Time Magazine: Mice With OCD Can Mean New Hope for Humans



Optogenetics cover scene.


A new study of mouse brains leads to new insights — and perhaps new treatments — for a common disorder

by Jeffrey Kluger ,June 07, 2013

There may be no torment quite like the sublime looniness that is obsessive-compulsive disorder (OCD).

Your hands are clean, the door is locked, you didn’t insult a colleague at work or drive over someone on the way home or mishear the 17 doctors you’ve seen in the past month who told you that no, you really, truly don’t have whatever disease you think you’ve got. And yet you keep washing or locking or checking or worrying.

Most people think they understand OCD — and most people are wrong.

It’s not just tidiness, it’s not just fretfulness, and it’s not a glib adjective (“You should see how neat my desk is. I’m so OCD!”). It is, instead, a profound malfunction in various regions of the brain — principally the amygdala, which processes fear, anxiety and other primal emotions — and the mere fact that it is exceedingly treatable with cognitive-behavioral therapy, medication or both does not make it any less awful if you’ve got a real case of it.

Now, thanks to a new study just published in Science, people suffering with OCD have at least a little more hope of recovery than they did before — and people studying the disorder have a lot more insight into what causes it in the first place.

The fact that OCD can be expressed in so many different ways has always suggested that it is caused by idiosyncratic interactions among several different brain regions. The amygdala likely plays a role in all of them, but the best-known forms of OCD — contamination anxiety and the excessive washing that can follow — are thought to be governed by the orbital frontal cortex (OFC) and the ventromedial striatum (VMS). The OFC governs decisionmaking and volitional activity; the VMS governs how we experience fear and risk. It’s not hard to see how an alarm set off by the VMS can lead to a decision to wash by the OFC — even if that decision defies reason.

To explore that circuitry — and the way it goes haywire — a team of researchers led by Dr. Susanne Ahmari, assistant professor of clinical psychiatry at Columbia University, turned to a new technology called optogenetics.

The researchers first engineered a common adenovirus — usually associated with upper-respiratory infections — to carry the genetic coding for a light-sensitive pigment known as rhodopsin. They then injected the virus into the OFC of lab mice, where it could enter brain cells carrying its rhodopsin payload with it.

That caused the otherwise normal cells to become light sensitive. Finally, the scientists inserted fiber optic strands into the mice’s brains and stimulated them with pulses of light. What they expected to see was an increase in grooming behavior, which is common among mice — and in their species-specific way is similar to hand washing in humans. But when they flicked the light on in the mice’s brains what they got was pretty much nothing — at least at first.

“When we hyperstimulated this specific circuit, we thought we were going to see an increase in abnormal behaviors,” Ahmari said in a video released along with the Science paper. “That stimulation did not lead directly to repetitive behavior, but if we repeatedly stimulated for several days in a row for just five minutes a day, what we got was the progressive evolution of grooming behavior.”

The mice, in effect, had been neurologically nudged to a full-blown case of OCD, and even when the researchers quit the stimulation, the behavior stuck around for at least a week. In some of the mice, small doses of fluoxetine — the generic form of Prozac and other selective serotonin reuptake inhibitors — hastened the disappearance of the behavior.

All that reveals a lot. For one thing, it may help explain why some OCD patients can go for years or decades without the disorder and then experience a single traumatic event — a near accident on a highway, a legitimate disease scare that turns out to be nothing — and shortly after, develop OCD symptoms related to the experience.

They may have been born with a predisposition to the disorder (the genetic roots of OCD are still not completely understood), but the triggering event, like the few days of light stimulation in the mice, tips them fully into it.

More important, the research maps the underlying neural wiring behind the disorder and could help in the development of better, more precisely targeted drugs.

For people with intractable cases of OCD that resist both behavioral and pharmacological therapy, other researchers have looked at deep-brain stimulation (DBS), using fine wires to activate or deactivate trouble spots. This is already being used successfully to treat the tremors associated with Parkinson’s disease. What science learns from studying mice could eventually lead to improved DBS.

None of this fully explains the mysteries of OCD, and drilling into the heads of human patients to insert wires is clearly a last therapeutic resort, especially since the large majority of cases do respond so well to less invasive treatment.

Still, for sufferers who long castigated themselves as weak-willed or otherwise responsible for their own suffering, it can be a relief to know that OCD is just a sickness like any other — and as with so many sicknesses, relief is increasingly possible.

