Linköping University Neuroscience Retreat 2024

Roger Adan

Title: How leptin talks to the dopamine system and its relevance to eating disorders

Highlights

The firing properties of the midbrain dopamine system as well as leptin levels change upon exposure to eating disorder models. We address the gap in knowledge how leptin impacts on the dopamine reward system.  Although leptin receptors are expressed on dopamine neurons, indirect effects appear to be the drivers of altered dopaminergic activity in eating disorders.

Articles

Identification of Novel Neurocircuitry Through Which Leptin Targets Multiple Inputs to the Dopamine System to Reduce Food Reward Seeking.Omrani A, de Vrind VAJ, Lodder B, Stoltenborg I, Kooij K, Wolterink-Donselaar IG, Luijendijk-Berg MCM, Garner KM, Van't Sant LJ, Rozeboom A, Dickson SL, Meye FJ, Adan RAH.Biol Psychiatry. 2021 Dec 15;90(12):843-852. PMID: 33867112. https://pubmed.ncbi.nlm.nih.gov/33867112/

Leptin Receptor Expressing Neurons in the Substantia Nigra Regulate Locomotion, and in The Ventral Tegmental Area Motivation and Feeding. de Vrind VAJ, van 't Sant LJ, Rozeboom A, Luijendijk-Berg MCM, Omrani A, Adan RAH. Front Endocrinol (Lausanne). 2021 Jul 1;12:680494. PMID: 34276560. https://pubmed.ncbi.nlm.nih.gov/34276560/

A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states. Verharen JPH, de Jong JW, Roelofs TJM, Huffels CFM, van Zessen R, Luijendijk MCM, Hamelink R, Willuhn I, den Ouden HEM, van der Plasse G, Adan RAH, Vanderschuren LJMJ.Nat Commun. 2018 Feb 21;9(1):731. PMID: 29467419. https://pubmed.ncbi.nlm.nih.gov/29467419/

Suzanne Dickson

Title: Neural circuit mapping of the brain’s orexigenic systems.

Highlights

• Ghrelin is a gut-brain hormone that targets a distributed neuronal network involved in appetite and feeding behaviours.

• Ghrelin’s effects on food motivated behaviours are exerted not only at the level of the reward system but also the hypothalamus.

• Primary food cues powerfully drive orexigenic behaviours and engage pathways that overlap with ghrelin.

Articles

Stoltenborg I, Peris-Sampedro F, Schéle E, Le May MV, Adan RAH, Dickson SL. TRAPing Ghrelin-Activated Circuits: A Novel Tool to Identify, Target and Control Hormone-Responsive Populations in TRAP2 Mice. Int J Mol Sci. 2022 Jan 5;23(1):559. doi: 10.3390/ijms23010559. PMID: 35008985; PMCID: PMC8745172. https://pubmed.ncbi.nlm.nih.gov/35008985/

Peris-Sampedro F, Stoltenborg I, Le May MV, Sole-Navais P, Adan RAH, Dickson SL. The Orexigenic Force of Olfactory Palatable Food Cues in Rats. Nutrients. 2021 Sep 3;13(9):3101. doi: 10.3390/nu13093101. PMID: 34578979; PMCID: PMC8471864. https://pubmed.ncbi.nlm.nih.gov/34578979/

Schéle E, Cook C, Le May M, Bake T, Luckman SM, Dickson SL. Central administration of ghrelin induces conditioned avoidance in rodents. Eur Neuropsychopharmacol. 2017 Aug;27(8):809-815. doi: 10.1016/j.euroneuro.2017.05.001. Epub 2017 Jun 21. PMID: 28647450; PMCID: PMC5529287. https://pubmed.ncbi.nlm.nih.gov/28647450/

Schéle E, Bake T, Rabasa C, Dickson SL. Centrally Administered Ghrelin Acutely Influences Food Choice in Rodents. PLoS One. 2016 Feb 29;11(2):e0149456. doi: 10.1371/journal.pone.0149456. PMID: 26925974; PMCID: PMC4771210. https://pubmed.ncbi.nlm.nih.gov/26925974/

Skibicka KP, Dickson SL. Ghrelin and food reward: the story of potential underlying substrates. Peptides. 2011 Nov;32(11):2265-73. doi: 10.1016/j.peptides.2011.05.016. Epub 2011 May 19. PMID: 21621573. https://pubmed.ncbi.nlm.nih.gov/21621573/

