Untangling the Mind: Brain Circuitry of Obsessive-Compulsive Disorder

Terms

1. Obsessive Compulsive Disorder (OCD): a mental disorder that causes people to have intrusive thoughts and repetitive behaviors
2. Prefrontal Cortex: front part of the brain, thought of as the “personality center” and is the cortical region that makes us uniquely human
3. Basal Ganglia: a group of structures near the center of your brain that form important connections
4. Thalamus: the main relay station for your brain
5. Cortico-striato-thalamo-cortical (CSTC) Loop: a brain circuit that controls movement execution, habit formation and reward

Abstract

Obsessive-Compulsive Disorder (OCD) is a mental health disorder that is characterized by intrusive thoughts which lead to repetitive behaviors. Many times, OCD is misunderstood as a purely psychological issue. However, research shows that the roots of the disorder are within the brain’s neural circuits. This review introduces the critical brain anatomy and neural circuitries related to OCD, unpacking the neural roots that cause OCD. Furthermore, we will investigate the advancements in brain imaging techniques, such as Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI), that have allowed scientists to observe functional and structural abnormalities in the brains of individuals with OCD. Lastly, this review will discuss the current treatments for OCD, including Cognitive Behavioral Therapy (CBT), Selective Serotonin Reuptake Inhibitors (SSRIs), and Deep Brain Stimulation (DBS) with associated advantages and setbacks of each.

Understanding the biological foundations of OCD can help reduce the stigma surrounding mental illness and increase understanding, which leads to better treatment plans and offers more effective therapies for those affected.

Introduction

Mental health conditions, such as obsessive-compulsive disorder (OCD), are often seen as purely mental and emotional, which can often lead to stigmatization; thus, fewer people seek help and diagnosis. However, there are fundamental changes in the brain structure and neural circuits. OCD, for example, includes changes in several neural circuits and brain regions that can be observed through imaging techniques.

OCD is characterized by obsessive thoughts and compulsive behaviors that can disturb a person’s everyday life. OCD affects millions of people worldwide, and by understanding the mechanistic basis that makes up the disorder, we can better understand and help those with OCD and mental illnesses in general: mental health is a physical illness. By treating mental health as a physical illness, it becomes more straightforward to reduce stigma and understanding around the topic, as well as lead to more comprehensive treatment approaches.

As science advances, imaging techniques like PET and MRI scans can help researchers and doctors understand the structural and functional differences in the brains of those with OCD. In this review, we will discuss the nature of OCD, its anatomical relations, and brain imaging techniques and evaluate possible treatments.

1. Overview

1.1 What is Obsessive Compulsive Disorder?

“One, two, three, just do it,” my father would always count after putting something back to its exact location.

Obsessive-compulsive disorder is the fourth most common mental disorder worldwide (Piras et al., 2013), affecting 2-3% of the population. Characterized by persistent, intrusive thoughts (obsessions) and repetitive behaviors (compulsions), OCD is a neuropsychiatric condition.

Common obsessions in OCD include fear of germs or contamination; fear of forgetting, losing, or misplacing something; fear of losing control over one’s behavior; aggressive thoughts toward others or oneself; desire to have things symmetrical or in perfect order; and more (Obsessive-Compulsive Disorder: When…, 2023). In response to the obsession, often, a person with OCD will have compulsions. Common compulsions include excessive cleaning or hand washing; ordering or arranging items in a particular, precise way; repeatedly checking things, such as that the door is locked or the oven is off; compulsive counting; praying or repeating words silently; and more (Obsessive-Compulsive Disorder: When…, 2023).

OCD affects millions of people worldwide (Obsessive-Compulsive Disorder, n.d.). Treatments are available to help people manage their symptoms and improve their quality of life. Please see an overview of the disorder below:

1.2 The Brain Components in OCD

The brain comprises many regions that ultimately control and regulate every part of us. From how we think and feel to our thoughts, memories, emotions, breathing, and temperature, the brain is the most complex organ in humans (Brain Anatomy and How the Brain Works, n.d.). We will introduce the critical components of the brain involved in OCD: the prefrontal cortex, the Basal ganglia, and the thalamus.

The prefrontal cortex is located at the front of the brain and is part of the frontal cortex. It is responsible for planning and controlling behaviors (Harms et al., 2014). We will discuss three parts of the prefrontal cortex related to OCD: the Orbitofrontal cortex, the Dorsolateral prefrontal cortex, and the Anterior cingulate cortex.

The Orbitofrontal cortex (OFC) is the key brain area involved in emotion, reward value and reward-related decision-making (Rolls et al., 2020); this includes tasks such as deciding whether a surface is clean enough or giving up short-term pleasure for long-term rewards. The dorsolateral prefrontal cortex (dlPFC) is associated with general executive control functions such as task switching and task-set reconfiguration, prevention of interference, inhibition, planning, and working memory (Hertrich et al., 2021). Lastly, the anterior cingulate cortex (ACC) detects errors and regulates emotions –such as spotting typos in an essay or the anxious feeling about forgetting to lock the door after leaving the house. Thus, the ACC is often overactive in OCD (Ahmari et al., 2022).

