The etiology and neurobiology of OCD are complex and multifaceted. The exact cause of OCD is unknown, but it is believed to be a combination of environmental, genetic, and neurobiological factors (Boileau, 2022). Studies have found that there is a genetic basis of at least some forms of OCD (Pauls, 2022). Neurotransmitters that moderate feedback circuits, such as serotonin, dopamine, and glutamate have been implicated in the development of OCD (Pittenger, 2017).

Many studies have examined the neurobiological underpinnings of OCD using brain imaging techniques. These studies have suggested that there are abnormalities in the brain circuits involving the basal ganglia, cortex, and thalamus in individuals with OCD. Abnormalities in these circuits can lead to overactivity or malfunction, resulting in the obsessions and compulsions associated with the disorder (Bijanki et al., 2021). These studies demonstrate the use of various neuroimaging techniques, including voxel-based morphometry (VBM), positron emission tomography (PET), and magnetic resonance imaging (MRI), to explore the changes in both the structure and function of brain circuits in individuals with OCD (Piras et al., 2015, Parmar and Sarkar, 2016, Alexander-Bloch et al., 2022). VBM techniques have been used to evaluate structural differences in the brain volume of people with OCD compared to healthy control groups. Other advanced modalities like functional imaging based on PET and MRI have been used to investigate the function of the areas involved in these circuits. These studies have discovered over-activity of the basal ganglia, particularly the caudate nucleus, which has been observed in many OCD patients. The imaging results also suggest that the caudate nucleus may play a central role in mediating the symptoms of OCD (Shephard et al., 2021).

Over the past twenty years, there have been significant advances in the field of diffusion tensor imaging research in OCD. DTI allows researchers to investigate white matter integrity and connectivity by utilizing canonical DTI indices such as fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). FA reflects the directionality of water diffusion and can indicate the degree of white matter integrity, while MD, RD, and AD offer insights into the magnitude of diffusion in different directions.These techniques have been used to investigate the structural connectivity of brain circuits in individuals with OCD. For example they have identified differences in white matter tract integrity in the brain regions that involve the cortico-striatal-thalamic-cortical (CSTC) circuit, which plays an essential role in the mediation of sensory, motor, and cognitive function (Kim et al., 2015, Kierońska-Siwak et al., 2022). However, DTI techniques have some limitations and challenges. For example, DTI studies may be affected by various confounding factors such as head motion, image distortion, and low signal-to-noise ratio (Le Bihan et al., 2006, Van Hecke et al., 2016, Jones and Cercignani, 2010). Furthermore, DTI measures may not be specific to the neural circuitry of OCD and may also be affected by comorbid conditions or medications (Kochunov et al., 2022).

Despite these limitations, DTI studies have significant potential implications for clinical practice, particularly the development of more targeted and effective treatment regimens based on the neuroimaging findings. Future research should focus on identifying and validating biomarkers that could facilitate the diagnosis, treatment planning, and monitoring of OCD. In summary, DTI studies have shed new light on the neurobiological mechanisms underlying OCD and provide exciting opportunities for further research and clinical practice.

