This episode explores the brain space of obsessive compulsive disorder (OCD) with a creative journey through neuroanatomy and brain circuitry. I try to make it much less boring than it sounds. After listening to this episode, it is my goal that the listener will understand the complex interactions of the cortico-striatal-thalamo-cortical (CSTC) circuit and have a fuller appreciating of how the brain decides what to do and how to do it.
Please leave feedback at https://www.psydactic.com.
References and readings (when available) are posted at the end of each episode transcript, located at psydactic.buzzsprout.com. All opinions expressed in this podcast are exclusively those of the person speaking and should not be confused with the opinions of anyone else. We reserve the right to be wrong. Nothing in this podcast should be treated as individual medical advice.
This episode explores the brain space of obsessive compulsive disorder (OCD) with a creative journey through neuroanatomy and brain circuitry. I try to make it much less boring than it sounds. After listening to this episode, it is my goal that the listener will understand the complex interactions of the cortico-striatal-thalamo-cortical (CSTC) circuit and have a fuller appreciating of how the brain decides what to do and how to do it.
Please leave feedback at https://www.psydactic.com.
References and readings (when available) are posted at the end of each episode transcript, located at psydactic.buzzsprout.com. All opinions expressed in this podcast are exclusively those of the person speaking and should not be confused with the opinions of anyone else. We reserve the right to be wrong. Nothing in this podcast should be treated as individual medical advice.
Welcome to PsyDactic - Residency Edition - Your podcast resource to survive and thrive in your psych residency.
I am Dr. O, and as of this recording I am a 2nd Year Resident in the National Capital Consortium Psychiatry Residency Program. However, make no mistake, I do not speak for this program, nor do I speak for the Department of Defense or the Federal Government or anyone else for that matter. What I say is my opinion, and I reserve the right to be wrong, so trust me at your own risk. It’s a risk some are willing to take.
References and recommended readings can be found at the end of the show transcript, located at psydactic.buzzsprout.com.
In the previous episode, I tried to communicate our current understanding of obsessions and compulsions (as defined by the DSM-5), and then put that into an historical and a diagnostic formulation. There is a lot more that could be said about this, but even I wouldn’t want to listen to myself ramble that long, so now I am going to move on in an attempt to convince you that OCD is not a disease of a degenerate intellect or an unresolved and repressed childhood sexual fantasy. It is a brain disease, and there are predictable brain changes that characterize many folks who get the diagnosis of OCD.
Let me start with a case. It is mid 2021 and a father brings his 10 year old son to the emergency room, complaining that his kiddo won’t eat with the family and has barely left his room in two weeks. He won’t shower and eats only cereal brought to him. The 10 year old denies any kind of abuse or maltreatment, but states that he feels like the only room in his house that is clean is his bedroom. He is especially afraid of some kind of contaminants in the bathroom and kitchen, hence he won’t eat with the family or take a shower. He knows this is not normal and can’t articulate his specific fear, but also can’t help how he feels. Surprisingly, he will still go outside and play, but much to the chagrin of his mother, he won’t shower after coming inside, and instead goes straight to his room. He has no problems in school whatsoever. No tics have been identified. Dad says this has caused conflict and the patient is now throwing tantrums when confronted by family about leaving his room, eating foods other than cereal, or taking a shower.
Here we have an obsession about contaminants in certain spaces. He has thoughts that something is not right in the bathroom or kitchen related to some vague feeling he can’t articulate well. He has avoidance and restrictive eating behaviors, but I haven’t given any clear compulsions. In fact, just prior to this he had started washing his hands so often that a rash appeared, but now that he avoids the sinks in the house, his rash has improved. His avoidance is causing him and his family significant distress and is also time consuming, as he is stuck in his room and violently resists showering. He is aware that there is no objective evidence to support his feelings, but he just can’t shake it. This is highly suspicious for OCD.
As a clinician, and given his age you might also have a suspicion of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections or PANDAS for short. Kids often get strep infections, so maybe this patient recently had a sore throat. Obsessions, compulsions and tics are a frequently reported symptom of PANDAs. Some have proposed this to be caused by the production of antibodies to group A strep that cross react with brain tissues, but the cause is still controversial. There are a couple other names describing similar syndromes called PANS or CANS – Pediatric acute-onset neuropsychiatric syndrome (PANS) or childhood acute neuropsychiatric symptoms (CANS). These syndromes are distinguished from PANDAs by not being limited to Group A Strep infections, but instead are thought to be the result of some other identifiable trigger: infectious, toxic, metabolic, etc. In all of these named entities, there is a high proportion of cases of either abrupt onset OCD symptoms or exacerbation of pre-existing OCD symptoms among other things.
