{"doi":"10.1093/braincomms/fcab093","title":"Motor cortex modulation and reward in children with attention-deficit/hyperactivity disorder","abstract":"Attention-deficit/hyperactivity disorder, the most prevalent developmental disorder in childhood, is a biologically heterogenous condition characterized by impaired attention and impulse control as well as motoric hyperactivity and anomalous motor skill development. Neuropsychological testing often demonstrates impairments in motivation and reward-related decision making in attention-deficit/hyperactivity disorder, believed to indicate dysfunction of the dopamine reward pathway. Development of reliable, non-invasive, easily obtained and quantitative biomarkers correlating with the presence and severity of clinical symptoms and impaired domains of function could aid in identifying meaningful attention-deficit/hyperactivity disorder subgroups and targeting appropriate treatments. To this end, 55 (37 male) 8-12-year-old children with attention-deficit/hyperactivity disorder and 50 (32 male) age-matched, typically-developing controls were enrolled in a transcranial magnetic stimulation protocol-used previously to quantify cortical disinhibition in both attention-deficit/hyperactivity disorder and Parkinson's Disease-with a child-friendly reward motivation task. The primary outcomes were reward task-induced changes in short interval cortical inhibition and up-modulation of motor evoked potential amplitudes, evaluated using mixed model, repeated measure regression. Our results show that both reward cues and reward receipt reduce short-interval cortical inhibition, and that baseline differences by diagnosis (less inhibition in attention-deficit/hyperactivity disorder) were no longer present when reward was cued or received. Similarly, both reward cues and reward receipt up-modulated motor evoked potential amplitudes, but, differentiating the two groups, this Task-Related-Up-Modulation was decreased in children with attention-deficit/hyperactivity disorder. Furthermore, more severe hyperactive/impulsive symptoms correlated significantly with less up-modulation with success in obtaining reward. These results suggest that in children with attention-deficit/hyperactivity disorder, short interval cortical inhibition may reflect baseline deficiencies as well as processes that normalize performance under rewarded conditions. Task-Related-Up-Modulation may reflect general hypo-responsiveness in attention-deficit/hyperactivity disorder to both reward cue and, especially in more hyperactive/impulsive children, to successful reward receipt. These findings support transcranial magnetic stimulation evoked cortical inhibition and task-induced excitability as biomarkers of clinically relevant domains of dysfunction in childhood attention-deficit/hyperactivity disorder.","journal":"Brain Communications","year":2021,"id":189947,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":412451,"name":"Caroline F. Zink","orcid":null,"position":1,"is_corresponding":false},{"id":416394,"name":"Keri S. Rosch","orcid":"0000-0002-1923-2552","position":2,"is_corresponding":false},{"id":379425,"name":"Paul S. Horn","orcid":"0000-0002-4990-5754","position":3,"is_corresponding":false},{"id":683971,"name":"David A. Huddleston","orcid":"0000-0001-5950-2062","position":4,"is_corresponding":false},{"id":677292,"name":"Deana Crocetti","orcid":"0000-0001-8311-4107","position":5,"is_corresponding":false},{"id":713013,"name":"Steve W. Wu","orcid":"0000-0001-5102-174X","position":6,"is_corresponding":false},{"id":419703,"name":"Ernest V. Pedapati","orcid":"0000-0002-7954-5104","position":7,"is_corresponding":false},{"id":106063,"name":"Eric M. Wassermann","orcid":"0000-0003-0628-0210","position":8,"is_corresponding":false},{"id":393251,"name":"Stewart H. Mostofsky","orcid":"0000-0002-8515-2411","position":9,"is_corresponding":false},{"id":106044,"name":"Donald L. Gilbert","orcid":"0000-0002-9245-6878","position":10,"is_corresponding":false},{"id":754066,"name":"Jordan A Detrick","orcid":null,"position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-18T23:49:22.671571Z","pmid":"34041478","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":[]}