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154. Correlated gene expression supports synchronous activity in brain networks

Author

IMAGEN consortium, Richiardi, Jonas, Altmann, Andre, Milazzo, Anna-Clare, Chang, Catie, Chakravarty, M. Mallar, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Conrod, Patricia, Fauth-Bühler, Mira, Flor, Herta, Frouin, Vincent, Gallinat, Jürgen, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Lemaître, Hervé, Mann, Karl F., Martinot, Jean-Luc, Nees, Frauke, Paus, Tomáš, Pausova, Zdenka, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Spanagel, Rainer, Ströhle, Andreas, Schumann, Gunter, Hawrylycz, Mike, Poline, Jean-Baptiste, and Greicius, Michael D.

Published
2015

155. Safety Signals as Instrumental Reinforcers during Free-Operant Avoidance

Author

Fernando, Anushka B. P., Urcelay, Gonzalo P., Mar, Adam C., Dickinson, Anthony, and Robbins, Trevor W.

Abstract

Safety signals provide "relief" through predicting the absence of an aversive event. At issue is whether these signals also act as instrumental reinforcers. Four experiments were conducted using a free-operant lever-press avoidance paradigm in which each press avoided shock and was followed by the presentation of a 5-sec auditory safety signal. When given a choice between two levers in Experiment 1, both avoiding shock, rats preferentially responded on the lever that produced the safety signal as feedback, even when footshock was omitted. Following avoidance training with a single lever in Experiment 2, removal of the signal led to a decrease in avoidance responses and an increase in responses during the safety period normally denoted by the signal. These behavioral changes demonstrate the dual conditioned reinforcing and fear inhibiting properties of the safety signal. The associative processes that support the reinforcing properties of a safety signal were tested using a novel revaluation procedure. Prior experience of systemic morphine during safety signal presentations resulted in an increased rate of avoidance responses to produce the safety signal during a drug-free extinction test, a finding not seen with d-amphetamine in Experiment 3. Morphine revaluation of the safety signal was repeated in Experiment 4 followed by a drug-free extinction test in which responses did not produce the signal for the first 10 min of the session. Instrumental avoidance in the absence of the signal was shown to be insensitive to prior signal revaluation, suggesting that the signal reinforces free-operant avoidance behavior through a habit-like mechanism.

Published
2014
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157. Structural Imaging in OCD

Author

Veltman, D. J., Fineberg, Naomi A., Robbins, Trevor W., Fineberg, Naomi A., Robbins, Trevor W., Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Brain Imaging, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep

Subjects
medicine.diagnostic_test, business.industry, Thalamus, Ventral striatum, Posterior parietal cortex, Hippocampus, Magnetic resonance imaging, behavioral disciplines and activities, 030227 psychiatry, White matter, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, mental disorders, medicine, Orbitofrontal cortex, business, Neuroscience, 030217 neurology & neurosurgery, Diffusion MRI
Abstract

Anatomical imaging in OCD using magnetic resonance imaging (MRI) has been performed since the late 1980s. MRI research was further stimulated with the advent of automated image processing techniques such as voxel-based morphometry (VBM) and surface-based methods (e.g., FreeSurfer) which allow for detailed whole-brain data analyses. Early studies suggesting involvement of corticostriatal circuitry (particularly orbitofrontal cortex and ventral striatum) have been complemented by meta-analyses and pooled analyses indicating additional involvement of posterior brain regions, in particular parietal cortex. Recent large-scale meta-analyses from the ENIGMA consortium have revealed greater pallidum and smaller hippocampus volume in adult OCD, coupled with parietal cortical thinning. Frontal cortical thinning was only observed in medicated patients. Previous reports of symptom dimension-specific alterations were not confirmed. In paediatric OCD, thalamus enlargement has been a consistent finding. Studies investigating white matter volume (VBM) or integrity (using diffusion tensor imaging (DTI)) have shown mixed results, with recent DTI meta-analyses mainly showing involvement of posterior cortical-subcortical tracts in addition to subcortical-prefrontal connections. To which extent these abnormalities are unique to OCD or common to other psychiatric disorders is unclear, as few comparative studies have been performed. Overall, neuroanatomical alterations in OCD appear to be subtle and may vary with time, stressing the need for adequately powered longitudinal studies. Although multivariate approaches using machine learning methodologies have so far been disappointing in distinguishing individual OCD patients from healthy controls, including multimodal data in such analyses may aid in further establishing a neurobiological profile of OCD.