How to Overcome Self-Defeating Thoughts and Actions




Rebecca Gladding, M.D., is an author of the new book, You Are Not Your Brain, co-written with Jeffrey M. Schwartz, M.D. Dr. Gladding is a clinical instructor and attending psychiatrist at UCLA who was featured in A&E's critically acclaimed series Obsessed. She is an expert in anxiety, depression, mindfulness and the Four Steps.

 

You Are Not Your Brain

Using the Four Steps to Overcome Negative Thoughts and Unhealthy Actions

Published on June 8, 2011 by Rebecca Gladding, M.D.

When I talk to people about a central idea in our book - that you are not your brain - they tend to respond in one of two ways. The first is with some version of "Of course I am not my brain! That's obvious." The other response often is one of confusion, something along the lines of, "Well, if I am not these thoughts, impulses, urges and actions, who am I? Doesn't my brain define me?"

Interestingly, these responses mirror the current debate raging in the neuroscience community on this very topic. Some scientists believe that there is nothing but the brain - that it controls what we think, who we are, our values and actions. To them, the mind simply does not exist. Rather, it is the brain that changes itself, not us or what we do. The other camp, which my mentor and co-author Dr. Jeffrey Schwartz and I are part of, believe that the mind is intimately connected with, and can exert some pretty powerful effects on, the brain.

In short, we believe that people are so much more than what their brain is trying to tell them they are and that the brain often gets in the way of our true, long-term goals and values in life (i.e., our true self).

While passionate academic disagreement can be quite interesting, and even entertaining at times, it doesn't help us much in our everyday lives. So, do we have the power to influence our brains or not? Obviously, Dr. Schwartz and I believe that we do have the ability to harness the power of focused attention to change our brain in ways that are healthy and beneficial to us. Even more to the point, many of the thoughts, impulses, urges and sensations we experience do not reflect who we are or the life we want to live. These false missives are not true representations of us, but rather are inaccurate, and highly deceptive, brain messages. 

Recognizing this fact, you likely will rapidly begin to see all the places where your brain is less than helpful - where it is working against you and your true goals and values in life. When you think about the brain and how it is structured, it makes sense. The brain's chief job is to keep you alive, so it tends to operate in a survival of the fittest mode. While that's certainly imperative when dealing with life-threatening situations, that approach does not help us much in society or in our relationships. Rather, it often gets us into trouble and cause us to act in ways we later regret.

In short, the brain likely has run your life in a less than optimal way and caused you to experience one or more of the following at some point in your life: anxiety, self-doubt, perfectionism, behaving in ways or engaging in habits that are not good for you (e.g., over-texting, over-analyzing, stress eating, drinking too much and so on), ignoring your true self and/or wholeheartedly believing the stream of negative thoughts coursing through your head.

Accepting that your brain often does not make your long-term goals a priority, the solution becomes clear: you need to learn how to activate your mind so that it can help sculpt your brain to work for, rather than against, you. One great way to learn how to do this is with the Four

Steps.

What are the Four Steps?

Originally developed by Dr. Schwartz to help people with obsessive-compulsive disorder (OCD), the Four Steps is a powerful, yet easy-to-follow method that teaches you how to enhance your awareness and focus your attention in the ways you want to, while simultaneously changing your brain in positive and healthy ways.

Together, Dr. Schwartz and I have spent the last few years revising and enhancing the Four Steps to ensure that they apply to all kinds of deceptive brain messages and situations in life, not just OCD. Here is a synopsis of each of the steps:

Step 1: Relabel.

Identify the deceptive brain messages (i.e., the unhelpful thoughts, urges, desires and impulses) and the uncomfortable sensations; call them what they really are.

Step 2: Reframe.

Change your perception of the importance of the deceptive brain messages; say why these thoughts, urges, and impulses keep bother you (it's not me, it's just the brain).

Step 3: Refocus.

Direct your attention toward an activity or mental process that is wholesome and productive - even while the false and deceptive urges, thoughts, impulses, and sensations are still present and bothering you.

Step 4: Revalue.

Clearly see the thoughts, urges, and impulses for what they are: sensations caused by deceptive brain messages that are not true and that have little to no value.

How could you use the Four Steps if you check your email every 5 minutes when you are at home on the weekend (and it is not necessary to check at all)?

Step 1: Relabel - say what is happening, "Oh, I am having the urge to check email again."

