English  |  正體中文  |  简体中文  |  Post-Print筆數 : 11 |  Items with full text/Total items : 88613/118155 (75%)
Visitors : 23471933      Online Users : 202
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
  • Adv. Search
    HomeLoginUploadHelpAboutAdminister Goto mobile version
    Please use this identifier to cite or link to this item: http://nccur.lib.nccu.edu.tw/handle/140.119/124198

    Title: 鼠腦前額葉皮質在風險選擇行為扮演的角色
    The role of rat prefrontal cortex in risk-dependent choice
    Authors: 楊依樺
    Yang, Yi-Hua
    Contributors: 廖瑞銘
    Liao, Ruey-Ming
    Yang, Yi-Hua
    Keywords: 前額葉皮質次級區域
    Prefrontal cortex subareas
    Pre-training lesion
    Peward-guided choice
    Decisions making under uncertainty
    Date: 2019
    Issue Date: 2019-07-01 10:59:58 (UTC+8)
    Abstract: 在決策相關的研究中,前額葉皮質一直被認為是負責處理不確定情境下決策的重要腦區。但是,前額葉的次級區域在風險選擇中的具體角色,卻仍難以捉摸。有鑑於此,本研究透過破壞大白鼠的旁側眼眶前額葉皮質,以及內側前額葉皮質,探討破壞腦區的效果對受試風險選擇行為的影響。本研究採用T迷津風險選擇作業。在此作業中,受試針對兩個選項進行選擇,分別是酬賞量小而確定會獲取的選項,以及相對的酬賞量大而不確定的選項。這項作業包含三種不同比率的酬賞,因特別設定兩個選項的期望值相等於1,其分別代表高中低三種不同程度的風險。本實驗採用受試者間實驗設計,在行為測試之前,大白鼠被隨機分派至不同的實驗組,分別是旁側眼眶前額葉皮質破壞組、內側前額葉皮質破壞組,以及控制組。上述各組大白鼠會再被隨機分派至三個不同程度的風險組別中進行行為測試。結果顯示不同風險程度的控制組大白鼠,習得不同的風險選擇模式。在低風險情境下,受試傾向風險選擇;在高風險情境下,受試傾向規避風險;而在中等風險情境下,受試表現出介於傾向風險和規避風險之間的選擇模式。破壞旁側眼眶前額葉皮質顯著的干擾了受試的風險選擇行為,使受試增加風險選擇。相反的,破壞內側前額葉皮質,並未改變受試在任何一種風險情境下的選擇行為。藉由其它三種行為測試證明,破壞旁側眼眶前額葉皮質造成的行為改變,並非因受試運動功能受損、出現類焦慮反應,或無法區辨酬賞數量大小所致。綜合以上結果,旁側眼眶前額葉皮質和內側前額葉皮質參與風險選擇具有異質性功能。本研究更進一步證實,在以酬賞大小和出現機率操弄的特定風險程度之下,旁側眼眶前額葉皮質對風險選擇行為的習得扮演重要角色。
    Prefrontal cortex (PFC) is suggested to be important in decision making under uncertainty, but the specific contribution of PFC subregions to risk-based decision making remains elusive. This study thus evaluated the lesion effects of lateral orbitofrontal cortex (lOFC) and medial PFC (mPFC) on risk choice behavior. A rat T-maze risk choice task was used where the subject would choose enter either a small and certain reward arm of the maze or a large but uncertain reward arm of the maze. This task was specifically set up to run with the expected value being equal (i.e., EV = 1) between the binary choice options which tests were carried out with three reward ratios representing different levels of risk, correspondingly notated as high, medium, and low. The rats were randomly assigned by following between-subject design in receiving excitotoxic lesion of lOFC or mPFC and sham controls prior to behavioral tests given by three reward ratios. For the results, the sham control rats acquired dissociable patterns of risk choice as depended on different risk levels; that is, risk-prone and risk-averse patterns respectively appeared in low-risk and high-risk conditions, whereas an intermediate choice style was shown in the medium-risk condition. The lOFC lesion significantly interfered with the risk choice behavior by shifting the choice toward a risk-prone style. In contrast, the mPFC lesion did not alter choice behavior given in any of three risk levels. The behavioral alterations in rats with lOFC lesion were not the result of motor deficit, anxiety-like response, or incapability to discriminate reward magnitudes from a large to a small one. Together, these findings highlight differential involvements of lOFC and mPFC in risk decision making and further suggest that the lOFC contributes to the acquisition of risk-dependent choice behavior given at a particular level of risk based on reward magnitude and probability.