The importance of these diagnostic categories is that they explicitly identify a biological process that is hypothesized to cause or worsen OCD. In these syndromes, there is an expectation that the symptoms may remit after treating the underlying cause or waiting for it to resolve on its own. What I want to highlight is that symptoms of OCD in these cases are not conceptualized as thought disorders or problems with a patient’s willpower, but as brain disorders.
There is increasing evidence from multiple sources that the brains of patients with OCD function differently than brains of those without OCD. OCD has heritability estimates of between 35 and 50 percent, which means that we know a person’s genetic material predisposes them to developing OCD, but something else in the environment needs to be present as well. As an example, I’ve already mentioned PANDAs, but another result of Acute Rheumatic Fever caused by GAS is Sydenham chorea, which often includes obsessions and compulsions along with other neuropsychiatric symptoms such as emotional lability, hypotonia, and chorea. Even some ischemic strokes affecting the globus pallidus and caudate have been shown to cause obsessions and compulsions.
One of the circuits in the brain that has received a lot of attention is often called the “orbitofrontal circuit,” which is more broadly including in the cortico-striato-thalamo-cortical circuit which consists of connections between cortical regions such as the orbital frontal cortex and the cingulate gyrus These also connect to the striatum, the globus pallidus, and the thalamus and then feed back to the frontal cortex, also involving the ventral medial prefrontal cortex.
Let me back up for a second. When all we had were EEGs and CT scanners to look at the brain, only relatively large abnormalities of structure could be identified, and functional measurement were very crude. Then fMRIs and PET scans came online, and previously hidden associations revealed themselves. In particular, increased activity in the orbitofrontal cortex, the anterior cingulate gyrus, and the caudate nucleus relative to controls have been consistently found. In the future, we will be able to get more granularity at the cellular level, and then we’ll really be cookin’ with gas.
Particular treatments like glutamate blocking agents and especially Serotonin Reuptake Inhibitors have shown some efficacy in treating OCD, and are thought (In OCD at least) to affect the cortico-striatal-thalamo-cortical or CSTC circuit among other things. I’ll talk about the efficacy of different treatments in the next episode, but to drive home the point that the CSTC circuit is a player in OCD, when all else fails, neurosurgery can help. Cingulotomy, anterior capsulotomy or subcaudate tractotomy have been shown to effectively reduce symptoms, but slicing brain circuits with cold steel is an extreme measure indeed.
Now that I’ve arrived at taking a knife to the brain, I want to try something new. I want to take you on an auditory journey through neuroanatomy, so that when you end this podcast, you and I have synced our brain rhythms and created an enduring mind palace that provides a map allowing us in the future to ride through the cortico-striatal-thalamo-cortical circuit any time we want.
Let's start by carving open the scalp of your forehead with an infinitely sharp knife. This fantastical blade also has no trouble scoring a large hole in the skull, revealing a tough outer coat. You carefully peel off the layers of meninges: the dura mater, the arachnoid mater, and the pia mater. Below the pia mater, pulsating with every heartbeat is the grey matter of the brain, neighborhoods of neurons and glial cells packed together without much insulation. These neurons are busy receiving information from the Thalamus, checking with their neighbors, then sending a message back, but not directly back to the Thalamus. The signal hits quite a few processing centers on its way back.
Miniaturize yourself and hop into the pulsating gray matter of the exposed cortex. We are going to catch a white matter train to the Deep regions. The station we are looking for is on the CSTC, cortical station, and the train you are catching is a Glutamate Express. It’s going to be a bumpy ride, the conductor says. At first, the train seems to inch along, but as soon as you hit the myelinated white matter tract it is like cresting the high point of a rollercoaster and you are plummeting down, lips flapping in the wind. “This stop, end of the Glutamate line, city of Putamen, in County Striatum” announces the conductor, and the train screeches to a halt.
