Laboratory of Behavioral Neuroscience

Peter Rapp , Ph.D., Acting Chief

The overarching goal of the Laboratory of Behavioral Neuroscience (LBN) is to improve cognitive outcomes with aging. The fundamental scientific paradigm guiding research in the Laboratory of Behavioral Neuroscience (LBN) is the study of individual differences and age-related changes in cognition, personality, brain structure and function, and their influences on cognitive outcomes. The mission of the LBN is to promote understanding of the mechanisms underlying these differences and age-associated variation in cognition that will translate to ameliorating age-related cognitive decline, reduce risk for cognitive impairment and dementia, and promote cognitive resilience. LBN investigators employ a multi-level approach from genes to molecules to cells to physiology to neural systems to behavior. The LBN uses animal models to elucidate neurobiological, including molecular and cellular, differences between aged impaired and unimpaired animals in comparison to young animals. Human studies focus on cognitive and brain changes during the earliest “preclinical” stages of AD and use blood and brain specimens and novel imaging technologies to identify the biological pathways associated with cognitive decline and AD, as well as new targets for intervention. In addition, LBN investigators study the mechanisms and factors that mediate the maintenance of cognitive health in both humans and animal models, with a particular interest in the adaptations of the neural physiology and networks that lead to cognitive resilience in the face of challenges posed by the aging process, including development of co-morbid conditions.

About the Laboratory of Behavioral Neuroscience

The Laboratory of Behavioral Neuroscience:

  1. Conducts basic and clinical research on individual differences in cognitive outcomes with aging, both predictors of impairment and maintenance of cognitive health or resilience;
  2. Investigates the molecular, cellular, neural systems and genetic contributions to these differences in animal models and humans;
  3. Examines predictors and modifiers of age-related neurodegenerative diseases and age-associated changes in behavior and brain-behavior associations;
  4. Identifies early biomarkers of Alzheimer’s disease and cognitive decline and examines factors that promote the maintenance of cognitive health;
  5. Develops and validates blood- and imaging-based biomarkers of age-related cognitive decline and AD using proteomic and metabolomic methods
  6. Develops MRI-based methods for imaging histopathology and for neuroimaging-pathology correlation.
  7. Performs systems-level analyses integrating multi-OMICs approaches to identify biological mechanisms and drug targets associated with Alzheimer’s disease;
  8. Develops an open data resource for research on neurocognitive reserve and resilience, Successful Trajectories of Aging: Reserve and Resilience in RatS (STARRRS)

Laboratory investigators employ a variety of methods, including experimental, longitudinal, epidemiological, neuroimaging, biomarker, neuropathological, and genetic methods in the analyses of behavioral, psychological, and biological aspects of aging.

Portfolio/Research Areas

  • Cognitive and brain aging;
  • Neuroimaging biomarkers of cognitive decline, impairment and resilience;
  • Blood-based biomarkers of cognitive impairment and Alzheimer's Disease using proteomic and metabolomic methods;
  • Systems-level analyses integrating multi-OMICs approaches to identify biological mechanisms and drug targets associated with Alzheimer’s disease
  • MRI-based methods for imaging histopathology and for neuroimaging-pathology correlation.
  • Molecular, cellular, anatomic and imaging approaches in animal models of cognitive aging and resilience;
  • Open data resource for research on neurocognitive reserve and resilience, Successful Trajectories of Aging: Reserve and Resilience in RatS (STARRRS)

Findings and Publications

Armstrong NM, An Y, Shin JJ, Williams OA, Doshi J, Erus G, Davatzikos C, Ferrucci L, Beason-Held LL, Resnick SM. Associations between cognitive and brain volume changes in cognitively normal older adults. Neuroimage. 2020 Dec;223:117289. PMID: 32835822; PMCID: PMC9020590.

Bilgel M, An Y, Walker KA, Moghekar AR, Ashton NJ, Kac PR, Karikari TK, Blennow K, Zetterberg H, Jedynak BM, Thambisetty M, Ferrucci L, Resnick SM. Longitudinal changes in Alzheimer's-related plasma biomarkers and brain amyloid. Alzheimers Dement. 2023 Oct;19(10):4335-4345. PMID: 37216632; PMCID: PMC10592628.

Beason-Held LL, Kerley CI, Chaganti S, Moghekar A, Thambisetty M, Ferrucci L, Resnick SM, Landman BA. Health Conditions Associated with Alzheimer's Disease and Vascular Dementia. Ann Neurol. 2023 Apr;93(4):805-818. PMID: 36571386.

Bañuelos C, Kittleson JR, LaNasa KH, Galiano CS, Roth SM, Perez EJ, Long JM, Roberts MT, Fong S, Rapp PR. Cognitive Aging and the Primate Basal Forebrain Revisited: Disproportionate GABAergic Vulnerability Revealed. J Neurosci. 2023 Dec 6;43(49):8425-8441. PMID: 37798131; PMCID: PMC10711728.