Published
2021

165. Neurobehavioral precursors of compulsive cocaine-seeking in dual fronto-striatal circuits

Author

Jones, Jolyon A., primary, Belin-Rauscent, Aude, additional, Jupp, Bianca, additional, Fouyssac, Maxime, additional, Sawiak, Stephen J., additional, Zuhlsdorff, Katharina, additional, Zhukovsky, Peter, additional, Hebdon, Lara, additional, Sanchez, Clara Velazquez, additional, Robbins, Trevor W., additional, Everitt, Barry J., additional, Belin, David, additional, and Dalley, Jeffrey W., additional

Published
2022
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166. Multi-omics study reveals associations among neurotransmitter, extracellular vesicle-derived microRNA and psychiatric comorbidities during heroin and methamphetamine withdrawal

Author

Chen, Fengrong, primary, Xu, Yu, additional, Shi, Kai, additional, Zhang, Zunyue, additional, Xie, Zhenrong, additional, Wu, Hongjin, additional, Ma, Yuru, additional, Zhou, Yong, additional, Chen, Cheng, additional, Yang, Jiqing, additional, Wang, Yuan, additional, Robbins, Trevor W., additional, Wang, Kunhua, additional, and Yu, Juehua, additional

Published
2022
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167. Selective D3 receptor antagonism modulates neural response during negative emotional processing in substance dependence

Author

Vamvakopoulou, Ioanna A., primary, Fonville, Leon, additional, Hayes, Alexandra, additional, McGonigle, John, additional, Elliott, Rebecca, additional, Ersche, Karen D., additional, Flechais, Remy, additional, Orban, Csaba, additional, Murphy, Anna, additional, Smith, Dana G., additional, Suckling, John, additional, Taylor, Eleanor M., additional, Deakin, Bill, additional, Robbins, Trevor W., additional, Nutt, David J., additional, Lingford-Hughes, Anne R., additional, and Paterson, Louise M., additional

Published
2022
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172. Stratified medicine for mental disorders

Author

Schumann, Gunter, Binder, Elisabeth B., Holte, Arne, de Kloet, E. Ronald, Oedegaard, Ketil J., Robbins, Trevor W., Walker-Tilley, Tom R., Bitter, Istvan, Brown, Verity J., Buitelaar, Jan, Ciccocioppo, Roberto, Cools, Roshan, Escera, Carles, Fleischhacker, Wolfgang, Flor, Herta, Frith, Chris D., Heinz, Andreas, Johnsen, Erik, Kirschbaum, Clemens, Klingberg, Torkel, Lesch, Klaus-Peter, Lewis, Shon, Maier, Wolfgang, Mann, Karl, Martinot, Jean-Luc, Meyer-Lindenberg, Andreas, Müller, Christian P., Müller, Walter E., Nutt, David J., Persico, Antonio, Perugi, Giulio, Pessiglione, Mathias, Preuss, Ulrich W., Roiser, Jonathan P., Rossini, Paolo M., Rybakowski, Janusz K., Sandi, Carmen, Stephan, Klaas E., Undurraga, Juan, Vieta, Eduard, van der Wee, Nic, Wykes, Til, Haro, Josep Maria, and Wittchen, Hans Ulrich

Published
2014
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176. Naltrexone ameliorates functional network abnormalities in alcohol‐dependent individuals

Author

Morris, Laurel S., Baek, Kwangyeol, Tait, Roger, Elliott, Rebecca, Ersche, Karen D., Flechais, Remy, McGonigle, John, Murphy, Anna, Nestor, Liam J., Orban, Csaba, Passetti, Filippo, Paterson, Louise M., Rabiner, Ilan, Reed, Laurence, Smith, Dana, Suckling, John, Taylor, Eleanor M., Bullmore, Edward T., Lingford‐Hughes, Anne R., Deakin, Bill, Nutt, David J., Sahakian, Barbara J., Robbins, Trevor W., and Voon, Valerie

