The Neuroscience of ObsessiveCompulsive Disorder

BY MATTHEW SEPTEMBER 6, 2014

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OCD, not surprisingly, is defined by the patients 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. Whats 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.
Lets 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
lets 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
didnt 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.

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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 didnt 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 didnt know it and I am dead now. It is profoundly difficult to describe ESs
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 ones thoughts with evidence in the external world. An
example of impaired reality testing can be seen in ESs 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.
Lets examine a final example from this same patient to further clarify my 3-part true
obsessive thought hypothesis.

ESs 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. ESs already smoldering hypochondriasis would be transformed from a
spark into a forest fire over the course of that week.

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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 ESs 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.

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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 ESs 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 didnt 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 lets 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.
Lets 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 corticothalamic 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 lets 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.
Lets 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 simplicitys 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.

Lets 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.
Lets 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. Lets 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, lets 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
didnt 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 ESs 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, ESs 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 Im 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 doesnt
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
Tourettes 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. Lets 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 drugs 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.

Brain Analogy Photo Credit: Eduardo Mueses viaCompfight cc

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 wouldnt 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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