The Robert J. and Nancy D. Carney Institute for Brain Science will provide $764,000 in seed funding for seven high-impact brain science research projects, led by 12 Brown faculty members. 

Now in its 12th year, the Zimmerman Innovation Awards in Brain Science fuels promising, high-risk research, enabling scientists to test their most exciting ideas and generate the data needed to secure long-term funding. As of this year, the institute has invested more than $6 million total in these awards. 

Four of this year’s projects will be supported by a total of $432,000. Three projects will receive a combined $332,000 to advance research that targets Alzheimer’s disease and related dementias. 

“It is critical to support bold, early-stage research that seeds breakthrough discoveries," said Diane Lipscombe, Reliance Dhirubhai Ambani Director of the Carney Institute. "Ideas left on the table will never advance our understanding of the human brain or lead to cures and treatments. We have to take informed risks to catalyze new discoveries.” 

This year's projects focused on Alzheimer’s disease leverage data collected in large longitudinal studies to address crucial research questions. 

“These projects are unique in that they will turn decades of data collection into a clearer picture of the disease trajectory,” said Bess Frost, Salame-Feraud Director of the Center for Alzheimer’s Disease Research. “They will allow us to gain insight into how genetic risk factors may manifest in early life, develop the sophisticated modeling tools needed to evaluate treatment responses and better understand the neural circuitry that allows some individuals to maintain cognitive resilience despite the presence of brain pathology.”

The Innovation Awards were created to fund up to $100,000 per project for one year, renewable for a second year on a competitive basis. Projects led by a junior faculty member are eligible for an additional $32,000 in funding.

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Innovation Awards across all areas of brain science

The following awards are funded in part by the Richard Bookman '75 Innovation Awards in Brain Science.

Boosting FGFBP1 to protect the neuromuscular junction and treat amyotrophic lateral sclerosis

Investigator: Gregorio Valdez, David and Nancy Kaplan Professor of Molecular Biology, Cell Biology and Biochemistry

The Valdez lab has identified a promising therapy for treating amyotrophic lateral sclerosis (ALS), a neurodegenerative disease that leads to progressive paralysis and death within five years of diagnosis. A hallmark of ALS is the early and progressive destruction of the neuromuscular junction, a synapse responsible for muscle contraction.

“Our exciting preliminary data suggests that a protein, FGFBP1, protects the neuromuscular junction,” said Valdez. “We will conduct a study in an ALS animal model where we increase levels of this protein involved in tissue repair to see if it prevents the disease from progressing. Such a therapy could go on to preserve motor function and extend the lifespan of people with ALS.”

Targeted, wireless subdural neuromodulation of spinal circuits by next generation neurotechnology

Investigators: David Borton, associate professor of engineering, neurosurgery and brain science, and Arto Nurmikko, L. Herbert Ballou University Professor of Engineering

Two labs will collaborate on a wireless device that can treat pain, neurological disease and traumatic injury. The team includes the Borton lab, which recently showed that electrical stimulation of the spinal cord can restore muscle control in paralyzed humans, and the Nurmikko lab, which has created a state-of-the-art wireless technology. The new device will be designed for placement in the subdural space, an area deeper inside the spinal cord than current technology can access.

“If we are successful, we will have a technology that can reach deeper into the spinal cord, more precisely targeting damaged areas without placing leads or wires,” said Borton and Nurmikko. “No one has placed so many wireless chiplets in the spinal cord before, including us. The data we collect will provide the preliminary data for an NIH application to continue to advance this work.”

Cross-species gene regulatory networks underlying addictive behaviors

Investigators: Alexander Fleischmann, Provost’s Professor of Brain Science, and Karla Kaun, associate professor of neuroscience

The team will identify the molecular mechanisms that link the sense of smell to addictive behaviors, specifically in the context of methamphetamine addiction. Drawing on Fleischmann’s expertise in olfaction and Kaun’s in addiction, the collaborative research group will conduct behavioral experiments in both fly and mouse models, followed by analysis that compares the cellular and circuit mechanisms underlying natural reward memories with addictive reward memories.

