The Neuroscience of Obsessive-Compulsive Disorder
OCD, not surprisingly, is defined by the patient’s experience of obsessions and compulsions. The Diagnostic and Statistical Manual of Mental Disorders (DSM) is the current standardized method of classifying mental disorders. The DSM-5 defines obsessions as “recurrent and persistent thoughts, urges, or images that are experienced as intrusive or unwanted” and compulsions as “repetitive behaviors or mental acts that an individual feels driven to perform in response to an obsession or according to rules that must be applied rigidly” (American Psychiatric Association, 2013).
If OCD were an iceberg, compulsions would be the tip while obsessions would be the 90% hidden beneath the surface. Obsessions are much more resistant to treatment than compulsions and produce profound distress.
In its newest edition, the DSM-5 lists OCD as categorically separate from anxiety disorders. This separation reflects the unique neurological and psychological underpinnings of OCD. The neuroanatomy of OCD is functionally different from that of anxiety disorders. The treatment is also different and reflects different neuroanatomical targets of therapy.
Patients will often ask how obsessional thoughts in OCD are different from the more common anxious thoughts that many of us experience on a daily basis. We all experience anxiety and often times we “obsess” about the subject of our anxiety. Many of us have “compulsions” that require us to check the lock, our bank account, or run a calculation again to verify an answer. What’s so different about OCD that it deserves its own classification?
I have come to identify a 3-part hypothesis of how obsessive thoughts in OCD differ from pure anxious thoughts based on experience with patients and reviews of the literature.
I hypothesize that the three unique components of an obsessive thought are its time course, delusional quality, and immunity to reality testing.
Let’s begin with the first component: time course. By time I mean the duration and frequency of a thought. An obsession is measured in hours and days not seconds and minutes. Patients will often report a single fixed obsession that lasts for months without variation.
Furthermore, the obsessive thought is ever present throughout the day. Sometimes a patient may get an hour of respite, but even then there is a roiling undercurrent to the subconscious that warns that all is not well. The obsession is there when the patient goes to bed and there when he or she wakes up. The intensity waxes and wanes like waves washing against the shore of the mind, but the onslaught persists unconstrained by rational thought.
My second hypothesis posits that an obsessive thought contains a delusional quality. A delusion is defined as a belief held with certainty, unresponsive to logical counterargument, and implausible or impossible in nature (Jaspers, 1913). For an example let’s discuss a patient of mine who graciously shared his stories of dealing with OCD with me. We will return to this patient who we will call ES throughout the article both because he exemplifies many of the aspects of OCD and because he happens to share my professional calling allowing him to describe his symptoms from a medical perspective.
ES recounted how during his daily run outdoors a few summers before my first meeting him he would often experience a recurrent obsession that he was struck by a car and didn’t know it. ES noted that at first blush this belief seemed impossible to hold if he was to consider himself a “sane” individual. It is difficult for the layperson to comprehend the experience of knowing both a delusion and reality to be true, but perhaps greater detail will allow the reader to understand more completely.
The obsession began one day as ES ran across an intersection and the passing thought of “What if I were hit by a car” turned into “What if I had been hit and didn’t know it?” The first thought is perfectly logical and likely occurs to everyone who has spent any time as a pedestrian at intersections, but the second thought begins to tiptoe into the realm of delusion. ES told me that before long, the thought had further morphed into “I did get hit and didn’t know it” and “I am dead now.” It is profoundly difficult to describe ES’s experience of believing these bizarre thoughts while also being aware that he had not been hit and, as evidenced by his continued ability to think the troublesome thought, was not dead. The delusional flavor of obsessions reveals the amazing plasticity of what we know to be “real.” Much of what is “real” is what we have invested a belief in, and concrete truth frolics somewhere with unicorns and Minotaurs.
The third component of my 3-part hypothesis reveals why obsessive thoughts are so frustratingly resilient: they are relatively impervious to reality testing. Reality testing refers to the process of comparing one’s thoughts with evidence in the external world. An example of impaired reality testing can be seen in ES’s inability to convince himself that a car, despite an obvious lack of injuries, had not hit him.
In fact, I would suggest that compulsions are, in essence, repeated and failed attempts at reality testing.
Let’s examine a final example from this same patient to further clarify my 3-part true obsessive thought hypothesis.