Furthermore, the Basal ganglia is a group of structures deep inside the brain. It controls movements and habits, such as learning how to play the piano through practicing every day. In OCD, the Basal ganglia can drive the repetitive behaviors that characterize the disorder (Maia et al., 2011).

Lastly, the thalamus is the relay station or control center as it relays signals between the different parts of the brain. The thalamus helps process the visual information, so, for example, it is active when dodging an incoming car or reacting to a ball being thrown. Thus, the thalamus is part of the cortico-striato-thalamo-cortical (CSTC) loop, a large circuit that involves the cortex, the basal ganglia, and the thalamus (Peters et al., 2016). In people with OCD, this loop doesn’t function properly, leading to

the repetitive thoughts and behaviors that are characteristic of the disorder. Scientists are also looking into how white matter—the brain’s communication network—might be altered in OCD, which could further explain these disruptions in brain function (Piras et al., 2013).

1.3 Brain Circuits in OCD

Brain circuits are groups of neurons–cells of the brain—connected by synapses–the spaces between two neurons—and work together to perform a specific function. Multiple circuits connect to form large-scale brain networks. In people with OCD, these circuits do not function properly, which can lead to the intrusive thoughts and repetitive actions that characterize the disorder.

We will mention five circuits in Figure 1 (Shephard et al., 2021).

The Fronto-Limbic Circuit (Red Area) parts of the brain are responsible for processing emotions like fear and anxiety and help regulate those emotions. In OCD, this circuit can be overactive, which can lead to heightened anxiety, such as worrying excessively about germs or harm. This overactivity leads to the obsessions of people with OCD experience.

The sensorimotor circuit (Green Area) involves multiple brain areas that work together to control physical movements and integrate sensory information. This circuit causes compulsive behaviors (Compulsions, as mentioned previously) in OCD.

Ventral Cognitive Circuit (Yellow Area) helps people control their behavior and stop themselves from acting on impulses. In individuals with OCD, this circuit malfunctions; thus, it is difficult to stop compulsions, even when they know their actions or thoughts are irrational.

The ventral affective circuit (the Purple Area) is involved in processing gratification and deciding what feels essential. This system is disrupted in OCD, which in turn causes people to feel like specific tasks are never fully “complete,” thus driving them to perform the same actions repeatedly in search of relief.

Finally, the Dorsal Cognitive Circuit (the Blue Area) plays a role in complex brain functions such as planning, working memory, and regulating emotions. Problems in this circuit in OCD make it harder to control obsessive thoughts and manage emotions.

Circuits and brain regions come together to form a complex network that can lead to the symptoms seen in OCD when disrupted.

2. The Role of Imaging in Obsessive Compulsive Disorder

Imaging plays a significant role in understanding how the brain functions with OCD. We will primarily discuss positron emission tomography (PET) and magnetic resonance imaging (MRI).

PET scans use a radioactive material (typically radioactive oxygen, carbon, nitrogen, or gallium) that emits energy; the scan works by creating 3D images of the inside of the body so scientists and doctors can see the metabolic activity in the brain by tracking glucose uptake. The metabolic activity from PET scans shows how much energy different brain areas are using.

MRI scan, on the other hand, is a non-invasive imaging technique; it creates detailed pictures of the body using radio waves and strong magnetic fields.

Both of these imaging techniques can be used to see the brain in action in patients with OCD.

2.1 PET Scans of Obsessive Compulsive Disorder: In the image above, we see a comparison between the brain of a healthy individual and that of an individual with OCD. The standard control can be used to compare with the OCD brain; the healthy brain shows typical patterns of activity, with moderate energy use in various regions. The brain of someone with OCD shows much higher activity (highlighted in red and yellow) in areas related to fear, decision-making, and behavior regulation (Christopher Pittenger, 2014). The heightened activity explains why people with OCD might experience obsession and compulsions.

2.2 MRI Scans of Obsessive Compulsive Disorder: The above shows examples of different MRI techniques: structural MRI, cortical thickness, diffusion MRI, and task-based functional MRI (Van den Heuvel et al., 2022). Structural MRI shows the brain’s anatomy; it is used to identify any structural differences or abnormalities. Cortical thickness is used to measure the thickness of the brain’s cortex. Diffusion MRI laps the white matter (WM) pathways–a network of nerve fibers in the brain that allows communication between different brain areas (Piras et al., 2013); thus, it shows how different parts of the brain communicate. Task-based functional MRI shows which areas of the brain are activated during specific tasks.