    Reference: Abela AR, Chudasama Y (2013) Dissociable contributions of the ventral hippocampus and orbitofrontal cortex to decision-making with a delayed or uncertain outcome. Eur J Neurosci 37:640-647.
    Balci F, Freestone D, Gallistel CR (2009) Risk assessment in man and mouse. Proc Natl Acad Sci USA 106:2459-2463.
    Bari A, Theobald DE, Caprioli D, Mar AC, Aidoo-Micah A, Dalley JW, Robbins TW (2010) Serotonin modulates sensitivity to reward and negative feedback in a probabilistic reversal learning task in rats. Neuropsychopharmacology 35:1290-1301.
    Barrus MM, Hosking JG, Cocker PJ, Winstanley CA (2017) Inactivation of the orbitofrontal cortex reduces irrational choice on a rodent betting Task. Neuroscience 345:38-48.
    Bechara A, Damasio H, Tranel D, Anderson SW (1998) Dissociation of working memory from decision making within the human prefrontal cortex. J Neurosci 18:428-437.
    Bell AH, Bultitude JH (2018) Methods matter: A primer on permanent and reversible interference techniques in animals for investigators of human neuropsychology. Neuropsychologia 115:211-219.
    Burke CJ, Brünger C, Kahnt T, Park SQ, Tobler PN (2013) Neural integration of risk and effort costs by the frontal pole: only upon request. J Neurosci 33:1706-1713.
    Cardinal RN, Howes NJ (2005) Effects of lesions of the nucleus accumbens core on choice between small certain rewards and large uncertain rewards in rats. BMC Neurosci 6:37.
    Cardinal RN (2006) Neural systems implicated in delayed and probabilistic reinforcement. Neural Net 19:1277-1301.
    Castane A, Theobald DEH, Robbins TW (2010) Selective lesions of the dorsomedial striatum impair serial spatial reversal learning in rats. Behav Brain Res 210:74-83.
    Charpentier CJ, Aylward J, Roiser JP, Robinson OJ (2017) Enhanced risk aversion, but not loss aversion, in unmedicated pathological anxiety. Biol Psychiatry 81:1014-1022.
    Chau BKH, Sallet J, Papageorgiou GK, Noonan MP, Bell AH, Walton ME, Rushworth MFS (2015) Contrasting roles for orbitofrontal cortex and amygdala in credit assignment and learning in macaques. Neuron 87:1106-1118.
    Cocker PJ, Dinelle K, Kornelson R, Sossi V, Winstanley CA (2012) Irrational choice under uncertainty correlates with lower striatal D2/3 receptor binding in rats. J Neurosci 32:15450-15457.
    Dalley JW, Cardinal RN, Robbins TW (2004) Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates. Neurosci Biobehav Rev 28:771-784.
    Dalton GL, Phillips AG, Floresco SB (2014) Preferential involvement by nucleus accumbens shell in mediating probabilistic learning and reversal shifts. J Neurosci 34:4618-1626.
    Dalton GL, Wang NY, Phillips AG, Floresco SB (2016) Multifaceted contributions by different regions of the orbitofrontal and medial prefrontal cortex to probabilistic reversal learning. J Neurosci 36:1996-2006.
    Davidson RJ (2002). Anxiety and affective style: role of prefrontal cortex and amygdala. Biol Psychiatry 51:68-80.
    De Visser L, Baars A, van't Klooster J, van den Bos R (2011) Transient inactivation of the medial prefrontal cortex affects both anxiety and decision-making in male wistar rats. Front Neurosci 5:102.
    De Visser L, Van der Knaap LJ, Van de Loo AJAE, Van der Weerd CMM, Ohl F, Van Den Bos R (2010) Trait anxiety affects decision-making differently in healthy men and women: towards gender-specific endophenotypes of anxiety. Neuropsychologia 48:1598-1606.
