Research Projects
Sulcal vulnerability to tau pathology in Alzheimer's disease (AD)
Prior research suggests the sulci (folds) of the cortex are uniquely affected by age- and AD-related morphological changes and amyloid pathology, but the pattern of vulnerability to tau pathology and its effects on cognition are incompletely understood. A pathological hallmark of another tauopathy, chronic traumatic encephalopathy (CTE), is tau pathology in sulcal depths, but it is unclear to what extent this may be the case in AD as well. In this project we examine whether tau pathology and tau-related cortical thinning in AD also preferentially affect sulcal regions, and whether this vulnerability may be related to connectivity patterns.
Related Publications:
- Maboudian SA, Fonseca CS, Martersteck AC, Chao Y, Chen Y, Ushizima D, Tosun D, Grinberg LT, Weiner KS, Jagust WJ. Tau pathology in Alzheimer's Disease uniquely affects sulcal depths. Annals of Neurology 2026 (In press)
Individual differences in sulcal morphology in aging and Alzheimer's disease (AD)
Recent work, including the above project, suggests that sulci are vulnerable to atrophy and pathology in aging and AD. However, these studies focus only on the largest, deepest, and most consistent sulci across individuals. Tertiary sulci (the smallest, shallowest, latest-developing and most individually-variable indentations) have been associated with the development of human-specific aspects of cognition and with symptoms of diseases such as schizophrenia and frontotemporal dementia, but have not been investigated in normal aging or AD. In this project, we are investigating relationships between individual differences in sulcal morphology (including tertiary sulci) and cognitive changes in aging and AD.
Related Publications:
- Maboudian SA, Willbrand EH, Kelly JP, Jagust WJ, Weiner KS. Defining overlooked structures reveals new associations between cortex and cognition in aging and Alzheimer’s disease. J Neurosci. 2024; 44(16):e1714232024
- Maboudian SA, Willbrand EH, Kellerman GK, Pezzoli S, Weiner KS, Jagust WJ. Variable presence of an evolutionarily new brain structure is associated with successful cognitive aging. (In revision)
Tertiary sulci in evolution and disorder
Traditional neuroanatomy studies have largely overlooked small, shallow, and highly variable folds in the brain. These tertiary sulci are the evolutionarily-newest and latest-developing cortical indentations, and recent work suggests their development is in turn related to the development of various higher-order cognitive functions (e.g., reasoning) and symptoms of neuropsychiatric disorders. This series of projects seeks to improve our understanding of the evolution of these structures and the relationships between their morphology and neuropsychiatric symptoms.
Related Publications:
- Willbrand EH*, Maboudian SA*, Kelly JP, Parker BJ, Foster B, Weiner KS. Sulcal morphology of posteromedial cortex substantially differs between humans and chimpanzees. Commun biol. 2023; 6(1), 586
- Willbrand EH, Maboudian SA, Kellerman GK, Elliott MV, Johnson SL, Weiner KS. Variable presence of an evolutionarily new brain structure is related to trait impulsivity. Biol Psychiatry CNNI. 2026; 11(1):8-16.
- Willbrand EH, Martinez E, Ludwig JJ, Maboudian SA, Weiner KS. Anterior cingulate folding pattern is altered in autism spectrum disorder. Cerebral Cortex 2026 (Accepted)
- Hastings III WL, Willbrand EH,…, Maboudian SA, Parker BJ, Elliott MV, Johnson SL, Weiner KS. Emotion-related impulsivity is related to orbitofrontal cortical sulcation. Cortex 2024;181:140-154.
- Kelly JP, Willbrand EH, Chen X, Maboudian SA, Parker BJ, Jiahui G, Garrido L, Zhen S, Duchaine B, Weiner KS. Overlooked sulci in human posteromedial cortex are related to face processing. (In revision)
- Maboudian SA*, Pracar AL*, Dronkers NF, Weiner KS. Sulcal correlates of language processing and recovery in aphasia. (in prep)
- Toueg TN*, Maboudian SA*, Ovaici N, Jagust WJ, Carhart-Harris R, Weiner KS, Silver M. Individual sulcal variation predicts visual experience alterations with psilocybin in a transdiagnostic sample. (in prep)
Contributions of memory to decision-making impairments in dementia
The decisions we make are often open-ended, relying on options we generate ourselves. Classical decision-making models do not consider this aspect of decision-making, but more recent work seeks to establish an updated framework linking memory retrieval and valuation processes to better reflect real-world decision-making. This project involves applying these updated models to investigating decision-making changes in aging and dementia.
Related Publications:
- Zhang Z, Maboudian SA, Jackson A, Ngo S, Manivannan M, Kayser AS, Hsu M, Chiong W. Mechanistic contributions of memory to decision-making impairments in Alzheimer’s disease. (in prep)
- Kayser A, Zhang Z, Maboudian S, Jackson A, Ngo S, Chiong W, Hsu M. Open-ended, value-based decision making requires semantic memory: a computational, imaging, and clinical study (P1-6.005) [abstract]. Neurology. 2022;98(18 Supplement):534.
- Maboudian S, Hsu M, Zhang Z. Visualizing and Quantifying Longitudinal Changes in Verbal Fluency Using Recurrence Plots. Front. Aging Neurosci. 2022;14:810799.