In OCD, changes in brain regions are involved in thought processing and behavior control, which can be seen using the cortical thickness MRI technique. Disruptions in WM pathways can explain why people with OCD might struggle with controlling compulsions: this can be visualized through a diffusion MRI (Piras et al., 2013). In OCD, areas related to decision-making and error detection (such as the orbitofrontal cortex) light up more than usual, reflecting the overactivity in these circuits, which can be seen in task-based function MRI.

3. Treatments

3.1 Cognitive Behavioral Therapy

Cognitive behavioral therapy (CBT) is a type of psychotherapy that helps people change their thoughts and behaviors to improve their mood and emotional regulation. CBT is based on the idea that thoughts and actions affect feeling, and thus, changing those thoughts and actions can lead to desired emotional changes (Moody et al., 2017).

CBT is used in OCD and has been proven quite effective. One specialized type of CBT for OCD is called Exposure and Ritual Prevention (Understanding CBT for OCD, n.d.). The two components of this therapy include an association between sensations of distress and the objects, situations, or thoughts that produce this distress and a second association between carrying out ritualistic behaviors and decreasing stress. The therapy, thus, aims to break the bond between distress and ritual behaviors and reduce anxiety from not ritualizing.

This therapy also includes three components: in vivo exposure, imaginal exposure, and ritual prevention. In vivo, exposure is actual exposure to situations or objects that evoke distress. Imaginal exposure includes mentally visualizing fear, situations, and consequences. Finally, ritual prevention includes refraining from performing ritualistic behaviors (Understanding CBT for OCD, n.d.).

Some downsides, however, include the difficulty as it requires confronting the situations that the patient would usually avoid; the chance of relapse as a portion of patients experience a relapse of symptoms after treatment ends; and the time-consuming nature as it takes consistent effort to see progress.

3.2 Serotonin Reuptake Inhibitors

Selective serotonin reuptake inhibitors are a class of drugs that are typically used as antidepressants in major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs block the reuptake of serotonin–a chemical messenger in the brain that affects mood, emotion, and sleep– in the synapse, which means SSRI blocks serotonin from reabsorbing. They are the established pharmacologic first-line treatment for OCD, the initial treatment a physician prescribes for the disorder, due to the convincing database from numerous published randomized controlled trials (Kellner, 2010).

Despite their proven efficacy and widespread use, about 40% to 60% of patients show no or just partial symptom improvement to treatment with a first-line drug (Kellner, 2010). Additionally, it usually takes at least three months to assess efficacy for medium to large dosages and acute treatment (Kellner, 2010). Many times, when first-line treatments do not work, a second-line treatment strategy is often used: this can include the use of SSRI augmentation with atypical antipsychotics (an established second-line treatment) or intravenous serotonergic antidepressants and combination with or switching to CBT (Kellner, 2010).

3.3 Deep Brain Stimulation: Treatment of Obsessive Compulsive Disorder

Deep Brain Stimulation (DBS) is a surgical procedure that uses electrical stimulation to treat neurological conditions and movement disorders. It can be used in severe, treatment-resistant cases of OCD. It involves the implantation of electrodes into specific brain regions (see Figure 4) that are part of the brain’s reward and emotional regulation circuits. The electrodes deliver impulses that help modulate abnormal neural activity, which can reduce the severity of OCD symptoms (Holtzheimer et al., 2015).

DBS has produced significant clinical improvement in patients who do not respond to conventional treatments, such as selective serotonin reuptake inhibitors (SSRIs) or cognitive behavioral therapy (CBT) (Holtzheimer et al., 2015). DBS is approved in many countries; it was approved by the Federal Food and Drug Administration for OCD in 2009; however, its use for OCD has diminished since the FDA’s Humanitarian Device Exemption (Pinckard-Dover et al., 2021).

4. Conclusion

Through understanding OCD by the physical changes to the brain, it is evident that the disorder is rooted in brain function. Advances in imaging technology and increasing understanding of brain circuits involved in OCD can lead us closer to effective treatments– as each treatment currently has its setbacks from effectiveness to inaccessibility. Current discrepancies in the field include the variability in individual responses to treatment plans, limitations in the understanding of some mechanisms related to OCD, as well as how different subtypes of OCD affect brain circuits, and the challenges of early diagnosis and intervention.

However, advancements in drug testing, such as for glutamatergic substances and other further drugs, may be promising for treatment options in the future. Furthermore, non-pharmacological approaches such as CBT and DBS (mentioned in previous sections) show promise but these treatments, but these treatments, particularly DBS in the United States, remain inaccessible to the public due to cost, lack of resources, and availability. There is a need to combine the social factors that contribute to OCD and the physiological factors, as economic status plays a significant role in every aspect of the disorder, from treatment to diagnosis. With the combination of both the social understanding and biological understanding of mental health illnesses in general, faster and more incredible advancements can be made.

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