    Déziel RA, Tasker RA (2018) Bilateral ischaemic lesions of the medial prefrontal cortex are anxiogenic in the rat. Acta Neuropsychiatr 30:181-186.
    Dixon ML, Christoff K (2014) The lateral prefrontal cortex and complex value-based learning and decision making. Neurosci Biobehav Rev 45:9-18.
    Domenech P, Koechlin E (2015) Executive control and decision-making in the prefrontal cortex. Curr Opin Behav Sci 1:101-106.
    Euston DR, Gruber AJ, McNaughton BL (2012) The role of medial prefrontal cortex in memory and decision making. Neuron 76:1057-1070.
    Fellows LK (2016) The Neuroscience of human decision-making through the lens of learning and memory. In Behavioral neuroscience of learning and memory, pp 231-251. Springer, Cham.
    Floresco SB, Onge JRS, Ghods-Sharifi S, Winstanley CA (2008) Cortico-limbic-striatal circuits subserving different forms of cost-benefit decision making. Cogn Affect Behav Neurosci 8:375-389.
    Funahashi S (2017) Prefrontal contribution to decision-making under free-choice conditions. Front Neurosci 11:431.
    Fuster JM (1997) The prefrontal cortex: anatomy, physiology, and neuropsychology of the frontal lobe, New York: Raven Press.
    Fuster JM (2015) The prefrontal cortex. Academic Press.
    Goldman-Rakic PS (1987) Circuitry of primate prefrontal cortex and regulation of behavior by representational memory. Handbook of physiology 5:373-417.
    Gourley SL, Lee AS, Howell JL, Pittenger C, Taylor JR (2010) Dissociable regulation of instrumental action within mouse prefrontal cortex. Eur J Neurosci 32:1726-1734.
    Granon S, Vidal C, Thinus-Blanc C, Changeux JP, Poucet B (1994) Working memory, response selection, and effortful processing in rats with medial prefrontal lesions. Behav Neurosci 108:883-891.
    Gray JA, McNaughton N (1996) The neuropsychology of anxiety: Reprise. InNebraska symposium on motivation pp 61-134. University of Nebraska Press.
    Green L, Myerson J (2004) A discounting framework for choice with delayed and probabilistic rewards. Psychol Bull 130:769-792.
    Hartley CA, Phelps EA (2012) Anxiety and decision-making. Biol Psychiatry 72:113-118.
    Handley SL, McBlane JW (1993) 5HT drugs in animal models of anxiety. Psychopharmacology, 112:13-20.
    Hiser J, Koenigs M (2018) The multifaceted role of the ventromedial prefrontal cortex in emotion, decision making, social cognition, and psychopathology. Biol Psychiatry 83:638-647.
    Ishii H, Ohara S, Tobler PN, Tsutsui K, Iijima T (2012) Inactivating anterior insular cortex reduces risk taking. J Neurosci 32:16031-16039.
    Izquierdo A (2017) Functional heterogeneity within rat orbitofrontal cortex in reward learning and decision making. J Neurosci 37:10529-10540.
    Jinks AL, McGregor IS (1997) Modulation of anxiety-related behaviours following lesions of the prelimbic or infralimbic cortex in the rat. Brain Res 772:181-190.
    Johansen-Berg H, Rushworth MF (2009) Using diffusion imaging to study human connectional anatomy. Annu Rev Neurosci 32:75-94.
    Kesner RP, Churchwell JC (2011) An analysis of rat prefrontal cortex in mediating executive function. Neurobiol Learn Mem 96:417-431.
    Kolb B (1984) Functions of the frontal cortex of the rat: a comparative review. Brain Res Rev 8:65-98.
    Kolb B (1990) Prefrontal cortex. In: The cerebral cortex of the rat (Kolb B, Tees RC, eds), pp 437-458. Cambridge, MA, US: The MIT Press.
    Kolb B, Gibb R (1991) Environmental enrichment and cortical injury: behavioral and anatomical consequences of frontal cortex lesions. Cereb Cortex 1:189-198.
    Kuniishi H, Ichisaka S, Matsuda S, Futora E, Harada R, Hata Y (2017) Chronic inactivation of the orbitofrontal cortex increases anxiety-like behavior and impulsive aggression, but decreases depression-like behavior in rats. Front Behav Neurosci 10:250.
