gretchen Y. López-Hernández, Elizabeth C. Ballinger, Shaohua Wang, David A. Talmage, Lorna W. Role in Neuron. Published online May 5 2016 doi:10.1016/j.neuron.2016.04.028

Difference between ‘Being’ and ‘Doing’ – from Mindfulness for Depression

Difference between ‘Being’ and ‘Doing’ – from Mindfulness for Depression

This article was adapted from Mindfulness Based Cognitive Therapy for Depression, by Zindel V. Segal, Ph.D., C.Psych.
The activities of the mind are related to patterns of brain activity. Different mental activities, such as reading a book, painting a picture, or talking to a loved one, each involve different patterns of interaction between networks of nerve cells in the brain. The networks involved in one activity are often different from those involved in another activity. Networks can also be linked together in different patterns. If we looked into the brain, we would see shifting patterns in the activity of networks and in their connections with each other as the mind moves from one task to another. For a while, one pattern predominates, then a shift occurs, so brain networks that previously interacted in one pattern now do so in a different configuration. Over time, we would see the different activities of the mind reflected in continually shifting and evolving patterns of interaction between brain networks.

mindfulness-based-cognitive-therapy-for-depression-meditationIf we looked long enough, we would see that a limited number of core patterns of brain activity and interaction seem to crop up as recurring features in a wide variety of different mental activities. These core patterns reflect some basic “modes of mind.”

We can think of these modes of mind as loosely analogous to the gears of a car. Just as each gear has a particular use (starting, accelerating, cruising, etc.), so each mode of mind has its own particular characteristics and functions. Over the course of a day, as the mind switches from one kind of activity to another, the underlying mode of mind changes—a little like the way that a car, driven through a busy city, there will be a continuous series of changes from one gear to another. And in much the same way a car can only be in one gear at a time, when the mind is in certain modes, it will not be in other modes at the same time.

Our continued dwelling on how we are not as we would like to be just makes us feel worse, taking us even further from our desired goal. This, in turn only serves to confirm our view that we are not the kind of person we feel we need to be in order to be happy.

The fact that a limited number of fundamental modes of mind underpin a wide variety of mental activities has important implications. It opens a way for us to use aspects of everyday experience to learn new ways to relate to the kind of mind states that lead to rumination. We can think of mindfulness training as a way to learn how to become more aware of your mode of mind (“mental gear”) at any moment, and the skills to disengage from unhelpful modes of mind and to engage more helpful modes. We might describe this as learning to shift mental gears. In practice, this task often comes down to recognizing two main modes in which the mind operates, and learning the skills to move from one to the other. These two modes are known as “doing” and “being.”

The “Doing” Mode

The ruminative state of mind is actually a variant of a much more general mode of mind that has been called the “doing” mode. The job of this mode of mind is to get things done—to achieve particular goals that the mind has set. These goals could relate to the external world—to make a meal, build a house, or travel to the moon—or to the internal world of self—to feel happy, not make mistakes, never be depressed again, or be a good person. The basic strategy to achieve such goals involves something we call the “discrepancy monitor”: a process that continually monitors and evaluates our current situation against a model or standard—an idea of what is desired, required, expected, or feared. Once this discrepancy monitor is switched on, it will find mismatches between how things are and how we think they should be. That is its job. Registering these mismatches motivates further attempts to reduce these discrepancies. But, crucially, dwelling on how things are not as we want them to be can, naturally enough, create further negative mood. In this way, our attempts to solve a “problem” by endlessly thinking about it can keep us locked into the state of mind from which we are doing our best to escape.

How the Discrepancy Monitor Works:
1) First we create an idea of how we want things to be, or how we think they should be.

2) Next, we compare that with our idea of how things are right now.

3) If there is a difference between how things are and how we want them to be, then we generate thoughts and actions to try to close the gap.

4) We monitor progress to see whether the gap is increasing or decreasing, and adjust our actions accordingly.

5) We know we have reached our goal when our idea of how things are coincides with our idea of how we want them to be.

There is nothing inherently wrong with this doing mode. In fact, quite the reverse: This approach has worked brilliantly as a general strategy for solving problems and achieving goals in the impersonal, external world—whether those goals be as humble as buying all the items on our weekly shopping list or as lofty as building a pyramid. It is natural, then, that we should turn to this same doing mode when things are not as we would like them to be in our personal, internal worlds—our feelings and thoughts, or the kind of person we see ourselves to be. And this is where things can go terribly wrong.

But before we go on to describe how, it is important to forestall any possible misunderstanding. We are in no way suggesting that the doing mode necessarily causes problems—it does not. It is only when, doing mode “volunteers for a job it can’t do” that problems arise. In many, many, areas of our lives, doing mode volunteers for a job it cando, and our lives are the better for it. To make the distinction clearer, we call problematic applications of this mode driven–doing, as opposed to the more general doing.

In being mode, the mind has “nothing to do, nowhere to go” and can focus fully on moment-by-moment experience, allowing us to be fully present and aware of whatever is here, right now.