ES’s first clear brush with OCD occurred at a summer camp during elementary school for students interested in science. The weeklong overnight camp at a university campus consisted of lectures on various diseases, tours of campus, and a walk through the anatomy lab. ES’s already smoldering hypochondriasis would be transformed from a spark into a forest fire over the course of that week.
After a day filled with lectures about HIV, hepatitis, and other bloodborne diseases, ES was on his way back to his dorm when he kicked something that felt like a tree branch. As he casually glanced down ES was horrified to realize that he had kicked a syringe rather than a branch.
ES had felt no pinch, and when he later examined his shoe and foot for puncture marks, he would find none. To this day he is not sure if that “syringe” was a marker, EpiPen, or nothing at all but that day ES was convinced it was a large bore needle filled with disease.
This was his first real brush with distrusting his thoughts, and since that time ES has had occasional obsessional flares focused on the feared contamination by bloodborne pathogens. This story also illustrates how dangerous a little information can be.
Drawing conclusions from too little information is like running with scissors: it transforms a harmless tool into a dangerous weapon.
ES ended up pursing a career in medicine and was accepted to medical school. As his education in medical school progressed he actually began to be less of a hypochondriac. ES had a type of reverse medical student syndrome. The more knowledge ES gained the less fear he had of the unknown. However, the human mind is limitlessly creative, and he soon found new ways to worry about old things.
As a medical student you are expected to help “close” after a surgical procedure. “Closing” means sowing the surgical incision closed with a suture (essentially a needle and thread). The daily exposure to needles and blood during ES’s surgical rotation reignited his previous obsessional focus.
During one surgical case ES came very close to nicking his gloved hand with a needle while he was closing an incision. ES felt no puncture and could clearly see that he had not perforated his glove. Nevertheless, the thought “I was close to puncturing my skin with this needle” flashed across his brain only to transform into, “What if I had punctured my skin without knowing it?” This thought soon evolved into the delusion “I did puncture my skin and did not realize it.”
After the case ES rechecked his glove for holes and found none. Next he checked his finger for puncture marks or abrasions and found none. But ES’s impaired reality testing and inability to trust his intellectual conclusions led him to check and recheck his hand long after he had left the operating room.
The knowledge that there was absolutely no evidence of the needle having penetrated his skin was intermixed with the certainty that it had and ES just didn’t know it.
The best analogy I can think of to approximate the experience of trying to reason logically with an obsession would be the experience of listening to driving directions in a foreign language. The directions are indeed valid and would no doubt lead you to your destination, but the meaning of the words is incomprehensible. Reality and obsession coexist without interaction.
“Cure for an obsession: get another one.” ~ Mason Cooley
Now that we have introduced OCD as a clinical entity let’s discuss the neurological underpinnings of the disorder.
The Neuroscience of Anxiety Disorders and The Neuroscience of Mindfulness & Anxiety would serve as excellent references for the proceeding discussion. As with previous articles I will introduce the various moving parts before investigating the brain in motion.
Let’s begin with a familiar structure: the thalamus. We have previously discussed the thalamus and its function as an informational relay station. When a stiff breeze ruffles our hair, the thalamus/Relay directs the sensory information to our cortex for conscious experience. The thalamus/Relay is the conduit not just for sensory information, but also for motor, emotional, and conceptual information.
Another important role of the thalamus/Relay is its role in reviewing our actions and thought processes. The thalamus/Relay forms a loop with the cortex called the cortico-thalamic loop. The cortex is the outer portion of our brain made up of grey matter (neuronal cell bodies). The cortex includes the frontal, parietal, temporal, and occipital lobes as well as anything with the word “cortex” in it (as we will see later – medial prefrontal cortex, anterior cingulate cortex, etc.). The term “cortical” refers to any region in the cortex.
The cortico-thalamic loop allows us to consciously review our actions and our thought processes for consistency. In effect this loop makes us conscious of ourselves. We will move on to our next structure, but let’s keep this loop in mind for later discussion.
Next up: the basal ganglia (BG).