    Lacroix L, Broersen LM, Weiner I, Feldon J (1998) The effects of excitotoxic lesion of the medial prefrontal cortex on latent inhibition, prepulse inhibition, food hoarding, elevated plus maze, active avoidance and locomotor activity in the rat. Neuroscience 84:431-442.
    Leblond M, Fan D, Brynildsen JK, Yin HH (2011) Motivational state and reward content determine choice behavior under risk in mice. PLoS ONE 6:e25342.
    Leblond M, Sukharnikova T, Yu C, Rossi MA, Yin HH (2014) The role of pedunculopontine nucleus in choice behavior under risk. Eur J Neurosci 39:1664-1670.
    Lee D, Seo H (2016) Neural basis of strategic decision making. Trends Neurosci 39:40-48.
    Lee D, Seo H, Jung MW (2012) Neural basis of reinforcement learning and decision making. Annu Rev Neurosci 35:287-308.
    Levy I, Snell J, Nelson AJ, Rustichini A, Glimcher PW (2010) Neural representation of subjective value under risk and ambiguity. J Neurophysiol 103:1036-1047.
    Liao RM, Lin HL (2008) Differential effects of lesions in the subareas of medial prefrontal cortex on the development of behavioral sensitization to amphetamine: the role of environmental context. Chin J Physiol 51:394-401.
    Lisboa SF, Stecchini MF, Corrêa FMA, Guimaraes FS, Resstel LBM (2010) Different role of the ventral medial prefrontal cortex on modulation of innate and associative learned fear. Neuroscience 171:760-768.
    Lockwood PL, Wittmann MK (2018) Ventral anterior cingulate cortex in social decision-making. Neurosci Biobehav Rev 92:187-191.
    Mar AC, Walker AL, Theobald DE, Eagle DM, Robbins TW (2011) Dissociable effects of lesions to orbitofrontal cortex subregions on impulsive choice in the rat. J Neurosci 31:6398-6404.
    Meyer HC, Bucci DJ (2016) Imbalanced activity in the orbitofrontal cortex and nucleus accumbens impairs behavioral inhibition. Curr Biol 26:2834-2839.
    Mobini S, Body S, Ho HY, Bradshaw CM, Szabadi E, Deakin JFW, Anderson IM (2002) Effects of lesions of the orbitofrontal cortex on sensitivity to delayed and probabilistic reinforcement. Psychopharmacology 160:290-298.
    Neubert FX, Mars RB, Sallet J, Rushworth MF (2015) Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex. Proc Natl Acad Sci 112:E2695-E2704.
    O’Neill M, Schultz W (2010) Coding of reward risk by orbitofrontal neurons is mostly distinct from coding of reward value. Neuron 68:789-800.
    O’Neill M, Schultz, W (2013) Risk prediction error coding in orbitofrontal neurons. J Neurosci 33:15810-15814.
    O’Neill M, Schultz W (2015) Economic risk coding by single neurons in the orbitofrontal cortex. J Physiol (Paris) 109:70-77.
    Orsini CA, Moorman DE, Young JW, Setlow B, Floresco SB (2015) Neural mechanisms, regulating different forms of risk-related decision making: insights from animal models. Neurosci Biobehav Rev 58:147-167.
    Orsini CA, Trotta RT, Bizon JL, Setlow B (2015) Dissociable roles for the basolateral amygdala and orbitofrontal cortex in decision-making under risk of punishment. J Neurosci 35:1368-1379.
    Orsini CA, Setlow B (2017) Sex differences in animal models of decision making. J Neurosci Res 95:260-269.
    Orsini CA, Heshmati SC, Garman TS, Wall SC, Bizon JL, Setlow B (2018) Contributions of medial prefrontal cortex to decision making involving risk of punishment. Neuropharmacology 139:205-216.
    Orsini CA, Moorman, DE, Young, JW, Setlow B, Floresco SB (2015) Neural mechanisms regulating different forms of risk-related decision-making: Insights from animal models. Neurosci Biobehav Rev 58:147-167.
