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Cerebellar Modulation of Cognition in Psychosis

Award Number: R01MH116170
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/07/2019
PERIOD OF PERFORMANCE END DATE: 10/31/2028

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Cerebellar Modulation of Cognition in Psychosis - PROJECT SUMMARY/ABSTRACT Psychotic disorders including schizophrenia, bipolar disorder, and related illnesses are severe, debilitating, and often fatal. Cognitive impairments in psychosis are among the leading predictors of disability and poor quality of life; despite this, there are no first line interventions to target these symptoms. Neuroimaging correlates of cognitive impairment in psychosis have been identified using fMRI techniques; however, these studies are mostly correlational in nature, limiting application of these findings to intervention. In order to develop targeted cognitive interventions, there is an urgent need to 1) identify neural circuits that are causally linked to cognitive function, and 2) demonstrate that circuits are modifiable and that circuit-level change is associated with cognitive change. This project is a renewal of a R01 funded multi-year, multi-PI plan to identify the circuit basis of medication refractory symptoms of psychotic disorders. With NIMH support we found that cerebellar-cortical functional connectivity is linked to both psychotic symptoms (hallucinations) and negative symptoms of schizophrenia. Functional connectivity can be engaged and manipulated non-invasively using neuromodulation techniques such as transcranial magnetic stimulation (TMS). The combination of TMS and longitudinal imaging can help establish causal links between circuits and cognition. In the current project we have identified distinct cortical-cerebellar circuits linked to cognitive deficits in psychosis and its prodrome. We replicated this finding and have pilot data that this circuit can be successfully engaged using rTMS. Thus, the goals of this project are 1) to test whether neural circuit dysfunction is dynamically and causally associated with cognitive impairments in people with psychotic disorders, and 2) to test whether TMS drives dynamic change in both neural circuitry and cognitive performance. We hypothesize that the relationship between circuit connectivity and cognition reflects dynamic states intra-individually and over time. Additionally, we hypothesize that the connectivity state of this circuit is modifiable by TMS and that circuit manipulation will result in cognitive change. The PIs have expertise in cognition and imaging in psychosis and the fMRI-guided TMS protocols proposed here, including successful engagement of cerebellar-cortical targets, as well as access to the equipment and resources necessary to carry out the study. If our hypotheses are supported, we will have identified an actionable target that can be immediately deployed in intervention trials to test the potential for fMRI-guided TMS to drive enduring change in cognitive circuitry and performance in psychosis.


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: 2025 ( Subtotal = $693,159 )
2025	2025	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	7	12/6/2024	NON-COMPETING CONTINUATION	$693,159
2025	2024	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	002	6	2/20/2025	COMPETING CONTINUATION	$112,725
2025	2023	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	5	2/20/2025	NON-COMPETING CONTINUATION	-$112,725
														Subtotal = $693,159

Issue Date FY: 2024 ( Subtotal = $822,401 )
2024	2024	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	6	12/19/2023	COMPETING CONTINUATION	$741,984
2024	2024	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	002	6	4/30/2024	COMPETING CONTINUATION	$80,417
2024	2023	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	5	12/18/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $822,401

Issue Date FY: 2023 ( Subtotal = $534,699 )
2023	2023	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	5	1/19/2023	NON-COMPETING CONTINUATION	$53,470
2023	2023	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	5	12/1/2022	NON-COMPETING CONTINUATION	$481,229
														Subtotal = $534,699

Issue Date FY: 2022 ( Subtotal = $607,516 )
2022	2022	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	4	11/16/2021	NON-COMPETING CONTINUATION	$546,764
2022	2022	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	4	5/13/2022	NON-COMPETING CONTINUATION	$60,752
														Subtotal = $607,516

Issue Date FY: 2021 ( Subtotal = $599,981 )
2021	2021	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	3	4/13/2021	NON-COMPETING CONTINUATION	$59,999
2021	2021	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	3	11/18/2020	NON-COMPETING CONTINUATION	$539,982
														Subtotal = $599,981

Issue Date FY: 2020 ( Subtotal = $635,126 )
2020	2020	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	2	3/11/2020	NON-COMPETING CONTINUATION	$63,513
2020	2020	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	2	11/19/2019	NON-COMPETING CONTINUATION	$571,613
														Subtotal = $635,126

Issue Date FY: 2019 ( Subtotal = $579,975 )
2019	2019	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	1	1/7/2019	NEW	$579,975
2019	2019	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	1	9/24/2019	NEW	$0
														Subtotal = $579,975

Grand Total All Awards = $4,472,857

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Cerebellar Modulation of Cognition in Psychosis

Award Number: R01MH116170

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/07/2019

PERIOD OF PERFORMANCE END DATE: 10/31/2028

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