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Characterizing intracortical feedforward and feedback sensory processes in ASD

Award Number: R01MH139643
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/25/2026
PERIOD OF PERFORMANCE END DATE: 12/31/2030

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Characterizing intracortical feedforward and feedback sensory processes in ASD - Project Summary Autism spectrum disorder (ASD) is a neurodevelopmental disorder long associated with functional connectivity abnormalities that are widespread throughout the brain. Despite countless studies on the topic, no single unifying model of functional connectivity abnormalities in ASD has emerged to date. Enthusiasm for studying functional connectivity differences in ASD has subsided in light of evidence of alterations that are more heterogeneous than some of the earlier hypotheses suggested, and because the links of these alterations to neural mechanisms of ASD have been challenging to map. Yet, one related theme that has garnered support has been that functional connectivity in ASD is increased in the bottom-up (or feedforward ) direction and decreased in the top-down (or feedback) direction. Here, we propose to test a hypothesis that the functional characteristics of ASD are rooted in a fundamental imbalance between feedforward and feedback influences. This hypothesis stems from our preliminary data and prior studies, and it is motivated by many aspects of the ASD phenotype: These include increased perceived salience of sensory stimuli and evidence of reduced top-down control in ASD, which manifest across a range of atypical behaviors characteristic of the disorder. Thus far, mapping feedforward and feedback inputs non-invasively in the human brain has been methodologically challenging. Here we propose a multimodal neuroimaging approach, which combines (a) effective connectivity measures using millisecond temporal resolution magnetoencephalography (MEG) with (b) highly novel submillimeter-resolution layer- specific 7T functional MRI. We will use these advanced techniques to characterize feedforward and feedback flow of information along the auditory cortical hierarchy, in 90 ASD and 60 neurotypical (NT) adults, ages 21- 35, with average or above average IQ. Using our multimodal research design, which is firmly rooted in laminar neurophysiological recordings in non- human primates, we will pursue the following Specific Aims: (1) Test the hypothesis that feedforward inputs are abnormally increased in ASD relative to NT individuals; (2) Test the hypothesis that feedback inputs are abnormally decreased in ASD relative to NT individuals; (3) Test the hypothesis that the extent to which feedforward and feedback inputs in the ASD group are indeed different, is predictive of ASD severity and the extent of auditory processing deficits, assessed behaviorally. We expect that the results of this study will lead to a substantially more detailed, comprehensive, and mechanistically motivated framework for the wide range of functional connectivity abnormalities observed in ASD.


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: 2026 ( Subtotal = $824,728 )
2026	2026	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	1	3/27/2026	NEW	$824,728
														Subtotal = $824,728

Grand Total All Awards = $824,728

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Characterizing intracortical feedforward and feedback sensory processes in ASD

Award Number: R01MH139643

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/25/2026

PERIOD OF PERFORMANCE END DATE: 12/31/2030

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