Impaired associative learning in schizophrenia: behavioral and computational studies

Abstract

Associative learning is a central building block of human cognition and in large part depends on mechanisms of synaptic plasticity, memory capacity and fronto-hippocampal interactions. A disorder like schizophrenia is thought to be characterized by altered plasticity, and impaired frontal and hippocampal function. Understanding the expression of this dysfunction through appropriate experimental studies, and understanding the processes that may give rise to impaired behavior through biologically plausible computational models will help clarify the nature of these deficits. We present a preliminary computational model designed to capture learning dynamics in healthy control and schizophrenia subjects. Experimental data was collected on a spatial-object paired-associate learning task. The task evinces classic patterns of negatively accelerated learning in both healthy control subjects and patients, with patients demonstrating lower rates of learning than controls. Our rudimentary computational model of the task was based on biologically plausible assumptions, including the separation of dorsal/spatial and ventral/object visual streams, implementation of rules of learning, the explicit parameterization of learning rates (a plausible surrogate for synaptic plasticity), and learning capacity (a plausible surrogate for memory capacity). Reductions in learning dynamics in schizophrenia were well-modeled by reductions in learning rate and learning capacity. The synergy between experimental research and a detailed computational model of performance provides a framework within which to infer plausible biological bases of impaired learning dynamics in schizophrenia.

The neural correlates of performance in adolescents at risk for schizophrenia: Inefficiently increased cortico-striatal responses measured with fMRI

“…Learning related deficits are also a hallmark of the schizophrenia diathesis (Diwadkar et al, 2008) and have been linked to deficits in visuo-spatial memory as well (Wood et al, 2002). In general, working memory and executive processes may be central to several cognitive domains including associative learning, which does rely on the temporary maintenance of memoranda (relying on frontal activity) before items can be consolidated in longer-term memory (Bunge et al, 2004; Ranganath et al, 2004).…”

Functional dynamics of hippocampal glutamate during associative learning assessed with in vivo 1 H functional magnetic resonance spectroscopy

“…Previous fMRI studies have shown that the task strongly modulates responses in the hippocampus, as well as effective connectivity between the hippocampus and neo-cortical regions (Banyai et al, 2011; Buchel et al, 1999; Woodcock et al, 2016; Woodcock et al, 2015). Moreover, behavioral proficiency on the task has been shown to conform to classic mechanisms of negatively accelerated learning (Diwadkar et al, 2016; Diwadkar et al, 2008), suggesting that the task characteristics strongly engage basic hippocampal mechanisms of learning and memory (Hasselmo, 1999; Rolls, 1996). …”

“…The course of paired-associate learning is well approximated by functions with a negatively accelerated or sigmoidal growth behavior, with limited free parameters estimating learning rate (Diwadkar et al, 2008). The dynamics of the task thus permits cleavage into sub-groups of relatively fast and slow learners based on the fitted response functions, and task performance has been linked to estimated fMRI metrics.…”

Modeling brain dynamics using computational neurogenetic approach

“…There are successful computational models of mental diseases, for instance of impaired associative learning in schizophrenia (Diwadkar et al 2008) or sleep disturbance in autism (Matsuura et al 2008) or other disorders (Reggia et al 1999). However, these models should be taken one step further as recent genetic studies show that serious mental diseases manifested as compromised cognitive and/ or affective status are thought to be linked to mutations of genes.…”