Published
2018
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179. Locus Coeruleus Integrity from 7 T MRI Relates to Apathy and Cognition in Parkinsonian Disorders

Author

Ye, Rong, O'Callaghan, Claire, Rua, Catarina, Hezemans, Frank H, Holland, Negin, Malpetti, Maura, Jones, P Simon, Barker, Roger A, Williams-Gray, Caroline H, Robbins, Trevor W, Passamonti, Luca, Rowe, James, Ye, Rong [0000-0003-2529-7755], O'Callaghan, Claire [0000-0001-5698-6364], Rua, Catarina [0000-0002-0404-4399], Malpetti, Maura [0000-0001-8923-9656], Williams-Gray, Caroline H [0000-0002-2648-9743], Passamonti, Luca [0000-0002-7937-0615], Rowe, James [0000-0001-7216-8679], and Apollo - University of Cambridge Repository

Subjects
cognition, Parkinsonian Disorders, locus coeruleus, magnetization-transfer imaging, Parkinson's disease, Apathy, noradrenaline, Humans, Parkinson Disease, Supranuclear Palsy, Progressive, 7 T magnetic resonance imaging, progressive supranuclear palsy, Magnetic Resonance Imaging
Abstract

BACKGROUND: Neurodegeneration in the locus coeruleus (LC) contributes to neuropsychiatric symptoms in both Parkinson's disease (PD) and progressive supranuclear palsy (PSP). Spatial precision of LC imaging is improved with ultrahigh field 7 T magnetic resonance imaging. OBJECTIVES: This study aimed to characterize the spatial patterns of LC pathological change in PD and PSP and the transdiagnostic relationship between LC signals and neuropsychiatric symptoms. METHODS: Twenty-five people with idiopathic PD, 14 people with probable PSP-Richardson's syndrome, and 24 age-matched healthy controls were recruited. Participants underwent clinical assessments and high-resolution (0.08 mm3 ) 7 T-magnetization-transfer imaging to measure LC integrity in vivo. Spatial patterns of LC change were obtained using subregional mean contrast ratios and significant LC clusters; we further correlated the LC contrast with measures of apathy and cognition, using both mixed-effect models and voxelwise analyses. RESULTS: PSP and PD groups showed significant LC degeneration in the caudal subregion relative to controls. Mixed-effect models revealed a significant interaction between disease-group and apathy-related correlations with LC degeneration (β = 0.46, SE [standard error] = 0.17, F(1, 35) = 7.46, P = 0.01), driven by a strong correlation in PSP (β = -0.58, SE = 0.21, t(35) = -2.76, P = 0.009). Across both disease groups, voxelwise analyses indicated that lower LC integrity was associated with worse cognition and higher apathy scores. CONCLUSIONS: The relationship between LC and nonmotor symptoms highlights a role for noradrenergic dysfunction across both PD and PSP, confirming the potential for noradrenergic therapeutic strategies to address transdiagnostic cognitive and behavioral features in neurodegenerative disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Published
2022

184. Impulsivity in abstinent alcohol and polydrug dependence: a multidimensional approach

Author

Taylor, Eleanor M., Murphy, Anna, Boyapati, Venkat, Ersche, Karen D., Flechais, Remy, Kuchibatla, Shankar, McGonigle, John, Metastasio, Anotonio, Nestor, Liam, Orban, Csaba, Passetti, Fillippo, Paterson, Louise, Smith, Dana, Suckling, John, Tait, Roger, Lingford-Hughes, Anne R., Robbins, Trevor W., Nutt, David J., Deakin, JF William, Elliott, Rebecca, and ICCAM Platform

Published
2016
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187. What is next for the neurobiology of temperament, personality and psychopathology?