If action can be taken straightaway to reduce a discrepancy, and the action is successful, there is no problem. But what if we cannot find any effective actions, and our attempts to think up possible solutions get nowhere? With an external problem we might simply give up and get on with some other aspect of our lives. But once the self becomes involved, it is much more difficult simply to let go of the goals we have set.

For example, if we are upset because a long-standing relationship has just ended, there will be many potential discrepancies between our current reality and how we wish things to be. We may wish for restoration of the relationship, or for the start of another relationship. Most likely, we also wish we were not so upset. There may be solutions we could find. But what if we begin to feel that we are bound to end up alone, concluding that there is, in us, some basic failure, a person that caused the relationship to fail? This conclusion suggests no ready solution, and the discrepancy remains. And yet we cannot let go because we have such a central need not to be this kind of person—what could be more important to us than our own sense of identity?

The result of all this is that the mind continues to process information in doing mode, going round and round, dwelling on the discrepancy and rehearsing possible ways to reduce it. And our continued dwelling on how we are not as we would like to be just makes us feel worse, taking us even further from our desired goal. This, in turn only serves to confirm our view that we are not the kind of person we feel we need to be in order to be happy.

The mind will continue to focus in this way until the discrepancy is reduced or some more immediately urgent task takes the focus of the mind elsewhere, only to return to the unresolved discrepancy once one has dealt with the other task. When the doing mode is working on internal, self-related goals like this, we can more accurately call it the “driven–doing” mode.

If we look closely, we will see the driven–doing mode in action in very many areas of our lives. Whenever there is a sense of “have to,” “must,” “should,” “ought,” or “need to,” we can suspect the presence of doing mode.

In doing mode, by contrast, this wonderful multidimensional complexity of experience is boiled down to a narrow, one-dimensional focus: What does this have to say about my progress in reaching my goals?

How else might we recognize the driven–doing mode subjectively? Its most common feature is a recurring sense of unsatisfactoriness, reflecting the fact that the mind is focused on processing mismatches between how we need things to be and how they actually are. Driven–doing mode also involves a sense of continuously monitoring and checking up on progress toward reducing the gap between these two states (“How well am I doing?”). Why? Because where no immediate action can be taken to reduce discrepancies, the only thing the mind can do is continue to work on its ideas about how things are and how they should be, in the hope of finding a way to reduce the gap between them. This it will do over and over again.

In this situation, because the “currency” with which the mind is working consists of thoughts about current situations, desired situations, explanations for the discrepancies between them, and possible ways to reduce those discrepancies, these thoughts and concepts will be experienced mentally as “real” rather than simply as events in the mind. Equally, the mind will not be fully tuned in to the full actuality of present experience. It will be so preoccupied with analyzing the past or anticipating the future that the present is given a low priority. In this case, we are only aware of the present in a very narrow sense: The only interest in it is to monitor success or failure at meeting goals. The broader sense of the present, in what might be called its “full multidimensional splendor,” is missed.

Driven–doing underlies many of our reactions to everyday emotional experiences—we habitually turn to this mode to free ourselves from many kinds of unwanted emotion. It follows that we can use such everyday emotional experiences, and other reflections of the general driven–doing mode of mind, as training opportunities to learn skills that enable us to recognize and disengage from this mode.

Let us consider an alternative mode of mind, “being.”

THE “BEING” MODE

The full richness of the mode of “being” is not easily conveyed in words—its flavor is best appreciated directly, experientially. In many ways, it is the opposite of the driven–doing mode. The driven-doing mode is goal-oriented, motivated to reduce the gap between how things are and how we think we need them to be; our attention is narrowly focused on these discrepancies between actual and desired states. By contrast, the being mode is not devoted to achieving particular goals. In this mode, there is no need to emphasize discrepancy-based processing or constantly to monitor and evaluate (“How am I doing in meeting my goals?”). Instead, the focus of the being mode is “accepting” and “allowing” what is, without any immediate pressure to change it.

“Allowing” arises naturally when there is no goal or standard to be reached, and no need to evaluate experience in order to reduce discrepancies between actual and desired states. This also means that attention is no longer focused narrowly on only those aspects of the present that are directly related to goal achievement; in being mode, the experience of the moment can be processed in its full depth, width, and richness.

Doing mode involves thinking about the present, the future, and the past, relating to each through a veil of concepts. Being mode, on the other hand, is characterized by direct, immediate, intimate experience of the present.

Doing and Being differ in their time focus. In doing, we often need to work out the likely future consequences of different actions, anticipate what might happen if we reach our goal, or look back to memories of times when we have dealt with similar situations to get ideas for how to proceed now. As a result, in doing mode, the mind often travels forward to the future or back to the past, and the experience is one of not actually being “here” in the present much of the time. By contrast, in being mode, the mind has “nothing to do, nowhere to go” and can focus fully on moment-by-moment experience, allowing us to be fully present and aware of whatever is here, right now. Doing mode involves thinking about the present, the future, and the past, relating to each through a veil of concepts. Being mode, on the other hand, is characterized by direct, immediate, intimate experience of the present.

