{"doi":"10.1162/imag_a_00462","title":"Dedifferentiation of caudate functional organization is linked to reduced D1 dopamine receptor availability and poorer memory function in aging","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Age-related alterations in cortico-striatal function have been highlighted as an important determinant of declines in flexible, higher-order, cognition in older age. However, the mechanisms underlying such alterations remain poorly understood. Computational accounts propose age-related dopaminergic decreases to impoverish neural gain control, possibly contributing to reduced specificity of cortico-striatal circuits, that are modulated by dopamine, in older age. Using multi-modal neuroimaging data (fMRI, PET) from a large lifespan cohort (n = 180), we assessed the relationship between dopamine D1-like receptors (D1DRs) and cortico-striatal function during rest and an n-back working memory task. The results revealed gradual age-related decreases in the specificity of functional coupling between the centrolateral caudate and cortical association networks during both rest and working memory, which, in turn, was associated with poorer short- and long-term memory performance with older age. Critically, reduced D1DR availability in the caudate and the prefrontal cortex predicted less differentiated caudate-cortical coupling across the lifespan, in part accounting for the age-related declines observed on this metric. These findings provide novel empirical evidence for a key role of dopamine in maintaining functional specialization of cortico-striatal circuits as individuals age, bridging with computational models of deficient catecholaminergic neuromodulation underpinning age-related dedifferentiation of brain function.</jats:p>","journal":"Imaging Neuroscience","year":2025,"id":609303,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1566011,"name":"Jarkko Johansson","orcid":null,"position":1,"is_corresponding":false},{"id":1566012,"name":"Kristin Nordin","orcid":null,"position":2,"is_corresponding":false},{"id":1566013,"name":"Robin Pedersen","orcid":null,"position":3,"is_corresponding":false},{"id":1525991,"name":"Lars Bäckman","orcid":null,"position":4,"is_corresponding":false},{"id":272831,"name":"Anna Rieckmann","orcid":null,"position":5,"is_corresponding":false},{"id":1525996,"name":"Alireza Salami","orcid":null,"position":6,"is_corresponding":false},{"id":1566010,"name":"Saana M. Korkki","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Dedifferentiation of caudate functional organization is linked to reduced D1 dopamine receptor availability and poorer memory function in aging","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Age-related alterations in cortico-striatal function have been highlighted as an important determinant of declines in flexible, higher-order, cognition in older age. However, the mechanisms underlying such alterations remain poorly understood. Computational accounts propose age-related dopaminergic decreases to impoverish neural gain control, possibly contributing to reduced specificity of cortico-striatal circuits, that are modulated by dopamine, in older age. Using multi-modal neuroimaging data (fMRI, PET) from a large lifespan cohort (n = 180), we assessed the relationship between dopamine D1-like receptors (D1DRs) and cortico-striatal function during rest and an n-back working memory task. The results revealed gradual age-related decreases in the specificity of functional coupling between the centrolateral caudate and cortical association networks during both rest and working memory, which, in turn, was associated with poorer short- and long-term memory performance with older age. Critically, reduced D1DR availability in the caudate and the prefrontal cortex predicted less differentiated caudate-cortical coupling across the lifespan, in part accounting for the age-related declines observed on this metric. These findings provide novel empirical evidence for a key role of dopamine in maintaining functional specialization of cortico-striatal circuits as individuals age, bridging with computational models of deficient catecholaminergic neuromodulation underpinning age-related dedifferentiation of brain function.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40800906","pmcid":"PMC12319749","openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://direct.mit.edu/imag/article-pdf/doi/10.1162/imag_a_00462/2497804/imag_a_00462.pdf","host_type":"publisher"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12319749/pdf/imag-3-00462.pdf","host_type":"repository"},{"url":"http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-239215","host_type":"repository"},{"url":"https://osf.io/t9nkm","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12319749","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12319749?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":[],"mesh_terms":[],"keywords":["Aging","Memory","Dopamine","Striatum","Functional Connectivity","Neural Dedifferentiation"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-31T05:47:09.652723Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}