title: Road work on memory lane--functional and structural alterations to the learning and memory circuit in adults born very preterm.
abstract: Very preterm (VPT) birth is considered a risk factor not only for neurological impairment, but also for reduced function in several cognitive domains in childhood and later in life. Individuals who were born VPT are more likely to demonstrate learning and memory difficulties compared to term-born controls. These problems contribute to more VPT-born children repeating grades and underachieving in school. This, in turn, affects their prospects in adult life. Here we aimed to 1) study how the VPT-born adult brain functionally recruited specific areas during learning, i.e. encoding and recall across four repeated blocks of verbal stimuli, and to investigate how these patterns of activation differed from term-born subjects; and 2) probe the microstructural differences of white-matter tracts connecting these areas to other parts of the learning and memory network. To investigate these functional-structural relationships we analyzed functional and diffusion-weighted MRI. Functional-MRI and a verbal paired associate learning (VPAL) task were used to extract Blood Oxygenation Level Dependent (BOLD) activity in 21 VPT-born adults (<33 weeks of gestation) (mean age: 19.68 years ± 0.85; IQ: 99.86 ± 11.20) and 10 term-born controls (mean age: 19.87 years ± 2.04; IQ: 108.9 ± 13.18). Areas in which differences in functional activation were observed between groups were used as seed regions for tractography. Fractional anisotropy (FA) of the tract-skeleton was then compared between groups on a voxel-wise basis. Results of functional MRI analysis showed a significantly different pattern of activation between groups during encoding in right anterior cingulate-caudate body, and during retrieval in left thalamus, hippocampus and parts of left posterior parahippocampal gyrus. The number of correctly recalled word pairs did not statistically differ between individuals who were born VPT and controls. The VPT-born group was found to have reduced FA in tracts passing through the thalamic/hippocampal region that was differently activated during the recall condition, with the hippocampal fornix, inferior longitudinal fasciculus and inferior fronto-occipital fasciculus particularly affected. Young adults who were born very preterm display a strikingly different pattern of activation during the process of learning in key structures of the learning and memory network, including anterior cingulate and caudate body during encoding and thalamus/parahippocampal gyrus during cued recall. Altered activation in thalamus/parahippocampal gyrus may be explained by reduced connections between these areas and the hippocampus, which may be a direct consequence of neonatal hypoxic/ischemic injury. These results could reflect the effect of adaptive plastic processes associated with high-order cognitive functions, at least when the cognitive load remains relatively low, as ex-preterm young adults displayed unimpaired performance in completing the verbal paired associate learning task.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, De Crespigny Park, London SE5 8AF, UK. Electronic address: piergiorgio.salvan@kcl.ac.uk.
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Salvan
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, De Crespigny Park, London SE5 8AF, UK. Electronic address: sean.1.froudist_walsh@kcl.ac.uk.
authors.forename: Seán
authors.initials: S
authors.lastname: Froudist Walsh
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, De Crespigny Park, London SE5 8AF, UK. Electronic address: matthew.allin@kcl.ac.uk.
authors.forename: Matthew P G
authors.initials: MP
authors.lastname: Allin
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, De Crespigny Park, London SE5 8AF, UK. Electronic address: muriel.m.walshe@kcl.ac.uk.
authors.forename: Muriel
authors.initials: M
authors.lastname: Walshe
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, De Crespigny Park, London SE5 8AF, UK. Electronic address: robin.murray@kcl.ac.uk.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, De Crespigny Park, London SE5 8AF, UK. Electronic address: sagnik.2.bhattacharyya@kcl.ac.uk.
authors.forename: Sagnik
authors.initials: S
authors.lastname: Bhattacharyya
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, De Crespigny Park, London SE5 8AF, UK. Electronic address: philip.p.mcguire@kcl.ac.uk.
authors.forename: Philip K
authors.initials: PK
authors.lastname: McGuire
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's Health Partners, King's College London, De Crespigny Park, London SE5 8AF, UK. Electronic address: steve.williams@kcl.ac.uk.
authors.forename: Steven C R
authors.initials: SC
authors.lastname: Williams
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, De Crespigny Park, London SE5 8AF, UK. Electronic address: chiara.nosarti@kcl.ac.uk.
authors.forename: Chiara
authors.initials: C
authors.lastname: Nosarti
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology*; D005260:Female; D006801:Humans; D062071:Infant, Extremely Premature; D007858:Learning / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology; D009415:Nerve Net / Q000033:anatomy & histology* / Q000502:physiology*; D012737:Sex Factors; D055815:Young Adult
keywords: DTI; Fornix; Hippocampus; Preterm; Thalamus; fMRI