The main classic suggested brain circuits of OCD are the cortico-striatal-thalamo-cortical (CSTC) circuits including the orbitofrontal cortex (OFC) circuit as one of the more important circuits between them (Saxena et al., 1998, Saxena and Rauch, 2000, Menzies et al., 2008, Chamberlain et al., 2008). As depicted in Figure 1 the CSTC circuits encompasses the prefrontal cortex, basal ganglia, thalamus, and other interconnected brain structures, forming a complex network responsible for the transmission and integration of information across these regions. This circuit plays a pivotal role in orchestrating motor and cognitive functions by facilitating the coordination of motor planning, response inhibition, decision-making, and emotional regulation processes. Its intricate connections enable the flow of information between the prefrontal cortex, responsible for higher-order cognitive functions, the basal ganglia, involved in motor control and habit formation, and the thalamus, acting as a relay station for sensory and motor signals. Understanding the abnormalities within the CSTC circuits provides valuable insights into the pathophysiology of obsessive-compulsive disorder (OCD), and sheds light on potential targets for therapeutic interventions. Individuals with OCD demonstrate increased activity in the CSTC circuits, resulting in an excessive response to obsessive thoughts, which leads to compulsive behaviors (He et al., 2018). The OFC circuit, as an important part of CSTC circuits, regulates decision-making, emotion processing, and impulsive behavior. The circuit comprises the medial orbitofrontal, temporolimbic cortices, and anterior cingulate, as well as the striatum and thalamus (Chamberlain et al., 2008). People with OCD have reduced activity in this circuit, leading to repetitive, impulsive behaviors as a way to regulate emotions. The OFC also processes reward and punishment information, which can lead to compulsion development (Chamberlain et al., 2008). Performing a compulsive behavior is registered as a reward by the OFC, perpetuating the OCD cycle. While these classic circuits provide insight into OCD, more advanced models and circuits are needed to fully understand the disorder and develop effective treatments (Milad and Rauch, 2012).

Recent advances in neuroimaging and genetic research have led to the identification of new and emerging brain circuits and networks associated with OCD, in addition to the classic suggested brain circuits. One such network is the default mode network (DMN), which is activated during self-reflection and has been implicated in various psychiatric disorders, including OCD (Fransson and Marrelec, 2008, Buckner et al., 2008). The DMN is connected by a set of white matter tracts, including the cingulum bundle, the inferior longitudinal fasciculus, and the uncinate fasciculus (Weiler et al., 2014). Studies have found that increased connectivity within the DMN is associated with greater OCD symptom severity, indicating that aberrant functioning of this network may contribute to the disorder (Harrison et al., 2009).

Another emerging brain circuit is the salience network (SN), which regulates attention, motivation, and emotion (Menon, 2011). Studies suggest that alterations in the SN may play a role in the pathophysiology of OCD, with evidence of increased activity in this network in individuals with OCD compared to healthy controls (Weiler et al., 2014). This increased activity was found to be associated with symptom severity (Jung et al., 2013).

Research also highlights the role of the cerebellum in the development and maintenance of OCD. The cerebellum is involved in motor control and learning, as well as cognitive and emotional processes. Dysregulation of the cerebellum may contribute to the development and persistence of OCD symptoms, as demonstrated by studies indicating reduced connectivity between the cerebellum and frontal cortex and increased connectivity with the temporal lobe in OCD patients (Zhang et al., 2019).

In summary, as researchers unraveled the intricate story of OCD, they realized the importance of integrating both gray matter regions and white matter tracts in understanding the disorder. The gray matter regions provided insights into localized brain activity and dysfunction, while the white matter tracts illuminated the pathways that facilitated communication and coordination between these regions. The story of OCD unfolded as a tale of disrupted activity in gray matter regions, intertwined with abnormalities in the connectivity and integrity of white matter tracts. With each discovery, researchers moved closer to unraveling the enigma of OCD and paving the way for more targeted treatments and interventions.

Diffusion tensor imaging (DTI) and tractography studies have emerged as valuable tools for investigating the white matter microstructure of the brain and its role in obsessive-compulsive disorder (OCD). While the disorder has been extensively studied using functional imaging techniques, the underlying white matter structural changes in the brain remain poorly understood. DTI and tractography studies can help fill this knowledge gap by providing a detailed view of the white matter microstructure and its connectivity within the brain, potentially leading to the development of more targeted treatments.

In the upcoming sections, we will examine the primary applications of DTI and tractography techniques in OCD research. These applications include the identification of abnormalities in white matter microstructure, the assessment of changes in structural connectivity before/after treatment, as well as the comparison of whole brain and ROI-based approaches. We will also discuss the use of these techniques in deep brain stimulation (DBS) treatment.