The BG arranges our thoughts and behavior into the appropriate patterns or order. Thought and motor information from the higher cortical regions are theorized to arrive at the BG/Pattern Generator in “chunks” (Graybiel, 1998). The BG/Pattern Generator unconsciously assembles these “chunks” into the appropriate order or pattern that is then relayed back to the cortex and rest of the body for execution. It is vital to realize that the BG/Pattern Generator operates at an unconscious level.
BG/Pattern Generator patterns are laid down as we execute an action or thought process. The more use a pattern gets, the greater the encoded strength. The patterns we use the most become habit. So the first time we pick up a glass we may be clumsy, but after years of executing this pattern our actions are precise and fluid.
Let’s examine the steps involved in picking up a glass more closely to get a better understanding of what the BG/Pattern Generator does. First we see the glass on the table filled with our favorite beverage and we form the intention to pick it up. In a split second this intention travels from the cortex to the BG/Pattern Generator in the form of a jumble of movements: squeeze hand, extend elbow, extend shoulder, open hand. The BG/Pattern Generator unconsciously assembles this disparate information into the correct order: extend shoulder, extend elbow, open hand, close hand. The BG/Pattern Generator relays this information, courtesy of the thalamus/Relay, back to the cortex and body for execution. Finally, we reach out and pick up the glass.
The cortico-thalamic loop then consciously reviews the thought process and corresponding behavior, comparing the expected output to the actual output. If no disagreement is detected we may not give the conscious evaluation a second glance. The process is obviously more complex than the simplistic steps I have listed here, but for our discussion it illustrates the concept well. The BG/Pattern Generator is hypothesized to function in much the same way with thoughts. But we will save this discussion for later in the article.
We might recall the ACC/Attender from preceding articles. The ACC/Attender helps focus our attention on emotional, cognitive, and sensory information and helps determine what to do with it. Importantly, the ACC/Attender is capable of inhibiting the BG/Pattern Generator.
A structure that we have yet to discuss is the orbitofrontal cortex (OFC). The OFC is included in the medial prefrontal cortex (mPFC) anatomical formation. Recall that we have nicknamed the mPFC the Emotional Sensor in previous discussions. The OFC is identified as a functionally separate structure because the neurons contained within it have unique connections and functions (Barbas et al., 2002). For simplicity’s sake we will use our familiar term mPFC/Emotional Sensor in lieu of introducing new vocabulary into an already complex verbiage. I provide this disclaimer because if the reader chooses to review the primary literature, they would observe that the OFC is listed as the structure central to the OCD loop rather than the mPFC/Emotional Sensor.
The mPFC/Emotional Sensor senses our social and emotional environment and is responsible for self-referential thought. Together the ACC/Attender and mPFC/Emotional Sensor act as a sort of gate between the subconscious and conscious experience. These two structures help to evaluate what emotional signals make their way into conscious awareness.
Let’s review the structures involved in OCD: thalamus/Relay, BG/Pattern Generator, ACC/Attender, and mPFC/Emotional Sensor.
An example from an individual who does not suffer from OCD may help us understand the pathway better.
Let’s imagine that you are stitching a surgical incision closed when the bloody needle comes close to nicking your glove. This sight is relayed through the thalamus/Relay to the mPFC/Emotional Sensor and ACC/Attender. The fear produced by this scene triggers the ACC/Attender to initiate a formal evaluation to assess the risk of a puncture wound to the skin. The ACC/Attender and mPFC/Emotional Sensor (among other cortical regions) send a jumble of thoughts to the BG/Pattern Generator: conclude that there is not a puncture wound — check skin for a puncture wound — visual experience of needle brushing too close to your glove — review memory of needle brushing past your glove — “I may have punctured my skin with a bloody needle” — check your glove for a puncture wound.
The BG/Pattern Generator unconsciously assembles these thoughts into the appropriate order: visual experience of needle brushing too close to your glove → “I may have punctured my skin with a bloody needle” → review memory of needle brushing past your glove → check your glove for a puncture wound → check skin for a puncture wound → conclude that there is not a puncture wound. This information is relayed back through the thalamus/Relay to your mPFC/Emotional Sensor, ACC/Attender, and the rest of the cortex. Finally you are able to execute the appropriate behaviors and evaluative thoughts as dictated by your BG/Pattern Generator.