The being mode involves a shift in our relation to thoughts and feelings. In doing mode, conceptual thinking is a core vehicle through which the mind seeks to achieve the goals to which this mode of mind is dedicated. This means, as we have seen, that thoughts are seen as a valid and accurate reflection of reality and are closely linked to action. In doing mode, the relationship to feelings is primarily one of evaluating them as “good things” to hang on to or “bad things” to get rid of. Making feelings into goal-related objects in this way effectively crystallizes the view that they have an independent and enduring reality.

By contrast, in being mode, the relation to thoughts and feelings is much the same as that to sounds or other aspects of moment-by-moment experience. Thoughts and feelings are seen as simply passing events in the mind that arise, become objects of awareness, and then pass away. In the being mode, feelings do not so immediately trigger old habits of action in the mind or body directed at hanging on to pleasant feelings or getting rid of unpleasant feelings. There is a greater ability to tolerate uncomfortable emotional states. In the same way, thoughts such as “do this, do that” do not necessarily automatically link to related actions, but we can relate to them simply as events in the mind.

“Allowing” arises naturally when there is no goal or standard to be reached, and no need to evaluate experience in order to reduce discrepancies between actual and desired states.

In being mode, there is a sense of freedom and freshness as experience unfolds in new ways. We can be responsive to the richness and complexity of the unique patterns that each moment presents. In doing mode, by contrast, this wonderful multidimensional complexity of experience is boiled down to a narrow, one-dimensional focus: What does this have to say about my progress in reaching my goals? Discrepancies between actual and goal states then trigger fairly well-worn, general-purpose habits of mind that may have worked well enough in other situations. But, as we have seen, when, in the driven–doing mode, the goal is to be rid of certain emotional states, these habits can backfire and lead to perpetuation rather than cessation of unwanted mind states.

Clearly, doing and being are fundamentally different modes of mind. Before drawing out the implications of this difference, it is important that we be very clear on one point: Being mode is not a special state in which all activity has to stop. Doing or being are both modes of mind that can accompany any activity or lack of activity. Recall that we gave a particular name to the type of doing mode that causes problems— “driven–doing”—and this point may become clearer.

For example, it is possible for one to try to meditate with so much focus on being someone who gets into a deeply relaxed state that if anything interrupts it, one feels angry and frustrated. That would be meditating in a driven–doing mode rather than a being mode because the meditation is “driven” by the need to become a relaxed person. Or take another example: It is your turn to do the dishes and there is no way out of it. No one is going to rescue you from this chore. If you do the dishes with the aim of finishing them as quickly as possible to get on to the next activity and are then interrupted, there will be frustration, since your goal has been thwarted. But if you accept that the dishes have to be done and approach the activity in being mode, then the activity exists for its own sake in its own time. An interruption is simply treated as something that presents a choice about what to do at that moment rather than as a source of frustration.

Try this guided mindfulness practice called “‘Two Ways of Knowing” to take a moment and examine how it feels to disengage from a busy mind and shift into “being” mode

 

A 7-Minute Mindfulness Practice to Shift out of “Doing” Mode

A 7-Minute Mindfulness Practice to Shift out of “Doing” Mode

Noticing self-perpetuating thought patterns is a core mindfulness skill. Take a moment to examine how it feels to disengage from a busy mind and shift into "being" mode. The ability to recognize and disengage from self-perpetuating patterns of ruminative, negative thought is a core mindfulness skill. The basic tool to shift mental gears is the intentional use of attemeditation-mindfulness-7-minutesntion and awareness. By choosing what we are going to attend to, and how we are going to attend to it, we place our hand on the lever that enables us to change mental gears. When can we find opportunities to cultivate “being mode? In principle, this mode of mind can be practiced in all situations. In being mode, the mind has nothing to do, nowhere to go and can focus fully on moment-by-moment experience, allowing us to be fully present and aware of whatever is here, right now. But the tendency to enter “doing mode” is pervasive, where the present moment is boiled down to a narrow, one-dimensional focus: “What does this have to say about my progress in reaching my goals?”

We can learn to switch out of automatic pilot by bringing our awareness to the present moment.

The doing mode has a strong tendency to keep itself going and to reassert itself once the mind has switched to another mode of processing. It is particularly important, therefore, that the mode to which the mind switches after disengaging from driven–doing be incompatible and inconsistent with that mode, in the same way that it is not possible to be in forward and reverse gears in a car at one and the same time. Being mode is an ideal candidate for such an initial, alternative mode into which to switch. In the end, we need to balance being and doing mode in our lives. Whether it is because the culture we live in exalts doing, or because driven–doing is oftemindful-way-workbookn propelled by automatic, well-worn routines, it can easily crowd out other ways of being with one’s experience. We can learn to switch out of automatic pilot by bringing our awareness to the present moment. When we do this, we start to see that we have a choice, and this is often the first step in taking care of ourselves differently in the face of sad moods.

To practice shifting into being mode, try this 7-minute guided practice called Two Ways of Knowing from The Mindful Way Workbook by John Teasdale.

Two Ways of Knowing: A 7-Minute Practice to Shift out of “Doing” and into “Being”

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