Multifaceted Contributions by Different Regions of the Orbitofrontal and Medial Prefrontal Cortex to Probabilistic Reversal Learning.

Different subregions of the prefrontal cortex (PFC) contribute to the ability to respond flexibly to changes in reward contingencies, with the medial versus orbitofrontal cortex (OFC) subregions contributing differentially to processes such as set-shifting and reversal learning. To date, the manner in which these regions may facilitate reversal learning in situations involving reward uncertainty remains relatively unexplored. We investigated the involvement of five distinct regions of the rat OFC (lateral and medial) and medial PFC (prelimbic, infralimbic, and anterior cingulate) on probabilistic reversal learning wherein "correct" versus "incorrect" responses were rewarded on 80% and 20% of trials, respectively. Contingencies were reversed repeatedly within a session. In well trained rats, inactivation of the medial or lateral OFC induced dissociable impairments in performance (indexed by fewer reversals completed) when outcomes were probabilistic, but not when they were assured. Medial OFC inactivation impaired probabilistic learning during the first discrimination, increased perseverative responding and reduced sensitivity to positive and negative feedback, suggestive of a deficit in incorporating information about previous action outcomes to guide subsequent behavior. Lateral OFC inactivation preferentially impaired performance during reversal phases. In contrast, prelimbic inactivation caused an apparent improvement in performance by increasing the number of reversals completed. This was associated with enhanced sensitivity to recently rewarded actions and reduced sensitivity to negative feedback. Infralimbic inactivation had no effect, whereas the anterior cingulate appeared to play a permissive role in this form of reversal learning. These results clarify the dissociable contributions of different regions of the frontal lobes to probabilistic learning. SIGNIFICANCE STATEMENT: The ability to adjust behavior in response to changes involving uncertain or probabilistic reward contingencies is an essential survival skill that is impaired in a variety of psychiatric disorders. It is well established that different forms of cognitive flexibility are mediated by anatomically distinct regions of the frontal lobes when reinforcement contingencies are assured, however, less is known about the contribution of these regions to probabilistic reinforcement learning. Here we show that different regions of the orbitofrontal and medial prefrontal cortex make distinct contributions to probabilistic reversal learning. These findings provide novel information about the complex interplay between frontal lobe regions in mediating these processes and accordingly provide insight into possible pathophysiology that underlies impairments in cognitive flexibility observed in mental illnesses.

Component Processes of Decision Making in a Community Sample of Precariously Housed Persons: Associations With Learning and Memory, and Health-Risk Behaviors.

The Iowa Gambling Task (IGT) is a widely used measure of decision making, but its value in signifying behaviors associated with adverse, "real-world" consequences has not been consistently demonstrated in persons who are precariously housed or homeless. Studies evaluating the ecological validity of the IGT have primarily relied on traditional IGT scores. However, computational modeling derives underlying component processes of the IGT, which capture specific facets of decision making that may be more closely related to engagement in behaviors associated with negative consequences. This study employed the Prospect Valence Learning (PVL) model to decompose IGT performance into component processes in 294 precariously housed community residents with substance use disorders. Results revealed a predominant focus on gains and a lack of sensitivity to losses in these vulnerable community residents. Hypothesized associations were not detected between component processes and self-reported health-risk behaviors. These findings provide insight into the processes underlying decision making in a vulnerable substance-using population and highlight the challenge of linking specific decision making processes to "real-world" behaviors.

Volumes of the Hippocampal Formation Differentiate Component Processes of Memory in a Community Sample of Homeless and Marginally Housed Persons.

OBJECTIVE: Persons who are homeless or marginally housed exhibit significant cognitive dysfunction, with memory being the most impaired domain. Hippocampal subfield volumes have been found to differentially relate to component processes of memory. The neural correlates of memory have not been previously examined in marginalized persons who are understudied and underserved. We examined whether hippocampal subfields and entorhinal cortex volumes are uniquely related to indices of verbal episodic memory using the Hopkins Verbal Learning Test - Revised. METHOD: Data was used from a large sample of community dwelling homeless and marginally housed adults (N = 227). Regression analyses were conducted to examine hippocampal subfield volumes (CA1, CA3, CA4, dentate gyrus, subiculum) and entorhinal cortex, and their associations with measures of verbal immediate recall, learning slope, and verbal delayed recall. RESULTS: Greater CA3 subfield volume was associated with better performance on an index of encoding (immediate recall), but only in older individuals. Greater CA1 and subiculum volumes were associated with better performance on immediate and delayed recall (measures that tap into retrieval processes), but not with learning slope (a more pure index of encoding). Entorhinal cortex volume was related to all components of memory beyond total hippocampal volume. CONCLUSIONS: Our results suggest common neuroanatomical correlates of memory dysfunction in large sample of marginalized persons, and these are uniquely related to different components of memory. These findings have clinical relevance for marginalized populations and theoretical relevance to the growing literature on functional specialization of the hippocampal subfields.