You then consciously review your thoughts, behaviors, and conclusions with your cortico-thalamic loop. You consciously experience a sense of decisive relief when your unconscious BG/Pattern Generator loop and conscious cortico-thalamic loop agree that you did not puncture your skin with a bloody needle.
The previous example was from a brain spared the pathology of OCD. Let’s examine the current scientific data on OCD pathology and then replay this scenario to understand what goes wrong in OCD.
As we discussed in my previous article, the volume (size) of the mPFC/Emotional Sensor and ACC/Attender are decreased in anxiety disorders. This decrease is also seen in OCD (Radua et al., 2010).
The difference between OCD and anxiety disorders lies in the BG/Pattern Generator. The volume of the BG/Pattern Generator is increased in OCD (Radua et al., 2009). Additionally, its function is believed to be aberrant (Graybiel & Rauch, 2000).
These abnormalities result in an OCD loop that transforms fearful thoughts into obsessions and compulsions. In an attempt to explain this further, let’s return to our previous scenario. Hopefully by viewing the OCD loop in action, the impact of the anatomic pathology of OCD will become clear. In this second example we will examine the same scenario as before, except you will now occupy the role of a person with OCD.
The initial series of events are the same in a person suffering from OCD. The thalamus/Relay hands off the image of brushing your glove with a bloody needle to the mPFC/Emotional Sensor and ACC/Attender. The ACC/Attender decides that this image could represent potential danger and unites with the mPFC/Emotional Sensor to provide the raw, jumbled cognitive program to the BG/Pattern Generator. This is where things get interesting.
Instead of unconsciously rearranging the jumble into the appropriate pattern as before, the BG/Pattern Generator unconsciously fumbles the hand off and passes along an unintelligible cognitive pattern to the cortex for execution: conclude that there is not a puncture wound — check skin for a puncture wound — visual experience of needle brushing too close to your glove — review memory of needle brushing past your glove — “I may have punctured my skin with a bloody needle” — check your glove for a puncture wound.
Without a complete plan to evaluate your dangerous encounter with the bloody surgical needle, your cortex is at a loss as to how to proceed. The “danger” signal then recycles its way through the loop a second time in the hopes of getting clear instructions regarding the steps needed to evaluate this potential needle stick. This danger signal continues sounding as the jumbled instructions travel a circuitous route round and round the unconscious BG/Pattern Generator loop. Unfortunately, this process is unconscious, and all you experience is a repeated signal of “Danger! I may have just punctured my skin with a bloody needle!”
While all of this is going on, the cortico-thalamic loop is consciously evaluating your potential exposure. The cortico-thalamic route is able to intellectually evaluate (without the aid of the BG/Pattern Generator) all factors involved in this potential needle stick. It reviews your memory of the event, intact glove, and intact skin and concludes that you didn’t puncture your skin with the needle. Nevertheless, your unconscious BG/Pattern Generator-OCD loop continues to make endless circles shouting “Danger! I may have just punctured my skin with a bloody needle!” at each turn.
Now we may be able to understand the dual nature of believing a delusion and reality at the same time. On the one hand, your intellectual cortico-thalamic loop tells you that you did not puncture your skin with the bloody needle. But your unconscious BG/Pattern Generator loop is unable to silence the original signal: “Danger! I may have just punctured my skin with a bloody needle!”
If we return to my earlier example of ES’s obsession about being hit by a car, we can see how he could hold two such divergent beliefs at the same time. On the one hand, ES intellectually knew (courtesy of his cortico-thalamic loop) that he was not struck by a car and was, in fact, alive. But on the other hand, his BG/Pattern Generator-OCD loop perpetuates the original thought without a resolution: “I may have been hit by a car!” As this thought makes its rounds in the BG/Pattern Generator-OCD loop, ES’s mind began to take it more seriously. “If I keep getting the warning signals then maybe I was hit by a car!” soon becomes “I was hit by a car and now I’m dead; why else would I keep experiencing these thoughts!”
We also can see why these bizarre thoughts are relatively invulnerable to logical reappraisal. The BG/Pattern Generator-OCD loop and the cortico-thalamic loop are functionally separate pathways in the brain. The two cannot logically reason with one another.