At this junction you are presented with a choice. There are two tracts of the Medium Spiny Class that carry loads of GABA to their destinations. These medium spiny class tracts are powered by the Dopamine Locomotive or Dopamotives for short. There is the D1 dopamotive and D2 dopamotive. Both the D1 and D2 trains have lines that basically run loops through Striatum County. These loops are great for hanging out the window and firing loads of GABA buckshot at other Dopamotive stations, but they don’t leave Striatum County. The D1 train can drop you off at the neighboring D2 station. Then the D2 station can drop you off at the D1.
But if you want to get somewhere, the D1 and D2 have other destinations as well. One D1 dopamotive travels directly through Globus Pallidus all the way to Substantia Nigra to unload its GABA. The second D1 line stops short in Globus Pallidus Interna station where it switches with another dopamotive headed to the Capital City of Thalamus. D2 lines from the striatum make a stop in Globus Pallidus Externa, then track into the suburbs, called Subthalamic Nucleus, where D2 trains drop their GABA load onto another Glutamate Express, which connects to the dopamine mines in the Substantia Nigra, which also has dopamine powered tracks connecting to Thalamus City. In some indirect way, all tracks make it to Thalamus where Glutamate loads are sent back to both Cortical Stations and Striatum County.
Are you confused yet? Lets spiral back out of the brain and hit some of the major points about the CSTC track.
Point 1: The tracks coming from the cortex and the thalamus use glutamatergic neurons to connect to the striatum.
Point 2: The striatum uses GABAergic neurons whose actions are potentiated by dopamine.
Point 3: The thalamus ends up getting GABAergic input from the Globus Pallidus.
Point 4: The thalamus sends out glutamatergic neurons back to the cortex and the striatum.
Point 5: All of this is done to help coordinate our actions.
If we take a look at a larger, simplified map, we see the tracts on the CSTC track include loops within loops that carry either Glutamate or GABA from one station to the next, and dopamine inputs help determine whether GABA is delivered or not. Zooming in, there is a complex interplay of inhibition and excitement that results finally in some kind of signal from the Thalamus back to the cortex, where the final decisions to act are located.
In order for us to do anything we don’t just decide what to do. We also decide what not to do. The complex interplay of neurons in the CSTC is necessary both to initiate any action we want, and to inhibit actions that would interfere with that. In general activation of D1-dopamotives facilitates movement initiation and activation of D2-dopamotives inhibits initiation of competing actions. If you start calling the Medium Spiny Neurons of the striatum dopamotives, people are going to look at you funny. To put that another way that is more neuroanatomically correct: activating D1 neurons has the overall downstream effect of telling the motor cortex, “Let's do this.” Activation of D2 neurons eventually tells the motor cortex, “Relax dude!” If you are trying to extend your arm, you don’t want it flexing at the same time.
Earlier, I mentioned some players in the cortex other than the motor cortex that seem to have some effect on this whole system of do’s and don’ts. There is the orbito-frontal cortex and the ventral medial prefrontal cortex. If you also listened to my transcranial magnetic stimulation episodes, you may remember that the FDA has approved rTMS of the ventral medial prefrontal cortex to help relieve OCD symptoms.
People with OCD most often know that they have already performed an action or that they don’t need to actually perform an action. Your patient won’t lack a memory of locking their car, but just they can’t resist looking out the window and pressing the key fob for the 30th time, just to see the lights blink on again. They know they have taken a shower for the 4th time today, but they can’t shake the feeling that they need to do it again. The cortical regions are responsible for planning and initiating a call to action, and the subcortical regions are responsible for facilitating the action and how we feel about it. Any imbalance in this system can throw it out of balance, and neuroscientists are still working to understand just how this happens, so we can know better what to do about it.
I want to leave you with one more analogy of a complex system that was recently in the news. Hundreds of shipping containers are sitting off US coasts unable to unload their cargo because there are not enough dock workers and drivers to handle the load. Manufacturers waiting on essential parts and materials are stuck. Piling up in their production lines are parts that need other parts to keep the line moving, but those parts aren’t there because of a problem occurring 1000 miles away. OCD might be something like that.
Thank you for imagining cutting a hole in your head and jumping inside. In the next episode, I’ll do something less spine chilling and talk about treatments for OCD.
I am Doctor O, and this has been an episode of PsyDactic Residency Edition.