    Orsini CA, Trotta RT, Bizon JL, Setlow B (2015) Dissociable roles for the basolateral amygdala and orbitofrontal cortex in decision-making under risk of punishment. J Neurosci 35:1368-1379.
    Paglieri F, Addessi E, De Petrillo F, Laviola G, Mirolli M, Parisi D, Petrosino G, Ventricelli M, Zoratto F, Adriani W (2014) Nonhuman gamblers: lessons from rodents, primates, and robots. Front Behav Neurosci 8:33.
    Pais-Vieira M, Lima D, Galhardo V (2007) Orbitofrontal cortex lesions disrupt risk assessment in a novel serial decision-making task for rats. Neuroscience 145:225-231.
    Passingham RE, Wise SP (2012) The neurobiology of the prefrontal cortex: anatomy, evolution, and the origin of insight Oxford University Press.
    Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. UK: Acdemic Press.
    Rich EL, Stoll FM, Rudebeck, PH (2018) Linking dynamic patterns of neural activity in orbitofrontal cortex with decision making. Curr Opin Neurobiol 49:24-32.
    Ridderinkhof KR, Van Den Wildenberg WP, Segalowitz SJ, Carter CS (2004) Neurocognitive mechanisms of cognitive control: the role of prefrontal cortex in action selection, response inhibition, performance monitoring, and reward-based learning. Brain Cognition 56:129-140.
    Roitman JD, Roitman MF (2010) Risk-preference differentiates orbitofrontal cortex responses to freely chosen reward outcomes. Eur J Neurosci 31:1492-1500.
    Rolls ET, McCabe C, Redoute J (2008) Expected value, reward outcome, and temporal difference error representations in a probabilistic decision task. Cereb Cortex 18:652-663.
    Rothschild M, Stiglitz JE (1970) Increasing risk: I. A definition. J Econom Theory 2:225-243.
    Rushworth MFS, Behrens TEJ (2008) Choice, uncertainty and value in prefrontal and cingulate cortex. Nat Neurosci 11:389-397.
    Rushworth MFS, Noonan MP, Boorman ED, Walton ME, Behrens TE (2011) Frontal cortex and reward-guided learning and decision-making. Neuron 70:1054-1069.
    Schoenbaum G, Roesch MR, Stalnaker TA (2006) Orbitofrontal cortex, decision-making and drug addiction. Trends Neurosci 29:116-124.
    Schultz W, O’Neill M, Tobler PN, Kobayashi S (2011) Neuronal signals for reward risk in frontal cortex. Annals New York Acad Sci 1239:109-117.
    Schultz W, Preuschoff K, Camerer C, Hsu M, Fiorillo CD, Tobler PN, Bossaerts P (2008) Explicit neural signals reflecting reward uncertainty. Phil Trans R Soc B 363:3801-3811.
    Schultz W (2010) Dopamine signals for reward value and risk: basic and recent data. Behav Brain Funct 6:24.
    Shah AA, Treit D (2003) Excitotoxic lesions of the medial prefrontal cortex attenuate fear responses in the elevated-plus maze, social interaction and shock probe burying tests. Brain Res 969:183-194.
    Simon NW, Gilbert RJ, Mayse JD, Bizon JL, Setlow B (2009) Balancing risk and reward: a rat model of risky decision making. Neuropsychopharmacology 34:2208-2217.
    St. Onge JR, Ahn S, Phillips AG, Floresco SB (2012a) Dynamic fluctuations in dopamine efflux in the prefrontal cortex and nucleus accumbens during risk-based decision making. J Neurosci 32:16880-16891.
    St. Onge JR, Chiu YC, Floresco SB (2010) Differential effects of dopaminergic manipulations on risky choice. Psychopharmacology 211:209-221.
    St. Onge JR, Floresco SB (2010) Prefrontal cortical contribution to risk-based decision making. Cereb Cortex 20:1816-1828.
    St. Onge JR, Stopper CM, Zahm DS, Floresco SB (2012b) Separate prefrontal-subcortical circuits mediate different components of risk-based decision making. J Neurosci 32:2886-2899.
    Steiner AP, Redish AD (2012) The road not taken: neural correlates of decision making in orbitofrontal cortex. Front Neurosci 6:131.