Step 2: Reframe - remind yourself why this is bothering you. Say, "I am having the urge to check email again because it gives me a rush when there's something in the inbox...it feels good. Checking my messages also decreases my anxiety that I might be missing out on something." Remind yourself that you are not your brain and you do not have to respond to every impulse your brain generates.

Step 3: Refocus - go for a walk, call a friend, play a game. Do something that will interest you and is fun. It's the weekend after all.

Step 4: Revalue - recognize that this urge to check email is nothing more than the feeling of a deceptive brain message. It is not something that needs to be taken seriously or paid attention to. In fact, giving into this urge just makes the underlying brain circuitry stronger. The more you check, the more frequent and intense the urges will become. So, dismiss this deceptive brain message and go do something healthy and productive instead.

The key to the Four Steps is practice. You literally need to keep using the Four Steps over and over. By becoming more aware of what is happening and learning how to Refocus your attention in healthier and productive ways whenever a deceptive brain message strikes, you teach your brain new, beneficial responses. With time, you will learn how to place your attention where you want it to go, not where your brain is beckoning you to follow.

OCD Trouble: Shift the Brain Into Manual Mode

When the "Brain Lock" OCD-disordered neural circuit hijacks the brain's natural, automatic gearbox's ability to shift its focus away from ceaseless obssessions, then's the time to overide the automatic gearbox with Dr. Jeffrey Schwartz's "manual" brain-shift.

Here's the condensed owner's manual for this four-step brain-shift:

Step 1: Relabel
Recognize that the intrusive obsessive thoughts and urges are the result of OCD. You don't want to do this in a merely superficial way; rather, you must work to gain a deep understanding that the feeling that is so bothersome at the moment is an obsessive feeling or a compulsive urge. To do so, it is important to increase your mindful awareness that these intrusive thoughts and urges are symptoms of a medical disorder.

Step 2: Reattribute
Realize that the intensity and intrusiveness of the thought or urge is caused by OCD; it is probably related to a biochemical imbalance in the brain. "It's not me -- it's my OCD." That is the battle cry. It's a reminder that OCD thoughts and urges are not meaningful, that they are false messages from the brain. Self-directed behavior therapy lets you gain a deeper understanding of this truth.

Step 3: Refocus
Work around the OCD thoughts by focusing your attention on something else, at least for a few minutes: Do another behavior. The Refocus step is where the real work is done. In the beginning, you may think of it as the "no pain, no gain" step. Mental exercise is like a physical workout. In Refocusing, you have work to do: You must shift the gears yourself. With effort and focused mindfulness, you are going to do what the caudate nucleus normally does easily and automatically, which is to let you know when to switch to another behavior.

Start the process of Refocusing by refusing to take the obsessive-compulsive symptoms at face value. Say to yourself, "I'm experiencing a symptom of OCD. I need to do another behavior." The goal of treatment is to stop responding to the OCD symptoms while acknowledging that, for the short term, these uncomfortable feelings will continue to bother you. You begin to "work around" them by doing another behavior. You learn that even though the OCD feeling is there, it doesn't have to control what you do. You make the decision about what you're going to do, rather than respond to OCD thoughts and urges as a robot would. By Refocusing, you reclaim your decision-making power. Those biochemical glitches in your brain are no longer running the show.

Step 4: Revalue

Do not take the OCD thought at face value. It is not significant in itself. The combined effect of these three steps is much greater than the sum of their individual parts. The process of Relabeling and Reattributing intensifies the learning that takes place during the hard work of Refocusing. As a result, you begin to Revalue those thoughts and urges that, before behavior therapy, would invariably lead you to perform compulsive behaviors. After adequate training in the first three steps, you are able in time to place a much lower value on the OCD thoughts and urges.

We who have OCD must learn to train our minds not to take intruding feelings at face value. We have to learn that these feelings mislead us. In a gradual but tempered way, we're going to change our responses to the feelings and resist them. We have a new view of the truth. In this way, we gain new insights into the truth. We learn that even persistent, intrusive feelings are transient and impermanent and will recede if not acted on. And, of course, we always remember that these feelings tend to intensify and overwhelm us when we give in to them. We must learn to recognize the urge for what it is -- and to resist it. In the course of performing this Four-Step Method of behavioral self-treatment, we are laying the foundation for building true personal mastery and the art of self-command. Through constructive resistance to OCD feelings and urges, we increase our self-esteem and experience a sense of freedom. Our ability to make conscious, self-directed choices is enhanced.

