Executive dysfunction in Parkinson's disease and timing deficits

Abstract

Patients with Parkinson's disease (PD) have deficits in perceptual timing, or the perception and estimation of time. PD patients can also have cognitive symptoms, including deficits in executive functions such as working memory, planning, and visuospatial attention. Here, we discuss how PD-related cognitive symptoms contribute to timing deficits. Timing is influenced by signaling of the neurotransmitter dopamine in the striatum. Timing also involves the frontal cortex, which is dysfunctional in PD. Frontal cortex impairments in PD may influence memory subsystems as well as decision processes during timing tasks. These data suggest that timing may be a type of executive function. As such, timing can be used to study the neural circuitry of cognitive symptoms of PD as they can be studied in animal models. Performance of timing tasks also maybe a useful clinical biomarker of frontal as well as striatal dysfunction in PD.

Keywords: Parkinson’s disease; cognitive impairment; executive function; interval timing; temporal processing.

FIGURE 1

Scalar timing theory of interval timing based on that proposed by Church (1984). In this model, an external signal such as a sensory cue starts an internal clock, which compares the passage of time with a criterion stored in working memory. When the criterion approaches the actual clock time, a timed response is initiated. Extensive evidence has suggested that the striatum is involved in all aspects of interval timing (Merchant et al., 2013). Both dorsal and ventral striatum receive dopaminergic input from the substantia nigra via the nigrostriatal pathway, and this pathway can influence timing (Meck, 2006). However, areas in the medial frontal cortex may also be involved (Coull et al., 2011), and likely influence memory as well as decision processes (Mehanna and Jankovic, 2013). These areas receive dopaminergic input (in red) from mesocortical dopamine projections originating from the ventral tegmental area. These mesocortical dopamine projections may contribute to perceptual timing deficits in PD patients.