OCD: Neurobiology and the Latest in Treatment

Brain Circuitry in OCD

Think of obsessions as redundant brain representations of events, concepts, or ideas. To have an idea of how brain malfunctions can give rise to obsessions and compulsions, some understanding of cortico-striato-thalamo-cortical (CSTC) networks is helpful. CSTC circuits form the basic information-processing structure of the brain;^[7] and information needs to be processed by the brain so that it makes sense to us. Unprocessed information received by the frontal lobes (specifically, the prefrontal cortex, or the thinking brain), such as images, symbols, and crude ideas, are filtered and organized subcortically by the basal ganglia and thalamus, and the information that comes back to the frontal lobes makes sense. That is the basis of the circuit: information is received by the prefrontal cortex, proceeds to the striatum, globus pallidus, and thalamus, and then returns to the prefrontal cortex.^[7]

Why is this significant? The behavioral expression or response of an internal/external input will depend on the effective circular flow from and to the frontal cortices. When structural abnormalities interrupt the efficient flow of information, redundancy creates a state of disarray that can lead to behavioral abnormalities. In part, that appears to be the case in patients with OCD.

Multiple lines of evidence have shown that dysfunction in different parts of the CSTC circuit give rise to symptoms that are consistent with the spectrum of obsessions and compulsions.^[8,9] Structural MRI shows reduced caudate and putamenal (striatum) volume, and functional MRI (assumed to reflect activity within brain networks) shows increased and decreased orbitofrontal and striatal activities, respectively.^[8,10]

Clinical observation of patients with lesions in distinct areas of the circuit—such as small infarctions or calcification in the caudate or putamen, with involvement of the thalamus—has shown acquired obsessions, tics, and perseverations.^[11] The role of the thalamus in CSTC loops is especially important to our understanding of the redundancy that results from obsessions that lead to compulsions.

The striatum comprises the caudate and putamen, both of which connect to the internal and external pallidum and, subsequently, to the thalamus and back to the cortex. The globus pallidus (GP) (pale spheres that can be seen by the naked eye) is made of the GP interna and the GP externa. Both structures are critical; they form part of the direct (GP interna) and indirect (GP externa) pathways that modulate the excitatory and inhibitory impulses from the striatum to the thalamus. The proper balance between excitation and inhibition of stimuli allows for the effective processing of information through the thalamus and back to the cortex. This is a key concept, given that evidence is mounting that in OCD, information processing in CSTC circuits is ineffective because of an imbalance between the activities of the direct and indirect pathways.

Preclinical animal and human translational research in OCD has clarified an increased disinhibition of the thalamus (increased stimulation) that is mediated by a neurochemical malfunction of the direct pathway.^[12] The primary function of the direct pathway is to disinhibit, and thus increase, the thalamic information flow to the frontal cortex. The indirect pathway modulates the activation/inactivation of the direct pathway, which means that, ultimately, information flow from the thalamus to the cortex will be modulated by the efficient interaction of the direct and indirect pathways of the basal ganglia.^[13]

In other words, the manifestation of obsessions (redundancy) appears to relate to an ineffective interaction between the excitatory direct and the inhibitory indirect pathways of the basal ganglia, which does not allow for fluid information processing from the frontal cortex to the striatum, globus pallidus, thalamus, and back to the cortex (CSTC). This means that the brake is not where it should be (direct/indirect pathway balance), and therefore does not control repetition.^[13]

Cognition and emotions are brain functions that are regulated by their own CSTC loop, and just as a proper interaction between direct/indirect pathways is needed to regulate information flow through each circuit/loop, a synergistic modulation between adjacent loops is required if the neocortex (thinking brain) is to appropriately manage the initiation and termination of goal-directed behavior, as well as the emotional tone those behaviors will carry.^[12] In OCD, the relation between the dorsolateral prefrontal cortical (thinking/rational brain) and the ventromedial prefrontal cortical loop (emotional, more primitive brain) is asynchronous, and there is a tendency for the ventromedial loop to dominate the relation, leading to perseverative, emotionally driven, obsessive-compulsive behavior.^[12,14] In other words, there is too much emotional, fear-driven repetition without the effective thinking brain's shut-down of perseverations.^[15]

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