{"doi":"10.21203/rs.3.rs-28618/v1","title":"Topographic Shifts in Functional Connectivity and Reduced Lateralization in 16p11.2 Deletion Carriers: A Genetics-First Approach to Understanding Autism","abstract":"Abstract Background : The study of autism has been confounded by genetic and etiologic heterogeneity. The current study utilized a genetics-first approach to investigate the underlying neurobiology of autism by studying individuals with copy number variation at 16p11.2. Our aim was to investigate the prevailing theories of brain connectivity in autism – specifically, in regard to (1) distributed brain networks, (2) local and distant connectivity, and (3) functional lateralization. Methods: We analyzed resting-state functional connectivity MRI acquired in 26 carriers of a 16p11.2 deletion and 42 age-matched control participants. We also compared the functional connectivity metrics with measures of language ability, IQ, and social behavior. Results: We do not find widespread disruption of canonical large-scale networks in the deletion carriers. Nor do we find quantitative differences in the degree of local and distant connections. Instead, we discover unique connections in 16p11.2 deletion carriers that are not present in the control participants. Specifically, functional coupling between auditory cortex and regions of the default network is present only in the deletion carriers. In addition to the topographic shifts in functional connectivity, we observe reduced right hemispheric lateralization in the deletion carriers and less left hemispheric lateralization in individuals with poorer language ability. Conclusions : Links or connections between primary sensory areas and higher-order association areas violate fundamental large-scale circuit properties by functionally connecting brain regions specialized in local (hierarchical) processing with those that specialize in distant (parallel) processing. Aberrant hemispheric lateralization and connections between auditory and default networks may underlie difficulties with language and social interactions.","journal":"Research Square (Research Square)","year":2020,"id":128351,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":295789,"name":"Jared A. Nielsen","orcid":"0000-0002-2717-193X","position":1,"is_corresponding":false},{"id":30829,"name":"Jorge Sepulcre","orcid":"0000-0002-4199-2304","position":2,"is_corresponding":false},{"id":482788,"name":"Abid Qureshi","orcid":"0000-0002-1498-6638","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:15:38.879956Z","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":[]}