{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:16:05Z","timestamp":1787008565071,"version":"build-2736575974"},"reference-count":93,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,1,2]],"date-time":"2021-01-02T00:00:00Z","timestamp":1609545600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Sciences Centre","award":["MC_U120085812"],"award-info":[{"award-number":["MC_U120085812"]}]},{"name":"Department of Health National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme"},{"name":"Medical Research Council Doctoral Training Account"},{"name":"Imperial College London, and subsequently by the Medical Research Council","award":["MR\/N013042\/1"],"award-info":[{"award-number":["MR\/N013042\/1"]}]},{"name":"Wellcome Trust\/Engineering and Physical Sciences Research Council (EPSRC) Centre for Medical Engineering","award":["WT 203148\/Z\/16\/Z"],"award-info":[{"award-number":["WT 203148\/Z\/16\/Z"]}]},{"name":"Engineering and Physical Sciences Research Council Centre for Doctoral Training in Medical Imaging"},{"name":"National Institute of Health Research University College London Hospitals Biomedical Research Centre"},{"name":"United Kingdom Department of Health\u2019s Research Centres funding scheme"},{"name":"Marvin Weil Epilepsy Research Fund and Christelijke Vereniging voor de Verpleging van Lijders aan Epilepsie"},{"name":"United Kingdom Epilepsy Society"},{"name":"Medical Research Council (United Kingdom) Clinician Scientist Fellowship","award":["G108\/585"],"award-info":[{"award-number":["G108\/585"]}]},{"name":"Neurodis Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>GABAA receptors containing the \u03b15 subunit mediate tonic inhibition and are widely expressed in the limbic system. In animals, activation of \u03b15-containing receptors impairs hippocampus-dependent memory. Temporal lobe epilepsy is associated with memory impairments related to neuron loss and other changes. The less selective PET ligand [11C]flumazenil has revealed reductions in GABAA receptors. The hypothesis that \u03b15 subunit receptor alterations are present in temporal lobe epilepsy and could contribute to impaired memory is untested. We compared \u03b15 subunit availability between individuals with temporal lobe epilepsy and normal structural MRI (\u2018MRI-negative\u2019) and healthy controls, and interrogated the relationship between \u03b15 subunit availability and episodic memory performance, in a cross-sectional study. Twenty-three healthy male controls (median \u00b1 interquartile age 49\u2009\u00b1\u200913\u2009years) and 11 individuals with MRI-negative temporal lobe epilepsy (seven males; 40\u2009\u00b1\u20098) had a 90-min PET scan after bolus injection of [11C]Ro15-4513, with arterial blood sampling and metabolite correction. All those with epilepsy and six controls completed the Adult Memory and Information Processing Battery on the scanning day. \u2018Bandpass\u2019 exponential spectral analyses were used to calculate volumes of distribution separately for the fast component [VF; dominated by signal from \u03b11 (\u03b12, \u03b13)-containing receptors] and the slow component (VS; dominated by signal from \u03b15-containing receptors). We made voxel-by-voxel comparisons between: the epilepsy and control groups; each individual case versus the controls. We obtained parametric maps of VF and VS measures from a single bolus injection of [11C]Ro15-4513. The epilepsy group had higher VS in anterior medial and lateral aspects of the temporal lobes, the anterior cingulate gyri, the presumed area tempestas (piriform cortex) and the insulae, in addition to increases of \u223c24% and \u223c26% in the ipsilateral and contralateral hippocampal areas (P\u2009&amp;lt;\u20090.004). This was associated with reduced VF:VS ratios within the same areas (P\u2009&amp;lt;\u20090.009). Comparisons of VS for each individual with epilepsy versus controls did not consistently lateralize the epileptogenic lobe. Memory scores were significantly lower in the epilepsy group than in controls (mean \u00b1 standard deviation \u22120.4\u2009\u00b1\u20091.0 versus 0.7\u2009\u00b1\u20090.3; P\u2009=\u20090.02). In individuals with epilepsy, hippocampal VS did not correlate with memory performance on the Adult Memory and Information Processing Battery. They had reduced VF in the hippocampal area, which was significant ipsilaterally (P\u2009=\u20090.03), as expected from [11C]flumazenil studies. We found increased tonic inhibitory neurotransmission in our cohort of MRI-negative temporal lobe epilepsy who also had co-morbid memory impairments. Our findings are consistent with a subunit shift from \u03b11\/2\/3 to \u03b15 in MRI-negative temporal lobe epilepsy.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaa190","type":"journal-article","created":{"date-parts":[[2021,1,2]],"date-time":"2021-01-02T08:40:11Z","timestamp":1609576811000},"source":"Crossref","is-referenced-by-count":14,"title":["\u0391lpha 5 subunit-containing GABAA receptors in temporal lobe epilepsy with normal MRI"],"prefix":"10.1093","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2692-918X","authenticated-orcid":false,"given":"Colm J","family":"McGinnity","sequence":"first","affiliation":[{"name":"Centre for Neuroscience, Department of Medicine, Imperial College London, London W12 0NN, UK"},{"name":"MRC Clinical Sciences Centre, Hammersmith Hospital, London W12 0NN, UK"},{"name":"King's College London & Guy's and St Thomas' PET Centre, School of Biomedical Engineering & Imaging Sciences, King\u2019s College London, London SE1 7EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela A","family":"Ria\u00f1o Barros","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience, Department of Medicine, Imperial College London, London W12 0NN, UK"},{"name":"MRC Clinical Sciences Centre, Hammersmith Hospital, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7808-9207","authenticated-orcid":false,"given":"Rainer","family":"Hinz","sequence":"additional","affiliation":[{"name":"Wolfson Molecular Imaging Centre, University of Manchester, Manchester M20 3LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F","family":"Myers","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience, Department of Medicine, Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siti N","family":"Yaakub","sequence":"additional","affiliation":[{"name":"King's College London & Guy's and St Thomas' PET Centre, School of Biomedical Engineering & Imaging Sciences, King\u2019s College London, London SE1 7EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Thyssen","sequence":"additional","affiliation":[{"name":"Medical Image and Signal Processing (MEDISIP), Department of Electronics and Information Systems, Faculty of Engineering and Architecture, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf A","family":"Heckemann","sequence":"additional","affiliation":[{"name":"Department of Medical Radiation Sciences, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"de Tisi","sequence":"additional","affiliation":[{"name":"NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK, and Chalfont Centre for Epilepsy, Chalfont St Peter SL9 0RJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S","family":"Duncan","sequence":"additional","affiliation":[{"name":"NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK, and Chalfont Centre for Epilepsy, Chalfont St Peter SL9 0RJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josemir W","family":"Sander","sequence":"additional","affiliation":[{"name":"NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK, and Chalfont Centre for Epilepsy, Chalfont St Peter SL9 0RJ, UK"},{"name":"Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede 2103SW, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Lingford-Hughes","sequence":"additional","affiliation":[{"name":"Neuropsychopharmacology Unit, Centre for Psychiatry, Department of Brain Sciences, Faculty of Medicine, Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias J","family":"Koepp","sequence":"additional","affiliation":[{"name":"NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK, and Chalfont Centre for Epilepsy, Chalfont St Peter SL9 0RJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Hammers","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience, Department of Medicine, Imperial College London, London W12 0NN, UK"},{"name":"MRC Clinical Sciences Centre, Hammersmith Hospital, London W12 0NN, UK"},{"name":"King's College London & 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