Baxter MG, Roberts MT, Roberts JA, Rapp PR. Neuropsychology of cognitive aging in rhesus monkeys. Neurobiol Aging. 2023 Oct;130:40-49. PMID: 37453251; PMCID: PMC10530179.

Stern Y, Albert M, Barnes CA, Cabeza R, Pascual-Leone A, Rapp PR. A framework for concepts of reserve and resilience in aging. Neurobiol Aging. 2023 Apr;124:100-103. PMID: 36653245; PMCID: PMC10424718.

Roberts JA, Varma VR, An Y, Varma S, Candia J, Fantoni G, Tiwari V, Anerillas C, Williamson A, Saito A, Loeffler T, Schilcher I, Moaddel R, Khadeer M, Lovett J, Tanaka T, Pletnikova O, Troncoso JC, Bennett DA, Albert MS, Yu K, Niu M, Haroutunian V, Zhang B, Peng J, Croteau DL, Resnick SM, Gorospe M, Bohr VA, Ferrucci L, Thambisetty M. A brain proteomic signature of incipient Alzheimer's disease in young APOE ε4 carriers identifies novel drug targets. Sci Adv. 2021 Nov 12;7(46):eabi8178. PMID: 34757788; PMCID: PMC8580310.

Varma VR, Desai RJ, Navakkode S, Wong LW, Anerillas C, Loeffler T, Schilcher I, Mahesri M, Chin K, Horton DB, Kim SC, Gerhard T, Segal JB, Schneeweiss S, Gorospe M, Sajikumar S, Thambisetty M. Hydroxychloroquine lowers Alzheimer's disease and related dementias risk and rescues molecular phenotypes related to Alzheimer's disease. Mol Psychiatry. 2023 Mar;28(3):1312-1326. PMID: 36577843; PMCID: PMC10005941.

Desai RJ, Varma VR, Gerhard T, Segal J, Mahesri M, Chin K, Horton DB, Kim SC, Schneeweiss S, Thambisetty M. Comparative Risk of Alzheimer Disease and Related Dementia Among Medicare Beneficiaries With Rheumatoid Arthritis Treated With Targeted Disease-Modifying Antirheumatic Agents. JAMA Netw Open. 2022 Apr 1;5(4):e226567. PMID: 35394510; PMCID: PMC8994126.

Walker KA, Chen J, Shi L, Yang Y, Fornage M, Zhou L, Schlosser P, Surapaneni A, Grams ME, Duggan MR, Peng Z, Gomez GT, Tin A, Hoogeveen RC, Sullivan KJ, Ganz P, Lindbohm JV, Kivimaki M, Nevado-Holgado AJ, Buckley N, Gottesman RF, Mosley TH, Boerwinkle E, Ballantyne CM, Coresh J. Proteomics analysis of plasma from middle-aged adults identifies protein markers of dementia risk in later life. JSci Transl Med. 2023 Jul 19;15(705):eadf5681. PMID: 37467317; PMCID: PMC10665113.

Cordon J, Duggan MR, Gomez GT, Pucha KA, Peng Z, Dark HE, Davatzikos C, Erus G, Lewis A, Moghekar A, Candia J, Ferrucci L, Kapogiannis D, Walker KA. Identification of Clinically Relevant Brain Endothelial Cell Biomarkers in Plasma. Stroke. 2023 Nov;54(11):2853-2863. PMID: 37814955; PMCID: PMC10608795.

Dark HE, Paterson C, Daya GN, Peng Z, Duggan MR, Bilgel M, An Y, Moghekar A, Davatzikos C, Resnick SM, Loupy K, Simpson M, Candia J, Mosley T, Coresh J, Palta P, Ferrucci L, Shapiro A, Williams SA, Walker KA. Proteomic Indicators of Health Predict Alzheimer's Disease Biomarker Levels and Dementia Risk. Ann Neurol. 2024 Feb;95(2):260-273. PMID: 37801487; PMCID: PMC10842994.

Singh K, Barsoum S, Schilling KG, An Y, Ferrucci L, Benjamini D. Neuronal microstructural changes in the human brain are associated with neurocognitive aging. Aging Cell. 2024 Apr 24:e14166. Epub ahead of print. PMID: 38659245.

Johnson JTE, Irfanoglu MO, Manninen E, Ross TJ, Yang Y, Laun FB, Martin J, Topgaard D, Benjamini D. In vivo disentanglement of diffusion frequency-dependence, tensor shape, and relaxation using multidimensional MRI. Hum Brain Mapp. 2024 May;45(7):e26697. PMID: 38726888; PMCID: PMC11082920.

Kundu S, Barsoum S, Ariza J, Nolan AL, Latimer CS, Keene CD, Basser PJ, Benjamini D. Mapping the individual human cortex using multidimensional MRI and unsupervised learning. Brain Commun. 2023 Oct 6;5(6):fcad258. PMID: 37953850; PMCID: PMC10638106.

Units/Sections

Brain Aging and Behavior Section
Cognitive Testing Group
Neurocognitive Aging Section
Multimodal Imaging of Neurodegenerative Disease (MIND) Unit
Multiscale Imaging and Integrative Biophysics (MiiB) Unit