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A "Circuits-First" Platform for Personalized Neurostimulation Treatment

Award Number: DP1MH116506
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 10/15/2019
PERIOD OF PERFORMANCE END DATE: 07/31/2023

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A "Circuits-First" Platform for Personalized Neurostimulation Treatment - SUMMARY/ABSTRACT Mental illnesses are the largest source of healthcare utilization costs in the US, and the costliest of non- communicable diseases worldwide – estimated to result in $6 Trillion in annual societal burden by 2030. The way in which we have defined psychiatric diagnoses (i.e. based only on symptom clusters) and identified treatments (i.e. capitalizing on serendipity), has failed to substantially mitigate the disabling burden of these diseases, which typically appear early in life and persist. Not surprisingly, individual psychiatric diagnoses are highly clinically and biologically heterogeneous, with as much or greater variability within a diagnosis as between diagnoses. The number of mechanistically distinct psychiatric drug targets has also not grown in decades, and typically only half of patients respond well in clinical trials. Public stigma towards psychiatric disorders remains palpable, as lay understanding of the brain bases of these conditions contrasts with the growing excitement amongst scientists for the potential of grounding diagnosis and treatment directly in neurobiology. Neuroimaging, as the dominant tool in human neuroscience, however, has been used largely for comparing these arbitrarily-defined diagnoses against healthy individuals not for robustly characterizing individual patients in objective biological terms. Imaging is also a purely observational method, and thus cannot by itself provide the causal understanding of circuitry that is necessary for transitioning from a descriptive to a circuit-based mechanistic understanding of mental illness that can directly guide novel interventions. Here, I propose a new diagnostic and treatment development framework that transcends the arbitrariness and heterogeneity of traditional diagnoses, the limitations of group-level imaging analyses and current trial-and- error approaches to treatment planning. Rather, this “Circuits-First” platform focuses on understanding causality in the brain circuits of individual patients as a means for personalized diagnosis and treatment using individually-tailored plasticity-inducing neurostimulation, establishing direct linkage between circuits and clinical outcome. Successful implementation of this “Circuits-First” approach will establish a platform for rapid translation to other psychiatric disorders, and beyond to specific neurological disorders (e.g. stroke, Parkinson’s) where circuit perturbations are prominent. Importantly, despite its novelty, my approach will create a readily scalable platform that, with simple modifications, can have the potential to transform clinical practice in the near term. This is facilitated by the use of broadly-applicable, already FDA-approved tools (e.g. transcranial magnetic stimulation (TMS) and electroencephalography (EEG)), and the fact that it can be performed in the office-based settings of the clinical practitioner, thus not restricted to specialized research labs.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	ALTO NEUROSCIENCE, INC.	369 S SAN ANTONIO RD	LOS ALTOS	CA	94022	SANTA CLARA	USA	Mental Health Research Grants	000	6	3/4/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	ALTO NEUROSCIENCE, INC.	369 S SAN ANTONIO RD	LOS ALTOS	CA	94022	SANTA CLARA	USA	Mental Health Research Grants	000	6	10/20/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $1,015,000 )
2021	2021	ALTO NEUROSCIENCE, INC.	369 S SAN ANTONIO RD	LOS ALTOS	CA	94022	SANTA CLARA	USA	Mental Health Research Grants	000	6	7/21/2021	NON-COMPETING CONTINUATION	$1,015,000
														Subtotal = $1,015,000

Issue Date FY: 2020 ( Subtotal = $931,000 )
2020	2020	ALTO NEUROSCIENCE, INC.	153 2ND ST STE 107	LOS ALTOS	CA	94022	SANTA CLARA	USA	Mental Health Research Grants	004	5	7/10/2020	NON-COMPETING CONTINUATION	$931,000
2020	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	000	3	11/26/2019	NON-COMPETING CONTINUATION	-$1,099,000
2020	2019	ALTO NEUROSCIENCE, INC.	165 LYELL ST	LOS ALTOS	CA	94022	SANTA CLARA	USA	Mental Health Research Grants	001	4	11/26/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,099,000
2020	2019	ALTO NEUROSCIENCE, INC.	153 2ND ST STE 107	LOS ALTOS	CA	94022	SANTA CLARA	USA	Mental Health Research Grants	003	4	5/7/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$308,852
2020	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	002	2	5/7/2020	NON-COMPETING CONTINUATION	-$308,852
														Subtotal = $931,000

Issue Date FY: 2019 ( Subtotal = $1,099,000 )
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	000	3	8/21/2019	NON-COMPETING CONTINUATION	$1,099,000
														Subtotal = $1,099,000

Issue Date FY: 2018 ( Subtotal = $1,099,000 )
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	000	2	8/17/2018	NON-COMPETING CONTINUATION	$1,099,000
														Subtotal = $1,099,000

Issue Date FY: 2017 ( Subtotal = $1,099,000 )
2017	2017	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	000	1	8/30/2017	NEW	$1,099,000
														Subtotal = $1,099,000

Grand Total All Awards = $5,243,000

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A "Circuits-First" Platform for Personalized Neurostimulation Treatment

Award Number: DP1MH116506

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 10/15/2019

PERIOD OF PERFORMANCE END DATE: 07/31/2023

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