Linda Engström

Title: The Dorsal Vagal Complex Mediates the Acute Central Effects of the Anti-Obesity Drug Semaglutide

Highlights

• Semaglutide is a long-acting GLP-1 analogue that is highly efficient against overweight and obesity. The effect on body weight loss is mediated by the brain.
• Peripheral administration of semaglutide activates neurons of the dorsal vagal complex (DVC) in the caudal brainstem
• Selective chemogenetic activation of these semaglutide-responsive DVC neurons mimics the effects of the drug on food intake and peripheral metabolism.
• Chemogenetic activation of this specific DVC population largely recapitulates the brain-wide activation pattern after semaglutide, via direct projections to the activated structures
• Removing a select neuronal population in the DVC rescues food intake and body weight loss upon acute semaglutide administration

Articles

Review article on the discovery and pharmacology behind long-acting GLP-1 analogues:
Knudsen LB, Lau J. The Discovery and Development of Liraglutide and Semaglutide. Front Endocrinol (Lausanne). 2019 Apr 12;10:155. doi: 10.3389/fendo.2019.00155. PMID: 31031702; PMCID: PMC6474072. https://pubmed.ncbi.nlm.nih.gov/31031702/

Article showing the selective uptake of semaglutide to certain brain regions, and the brain activation pattern upon semaglutide administration:
Gabery S, Salinas CG, Paulsen SJ, Ahnfelt-Rønne J, Alanentalo T, Baquero AF, Buckley ST, Farkas E, Fekete C, Frederiksen KS, Helms HCC, Jeppesen JF, John LM, Pyke C, Nøhr J, Lu TT, Polex-Wolf J, Prevot V, Raun K, Simonsen L, Sun G, Szilvásy-Szabó A, Willenbrock H, Secher A, Knudsen LB, Hogendorf WFJ. Semaglutide lowers body weight in rodents via distributed neural pathways. JCI Insight. 2020 Mar 26;5(6):e133429. doi: 10.1172/jci.insight.133429. PMID: 32213703; PMCID: PMC7213778. https://pubmed.ncbi.nlm.nih.gov/32213703/

Vincent Prevot

Title: Tanycytes as hypothalamic integrators of energy metabolism

Highlights

An individual's survival relies on the periphery's ability to promptly, effectively, and reproducibly communicate with brain neural networks that control food intake and energy homeostasis. Tanycytes, a specialized glial cell type lining the wall of the third ventricle in the median eminence of the hypothalamus, appear to act as the linchpin of these processes by dynamically controlling blood-brain and blood-cerebrospinal fluid exchanges, both processes that depend on the ability of these cells to adapt their morphology to the physiological state of the individual. In addition to their barrier properties, they possess the ability to sense blood glucose levels and translate this information to neurons, and play a fundamental and active role in shuttling circulating metabolic signals to hypothalamic neurons that control food intake and pancreatic function. Tanycytes could thus constitute the missing link in the loop connecting behavior, hormonal changes, signal transduction, central neuronal activation, and, finally, behavior again. I will discuss these recent advances in understanding tanycytic function in the hypothalamus and the underlying molecular mechanisms. I will also discuss hypothalamic tanycytes' putative involvement and therapeutic potential in metabolic disorders.

Selected articles

Imbernon M, Saponaro C, Helms HCC, Duquenne M, Fernandois D, Deligia E, Denis RGP, Chao DHM, Rasika S, Staels B, Pattou F, Pfrieger FW, Brodin B, Luquet S, Bonner C, Prevot V. Tanycytes control hypothalamic liraglutide uptake and its anti-obesity actions. Cell Metab. 2022 Jul 5;34(7):1054-1063.e7. doi: 10.1016/j.cmet.2022.06.002. Epub 2022 Jun 17. PMID: 35716660; PMCID: PMC7613793. https://pubmed.ncbi.nlm.nih.gov/35716660/

