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Brain Regions Involved in Object-Location Memory Across the Human Lifespan: A Systematic Review and Activation Likelihood Estimation Meta-Analysis of Task-Based fMRI

Fromm, A.; Abdelmotaleb, M.; Olschewski, F.; Limanowski, J.; Meinzer, M.; Flöel, A.; Antonenko, D.

2026-07-06 neuroscience
10.64898/2026.07.01.735849 bioRxiv
Show abstract

Background: The ability to remember object locations in real life is a fundamental cognitive process that supports goal-directed behavior and is particularly vulnerable to aging and neurodegenerative disease. Despite a growing body of functional magnetic resonance imaging (fMRI) research on object-location memory (OLM), the neural substrates of establishing and retrieving location information are largely unknown. Objective: This systematic review and coordinate-based meta-analysis aimed to identify brain regions consistently activated during OLM in healthy adults, primarily for encoding and - on an exploratory basis - for retrieval, and to characterize age-related differences in OLM-related neural activity. Methods: A systematic search was conducted across three databases (PubMed, PsycInfo, Cochrane Library) up to February 2026. Studies employing task-based fMRI during the encoding and retrieval of object-location associations in healthy adults were eligible. Age-related differences in OLM-related brain activity were examined via narrative synthesis. An activation likelihood estimation (ALE) meta-analysis was performed on studies reporting stereotactic peak coordinates. The review was pre-registered on PROSPERO (CRD420251023695). Results: Twenty-one studies comprising 637 participants were included in the systematic review, with 12 studies being eligible for the encoding ALE meta-analysis. The retrieval ALE meta-analysis was not possible due to the limited number of included studies and reported foci. The systematic review indicated that OLM encoding consistently recruited bilateral fusiform gyri and parahippocampal cortices, with additional engagement of parietal and prefrontal regions across individual studies, whereas OLM retrieval recruited mainly the hippocampus and precuneus. The coordinate-based ALE meta-analysis revealed two significant clusters of activation during OLM encoding: a left-lateralized cluster encompassing the fusiform gyrus, parahippocampal gyrus, and inferior temporal gyrus (peak MNI: -28, -38, -16), and a right-hemisphere cluster spanning the parahippocampal gyrus and fusiform gyrus (peak MNI: 30, -46, -16). Age-related differences, based on a small number of studies with direct age comparison, pointed toward reduced activity in posterior cortical regions coupled with increased activity in prefrontal and midline regions. Additionally, younger adults showed greater hippocampal activation for successful than unsuccessful spatial retrieval, whereas older adults showed the opposite pattern. Conclusion: The systematic review and meta-analysis identify the fusiform gyri and parahippocampal cortices as the most reliably activated regions during OLM encoding, locating OLM formation primarily within the ventral visual-to-medial-temporal processing stream. Retrieval additionally engaged the hippocampus and precuneus, consistent with their established roles in episodic memory. Age-related differences included reduced posterior cortical encoding activity in older adults, a reversal of the hippocampal activation pattern during retrieval, and weaker suppression of midline regions during task performance. The identified encoding pathway may inform targeted network-level interventions such as non-invasive brain stimulation to counteract cognitive decline in aging and neurodegenerative disease.

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