A neural model of hippocampal–striatal interactions in associative learning and transfer generalization in various neurological and psychiatric patients

Abstract

Building on our previous neurocomputational models of basal ganglia and hippocampal-region function (and their modulation by dopamine and acetylcholine, respectively), we show here how an integration of these models can inform our understanding of the interaction between the basal ganglia and hippocampal region in associative learning and transfer generalization across various patient populations. As a common test bed for exploring interactions between these brain regions and neuromodulators, we focus on the acquired equivalence task, an associative learning paradigm in which stimuli that have been associated with the same outcome acquire a functional similarity such that subsequent generalization between these stimuli increases. This task has been used to test cognitive dysfunction in various patient populations with damages to the hippocampal region and basal ganglia, including studies of patients with Parkinson's disease (PD), schizophrenia, basal forebrain amnesia, and hippocampal atrophy. Simulation results show that damage to the hippocampal region-as in patients with hippocampal atrophy (HA), hypoxia, mild Alzheimer's (AD), or schizophrenia-leads to intact associative learning but impaired transfer generalization performance. Moreover, the model demonstrates how PD and anterior communicating artery (ACoA) aneurysm-two very different brain disorders that affect different neural mechanisms-can have similar effects on acquired equivalence performance. In particular, the model shows that simulating a loss of dopamine function in the basal ganglia module (as in PD) leads to slow acquisition learning but intact transfer generalization. Similarly, the model shows that simulating the loss of acetylcholine in the hippocampal region (as in ACoA aneurysm) also results in slower acquisition learning. We argue from this that changes in associative learning of stimulus-action pathways (in the basal ganglia) or changes in the learning of stimulus representations (in the hippocampal region) can have similar functional effects.

How Glitter Relates to Gold: Similarity-Dependent Reward Prediction Errors in the Human Striatum

“…Our findings concur with reports of interactions between both systems (Poldrack et al, 2001), specifically in mediating generalization phenomena such as transitive inference or acquired equivalence Shohamy and Wagner, 2008;Moustafa et al, 2010;Wimmer et al, 2012). Unlike stimulus generalization tasks, in which sensory similarity builds the basis for generalization, in acquired equivalence tasks, physically different stimuli acquire relational similarity through their association with the same stimulus or outcome.…”

“…Unlike stimulus generalization tasks, in which sensory similarity builds the basis for generalization, in acquired equivalence tasks, physically different stimuli acquire relational similarity through their association with the same stimulus or outcome. Interestingly, an integrated computational model of basal ganglia and hippocampus function predicts specific performance alterations on such tasks in different neurological and psychiatric disorders involving damage in both regions (Moustafa et al, 2010). Moreover, connectivity between the striatum and the hippocampus correlates with the degree to which subjects acquire and use relational similarity information in a reward-based acquired equivalence task (Wimmer et al, 2012).…”

Learning and generalization from reward and punishment in opioid addiction

“…A computer-based version of acquired equivalence has previously been used to demonstrate qualitative differences in learning vs. generalization in a number of psychiatric and neurological patient groups (for review, see 16). For example, the learning of stimulus-response pairs appears to depend on frontostriatal circuits, and is disrupted in individuals with frontostriatal dysfunction, such as patients with Parkinson’s disease tested on normal dopaminergic medication (15, 17), who show slow learning followed by successful generalization.…”

Fronto-striatal gray matter contributions to discrimination learning in Parkinson's disease

“…These dopamine dependent learning deficits in PD have been informative in the development of theoretical accounts of learning function and have provided important advances and testable predictions for computational explanations of learning (Frank, 2005). In particular, PD has been associated with acquisition deficits in feedback-based discrimination learning (Myers et al, 2003; de Wit et al, 2011), which have also been described via computational approaches (Moustafa et al, 2010). …”