Author

Trofimova, Irina, primary, Bajaj, Sahil, additional, Bashkatov, Sergey A, additional, Blair, James, additional, Brandt, Anika, additional, Chan, Raymond C K, additional, Clemens, Benjamin, additional, Corr, Philip J, additional, Cyniak-Cieciura, Maria, additional, Demidova, Liubov, additional, Filippi, Courtney A, additional, Garipova, Margarita, additional, Habel, Ute, additional, Haines, Nathaniel, additional, Heym, Nadja, additional, Hunter, Kirsty, additional, Jones, Nancy A, additional, Kanen, Jonathan, additional, Kirenskaya, Anna, additional, Kumari, Veena, additional, Lenzoni, Sabrina, additional, Lui, Simon S Y, additional, Mathur, Avantika, additional, McNaughton, Neil, additional, Mize, Krystal D, additional, Mueller, Erik, additional, Netter, Petra, additional, Paul, Katharina, additional, Plieger, Thomas, additional, Premkumar, Preethi, additional, Raine, Adrian, additional, Reuter, Martin, additional, Robbins, Trevor W, additional, Samylkin, Denis, additional, Storozheva, Zinaida, additional, Sulis, William, additional, Sumich, Alexander, additional, Tkachenko, Andrey, additional, Valadez, Emilio A, additional, Wacker, Jan, additional, Wagels, Lisa, additional, Wang, Ling-ling, additional, Zawadzki, Bogdan, additional, and Pickering, Alan D, additional

Published
2022
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194. A randomized trial directly comparing ventral capsule and anteromedial subthalamic nucleus stimulation in obsessive-compulsive disorder : Clinical and imaging evidence for dissociable effects

Author

Tyagi, Himanshu, Apergis-Schoute, Annemieke M., Akram, Harith, Foltynie, Tom, Limousin, Patricia, Drummond, Lynne M., Fineberg, Naomi A., Matthews, Keith, Jahanshahi, Marjan, Robbins, Trevor W., Sahakian, Barbara J., Zrinzo, Ludvic, Hariz, Marwan, Joyce, Eileen M., Tyagi, Himanshu, Apergis-Schoute, Annemieke M., Akram, Harith, Foltynie, Tom, Limousin, Patricia, Drummond, Lynne M., Fineberg, Naomi A., Matthews, Keith, Jahanshahi, Marjan, Robbins, Trevor W., Sahakian, Barbara J., Zrinzo, Ludvic, Hariz, Marwan, and Joyce, Eileen M.

Abstract

Background: Deep brain stimulation (DBS) is an emerging treatment for severe obsessive-compulsive disorder (OCD). We compared the efficacy of ventral capsule/ventral striatal (VC/VS) and anteromedial subthalamic nucleus (amSTN) DBS in the same patients and tested for mechanistic differences on mood and cognitive flexibility and associated neural circuitry. The possible synergistic benefit of DBS at both sites and cognitive behavioral therapy was explored. Methods: Six patients with treatment-refractory OCD (5 men; Yale-Brown Obsessive Compulsive Scale score >32) entered double-blind counterbalanced phases of 12-week amSTN or VC/VS DBS, followed by 12-week open phases when amSTN and VC/VS were stimulated together, in which optimal stimulation parameters were achieved and adjunctive inpatient cognitive behavioral therapy was delivered. OCD and mood were assessed with standardized scales and cognitive flexibility with the Cambridge Neuropsychological Test Automated Battery Intra-Extra Dimensional Set-Shift task. Diffusion-weighted and intraoperative magnetic resonance imaging scans were performed for tractography from optimally activated electrode contacts. Results: DBS at each site significantly and equivalently reduced OCD symptoms with little additional gain following combined stimulation. amSTN but not VC/VS DBS significantly improved cognitive flexibility, whereas VC/VS DBS had a greater effect on mood. The VC/VS effective site was within the VC. VC DBS connected primarily to the medial orbitofrontal cortex, and amSTN DBS to the lateral orbitofrontal cortex, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex. No further improvement followed cognitive behavioral therapy, reflecting a floor effect of DBS on OCD. Conclusions: Both the VC/VS and amSTN are effective targets for severe treatment-refractory OCD. Differential improvements in mood and cognitive flexibility and their associated connectivity suggest that DBS at these sites modulates dist, Appeared originally in Biological Psychiatry 2019; 85:726-734. Reprinted under Creative Commons CC-BY license.Reprint from: Himanshu Tyagi, Annemieke M. Apergis-Schoute et al., "A Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder: Clinical and Imaging Evidence for Dissociable Effects", Biiological Psychiatry, 2019:85, 726-734, DOI: 10.1016/j.biopsych.2019.01.017

