title: Anything goes? Regulation of the neural processes underlying response inhibition in TBI patients.
abstract: Despite evidence for beneficial use of methylphenidate in response inhibition, no studies so far have investigated the effects of this drug in the neurobiology of inhibitory control in traumatic brain injury (TBI), even though impulsive behaviours are frequently reported in this patient group. We investigated the neural basis of response inhibition in a group of TBI patients using functional magnetic resonance imaging and a stop-signal paradigm. In a randomised double-blinded crossover study, the patients received either a single 30mg dose of methylphenidate or placebo and performed the stop-signal task. Activation in the right inferior frontal gyrus (RIFG), an area associated with response inhibition, was significantly lower in patients compared to healthy controls. Poor response inhibition in this group was associated with greater connectivity between the RIFG and a set of regions considered to be part of the default mode network (DMN), a finding that suggests the interplay between DMN and frontal executive networks maybe compromised. A single dose of methylphenidate rendered activity and connectivity profiles of the patients RIFG near normal. The results of this study indicate that the neural circuitry involved in response inhibition in TBI patients may be partially restored with methylphenidate. Given the known mechanisms of action of methylphenidate, the effect we observed may be due to increased dopamine and noradrenaline levels.
authors.affiliation: Division of Anaesthesia, University of Cambridge, Addenbrooke׳s Hospital, Box 93, Hills Road, Cambridge CB2 0QQ, UK. Electronic address: lm618@cam.ac.uk.
authors.forename: Laura
authors.initials: L
authors.lastname: Moreno-López
authors.affiliation: Division of Anaesthesia, University of Cambridge, Addenbrooke׳s Hospital, Box 93, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Manktelow
authors.affiliation: Department of Psychiatry, University of Cambridge, Herchel Smith Building for Brain and Mind Sciences, Forvie Site, Robinson Way, Cambridge CB2 0SZ, UK; MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Sahakian
authors.affiliation: Division of Anaesthesia, University of Cambridge, Addenbrooke׳s Hospital, Box 93, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: David K
authors.initials: DK
authors.lastname: Menon
authors.affiliation: Division of Anaesthesia, University of Cambridge, Addenbrooke׳s Hospital, Box 93, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Stamatakis
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D000070642:Brain Injuries, Traumatic / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D001931:Brain Mapping; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D056344:Executive Function / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate
keywords: Functional connectivity; Methylphenidate; Response inhibition; Traumatic brain injury