Lhomme T, Clasadonte J, Imbernon M, Fernandois D, Sauve F, Caron E, da Silva Lima N, Heras V, Martinez-Corral I, Mueller-Fielitz H, Rasika S, Schwaninger M, Nogueiras R, Prevot V. Tanycytic networks mediate energy balance by feeding lactate to glucose-insensitive POMC neurons. J Clin Invest. 2021 Sep 15;131(18):e140521. doi: 10.1172/JCI140521. PMID: 34324439; PMCID: PMC8439611. https://pubmed.ncbi.nlm.nih.gov/34324439/

Duquenne M, Folgueira C, Bourouh C, Millet M, Silva A, Clasadonte J, Imbernon M, Fernandois D, Martinez-Corral I, Kusumakshi S, Caron E, Rasika S, Deliglia E, Jouy N, Oishi A, Mazzone M, Trinquet E, Tavernier J, Kim YB, Ory S, Jockers R, Schwaninger M, Boehm U, Nogueiras R, Annicotte JS, Gasman S, Dam J, Prévot V. Leptin brain entry via a tanycytic LepR-EGFR shuttle controls lipid metabolism and pancreas function. Nat Metab. 2021 Aug;3(8):1071-1090. doi: 10.1038/s42255-021-00432-5. Epub 2021 Aug 2. PMID: 34341568; PMCID: PMC7611554. https://pubmed.ncbi.nlm.nih.gov/34341568/

Prevot V, Nogueiras R, Schwaninger M. Tanycytes in the infundibular nucleus and median eminence and their role in the blood-brain barrier. Handb Clin Neurol. 2021;180:253-273. doi: 10.1016/B978-0-12-820107-7.00016-1. PMID: 34225934. https://pubmed.ncbi.nlm.nih.gov/34225934/

Prevot V, Dehouck B, Sharif A, Ciofi P, Giacobini P, Clasadonte J. The Versatile Tanycyte: A Hypothalamic Integrator of Reproduction and Energy Metabolism. Endocr Rev. 2018 Jun 1;39(3):333-368. doi: 10.1210/er.2017-00235. PMID: 29351662. https://pubmed.ncbi.nlm.nih.gov/29351662/ 

Anders Blomqvist

Title: Bud Craig: Life and legacy

Highlights

I will discuss Bud Craig’s redefinition of Sherrington’s concept of interoception to include not only information from the viscera but the sense of the physiological condition of the entire body, including what traditionally have been considered exteroceptive senses like pain and temperature. I will describe Craig’s identification of a primate specific pathway for interoception with its cortical representation in the posterior dorsal fundus of the insula and his idea that its integration and re-representation in the anterior insula is the basis for all subjective feelings.

Articles

Craig AD. A new view of pain as a homeostatic emotion. Trends Neurosci. 2003 Jun;26(6):303-7. doi: 10.1016/s0166-2236(03)00123-1. https://pubmed.ncbi.nlm.nih.gov/12798599/

Craig AD. Interoception: the sense of the physiological condition of the body. Curr Opin Neurobiol. 2003 Aug;13(4):500-5. doi: 10.1016/s0959-4388(03)00090-4. https://pubmed.ncbi.nlm.nih.gov/12965300/

Craig AD. How do you feel--now? The anterior insula and human awareness. Nat Rev Neurosci. 2009 Jan;10(1):59-70. doi: 10.1038/nrn2555. https://pubmed.ncbi.nlm.nih.gov/19096369/

Blomqvist A. Pain and temperature, and human awareness: The legacy of Bud Craig. Temperature (Austin). 2023 Dec 6;10(4):395-401. doi: 10.1080/23328940.2023.2265946. https://pubmed.ncbi.nlm.nih.gov/38130660/

Henry C. Evrard

Title: Functional & Comparative Neuroanatomy of Feelings: from the Body to the Brain, and Back

Highlights

The notion that the physiological condition of the body (interoception) shapes subjective feelings considers the vital homeostasis of the organism as the evolutionary blueprint of the sentient self. A wealth of evidence suggests that the anterior insula has a crucial role in the body-brain interfacing that substantiates subjective feelings. Following the footsteps of Bud Craig’s ascending interoceptive pathway, I will present novel architectonic, connectional, and functional works of the insula. In an updated model, the anterior insula and its von Economo neuron area integrate interoception and simultaneously regulate cortical network dynamics and descending autonomic activities known to accompany the experience of subjective feelings.

