brain sciences The Multi-Dimensional Contributions of Prefrontal Circuits to Emotion Regulation during Adulthood and Critical Stages of Development Edited by Angela Roberts Printed Edition of the Special Issue Published in Brain Sciences www.mdpi.com/journal/brainsci The Multi-Dimensional Contributions of Prefrontal Circuits to Emotion Regulation during Adulthood and Critical Stages of Development The Multi-Dimensional Contributions of Prefrontal Circuits to Emotion Regulation during Adulthood and Critical Stages of Development Special Issue Editor Angela Roberts MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade Special Issue Editor Angela Roberts University of Cambridge UK Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Actuators (ISSN 2076-0825) from 2018 to 2019 (available at: https://www.mdpi.com/journal/brainsci/special issues/Neuro Emotion). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Article Number, Page Range. ISBN 978-3-03921-702-1 (Pbk) ISBN 978-3-03921-703-8 (PDF) c 2019 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Special Issue Editor ...................................... vii Preface to ”The Multi-Dimensional Contributions of Prefrontal Circuits to Emotion Regulation during Adulthood and Critical Stages of Development” ................ ix Laith Alexander, Hannah F. Clarke and Angela C. Roberts A Focus on the Functions of Area 25 Reprinted from: Brain Sci. 2019, 9, 129, doi:10.3390/brainsci9060129 ................. 1 Stephanie Roughley and Simon Killcross Loss of Hierarchical Control by Occasion Setters Following Lesions of the Prelimbic and Infralimbic Medial Prefrontal Cortex in Rats Reprinted from: Brain Sci. 2019, 9, 48, doi:10.3390/brainsci9030048 .................. 34 Dibyadeep Datta and Amy F.T. Arnsten Loss of Prefrontal Cortical Higher Cognition with Uncontrollable Stress: Molecular Mechanisms, Changes with Age, and Relevance to Treatment Reprinted from: Brain Sci. 2019, 9, 113, doi:10.3390/brainsci9050113 ................. 50 Camilla L Nord, Alan Gray, Oliver J Robinson and Jonathan P Roiser Reliability of Fronto–Amygdala Coupling during Emotional Face Processing Reprinted from: Brain Sci. 2019, 9, 89, doi:10.3390/brainsci9040089 .................. 66 Monique Ernst, Joshua L. Gowin, Claudie Gaillard, Ryan T. Philips and Christian Grillon Sketching the Power of Machine Learning to Decrypt a Neural Systems Model of Behavior Reprinted from: Brain Sci. 2019, 9, 67, doi:10.3390/brainsci9030067 .................. 78 Linnea Wilder, Kari L. Hanson, Caroline H. Lew, Ursula Bellugi and Katerina Semendeferi Decreased Neuron Density and Increased Glia Density in the Ventromedial Prefrontal Cortex (Brodmann Area 25) in Williams Syndrome Reprinted from: Brain Sci. 2018, 8, 209, doi:10.3390/brainsci8120209 ................. 95 Siyabend Kaya and Ciara McCabe What Role Does the Prefrontal Cortex Play in the Processing of Negative and Positive Stimuli in Adolescent Depression? Reprinted from: Brain Sci. 2019, 9, 104, doi:10.3390/brainsci9050104 .................108 Katherine S. Young, Christina F. Sandman and Michelle G. Craske Positive and Negative Emotion Regulation in Adolescence: Links to Anxiety and Depression Reprinted from: Brain Sci. 2019, 9, 76, doi:10.3390/brainsci9040076 ..................117 Kelsey S. Zimmermann, Rick Richardson and Kathryn D. Baker Maturational Changes in Prefrontal and Amygdala Circuits in Adolescence: Implications for Understanding Fear Inhibition during a Vulnerable Period of Development Reprinted from: Brain Sci. 2019, 9, 65, doi:10.3390/brainsci9030065 ..................137 Pieter Schipper, Paola Brivio, David de Leest, Leonie Madder, Beenish Asrar, Federica Rebuglio, Michel M. M. Verheij, Tamas Kozicz, Marco A. Riva, Francesca Calabrese, Marloes J. A. G. Henckens and Judith R. Homberg Impaired Fear Extinction Recall in Serotonin Transporter Knockout Rats Is Transiently Alleviated during Adolescence Reprinted from: Brain Sci. 2019, 9, 118, doi:10.3390/brainsci9050118 .................157 v About the Special Issue Editor Angela Roberts received her degree in Neurobiology from the University of Sussex and her PhD in neuroendocrine control of reproduction from the University of Cambridge under the supervision of Joe Herbert in the Department of Anatomy. She stayed on in Cambridge and did her postdoctoral training in the Department of Experimental Psychology with Trevor Robbins where she held a Royal Society Research Fellowship