At this point you may be asking yourself why this BG/Pattern Generator defect doesn’t affect other processes in the brain such as motor function. To understand the answer we must appreciate that the BG/Pattern generator is actually comprised of many different components. One such component is the caudate nucleus. This nucleus is involved in thoughts while another component of the BG/Pattern Generator known as the putamen is involved in motor commands. In OCD the primary pathology seems to be focused in the caudate nucleus. Interestingly, it is hypothesized that the putamen is involved in Tourette’s syndrome in which a person cannot resist repeating a motor (or phonological) behavior (Graybiel & Rauch, 2000).
Until now we have focused primarily on obsessions, but compulsions can be understood using the same neuroanatomic circuits. Let’s return to the operating room in which you have narrowly avoided nicking your glove with a surgical needle. You may unconsciously attempt to neutralize your obsession by compulsively checking and rechecking your hand for a puncture wound well after the surgery is complete. This checking cycle would be considered a compulsion.
To understand why we perform an action over and over despite its inability to relieve our anxiety, we must remember that our BG/Pattern Generator is normally part of an unconscious loop. However, sometimes when the pattern is fumbled and a jumbled series of commands is relayed to the cortex, an interesting thing happens. Sometimes the unconscious begins to intrude on the conscious (Graybiel & Rauch, 2000). That is, a part of the command series is executed despite the lack of a pattern. Maybe the portion “check skin for puncture wound” is played on repeat as the loop makes its endless circles. Your cortex receives the command to check your skin for puncture wounds but lacks the full command structure to draw a satisfactory conclusion from this action and thus you keep checking over and over again.
This is all well and good but what can we do about treating obsessions and compulsions in OCD?
Cognitive behavioral therapy (CBT), or more specifically exposure and response prevention, has been shown to be very effective for treating compulsions with slightly less success in the treatment of obsessions. The treatment program is short and can be continued by the patient without further intervention once the therapy is complete, so it is a cost and time efficient therapeutic option. Approximately 80% of patients with OCD respond well to CBT (Soomro et al., 2008).
Selective serotonin reuptake inhibitors (SSRIs) are the mainstay of pharmacological treatment for OCD. The effect size (a standardized measure of a drug’s therapeutic benefit) of SSRIs in the treatment of OCD is 0.44 (Soomro et al., 2008). To put this number into perspective, the effect size of our antihypertensive medications for high blood pressure is 0.56 and the effect size for antibiotics in ear infections is 0.22 (Leucht et al., 2012). Despite claims to the contrary, SSRIs are an equal and valuable component of our pharmacologic armamentarium.
Studies of SSRIs in OCD have demonstrated a therapeutic decrease in aberrant activity and volume in the BG/Pattern Generator after 12 weeks of treatment (Hoexter et al., 2011). However, the dose needed to achieve response is oftentimes much higher than in other anxiety disorders, so side effects can become more of an issue.
Like many things in life, OCD grows more complex the closer one looks. There are many good treatments, but a cure still hovers somewhere beyond the horizon.
The good news is that the combination of psychotherapy and medication offers tremendous relief for many people suffering from OCD. My patient ES has been able to overcome his obsession surrounding bloodborne pathogens through his on-the-job exposure therapy and skills gathered from CBT. ES tells me that he considers himself lucky for being a member of the 80% who respond well to CBT.
Through years of hard work ES has been able to alleviate almost all external compulsions. He continues to deal with obsessions and the mental compulsions that correlate with these obsessions, but ES has learned to manage his OCD to a degree that he never would have thought possible in the years of his crosswalk obsessions.
ES tells me that his most prominent compulsion these days is conducting research into the topic of his obsessions. For instance he recently began obsessing about Lyme disease, and despite his better judgment, gave in to the compulsion to research (patients are taught in CBT to resist the compulsion). However, as a result of his compulsion, ES read nearly 20 papers on Lyme disease and expanded his realm of medical knowledge exponentially. ES has conducted this same exhaustive research for many conditions, and he actually views some of his current expansive medical knowledge as being a byproduct of the oftentimes cumbersome experience of living with OCD.
By viewing his OCD in a positive light ES has been able to learn to love his brain and its little quirks. This is not to say that if a magic pill were offered to cure his OCD that ES wouldn’t take it; he assures me that he most certainly would. But this is not the world he lives in and ES tells me that he is a lover of reality, as Byron Katie is fond of saying, so he chooses to love his reality as it exists today.
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