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Next-Generation MEG Imaging for Quantifying Cortical-Subcortical Dynamics in the Context of HIV and Cannabis Use

Award Number: R01DA059542
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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Next-Generation MEG Imaging for Quantifying Cortical-Subcortical Dynamics in the Context of HIV and Cannabis Use - Project Summary/Abstract Persons with HIV (PWH) living in the western world have a life expectancy near that of the general population, but remain at a significantly elevated risk of developing cognitive impairments. Such impairments are the most common neurological complication of HIV disease, and research targeting these comorbidities is one of four overarching priorities identified by the Office of AIDS Research (NOT-OD-20-018). Substance use disorders (SUD) are also more prevalent in PWH, yet their contribution to the increased rate of cognitive impairment in this group remains poorly understood. A major barrier to progress has been the historic lack of diagnostic tests and biomarkers that can precisely assess the neurological complications of HIV-infection, which has all but precluded quantification of the additive impact of SUD comorbidity. This lack of tests and markers is at least partially attributable to the field’s limited consensus on the key neuropathological features of HIV-infection. For example, whether HIV-related cognitive decline is primarily attributable to cortical or subcortical circuits remains widely debated, despite literally hundreds of neuroimaging studies over the past 20 years. We recently received a NIH S10 High-End Instrumentation award from the Office of the Director to acquire a next-generation magnetoencephalography (MEG) system. This $3M instrument was the third such unit installed in the United States and remains the only one being used for HIV and/or SUD research. This award follows on the heels of several remarkable discoveries in our ongoing effort to develop quantitative neuro-metrics that can distinguish impaired from unimpaired PWH. Briefly, these findings revealed highly specific cortical oscillatory deficits in PWH, which generated significant excitement and were published in a series of high-impact papers. Most recently, we have shown that regular cannabis use is associated with a normalization of these oscillatory deficits in PWH. While remarkable, all of this work was based on MEG measurements acquired with a previous generation system (circa 2008), which was far more sensitive to cortical versus subcortical neural responses. Of note, this greater sensitivity to cortical activity is true of many modern neuroimaging tools and consequently the extensive evidence supporting cortical aberrations in virally suppressed PWH could be mistaken. Our new next- generation MEG system provides an unprecedented opportunity to quantify human brain dynamics with enhanced precision across multiple parameters, including far greater sensitivity to subcortical brain responses. Thus, through this project we will determine whether HIV-related deficits in cortical oscillatory and spontaneous activity are a primary or secondary neural abnormality in PWH, and whether the apparently beneficial effects of cannabis use on neuronal dynamics in PWH are primarily attributable to modulation of cortical or subcortical neurophysiological activity. While the pathological spontaneous and oscillatory neural activity observed in PWH could arise from increased subcortical drive from the thalamus, we hypothesize that these cortical deficits will be independent of any subcortical aberrations and that the beneficial effects of cannabis will be limited to the cortex.


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 = $645,710 )
2026	2026	FATHER FLANAGAN'S BOYS' HOME	14100 CRAWFORD ST	BOYS TOWN	NE	68010	DOUGLAS	USA	Drug Use and Addiction Research Programs	000	3	5/7/2026	NON-COMPETING CONTINUATION	$645,710
														Subtotal = $645,710

Issue Date FY: 2025 ( Subtotal = $641,043 )
2025	2025	FATHER FLANAGAN'S BOYS' HOME	14100 CRAWFORD ST	BOYS TOWN	NE	68010	DOUGLAS	USA	Drug Use and Addiction Research Programs	000	2	4/14/2025	NON-COMPETING CONTINUATION	$641,043
														Subtotal = $641,043

Issue Date FY: 2024 ( Subtotal = $639,658 )
2024	2024	FATHER FLANAGAN'S BOYS' HOME	14100 CRAWFORD ST	BOYS TOWN	NE	68010	DOUGLAS	USA	Drug Use and Addiction Research Programs	000	1	6/25/2024	NEW	$639,658
														Subtotal = $639,658

Grand Total All Awards = $1,926,411

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Next-Generation MEG Imaging for Quantifying Cortical-Subcortical Dynamics in the Context of HIV and Cannabis Use

Award Number: R01DA059542

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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