Published
2022
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195. Heritability of specific cognitive functions and associations with schizophrenia spectrum disorders using CANTAB:a nation-wide twin study

Author

Lemvigh, Cecilie K., Brouwer, Rachel M, Pantelis, Christos, Jensen, Maria H., Hilker, Rikke W., Legind, Christian S., Anhøj, Simon J., Robbins, Trevor W, Sahakian, Barbara J, Glenthøj, Birte Y., Fagerlund, Birgitte, Lemvigh, Cecilie K., Brouwer, Rachel M, Pantelis, Christos, Jensen, Maria H., Hilker, Rikke W., Legind, Christian S., Anhøj, Simon J., Robbins, Trevor W, Sahakian, Barbara J, Glenthøj, Birte Y., and Fagerlund, Birgitte

Abstract

BACKGROUND: Many cognitive functions are under strong genetic control and twin studies have demonstrated genetic overlap between some aspects of cognition and schizophrenia. How the genetic relationship between specific cognitive functions and schizophrenia is influenced by IQ is currently unknown.METHODS: We applied selected tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) to examine the heritability of specific cognitive functions and associations with schizophrenia liability. Verbal and performance IQ were estimated using The Wechsler Adult Intelligence Scale-III and the Danish Adult Reading Test. In total, 214 twins including monozygotic (MZ = 32) and dizygotic (DZ = 22) pairs concordant or discordant for a schizophrenia spectrum disorder, and healthy control pairs (MZ = 29, DZ = 20) were recruited through the Danish national registers. Additionally, eight twins from affected pairs participated without their sibling.RESULTS: Significant heritability was observed for planning/spatial span (h2 = 25%), self-ordered spatial working memory (h2 = 64%), sustained attention (h2 = 56%), and movement time (h2 = 47%), whereas only unique environmental factors contributed to set-shifting, reflection impulsivity, and thinking time. Schizophrenia liability was associated with planning/spatial span (rph = -0.34), self-ordered spatial working memory (rph = -0.24), sustained attention (rph = -0.23), and set-shifting (rph = -0.21). The association with planning/spatial span was not driven by either performance or verbal IQ. The remaining associations were shared with performance, but not verbal IQ.CONCLUSIONS: This study provides further evidence that some cognitive functions are heritable and associated with schizophrenia, suggesting a partially shared genetic etiology. These functions may constitute endophenotypes for the disorder and provide a basis to explore genes common to cognition and schizophrenia.

Published
2022

196. Heritability of specific cognitive functions and associations with schizophrenia spectrum disorders using CANTAB: a nation-wide twin study

Author

Onderzoeksgroep 1, Brain, Lemvigh, Cecilie K, Brouwer, Rachel M, Pantelis, Christos, Jensen, Maria H, Hilker, Rikke W, Legind, Christian S, Anhøj, Simon J, Robbins, Trevor W, Sahakian, Barbara J, Glenthøj, Birte Y, Fagerlund, Birgitte, Onderzoeksgroep 1, Brain, Lemvigh, Cecilie K, Brouwer, Rachel M, Pantelis, Christos, Jensen, Maria H, Hilker, Rikke W, Legind, Christian S, Anhøj, Simon J, Robbins, Trevor W, Sahakian, Barbara J, Glenthøj, Birte Y, and Fagerlund, Birgitte

Published
2022

197. Acute naltrexone does not remediate fronto‐striatal disturbances in alcoholic and alcoholic polysubstance‐dependent populations during a monetary incentive delay task

Author

Nestor, Liam J, Murphy, Anna, McGonigle, John, Orban, Csaba, Reed, Laurence, Taylor, Eleanor, Flechais, Remy, Paterson, Louise M, Smith, Dana, Bullmore, Edward T, Ersche, Karen D, Suckling, John, Tait, Roger, Elliott, Rebecca, Deakin, Bill, Rabiner, Ilan, Lingford‐Hughes, Anne, Nutt, David J, Sahakian, Barbara, and Robbins, Trevor W

Published
2017
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