Neuroanatomy and Neurocircuitry

The contemporary neurobiological explanation for OCD has focused on aberrant functioning of cortico–striatal–thalamic–cortical (CSTC) circuits. These circuits are functionally distinct neural ‘loops,’ originating from specific cortical areas that are also the site of feedback projections from the thalamus (Figure 1). Several different CSTC circuits have been identified, each arising from specific frontal cortical areas and being associated with either emotional, cognitive, or motor inputs (Figure 1). Evidence has shown that in individuals with OCD, these circuits are hyperactive at rest and during episodes of symptom provocation; however, normalization of activity has been observed following treatments (psychopharmacological, behavioral, and psychosurgical).

These neuronal circuits continue from cortical areas and pass through the basal ganglia (including the striatum) through either ‘direct’ or ‘indirect’ pathways, with a final projection through to the thalamus (Figure 1). The ‘direct’ and ‘indirect’ basal ganglia pathways have, through glutamatergic and GABAergic neurotransmission, opposing actions on the thalamus and in turn on the feedback to the frontal cortex. The ‘direct’ pathway results in a disinhibition of thalamic activity through two inhibitory neuronal connections (thereby increasing both thalamic and frontal cortical activity). In contrast, the ‘indirect’ pathway has three inhibitory connections that result in net inhibition of the thalamus and frontal cortex. The ‘direct’ and ‘indirect’ pathways appear to work antagonistically to modulate thalamic and cortical activation, with an imbalance between the pathways being theorized as a contributing pathophysiological factor in OCD.

Of particular importance to the study of OCD are circuits arising from the orbitofrontal cortex (OFC), the dorsolateral prefrontal cortex (DLPFC), and the anterior cingulate cortex (ACC). It appears that these circuits have different primary functions, the OFC circuit being responsible for context-related processing and response inhibition (Figure 2, ventral cognitive circuit), the DLPFC circuit being involved in working memory (Figure 2, dorsal cognitive circuit), and the ACC circuit being responsible for emotional and reward processing (Figure 2, affective circuit). In particular, the OFC and associated circuitry are believed to have a substantial role in the neurobiology of OCD, with OFC overactivity being possibly due to pathological overactivity in the striatum.

Read More about OCD in the below SciTech Connect article:

Obsessive Compulsive Disorder (OCD) Explained

This excerpt was taken from the article Obsessive–Compulsive Disorder by A. Vahabzadeh and C.J. McDougle. The article discusses the phenomenology and epidemiology of OCD, the neurobiology of OCD, current concepts surrounding the role of the immune system in OCD and finally, the major challenges of OCD research and future directions. Read Obsessive–Compulsive Disorder here.

This article was taken from the Major Reference Work, Pathobiology of Human Disease, which provides the definitive knowledge on morphologic, experimental, and molecular pathology. View the table of contents here.