    Steiner AP, Redish AD (2014) Behavioral and neurophysiological correlates of regret in rat decision-making on a neuroeconomic task. Nat Neuorsci 17:995-1002.
    Stolyarova A, Izquierdo A (2017) Complementary contributions of basolateral amygdala and orbitofrontal cortex to value learning under uncertainty. Elife 6:e27483.
    Stopper CM, Floresco SB (2011) Contributions of the nucleus accumbens and its subregions to different aspects of risk-based decision making. Cogn Affect Behav Neurosci 11:97-112.
    Stopper CM, Green EB, Floresco SB (2014) Selective involvement of the medial prefrontal cortex in biasing risky, but not impulsive, choice. Cereb Cortex 24:154-162.
    Stopper CM, Khayambash S, Floresco SB (2013) Receptor-specific modulation of risk-based decision making by nucleus accumbens dopamine. Neuropsychopharmacology 38:715-728.
    Stott JJ, Redish AD (2014) A functional difference in information processing between orbitofrontal cortex and ventral striatum during decision-making behaviour. Phil Trans R Soc B 369:20130472.
    Tobler PN, O’Doherty JP, Dolan RJ, Schultz W (2007) Reward value coding distinct from risk attitude-related uncertainty coding in human reward systems. J Neurophysiol 97:1621-1632.
    Trimmer PC, Houston AI, Marshall JAR, Mendl MT, Paul ES, McNamara JM (2011) Decision-making under uncertainty: biases and Bayesians. Anim Cogn 14:465-476.
    Westbrook SR, Hankosky ER, Dwyer MR, Gulley JM (2018) Age and sex differences in behavioral flexibility, sensitivity to reward value, and risky decision-making. Behav Neurosci 132:75-87.
    Winstanley CA, Floresco SB (2016) Deciphering decision making: variation in animal models of effort-and uncertainty-based choice reveals distinct neural circuitries underlying core cognitive processes. J Neurosci 36:12069-12079.
    Yang JH, Liao RM (2015) Dissociable contribution of nucleus accumbens and dorsolateral striatum to the acquisition of risk choice behavior in the rat. Neurobiol Learn Mem 126:67-77.
    Yang JH, Cheng CP, Liao RM (2018) Effects of d-amphetamine on risk choice in rats depend on the manner in which the expected reward value is varied. Pharmacol Biochem Behav 171:20-29.
    Yates JR (2018) Examining the neurochemical underpinnings of animal models of risky choice: Methodological and analytic considerations. Exp Clin Psychopharm 27:178-201.
    Zangrossi Jr. H, Graeff FG (1997) Behavioral validation of the elevated T-maze, a new animal model of anxiety. Brain Res Bull 44:1-5.
    Zangrossi Jr. H, Graeff FG (2014) Serotonin in anxiety and panic: contributions of the elevated T-maze. Neurosci Biobehav Rev 46:397-406.
    Zeeb FD, Baarendse PJJ, Vanderschuren LJMJ, Winstanly CA (2015) Inactivation of the prelimbic or infralimbic cortex impairs decision-making in the rat gambling task. Psychopharmacology 232:4481-4491.
    Zeeb FD, Winstanly CA (2011) Lesions of the basolateral amygdala and orbitofrontal cortex differentially affect acquisition and performance of a rodent gambling task. J Neurosci 31:2197-2204.
    Zeeb FD, Baarendse PJJ, Vanderschuren LJMJ, Winstanley CA (2015) Inactivation of the prelimbic or infralimbic cortex impairs decision-making in the rat gambling task. Psychopharmacology 232:4481-4491.
    Zeeb FD, Floresco SB, Winstanley CA (2010) Contributions of the orbitofrontal cortex to impulsive choice: interactions with basal levels of impulsivity, dopamine signaling, and reward-related cues. Psychopharmacology 211:87-98.
    Description: 碩士
    Source URI: http://thesis.lib.nccu.edu.tw/record/#G0105754001
    Data Type: thesis
    DOI: 10.6814/NCCU201900150
    Appears in Collections:[神經科學研究所 ] 學位論文

    Files in This Item:

    File SizeFormat
    400101.pdf1840KbAdobe PDF0View/Open

    All items in 政大典藏 are protected by copyright, with all rights reserved.

    社群 sharing

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback