The Mind and the Brain by Jeffrey M. Schwartz, Sharon Begley Page B

then straight to the thalamus and back to the cortex. The crucial difference is that the direct pathway provides activating input to the thalamus, but the indirect pathway provides inhibitory input. Thus the direct and indirect output pathways from the striatum have opposite effects. The direct pathway tends to activate the cortex, the indirect pathway tends to quiet the cortex.
    The striatal gate determines which pathway nerve impulses will follow. Recall that the striatum receives input from the entire cortex, with the caudate specifically receiving strong input from the prefrontal areas. Prefrontal inputs include those from the orbital frontal cortex and anterior cingulate error-detection circuitry. In 1992 Lew Baxter, my longtime colleague at UCLA, dubbed the circuit containing the orbital frontal cortex and its connections to the basal ganglia the “worry circuit.” It is now often called “the OCD circuit.” When this circuit is working properly, the result is a finely tuned mechanism that can precisely modulate the orbital frontal cortex and anterior cingulate by adjusting the degree to which the thalamus drives these areas. When that modulation is faulty, as it is when OCD acts up, the error detector centered in the orbital frontal cortex and anterior cingulate can be overactivated and thus locked into a pattern of repetitive firing. This triggers an overpowering feeling that something is wrong, accompanied by compulsive attempts somehow to make it right. The malfunction of the OCD circuit that our UCLA group found in OCD patients therefore makes sense. If the exquisite balance of the direct and indirect pathway outputs from the basal ganglia is impaired, it can causethe orbital frontal cortex to become stuck in the “ERROR! ERROR!” mode.
    When the striatum is working normally, it gates the vast array of information about the environment that flows into it from the cortex and initiates what Ann Graybiel has termed “chunks of action repertoires.” These chunks help form “coordinated, sequential motor actions” and develop “streams of thought and motivation.” Thus a single bit of information, such as the feel of a stick shift in your hand, can initiate a complex behavior, for instance, a series of foot movements on the clutch and hand movements on the stick. But in OCD patients the striatum, our PET scans showed, is not even close to functioning normally. It does not gate properly, leading to serious overactivity in the orbital frontal cortex. The intrusive, persistent sense in OCD that something is wrong seems to be the result of orbital frontal cortex neurons’ becoming chronically activated (or inadequately inactivated) as a result of a gating problem, which causes the direct-output pathway to overwhelm the indirect one.
    In OCD, the striatum—in particular, the caudate nucleus—appears to be failing to perform its gating function properly. It has become like an automobile transmission that fails to shift. Most people have brains that shift gears automatically, but OCD patients have a sticky manual transmission. As a result, the direct pathway seems stuck in the “on” position. This is what I came to call Brain Lock: the brain can’t move on to the next thought and its related behavior. Instead, such evolutionarily ancient drives as washing and checking for danger keep breaking through, creating a sense of being overwhelmed by these feelings and urges. The feeling of being “stuck in gear,” which often manifests itself as the feeling of needing to get things just right, also explains why an OCD patient finds it so hard to change the compulsive behavior, and why doing so requires such focused and even heroic effort. Medications that block the neuronal reuptake of serotonin can help by at least partiallydecreasing the intensity of OCD urges, probably by helping to rebalance the direct and indirect pathways.
    A third brain region implicated in OCD is the anterior cingulate gyrus, which also