Sharon McDowell,1,2 John Whyte1,2 and Mark D’Esposito3

1Moss Rehabilitation Research Institute, 2Department of Correspondence to: Mark D’Esposito, Department of Physical Medicine and Rehabilitation, Temple University Neurology, University of Pennsylvania Medical Center, School of Medicine, 3Department of Neurology, University 3400 Spruce Street, Philadelphia, PA 19104-4283, USA. of Pennsylvania Medical Center, Philadelphia, PA, USA E-mail: despo@mail.med.upenn.edu

Summary

We examined the effects of low-dose bromocriptine, a D2 dopamine receptor agonist, on processes thought to be subserved by the prefrontal cortex, including working memory and executive function, in individuals with traumatic brain injury. A group of 24 subjects was tested using a double-blind, placebo-controlled crossover trial, counterbalanced for order. Bromocriptine was found to improve performance on some tasks thought to be subserved by prefrontal function, but not others. Specifically, there was improvement in performance on Keywords: dopamine; executive function; frontal lobes; traumatic brain injury; working memory Abbreviations: MANOVA 5 multivariate analysis of variance; TBI 5 traumatic brain injury.

Introduction

Executive function is a loosely defined term that is meant to capture a wide range of cognitive abilities such as planning, set-shifting, sustaining and dividing attention, organization and goal-integration. Numerous clinical neuropsychological measures, such as the Wisconsin Card Sorting Test and the Stroop Test (Lezak, 1995), have been designed to tap this
function, and patients with lesions of the prefrontal cortex are often impaired on these measures relative to patients with posterior lesions (e.g. Milner, 1963; Vendrell et al., 1995). Also, some of the neuropsychological measures which have been adapted for study during PET scanning have demonstrated activation of the prefrontal cortex during
performance by normal subjects (e.g. Bench et al., 1993; Berman et al., 1995). Such empirical evidence has provided a link between executive processes and prefrontal function.

More recently, investigators have sought to define the cognitive processes that may be subserved by the prefrontal cortex more specifically. One such process is working memory, which refers to the short-term storage of information that is not accessible in the environment, and the set of processes that keep this information active for later use in behaviour. Baddeley (1992) has proposed a multicomponent model of working memory. One component of this model, the ‘central executive system’, analogous to Shallice’s ‘supervisory attentional system’ (Shallice, 1982), is thought to regulate the allocation of limited attentional resources and to co-ordinate the manipulation of the information required in complex or novel tasks. Dual-task paradigms, which are thought to tap these systems, have been demonstrated to be more impaired in patients with focal frontal lesions (Baddeley et al., 1997), as well as frontal lesions secondary to traumatic brain injury (TBI) (Hartman et al., 1992; Cicerone, 1996; McDowell et al., 1997). Also, a functional MRI study in normal subjects during dual-task performance showed activation of the prefrontal cortex (D’Esposito et al., 1995). (continue reading)