Articles

Blomqvist A, Evrard HC, Dostrovsky JO, Strigo IA, Jänig W. A. D. (Bud) Craig, Jr. (1951-2023). Nat Neurosci. 2023 Nov;26(11):1835-1836. doi: 10.1038/s41593-023-01463-9. PMID: 37749257. https://pubmed.ncbi.nlm.nih.gov/37749257/

Krockenberger MS, Saleh-Mattesich TO, Evrard HC. Cytoarchitectonic and connection stripes in the dysgranular insular cortex in the macaque monkey. J Comp Neurol. 2023 Dec;531(18):2019-2043. doi: 10.1002/cne.25571. Epub 2023 Dec 17. PMID: 38105579. https://pubmed.ncbi.nlm.nih.gov/38105579/

Evrard HC. The Organization of the Primate Insular Cortex. Front Neuroanat. 2019 May 8;13:43. doi: 10.3389/fnana.2019.00043. PMID: 31133822; PMCID: PMC6517547. https://pubmed.ncbi.nlm.nih.gov/31133822/

Fabienne Picard

Title: The sentient self : a bridge between ecstatic epilepsy and anterior insula

Highlights

• Ecstatic epilepsy is a rare form of focal epilepsy, in which the beginning of the seizures is similar to a mystical experience.
• Ecstatic epilepsy consists in a sense of physical well-being, a feeling of increased self-awareness (with a sense of unity with the « All ») and a feeling of mental clarity (as if everything seemed to make sense).
• We could demonstrate a major involvement of the anterior insula in the genesis of ecstatic symptoms.
• The deep electrical stimulation of the dorsal anterior insula reproduced the ecstatic auras in several patients with ecstatic epilepsy.
• We hypothesize that an interruption of interoceptive prediction error processing in the anterior insula is at the origin of the ecstatic phenomenon.
• In ecstatic epilepsy, the mimic of a perfect prediction of the physiological state of the body, during the anterior insular discharge, explains the ecstatic quality of the experience.

Articles

Picard F, Craig AD. Ecstatic epileptic seizures: a potential window on the neural basis for human self-awareness. Epilepsy Behav. 2009 Nov;16(3):539-46. doi: 10.1016/j.yebeh.2009.09.013. PMID: 19836310. https://pubmed.ncbi.nlm.nih.gov/19836310/

Picard F, Scavarda D, Bartolomei F. Induction of a sense of bliss by electrical stimulation of the anterior insula. Cortex. 2013 Nov-Dec;49(10):2935-7. doi: 10.1016/j.cortex.2013.08.013. Epub 2013 Sep 3. PMID: 24074887. https://pubmed.ncbi.nlm.nih.gov/24074887/

Picard F. State of belief, subjective certainty and bliss as a product of cortical dysfunction. Cortex. 2013 Oct;49(9):2494-500. doi: 10.1016/j.cortex.2013.01.006. Epub 2013 Jan 23. PMID: 23415878. https://pubmed.ncbi.nlm.nih.gov/23415878/

Gschwind M, Picard F. Ecstatic Epileptic Seizures: A Glimpse into the Multiple Roles of the Insula. Front Behav Neurosci. 2016 Feb 17;10:21. doi: 10.3389/fnbeh.2016.00021. PMID: 26924970; PMCID: PMC4756129. https://pubmed.ncbi.nlm.nih.gov/26924970/

Bartolomei F, Lagarde S, Scavarda D, Carron R, Bénar CG, Picard F. The role of the dorsal anterior insula in ecstatic sensation revealed by direct electrical brain stimulation. Brain Stimul. 2019 Sep-Oct;12(5):1121-1126. doi: 10.1016/j.brs.2019.06.005. Epub 2019 Jun 5. PMID: 31196836. https://pubmed.ncbi.nlm.nih.gov/31196836/

Picard F. Ecstatic or Mystical Experience through Epilepsy. J Cogn Neurosci. 2023 Sep 1;35(9):1372-1381. doi: 10.1162/jocn_a_02031. PMID: 37432752; PMCID: PMC10513764. https://pubmed.ncbi.nlm.nih.gov/37432752/

Marc Wittmann

Title: Insular time: How the body informs us about the passage of time

Highlights

• Subjective experience suggests that the sense of time builds upon our bodily feelings
• Brain imaging studies point to the insular cortex as most important structure for the sense of time
• Cardiac periods slow down during the perception of duration and correlate with time perception accuracy

Articles

Two original articles

Wittmann M, Simmons AN, Aron JL, Paulus MP. Accumulation of neural activity in the posterior insula encodes the passage of time. Neuropsychologia. 2010 Aug;48(10):3110-20. doi: 10.1016/j.neuropsychologia.2010.06.023. Epub 2010 Jun 19. PMID: 20600186; PMCID: PMC2933788. https://www.sciencedirect.com/science/article/abs/pii/S0028393210002629

Meissner K, Wittmann M. Body signals, cardiac awareness, and the perception of time. Biol Psychol. 2011 Mar;86(3):289-97. doi: 10.1016/j.biopsycho.2011.01.001. Epub 2011 Jan 22. PMID: 21262314. https://www.sciencedirect.com/science/article/abs/pii/S0301051111000032

The review article

Wittmann M. The inner sense of time: how the brain creates a representation of duration. Nat Rev Neurosci. 2013 Mar;14(3):217-23. doi: 10.1038/nrn3452. Epub 2013 Feb 13. PMID: 23403747. https://www.nature.com/articles/nrn3452

The latest research (Preprint)

https://www.biorxiv.org/content/10.1101/2023.09.20.558404v1.abstract

Hugo Critchley

Title: Interoception, insula, and autonomic integration relevant to the expression and treatment of psychiatric symptoms.

Highlights

With reference to neural pathways communicating and controlling interoceptive state, a framework for interoception will be considered against data regarding the central representation of physiological (mainly cardiovascular) arousal.  Based on this, contributions of insular mechanisms to the production of motivational, affective, and dissociative symptoms will be examined. Lastly, the harnessing of interoceptive mechanisms in old and new therapies for psychiatry disorders will be reviewed.

Articles

Neural systems supporting interoceptive awareness https://www.nature.com/articles/nn1176

Neural mechanisms of autonomic, affective, and cognitive integration https://onlinelibrary.wiley.com/doi/full/10.1002/cne.20749

Interoceptive cardiac signals selectively enhance fear memories. https://psycnet.apa.org/record/2020-84569-001

Cognition, emotion, and the central autonomic network (review) https://www.sciencedirect.com/science/article/pii/S1566070222000078

Interoceptive training to target anxiety in autistic adults (ADIE): A single-center, superiority randomized controlled trial. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00322-9/fulltext

Claes Wahlestedt

Title: Strategies to optimize expression of individual endogenous genes/proteins in brain

Highlights

Many diseases of the nervous system are caused by insufficient expression of mutated genes and would benefit from increased expression of the corresponding protein. However, in drug development, it has been historically easier to develop drugs with inhibitory or antagonistic effects. Protein replacement and exogenous gene therapy can sometimes achieve the goal of increased protein expression but have limitations. This presentation will highlight emerging RNA-targeted therapeutics for gene amplification, focusing on opportunities and challenges for translation to the clinic. The gene SCN1A, encoding for the brain sodium channel NaV1.1, will be discussed in the context of Dravet syndrome, a severe form of childhood epilepsy.

Articles

1. Khorkova O, Stahl J, Joji A, Volmar CH, Wahlestedt C. Amplifying gene expression with RNA-targeted therapeutics. Nat Rev Drug Discov. 2023 Jul;22(7):539-561. doi: 10.1038/s41573-023-00704-7. Epub 2023 May 30. PMID: 37253858; PMCID: PMC10227815.
2. Modarresi F, Faghihi MA, Lopez-Toledano MA, Fatemi RP, Magistri M, Brothers SP, van der Brug MP, Wahlestedt C. Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation. Nat Biotechnol. 2012 Mar 25;30(5):453-9. doi: 10.1038/nbt.2158. PMID: 22446693; PMCID: PMC4144683.
3. Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M, Nishida H, Yap CC, Suzuki M, Kawai J, Suzuki H, Carninci P, Hayashizaki Y, Wells C, Frith M, Ravasi T, Pang KC, Hallinan J, Mattick J, Hume DA, Lipovich L, Batalov S, Engström PG, Mizuno Y, Faghihi MA, Sandelin A, Chalk AM, Mottagui-Tabar S, Liang Z, Lenhard B, Wahlestedt C. Antisense transcription in the mammalian transcriptome. Science. 2005 Sep 2;309(5740):1564-6. doi: 10.1126/science.1112009. PMID: 16141073.

Stefan Thor

Title: Specification of hypothalamic sleep neurons

• sleep is an essential human behavior
• sleep disturbances are common in a range of human ailments, including narcolepsy
• the specification of sleep neurons is poorly understood
• our work is aimed at decoding the genetic pathways specifying sleep neurons

Articles

From us

Yaghmaeian Salmani B, Balderson B, Bauer S, Ekman H, Starkenberg A, Perlmann T, Piper M, Bodén M, Thor S. Selective requirement for polycomb repressor complex 2 in the generation of specific hypothalamic neuronal subtypes. Development. 2022 Mar 1;149(5):dev200076. doi: 10.1242/dev.200076. Epub 2022 Mar 4. PMID: 35245348; PMCID: PMC8959139. https://pubmed.ncbi.nlm.nih.gov/35245348/

From others

Steuernagel L, Lam BYH, Klemm P, Dowsett GKC, Bauder CA, Tadross JA, Hitschfeld TS, Del Rio Martin A, Chen W, de Solis AJ, Fenselau H, Davidsen P, Cimino I, Kohnke SN, Rimmington D, Coll AP, Beyer A, Yeo GSH, Brüning JC. HypoMap-a unified single-cell gene expression atlas of the murine hypothalamus. Nat Metab. 2022 Oct;4(10):1402-1419. doi: 10.1038/s42255-022-00657-y. Epub 2022 Oct 20. PMID: 36266547; PMCID: PMC9584816. https://pubmed.ncbi.nlm.nih.gov/36266547/

Fredrik Lanner, Karolinska Institutet

Title: Charting early human development using embryo culture and stem cell models

Highlights

Studies of the processes and mechanisms underlying early human embryo development has potential for insights into clinical issues such as early pregnancy loss, origins of congenital anomalies and developmental origins of adult disease, as well as fundamental insights into human biology. Studies of the human embryo is challenging not only to ethical reasons but also due to the scarcity of donated embryos. Stem cell-derived models of human development can potentially overcome these limitations and provide a scalable source of material to explore the early post implantation stages of human development.

In this talk I will present some of the collaborative efforts my team has undertaken to chart early human development from preimplantation to early post-implantation stages. We have uncovered epigenetic mechanisms controlling the first lineage specification, identified that the amnion  act as an important signaling center to initiate gastrulation and finally built a single cell RNA sequencing tool to validate stem cell-based embryo models.

Articles

Zhao C. et al. A Comprehensive Human Embryogenesis Reference Tool using Single-Cell RNA-Sequencing Data. BioRxiv 2024

Oldak B,  et al. Complete human day 14 post-implantation embryo models from naïve ES cells. Nature 2023

Kumar B, et al. Polycomb repressive complex 2 shields naïve human pluripotent cells from trophectoderm differentiation. Nature cell biology 2022 24;6 845-857

Yang R et al. Amnion signals are essential for mesoderm formation in primates. Nature communications 2021 12;1 5126

Posfai E et al. Evaluating totipotency using criteria of increasing stringency. Nature cell biology 2021 23;1 49-60

Rebecca Knickmeyer

Title: "Using global multicohort studies to determine how genetic and environmental factors influence brain development in infancy and early childhood."

Highlights
In this talk, Dr. Knickmeyer, founder and director of the Organization for Imaging Genomics in Infancy (ORIGINs), will describe who will be included in this dataset, what is being measured, and our data analysis plans. She will provide highlights from our first major analysis in which we mapped the trajectory of intracranial volume (ICV), subcortical structures (Thalamus, Hippocampus, Amygdala, Caudate, Putamen and Pallidum) and cognitive development from birth to six years in over 2000 children from four countries (Germany, Singapore, South Africa, and the US), investigated the effect of sex, preterm birth, birthweight, maternal education, and family income on trajectories of ICV and subcortical volumes and on cognitive development, and examined brain-cognition correlations.