Medical Diagrams of the "Brain Lock" OCD Circuit

Some researchers have identified up to five brain areas that may be implicated in the "Brain Lock" circuit.

Brain Lock: The Biology of OCD and Its Circular Dance of Doubt/Fear/Rumination

Everyone suffers anxieties, doubts, and fears about uncertainty. They are a natural and necessary part of the very successful survival mechanism “softwired” into the human brain by evolution. But people who ruminate or obsess endlessly are suffering from a biological, brain-based disorder. Excessive worrying, rumination, and OCD were once thought to have been caused by “bad parenting,” perhaps as a “neurosis” due to improper upbringing or conditioning. Not anymore.

With the advent of neuropsychology and brain imaging, a new understanding of the way the brain areas have evolved and how they function, has offered a primarily biological and anatomical explanation for unreasonable, excessive rumination – or “brain lock,” the term coined by OCD expert Jeffrey M. Schwartz, M.D.

Here’s the basic theory -- OCD involves three regions of the brain’s “circuitry,” and the primary causal factor is located in the area known as the caudate nucleus. Any damage to this area, either by “bad genes,” head injury, or autoimmune attack, can result in OCD. Damage to the other two areas implicated, the cingulate gyrus and the orbital cortex, will not lead to OCD as such.

Brain area #1. The caudate nucleus, metaphorically speaking, is the “automatic transmission” of the brain’s thought process. It is the area of the brain that allows thought to flow smoothly, easily, “naturally.” The person suffering from OCD loses the capacity to automatically filter the flow of thought or “gate” the worries.

In the neurotypical person, the brain moves on after a worrying thought is dealt with, but in OCD the doubts never cease, and the “gating” function of the caudate cannot suppress them. The malfunctioning caudate results in thought “leakage” or a hyperactivity of thought and compulsion.

Brain area #2. The orbital cortex, part of the cerebral cortex, houses the brain’s “error detection circuit.” The caudate nucleus normally modulates the orbital cortex, but a damaged caudate cannot turn off the terrible feeling “that something is wrong,” and so the feelings don’t go away. The feelings are never satisfied. These repeated “error message” feelings remain as fresh, new, and jarring as the very first time they appeared – there is no “leveling off.”

Brain area #3. The final implicated area, the cingulate gyrus, is a part of the emotional system of the brain known as the limbic system. This is the area responsible for the terrible psychic pain of OCD. The disorder is profoundly painful, so painful that sufferers often speak of “being tortured by their own thoughts.” OCD brings with its unsettling, recurring doubts, pain in the form of terror, thanks to the involvement of the cingulate gyrus. Each “error message” from the orbital cortex shoots down to the cingulate gyrus, which cranks up an extreme state of fear, panic, and alarm. For what should be a neutral or mildly worrisome stimulus, the over-amped OCD sufferer feels the overwhelming fear that a neurotypical would experience only from a catastrophic threat. OCD, in its classic form, torments sufferers who are driven against their better judgment, reason, and will to “check” over and over again, even though they absolutely do not want to continue this checking. They have an “objective bystander” part of their mind that knows these actions/reactions are illogical, but due to bad brain biology. they simply cannot stop themselves. They are gripped by terror, and must act now.

The Good News: After years of research, progress in treating the condition has improved greatly. The treatment for the disorder is to break through the “brain lock” with a combination of medication, exposure and response prevention, and by harnessing the healing power of neuroplasticity (or “rewiring the brain”).  Parents are no longer blamed or need feel guilt over the way they raised their kids. Unfortunately, OCD is a chronic condition that must be treated long-term. More on all of that in my future posts.

Neuroplasticity: Think Yourself Well

Neuroplasticy is an exciting topic. The basic premise is that the brain is always growing and changing and is very adaptable, thus "plastic." When one part of the brain is damaged, with proper training another part can sometines assume the functions of the damaged part. Behavioral changes and new thinking can actually modify the brain's biology. "Neurons that fire together, wire together" is the sound bite. By resisting OCD compulsions with Jeffrey M. Schwartz's "Brain Lock" techniques, the areas of the brain that are implicated in the OCD disorder can be changed. I definitely plan on exploring this topic at length. I've read these books on the subject and highly recommend them. There is also a top-notch DVD on the topic. Hey Benjamin Braddock, the future is not "plastics," it's "neuroplacticity."