Dopamine and the development of executive dysfunction in autism spectrum disorders.

Persons with autism regularly exhibit executive dysfunction (ED), including problems with deliberate goal-directed behavior, planning, and flexible responding in changing environments. Indeed, this array of deficits is sufficiently prominent to have prompted a theory that executive dysfunction is at the heart of these disorders. A more detailed examination of these behaviors reveals, however, that some aspects of executive function remain developmentaly appropriate. In particular, while people with autism often have difficulty with tasks requiring cognitive flexibility, their fundamental cognitive control capabilities, such as those involved in inhibiting an inappropriate but relatively automatic response, show no significant impairment on many tasks. In this article, an existing computational model of the prefrontal cortex and its role in executive control is shown to explain this dichotomous pattern of behavior by positing abnormalities in the dopamine-based modulation of frontal systems in individuals with autism. This model offers excellent qualitative and quantitative fits to performance on standard tests of cognitive control and cognitive flexibility in this clinical population. By simulating the development of the prefrontal cortex, the computational model also offers a potential explanation for an observed lack of executive dysfunction early in life

Strategic Cognitive Sequencing: A Computational Cognitive Neuroscience Approach

We address strategic cognitive sequencing, the “outer loop” of human cognition: how the brain decides what cognitive process to apply at a given moment to solve complex, multistep cognitive tasks. We argue that this topic has been neglected relative to its importance for systematic reasons but that recent work on how individual brain systems accomplish their computations has set the stage for productively addressing how brain regions coordinate over time to accomplish our most impressive thinking. We present four preliminary neural network models. The first addresses how the prefrontal cortex (PFC) and basal ganglia (BG) cooperate to perform trial-and-error learning of short sequences; the next, how several areas of PFC learn to make predictions of likely reward, and how this contributes to the BG making decisions at the level of strategies. The third models address how PFC, BG, parietal cortex, and hippocampus can work together to memorize sequences of cognitive actions from instruction (or “self-instruction”). The last shows how a constraint satisfaction process can find useful plans. The PFC maintains current and goal states and associates from both of these to find a “bridging” state, an abstract plan. We discuss how these processes could work together to produce strategic cognitive sequencing and discuss future directions in this area

Computational explorations of dopamine dysfunction in autism spectrum disorders

Autism is a developmental disorder characterized by a diverse set of behavioral characteristics, including social difficulties, seizures, motor abnormalities, executive dysfunction, and problems of inflexibility and overselectivity in learning. The breadth of this behavioral profile has made identifying the underlying neural mechanisms difficult for researchers seeking an explanation. An examination of the various roles played by the dopamine (DA) system in learning, attention, and cognitive control uncovers a surprising connection between DA and the symptoms of autism. DA abnormalities are associated with motor problems, repetitive behaviors, seizures, poor implicit learning, learning to follow eye gaze, and executive dysfunction. Led by these facts, I hypothesize that impaired interactions between DA and the prefrontal cortex (PFC) can explain many of the behavioral patterns observed in autism. Under my account, the PFC actively maintains context information that modulates processing in other brain areas so as to produce behavior appropriate for the current setting or situation. The DA system provides a mechanism for learning when PFC contents should be updated to support shifting task contingencies. I hypothesize that inflexibility in the updating of PFC contents, caused by dysfunctional DA/PFC interactions, is at the heart of many behaviors seen in autism. In this document I demonstrate the viability of this hypothesis by perturbing the updating of PFC in five computational models of healthy cognition, covering five distinct behavioral domains, producing autistic patterns of performance in all five cases through this common biological deficit. Specifically, I show how abnormal DA/PFC interactions can explain executive dysfunction, differences during the learning of category structures, impaired implicit learning, difficulties utilizing contextual information to disambiguate homographs, and overselective behavior in people with autism. Thus, I offer a unifying biological account of phenomena that have previously been treated separately in the autism literature and demonstrate the usefulness of the tools of computational modeling in this endeavour

Dopamine and the development of executive dysfunction in autism spectrum disorders.

Persons with autism regularly exhibit executive dysfunction (ED), including problems with deliberate goal-directed behavior, planning, and flexible responding in changing environments. Indeed, this array of deficits is sufficiently prominent to have prompted a theory that executive dysfunction is at the heart of these disorders. A more detailed examination of these behaviors reveals, however, that some aspects of executive function remain developmentaly appropriate. In particular, while people with autism often have difficulty with tasks requiring cognitive flexibility, their fundamental cognitive control capabilities, such as those involved in inhibiting an inappropriate but relatively automatic response, show no significant impairment on many tasks. In this article, an existing computational model of the prefrontal cortex and its role in executive control is shown to explain this dichotomous pattern of behavior by positing abnormalities in the dopamine-based modulation of frontal systems in individuals with autism. This model offers excellent qualitative and quantitative fits to performance on standard tests of cognitive control and cognitive flexibility in this clinical population. By simulating the development of the prefrontal cortex, the computational model also offers a potential explanation for an observed lack of executive dysfunction early in life

Comparing the development of PFC representations (synaptic strengths) between representative control (A, B) and autistic (C, D) networks.

<p>Comparisons are made early in development (Epoch 5, left side) and late (100 epochs, right side). Each image shows the strength of the PFC connections to the response layer, with the strength represented by the brightness of the smaller box (lighter means stronger). Each row designates connections to response units representing features in the same stimulus dimension (as illustrated in E). Images A and B show strength of the PFC representations in early and late stages respectively, and images C and D show the same information for the network modeling autistic performance. Note the lack of strong dimensional representations for both experimental groups early in development (A and C) and the relatively strong dimensional representations late (B and D). Please see text for a more in depth explanation.</p

The XT Model Architecture.

<p>Boxes represent layers of simulated neural processing units. Arrows represent complete connectivity from all of the neurons in one layer to all of the neurons in another. Fast, pooled, lateral inhibition is implemented within each layer, but is not shown. Note the recurrent excitatory connections present in the PFC layer.</p