46ournal ofNeurology, Neurosurgery, and Psychiatry 1996;60:416-421 Motivational deficits after brain injury: effects of bromocriptine in 1 1 patients J H Powell, S Al-Adawi, J Morgan, R J Greenwood Abstract Objective-To test the hypothesis that treatment with bromocriptine would ameliorate deficits in clinical motivation, responsiveness to reward, and frontal cognitive function after brain injury. Method-An open trial in six men and five women who had had either traumatic brain injury or subarachnoid haemor- rhage between two months and five years previously. After repeated baseline assessments, bromocriptine was given in gradually increasing doses. Assessments were repeated at increasing doses, during maintenance, and after withdrawal. Novel structured instruments for quantifying motivation were developed; measures of anxiety and depression, and cognitive tests sensitive to motivation or frontal lobe involvement were also given. Results-Bromocriptine treatment was followed by improved scores on all mea- sures other than mood. Improvement was maintained after bromocriptine with- drawal in eight of the patients. Conclusion-Poor motivation in patients with brain injury may result from dys- function in the mesolimbic/mesocortical dopaminergic circuitry, giving rise to associated deficiencies in reward respon- siveness and frontal cognitive function. (J Neurol Neurosurg Psychiatry 1996;60:416-421) Departrnent of Psychology, Goldsmiths College, Lewisham Way, New Cross, London SE14 6NW, UK J H Powell Regional Neurological Rehabilitation Unit, Homerton Hospital, Homerton Row, London E9 6SR,UK J H Powell S Al-Adawi J Morgan R J Greenwood Departent of Psychology, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK S Al-Adawi Correspondence to: Dr Jane Powell, Department of Psychology, Goldsmiths College, Lewisham Way, London SE14 6NW, UK. Received 21 August 1995 and in revised form 14 December 1995 Accepted 22 December 1995 Keywords: motivation; abulia; dopamine; bromo- criptine Of the many behavioural problems that can follow brain injury, passivity and loss of drive (abulia) must rank among the most pro- foundly debilitating and intractable. A perva- sive failure to initiate activities spontaneously or to respond to encouragement and prompt- ing can not only result in social alienation but also impede rehabilitation. Behaviour modifi- cation techniques are of documented success in reducing the frequency of overtly disruptive behaviours' but there is far less evidence of their success in increasing levels of effortful behaviour. Indeed, a recent follow up study2 has confirmed that poor psychosocial outcome a year after brain injury is predicted by initial impairment on cognition and energy items in the neurobehavioural rating scale.3 By contrast, there have recently been reports that such motivational deficits respond well to treatment with drugs which have dopaminergic effects.4Y10 Most of these reports consist of anecdotal descriptions of single cases or series of single cases, and it is not clear, for example, whether similar unreported cases have failed to respond to treatment. However, in the light of growing evidence from both animal and human research impli- cating the mesolimbic and mesocortical dopamine system in normal motivation, a clear theoretical basis for the efficacy of such treatment can be constructed, and the prelimi- nary clinical findings therefore take on a greater relevance. The dopaminergic pathways implicated in motivation originate in the ventral tegmentum, and project to the nucleus accumbens and medial/sulcal prefrontal cortex" 12; there are reciprocal glutamatergic projections from the frontal cortex to the nucleus accumbens via the entorhinal cortex. An extensive scientific literature suggests that dopamine release in the nucleus accumbens or ventral tegmentum may underlie the instantaneous experience of pleasure elicited by potent reinforcers such as opiate and stimulant drugs,'3 14 electrostimula- tion,'5 16 food and water,'7 18 and sex.'8 The nigrostriatal dopamine system may also be implicated in rewarding brain stimulation.19 However, there is also evidence that dopamine is released in response to aversive stimula- tion,20 and one current view2' is that dopamine release mediates the behavioural response to motivationally relevant stimuli rather than the experience of reward itself. If organic brain injury disrupted dopamine transmission within this system, a predictable consequence would be a failure to respond to normally motivating events, due either to reduced capacity for the experience of pleasure or to reduced ability to respond to available rewards with the requisite behavioural output. In either case, patients should show reduced levels of goal directed behaviour. Consistent with this model, impairments of effortful behaviour do characterise several neuro- psychiatric conditions in which there is evidence of dysfunction in mesolimbic/ mesocortical dopamine systems-namely, Parkinson's disease,22 negative type schizo- phrenia,23 and major depression.24 In all three conditions dopamine agonists have had some success in enhancing activity levels.22 2530 Whereas the organic basis of these neuropsy- chiatric conditions remains to some extent speculative, there is extensive evidence that focal lesions to the frontal cortex, innervated by mesocortical dopamine projections, can indeed lead to cognitive and behavioural deficits consistent with the dopaminergic model of motivation. Damage to the dorsolat- 416 on February 22, 2022 by guest. Protected by copyright. http://jnnp.bmj.com/ J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.4.416 on 1 April 1996. Downloaded from