from 1992–96. She then took up a teaching appointment in the Department of Anatomy and there began her studies on the prefrontal control of emotion regulation. Currently she undertakes the scientific leadership of the marmoset research centre at Cambridge and is Chair of the steering committee for a new Laboratory of Translational Neuroimaging. She also sits on the Executive committee of Cambridge Neuroscience. She is currently an associate editor for Frontiers in Behavioral Neuroscience, a field Editor for the International Journal of Neuropsychopharmacology and sits on the council of the British Association of Psychopharmacology. In 2016 she was elected to the Fellowship of the Academy of Medical Sciences. vii Prefaceto”TheMulti-DimensionalContributions ofPrefrontalCircuitstoEmotionRegulationduring Adulthoodand Critical Stages ofDevelopment” The Multidimensional Contributions of Prefrontal Circuits to Emotion Regulation during AdulthoodandCriticalStagesofDevelopment. The prefrontal cortex (PFC) and neighbouring anterior cingulate cortex play a pivotal role in regulating our emotions, as shown by the marked alterations in activity within prefrontal and cingulate circuits that accompany mood and anxiety disorders. These regions are functionally diverse. Thus, a critical step towards better stratification of the symptoms of mood and anxiety disorders and more effective individualised treatment strategies is to define their unique contributionstotheregulationofpositiveandnegativeemotions. Since many disorders of emotion have their onset during childhood and adolescence, it is also important to extend our understanding of these prefrontal circuits to the developing brain. This Special Issue brings together the most recent research in humans and other animals that addresses these important questions. Alterations in activity and structural morphology in specific prefrontalcircuitsidentifiedinadultandadolescentclinicalpopulationsareinvestigatedinrodents and monkeys to determine their causal contribution to emotion and cognitive dysregulation. The importance of stress and altered neurodevelopmental trajectories, highlighted as important factorsleadingtosymptomsofanxietyanddepressioninclinicalstudies,isexploredatthesystem, cellular, andmolecularlevelsofprefrontalcircuitsinanimals. Togetherthesepapersillustratethe importanceofthecross-speciestranslationofprefrontalfunctiontoinformourunderstandingofthe psychologicalandphysiologicalmechanismsunderlyingaffectivedisorders. The first set of papers consider the adult prefrontal cortex. The functions of area 25 in humansandmonkeysanditsputativehomologue,theinfralimbiccortexinrodents,arereviewedin Alexanderandcolleaguesalongwiththeirrelevancetoourunderstandingofanxietyandanhedonia. One particular cognitive function, occasion setting, is explored in rats by Roughley and Killcross, specifically focussing on the role of the infralimbic and prelimbic cortices. The role of stress in inducingdysregulationwithintheprefrontalcortexisthendiscussedbyDattaandArnsten,drawing upondatafromhumans, monkeysandratstoprovideadescriptionofthemolecularmechanisms thatmaymediatesucheffectsandtheensuinglossofhierarchicalcontrol. Tocompletethissection, theprospectsofusingfunctionalmagneticresonanceimagingtodiscoverbiomarkersthatwillpredict an individual’s risk of developing a psychiatric disorder are considered by Nord and colleagues, focussing on fronto-amygdala connectivity. Turning to adolescence, Ernst and colleagues discuss the use of machine learning to test models of brain–behaviour interactions during development. Threepapersthendescribealteredprefrontalfunction,thefirstinrelationtotheneurodevelopmental disorderWilliamssyndrome,involvingreductionsingreymatterwithinarea25associatedwiththe symptoms of anxiety and hypersociability (Wilder and colleagues). A second reviews the altered intrinsicandextrinsicconnectivityoftheprefrontalcortexinrelationtopositiveandnegativeemotion inadolescentssufferingfromdepression(KayaandMcCabe).Theontogenyofstrategiestoeffectively regulateemotionisdiscussedbyYoungandcolleaguesfrombehavioural,psychophysiologicaland neural perspectives considering how their dysregulation may underlie symptoms of anxiety and ix depression in adolescents. The final two papers by Zimmerman and Schipper and their colleagues provide insights into the neurodevelopmental time-course underlying the regulation of threat in rodents focussing on prefrontal–amygdala