Articles
Alex AM, Buss C, Davis EP, Campos GL, Donald KA, Fair DA, Gaab N, Gao W, Gilmore JH, Girault JB, Grewen K, Groenewold NA, Hankin BL, Ipser J, Kapoor S, Kim P, Lin W, Luo S, Norton ES, O'Connor TG, Piven J, Qiu A, Rasmussen JM, Skeide MA, Stein DJ, Styner MA, Thompson PM, Wakschlag L, Knickmeyer R; ENIGMA ORIGINs group. Genetic Influences on the Developing Young Brain and Risk for Neuropsychiatric Disorders. Biol Psychiatry. 2023 May 15;93(10):905-920. doi: 10.1016/j.biopsych.2023.01.013. Epub 2023 Jan 28. PMID: 36932005; PMCID: PMC10136952. https://pubmed.ncbi.nlm.nih.gov/36932005/

Alex AM, Aguate F, Botteron K, Buss C, Chong YS, Dager SR, Donald KA, Entringer S, Fair DA, Fortier MV, Gaab N, Gilmore JH, Girault JB, Graham AM, Groenewold NA, Hazlett H, Lin W, Meaney MJ, Piven J, Qiu A, Rasmussen JM, Roos A, Schultz RT, Skeide MA, Stein DJ, Styner M, Thompson PM, Turesky TK, Wadhwa PD, Zar HJ, Zöllei L, de Los Campos G, Knickmeyer RC; ENIGMA ORIGINs group. A global multicohort study to map subcortical brain development and cognition in infancy and early childhood. Nat Neurosci. 2024 Jan;27(1):176-186. doi: 10.1038/s41593-023-01501-6. Epub 2023 Nov 23. PMID: 37996530; PMCID: PMC10774128. https://pubmed.ncbi.nlm.nih.gov/37996530/

Zhang J, Xia K, Ahn M, Jha SC, Blanchett R, Crowley JJ, Szatkiewicz JP, Zou F, Zhu H, Styner M, Gilmore JH, Knickmeyer RC. Genome-Wide Association Analysis of Neonatal White Matter Microstructure. Cereb Cortex. 2021 Jan 5;31(2):933-948. doi: 10.1093/cercor/bhaa266. PMID: 33009551; PMCID: PMC7786356. https://pubmed.ncbi.nlm.nih.gov/33009551/

Ulrika Ådén

Title: Critical stages in brain development. Lessons learned from children born preterm.

Highlights

Typical brain development involves a sequence of events, such as cell division, migration, differentiation, axonal growth, network formation, and maturation. Genes guide the first steps of brain development and the initial circuit architecture. Once the sensory systems have become responsive to environmental information, experience plays a fundamental role in forming and refining neural circuits. Thus the maturation is dependent on synchronized neural activity and activity-dependent plasticity during critical time windows.

Being born preterm disrupts the typical developmental trajectory of the brain. Preterm born have alterations in gray and white matter growth, structural and functional network organization in neonatal life that persist over childhood. These alterations in development are related to cognitive and behavioral functions and neurodevelopmental disorders.

Articles

Padilla N, Escrichs A, Del Agua E, Kringelbach M, Donaire A, Deco G, Åden U. Disrupted resting-sate brain network dynamics in children born extremely preterm. Cereb Cortex. 2023 Jun 20;33(13):8101-8109. doi: 10.1093/cercor/bhad101. PMID: 37083266; PMCID: PMC10321088. https://pubmed.ncbi.nlm.nih.gov/37083266/

Padilla N, Saenger VM, van Hartevelt TJ, Fernandes HM, Lennartsson F, Andersson JLR, Kringelbach M, Deco G, Åden U. Breakdown of Whole-brain Dynamics in Preterm-born Children. Cereb Cortex. 2020 Mar 14;30(3):1159-1170. doi: 10.1093/cercor/bhz156. PMID: 31504269; PMCID: PMC7132942. https://pubmed.ncbi.nlm.nih.gov/31504269/

Padilla N, Alexandrou G, Blennow M, Lagercrantz H, Ådén U. Brain Growth Gains and Losses in Extremely Preterm Infants at Term. Cereb Cortex. 2015 Jul;25(7):1897-905. doi: 10.1093/cercor/bht431. Epub 2014 Jan 31. PMID: 24488941. https://pubmed.ncbi.nlm.nih.gov/24488941/