Paradoxical Decision-Making: A Framework for Understanding Cognition in Parkinson's Disease.

People with Parkinson's disease (PD) show impaired decision-making when sensory and memory information must be combined. This recently identified impairment results from an inability to accumulate the proper amount of information needed to make a decision and appears to be independent of dopamine tone and reinforcement learning mechanisms. Although considerable work focuses on PD and decisions involving risk and reward, in this Opinion article we propose that the emerging findings in perceptual decision-making highlight the multisystem nature of PD, and that unraveling the neuronal circuits underlying perceptual decision-making impairment may help in understanding other cognitive impairments in people with PD. We also discuss how a decision-making framework may be extended to gain insights into mechanisms of motor impairments in PD.

Perceptual decisions based on previously learned information are independent of dopaminergic tone.

Both cognitive and motor symptoms in people with Parkinson's disease (PD) arise from either too little or too much dopamine (DA). Akinesia stems from DA neuronal cell loss, and dyskinesia often stems from an overdose of DA medication. Cognitive behaviors typically associated with frontal cortical function, such as working memory and task switching, are also affected by too little or too much DA in PD. Whether motor and cognitive circuits overlap in PD is unknown. In this article, we show that whereas motor performance improves in people with PD when on dopaminergic medication compared with off medication, perceptual decision-making based on previously learned information (priors) remains impaired whether on or off medications. To rule out effects of long-term DA treatment and dopaminergic neuronal loss such as occur in PD, we also tested a group of people with dopa-unresponsive focal dystonia, a disease that involves the basal ganglia, like PD, but has motor symptoms that are insensitive to dopamine treatment and is not thought to involve frontal cortical DA circuits, unlike PD. We found that people with focal dystonia showed intact perceptual decision-making performance but impaired use of priors in perceptual decision-making, similar to people with PD. Together, the results show a dissociation between motor and cognitive performance in people with PD and reveal a novel cognitive impairment, independent of sensory and motor impairment, in people with focal dystonia. The combined results from people with PD and people with focal dystonia provide mechanistic insights into the role of basal ganglia non-dopaminergic circuits in perceptual decision-making based on priors.

Patients with Parkinson's Disease Show Impaired Use of Priors in Conditions of Sensory Uncertainty.

Perceptual decisions arise after considering the available sensory evidence [1]. When sensory information is unreliable, a good strategy is to rely on previous experience in similar situations to guide decisions [2-6]. It is well known that patients with Parkinson's disease (PD) are impaired at value-based decision-making [7-11]. How patients combine past experience and sensory information to make perceptual decisions is unknown. We developed a novel, perceptual decision-making task and manipulated the statistics of the sensory stimuli presented to patients with PD and healthy participants to determine the influence of past experience on decision-making. We show that patients with PD are impaired at combining previously learned information with current sensory information to guide decisions. We modeled the results using the drift-diffusion model (DDM) and found that the impairment corresponds to a failure in adjusting the amount of sensory evidence needed to make a decision. Our modeling results also show that two complementary mechanisms operate to implement a bias when two sets of priors are learned concurrently. Asymmetric decision threshold adjustments, as reflected by changes in the starting point of evidence accumulation, are responsible for a general choice bias, whereas the adjustment of a dynamic bias that develops over the course of a trial, as reflected by a drift-rate offset, provides the stimulus-specific component of the prior. A proper interplay between these two processes is required to implement a bias based on concurrent, stimulus-specific priors in decision-making. We show here that patients with PD are impaired in these across-trial decision threshold adjustments.

Synaptic plasticity from amygdala to perirhinal cortex: a possible mechanism for emotional enhancement of visual recognition memory?

Emotionally salient experiences are better remembered than events that have little emotional context. Several lines of evidence indicate that the amygdala plays an important role in this emotional enhancement of memory. Visual recognition memory relies on synaptic plasticity in the perirhinal cortex, but little is known about the mechanisms involved in emotional enhancement of this form of memory. The results of the present study, performed in rat brain slices, show for the first time that the amygdala input to the perirhinal cortex undergoes synaptic plasticity. Stimulation in the amygdala resulted in long-term potentiation (LTP) in perirhinal cortex that was dependent on ß-adrenoceptors and L-type voltage-dependent calcium channels (L-VDCCs) but was NMDAR-independent. In contrast, intracortical perirhinal stimulation resulted in LTP that was NMDAR-dependent but ß-adrenoceptor- and L-VDCC-independent. In addition, the present results provide the first evidence that stimulation of the amygdala can reduce the threshold for LTP in the perirhinal cortex. Interestingly, this associative form of LTP requires ß-adrenoceptor activation but not NMDA or L-VDCC activation. Knowing the mechanisms that control amygdala-perirhinal cortex interactions will allow better understanding of how emotionally charged visual events are remembered, and may help to understand how memories can consolidate and become intrusive in anxiety-related disorders.