{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T03:45:29Z","timestamp":1783395929869,"version":"3.54.6"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T00:00:00Z","timestamp":1703635200000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Antonio Meneghetti Award 2019","award":["610134-EPP-1-2019-1-JO-EPPKA2-CBHE-JP"],"award-info":[{"award-number":["610134-EPP-1-2019-1-JO-EPPKA2-CBHE-JP"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motor inhibitory control, a core component of cognitive control, is impaired in Parkinson\u2019s disease, dramatically impacting patients\u2019 abilities to implement goal-oriented adaptive strategies. A progressive loss of the midbrain\u2019s dopamine neurons characterizes Parkinson\u2019s disease and causes motor features responsive to dopaminergic treatments. Although such treatments restore motor symptoms, their impact on response inhibition is controversial. Most studies failed to show any effect of dopaminergic medicaments, although three studies found that these drugs selectively improved inhibitory control in early-stage patients. Importantly, all previous studies assessed only one domain of motor inhibition, i.e. reactive inhibition (the ability to react to a stop signal). The other domain, i.e. proactive inhibition (the ability to modulate reactive inhibition pre-emptively according to the current context), was utterly neglected. To re-examine this issue, we recruited cognitively unimpaired Parkinson\u2019s patients under dopaminergic treatment in the early (Hoehn and Yahr, 1\u20131.5, n = 20), intermediate (Hoehn and Yahr 2, n = 20), and moderate\/advanced (Hoehn and Yahr, 2.5\u20133, n = 20) stages of the disease. Using a cross-sectional study design, we compared their performance on a simple reaction-time task and a stop-signal task randomly performed twice on dopaminergic medication (ON) and after medication withdrawal (OFF). Normative data were collected on 30 healthy controls. Results suggest that medication effects are stage-dependent. In Hoehn and Yahr 1\u20131.5 patients, drugs selectively impair reactive inhibition, leaving proactive inhibition unaffected. In the ON state, Hoehn and Yahr two patients experienced impaired proactive inhibition, whereas reactive inhibition is no longer affected, as it deteriorates even during the OFF state. By contrast, Hoehn and Yahr 2.5\u20133 patients exhibited less efficient reactive and proactive inhibition in the OFF state, and medication slightly improved proactive inhibition. This evidence aligns with the dopamine overdose hypothesis, indicating that drug administration may overdose intact dopamine circuitry in the earliest stages, impairing associated cognitive functions. In later stages, the progressive degeneration of dopaminergic neurons prevents the overdose and can exert some beneficial effects. Thus, our findings suggest that inhibitory control assessment might help tailor pharmacological therapy across the disease stage to enhance Parkinson\u2019s disease patients\u2019 quality of life by minimizing the hampering of inhibitory control and maximizing the reduction of motor symptoms.<\/jats:p>","DOI":"10.1093\/braincomms\/fcad350","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T03:47:58Z","timestamp":1703130478000},"source":"Crossref","is-referenced-by-count":13,"title":["Effects of dopaminergic treatment on inhibitory control differ across Hoehn and Yahr stages of Parkinson\u2019s disease"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4405-2609","authenticated-orcid":false,"given":"Giovanni","family":"Mirabella","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Sciences, University of Brescia , 25123 Brescia, BS , Italy"},{"name":"IRCCS Neuromed , 86077 Pozzilli, IS 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