title: Fronto-striatal organization: Defining functional and microstructural substrates of behavioural flexibility.
abstract: Discrete yet overlapping frontal-striatal circuits mediate broadly dissociable cognitive and behavioural processes. Using a recently developed multi-echo resting-state functional MRI (magnetic resonance imaging) sequence with greatly enhanced signal compared to noise ratios, we map frontal cortical functional projections to the striatum and striatal projections through the direct and indirect basal ganglia circuit. We demonstrate distinct limbic (ventromedial prefrontal regions, ventral striatum - VS, ventral tegmental area - VTA), motor (supplementary motor areas - SMAs, putamen, substantia nigra) and cognitive (lateral prefrontal and caudate) functional connectivity. We confirm the functional nature of the cortico-striatal connections, demonstrating correlates of well-established goal-directed behaviour (involving medial orbitofrontal cortex - mOFC and VS), probabilistic reversal learning (lateral orbitofrontal cortex - lOFC and VS) and attentional shifting (dorsolateral prefrontal cortex - dlPFC and VS) while assessing habitual model-free (SMA and putamen) behaviours on an exploratory basis. We further use neurite orientation dispersion and density imaging (NODDI) to show that more goal-directed model-based learning (MBc) is also associated with higher mOFC neurite density and habitual model-free learning (MFc) implicates neurite complexity in the putamen. This data highlights similarities between a computational account of MFc and conventional measures of habit learning. We highlight the intrinsic functional and structural architecture of parallel systems of behavioural control.
authors.affiliation: Department of Psychology, University of Cambridge, Cambridge, United Kingdom; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Laurel S
authors.initials: LS
authors.lastname: Morris
authors.affiliation: Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Section on Functional Imaging Methods, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: Prantik
authors.initials: P
authors.lastname: Kundu
authors.affiliation: Department of Psychiatry, Brighton and Sussex Medical School, Brighton, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Dowell
authors.affiliation: Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Daisy J
authors.initials: DJ
authors.lastname: Mechelmans
authors.affiliation: Laboratory of Psychology and Neurocognition, University Grenoble Alpes, Grenoble, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Favre
authors.affiliation: Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Irvine
authors.affiliation: Department of Psychology, University of Cambridge, Cambridge, United Kingdom; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.affiliation: Center for Neural Science and Department of Psychology, New York University, New York, NY, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Daw
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom; Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom; NIHR Cambridge Biomedical Research Centre, Cambridge, United Kingdom.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Bullmore
authors.affiliation: Department of Psychiatry, Brighton and Sussex Medical School, Brighton, United Kingdom.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Harrison
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom; Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom; NIHR Cambridge Biomedical Research Centre, Cambridge, United Kingdom. Electronic address: vv247@cam.ac.uk.
authors.forename: Valerie
authors.initials: V
authors.lastname: Voon
mesh_terms: D000328:Adult; D001288:Attention / Q000502:physiology*; D003342:Corpus Striatum / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000502:physiology*; D006040:Goals; D006801:Humans; D008032:Limbic System / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D009483:Neuropsychological Tests; D012193:Reversal Learning / Q000502:physiology*; D055815:Young Adult
keywords: Fronto-striatal loops; Goal-directed; Habit; Microstructure; Neurite density