A neuroimaging proof of principle study of Down's syndrome and dementia: ethical and methodological challenges in intrusive research.

BACKGROUND: Research into specific illnesses and the development of new treatments may only become possible as new technologies become available. When used for research, such technologies may best be described as 'intrusive', in that they require a considerable willingness and commitment on the part of the participants. This has increasingly been the case for brain disorders and illnesses where novel neuroimaging techniques, often combined with clinical and psychological assessments, have the potential to result in new understanding. People with intellectual disabilities (ID) have a history of under-representation as participants in research using such technologies and are therefore at risk of not receiving equal access to state-of-the-art treatments. We propose that 'intrusive' biomedical research is both possible and ethical in ID, and explore some of the methodological challenges by reference to a recent proof of principle study that used a relatively new ligand-based brain scanning technique in a group of volunteers with Down's syndrome. METHODS: Five overlapping stages of the study methodology were identified and evaluated for their acceptability to volunteers with mild to moderate ID through discussion, reflection, and analysis of structured feedback in the context of key policy documents, ethical guidelines and relevant legislation. RESULTS: Identification of key ethical and methodological challenges from reflective practice and participant feedback facilitated the emergence of strategies that permitted continual refinement of the study design. Important areas considered included (1) being clear about the purpose and scientific justification for the study; (2) reconciling the potential risks and benefits with relevant ethical guidelines and legislation; (3) identifying and implementing effective recruitment strategies; (4) optimising and assessing capacity to consent; and (5) making the 'intrusive' procedures as acceptable as possible to people with ID. CONCLUSION: We were able to demonstrate that a proof of principle study incorporating a novel brain scanning technique in a group of volunteers with ID was feasible, safe and well tolerated, despite the vulnerabilities of the study cohort and the intrusive nature of the research. We consider the study within an ethical and historical discourse about the principles that define current 'best practice' in ID research and propose a number of key recommendations for making intrusive research acceptable in people with ID.

Abnormal frontal activations related to decision-making in current and former amphetamine and opiate dependent individuals.

RATIONALE: There is converging evidence for impairments in decision-making in chronic substance users. In the light of findings that substance abuse is associated with disruptions of the functioning of the striato-thalamo-orbitofrontal circuits, it has been suggested that decision-making impairments are linked to frontal lobe dysfunction. We sought to investigate this possibility using functional neuroimaging. METHODS: Decision-making was investigated using the Cambridge Risk Task during H2(15)O PET scans. A specific feature of the Risk Task is the decisional conflict between an unlikely high reward option and a likely low reward option. Four groups, each consisting of 15 participants, were compared: chronic amphetamine users, chronic opiate users, ex-drug users who had been long-term amphetamine/opiate users but are abstinent from all drugs of abuse for at least 1 year and healthy matched controls without a drug-taking history. RESULTS: During decision-making, control participants showed relatively greater activation in the right dorsolateral prefrontal cortex, whereas participants engaged in current or previous drug use showed relatively greater activation in the left orbitofrontal cortex. CONCLUSION: Our results indicate a disturbance in the mediation by the prefrontal cortex of a risky decision-making task associated with amphetamine and opiate abuse. Moreover, this disturbance was observed in a group of former drug users who had been abstinent for at least 1 year.