Background image for Genes, Brains and Decisions. Photo by Robbin Huang on Unsplash.
Genes, Brains and Decisions

Patients with frontotemporal dementia (FTD) are prone to making bad decisions; unfortunately, FTD is often only diagnosed after patients have made significant errors. Such delays reflect the absence of objective clinical tests for decision-making, and represent missed opportunities to prevent serious harms.

We are studying decision-making in familial FTD kindreds from two large NIH-funded multicenter networks spanning the US and Canada. We hypothesize that early behavioral and physiological changes in FTD mutation carriers will reveal initial signs and mechanisms of impaired judgment in FTD, potentially also elucidating neural mechanisms of impaired decision-making in other neuropsychiatric disorders. Presymptomatic mutation carriers and noncarrier family members from these multicenter networks are recruited to perform tests of decision-making on a secure web-enabled platform that enables rapid and flexible data collection from participants across North America. Linking our behavioral measures to a rich dataset of cognitive and neuroimaging measures already being collected across network sites allows us to combine the strengths of traditional on-site evaluation with the flexibility and scaling advantages of newer online methods.

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Neuroethics in Novel Neurotechnologies

New technologies that modulate brain function have tremendous potential for alleviating the burden of neuropsychiatric illness, but raise challenging ethical and societal questions. The President’s Bioethics Commission and other experts have called for the integration of ethics and neuroscience, which will require collaboration across humanistic and scientific disciplines as well as the engagement of patients and researchers at the forefront of novel neurotechnologies.

To address these issues, we have built a cohesive interdisciplinary team with expertise in neuroscience, clinical care, law, philosophy and social science. Our work focuses on the development of implantable “closed-loop” devices that can both monitor and adaptively modify brain systems involved in mood and behavior regulation. We are observing and interviewing patients undergoing novel closed-loop interventions for epilepsy, Parkinson’s disease, and mood disorders, along with their family members. We are also studying how their experiences and concerns can be incorporated in clinicians’ and researchers’ views about the ethical development of neurotechnology.

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Decision-Making in Alzheimer's and Related Dementias

Decisional impairments in Alzheimer’s disease and related dementias can have disastrous consequences for patients and their families. While recent research in decision neuroscience and neuroeconomics holds great promise for elucidating neural mechanisms underlying these impairments, in many cases it remains unclear how neuroscientific findings can be applied to the decision-making errors that patients exhibit in real life.

We address this gap by linking current decision neuroscience to clinical standards routinely applied in the assessment of patients’ decision-making abilities. On a widely-accepted standard, impaired decisions in dementia and other cognitive disorders can result from failures to: (1) understand relevant features of a decision, (2) appreciate how this relates to one’s own situation, (3) rationally manipulate information to arrive at a decision, or (4) consistently evidence a choice. These criteria reflect clinicians’ expertise with patients’ impairments and embody mechanistic assumptions about how decision-making is compromised in disease–assumptions that can now be investigated empirically.

Our work links these accepted clinical standards to current constructs in decision neuroscience, utilizing task-based functional MRI and computational modeling of decision-making in well-characterized cohorts of patients with Alzheimer’s disease, patients with frontotemporal dementia, and healthy older controls, all with linked clinical and neuroimaging data. We aim to advance our understanding of mechanisms of clinical decision-making impairments, ultimately resulting in improved assessment tools and in targets for future interventions to prevent serious harms to patients.

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Online Studies of Decision-Making in Healthy Aging

Traditionally, research subjects undergo behavioral testing and other data collection during on-site evaluations in dedicated research laboratories. While this allows for detailed cognitive, clinical and neuroimaging characterization of each subject, the labor and time costs associated with sequential on-site subject evaluation often place severe constraints on sample size and flexibility. Some researchers have addressed these limitations by using online panels to administer behavioral tasks to large numbers of subjects at home. This approach is highly flexible and scalable, but cannot evaluate hypotheses that require neuroimaging or standardized cognitive measurements.

Our research program combines the detailed subject characterization enabled by on-site evaluation with the flexibility and scaling advantages of online testing. Participants in this project (currently ~140 neurologically normal adults ages 65-95) undergo extensive in-person cognitive testing and neuroimaging through the UCSF Healthy Aging Study and Normal Aging and Cognitive Decline Study. These investigations are linked to behavioral data collected on secure, web-enabled platform allowing these subjects to complete study tasks at home.