42. The contribution of orbitofrontal cortex to episodic memory impairment in OCD

Abstract

Biological studies of obsessive-compulsive disorder (OCD) provide consistent evidence of dysfunction in orbitofrontal cortex (OFC). We have used the California Verbal Learning Test (CVLT) in behavioral studies to examine episodic memory in OCD. In two separate investigations, we found that OCD patients failed to spontaneously apply semantic organizational strategies during encoding and this led to problems in delayed recall. We will present new data from a PET study in normal subjects examining the neural systems underlying semantic organization using a verbal memory paradigm patterned after the CVLT. Eight normal subjects listened to lists of 24 words, in three conditions: 1) Unrelated: words were semantically unrelated; 2) Spontaneous: words were related in four semantic categories, and subjects were not instructed of this beforehand; 3) Directed: same as (2) but subjects were explicitly instructed to notice the relationships and use them to improve memory. Behavioral data included a Semantic Clustering score, measuring active regrouping of words into semantic categories during recall. In a graded PET contrast (Directed . Spontaneous . Unrelated), two distinct activations were found in left inferior prefrontal cortex and left dorsolateral prefrontal cortex. Correlation analyses in the Spontaneous condition indicated that blood flow in OFC during encoding predicted the use of semantic clustering strategies during immediate recall. These results indicate that OFC plays a role in episodic memory by supporting the mobilization of effective strategic processes, mediated in other regions of PFC. Disruptions in learning strategies in OCD are likely related to OFC dysfunction.