“We know smell plays an important role in triggering cravings and relapse, but how it does so remains unknown,” said Fleischmann and Kaun. “Our research has the potential to uncover the genetic and epigenetic changes that drive these cravings, thereby laying the groundwork for discovering new therapeutic targets and strategies.”

Modulating interoceptive circuits to change fear regulation in anxiety

Investigator: Frederike Petzschner, assistant professor of cognitive and psychological sciences

The Petzschner lab will investigate the potential to target bodily feedback mechanisms that sustain fear to help treat anxiety. Using transcranial focused ultrasound, the team will modulate activity in the insular cortex –– the brain region that processes signals such as changes in heart rate or rhythm –– to determine whether they can interrupt the feedback loop that drives persistent fear responses.

"If we are successful in identifying bodily feedback as a modifiable target, our study will lay the groundwork for next-generation interventions for anxiety that combine tried-and-true approaches like exposure therapy with transcranial focused ultrasound," said Petzschner.

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Innovation Awards for Alzheimer's disease and related dementias

Genetic risk and resilience for cognitive decline from childhood through later life: implications for Alzheimer's disease and related dementias

Investigators: Stephen Buka, professor of epidemiology, Sarah Ackley, assistant professor of epidemiology, and Michelle Rogers, assistant professor of behavioral and social sciences (research)

Using data from the New England Family Study (NEFS) –– a three-generation longitudinal study launched in 1959, the collaborative team will unpack how genetic risk for developing late-onset Alzheimer’s shapes cognitive trajectories across the lifecourse.

“While we know that the genetic variant APOE-ε4 is the strongest known risk factor for developing late-onset Alzheimer’s disease, the impact of the gene on early and mid-life remains unknown,” said Ackley, Buka and Rogers. “By integrating genetic data from 1,000 NEFS participants together with repeated cognitive assessments, educational and occupational histories, and early-life socioeconomic information, we will fill in this critical gap in the literature –– as well as glean how social and behavioral factors might buffer against that risk.”

Supported by the Innovation Fund for Alzheimer's Disease and Neurodegeneration, the Stanley and Josephine Chen Research Innovation Fund, and the Center for Alzheimer’s Disease Research Human-Centered Research Fund.

Alzheimer’s disease treatment effect evaluation methods

Investigator: Ani Eloyan, associate professor of biostatistics

To pin down whether Alzheimer’s disease treatments in large observational studies are improving patient outcomes, researchers need sound statistical models for evaluating complex treatment effects. Using data collected in the Longitudinal Early-onset Alzheimer’s Disease Study (LEADS) –– an NIA-funded study with the goal of addressing major research gaps in early-onset Alzheimer’s disease –– researchers from the Eloyan-led Biostatistics in Medical Imaging lab will create novel modeling tools to unlock important insights about the LEADS cohort response to treatment. These insights can also be used in other Alzheimer's disease studies.

“The preliminary results from LEADS are promising and give us hope for slowing disease progression,” said Eloyan. “To validate these initial results and make this hope tangible, we need to create rigorous evaluative tools and novel modeling methods that will benefit the entire field.”

Supported by the Innovation Fund for Alzheimer's Disease and Neurodegeneration.

Neural mechanisms of resilience to age-related cognitive decline: a 65-year prospective cohort study

Investigators: William Heindel, professor of cognitive and psychological sciences, and Elena Festa, teaching professor of cognitive and psychological sciences

Heindel and Festa, who are co-directors of the Aging and Cognition Laboratory, will track down the neural mechanisms of resilience –– the brain circuitry in individuals who have maintained effective cognitive function despite significant age-related brain changes. Drawing on the wealth of longitudinal data provided by the New England Family Study, the team will re-assess 60 NEFS participants, studying two brain systems central to maintaining cognitive control and neural flexibility, the noradrenergic locus coeruleus and the cognitive control network.

“This project will enable us to gather the empirical data and develop the conceptual framework needed for an application for a large NIH grant to better understand resilience, knowledge essential for developing interventions that preserve cognitive health across the lifespan,” said Heindel and Festa.

Supported by the Innovation Fund for Alzheimer's Disease and Neurodegeneration and the Center for Alzheimer's Disease Research Human-Center Research Fund.