Reward sensitivity and impulsivity 한국중독정신의학회 20주년 추계 심포지엄 Reward sensitivity and impulsivity Reward and impulsivity 2016. 11. 18. 백범기념관 건국대학교 의전원 및 중주병원 정신건강의학과 교수 서정석

Contents impulsive Reward sensitive Reward seeking↑ addiction

뇌 보상 회로 and reward sensitivity

Figure 2 The human reward circuit. Notes: Reprinted by permission from Macmillan Publishers Ltd: Neuropsychopharmacology. Haber SN, Knutson B. The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology. 2010;35(1):4–26.9 Copyright © 2010. Evidence from self-stimulation, pharmacological, physiological, and behavioral studies emphasizes the key role of the nucleus accumbens and the ventral tegmental area dopamine neurons in the human reward circuit. However striatal and midbrain areas involved during reward processing are more extensive than previously thought, including the entire ventral striatum and the dopamine neurons of the substantia nigra, respectively. Thereby, the orbital frontal cortex (dark orange arrow) and the anterior cingulate cortex (light orange arrow) provide the main cortical input to the ventral striatum. Moreover, the ventral striatum receives substantial dopaminergic input from the midbrain. On the other hand, ventral striatum projections target the ventral pallidum and the ventral tegmental area/substantia nigra, which, in turn, via the medial dorsal nucleus of the thalamus, project back to the prefrontal cortex. Additionally, other structures, such as the amygdala, hippocampus, lateral habenular nucleus, and specific brainstem structures, such as the pedunculopontine nucleus and the raphe nuclei, play a key role in the regulation of the reward circuit. Abbreviations: Amy, amygdala; Hipp, hippocampus; NAcc, nucleus accumbens; dACC, dorsal anterior cingulate cortex; dPFC, dorsal prefrontal cortex; Hypo, hypothalamus; S, shell; STN, subthalamic nucleus; VP, ventral pallidum; vmPFC, ventral medial prefrontal cortex; THAL, thalamus; LHb, lateral habenular; PPT, pedunculopontine nucleus. Haber and  Knutson , Neuropsychopharmacology. 2010;35(1):4–26

베르나르 베르베르의 “뇌” 중에서

Addiction disorder and impulsivity Addiction = conditioned reaction to reward(incentive) stimuli Addiction disorder and impulsivity

Contents Impulsive Reward sensitive Reward seeking addiction 보상 민감성은 유전적, 환경적 그리고 불안, 스트레스 등의 복합된 결과 이므로 다음 주제와 연관되어 있어서 여기서는 충동성을 위주로 설명할 예정 addiction

Impulsivity and S. misuse

Impulsivity a construct with relevance to PG and multiple other psychiatric conditions (Chambers et al, 2003; Pagani et al, 2009) the most ubiquitous personality traits found in the fields of psychology and psychiatry Multifactorial trait characterized by unplanned responding and hasty decision making that may be unduly risky or neglect negative consequences (Brewer and Potenza, 2008; Moeller et al., 2004) a disturbance in reward motivation (Zuckerman , 1993) and identified through risk-taking (Evenden , 1999) a deficit in inhibitory control (Schachar & Logan, 1990; Schachar & Wachsmuth, 1991) an inability to delay gratification because of the aversive nature of waiting in children (Sonuga-Barke & Taylor, 1992; Sonuga-Barke et al., 1992) 어린이들은 즉각적인 작은 보상이 더 중요 특히 도박에서 충동성 상관연구 많다. 그럴 것이 기원이 충동 조절장애 였으니.

As a component in personality major model of personality Five-Factor Model Eysenck’s P–E–N (Costa & McCrae, 1992; Goldberg, 1993) Tellegen’s three-factor model DSM-IV and ICD-10 Whiteside and Lynam, Personality and Individual Differences, 2001;30: 669–689

Scale for impulsivity Personality tests and reports Behavioral paradigms Marshmallow test Delay discounting Go/no-go and Stop-signal reaction time tasks Balloon Analogue Risk Task Iowa Gambling Task Differential Reinforcement of Low Response Rate Task Other Continuous performance task 5-choice serial reaction time task Stroop task Matching Familiar Figures Task. Personality tests and reports Barratt Impulsiveness Scale Eysenck Impulsiveness Scale Dickman Impulsivity Inventory UPPS Impulsive Behavior Scale Lifetime History of Impulsive Behaviors Behavioral Inhibition System/Behavioral Activation System Impulsive/Premeditated Aggression Scale Padua Inventory

Activity 5 충동성이 무엇인지 한번 해봅시다. 재미있는 두뇌 검사

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이런 검사를 통해 충동성 이 증가되었다면? 담배 등에 의해 뇌가 과부하가 걸렸거나 조절력에 문제가 생겼다는 것을 의미합니다. 이런 검사를 통해 충동성 이 증가되었다면? 담배 등에 의해 뇌가 과부하가 걸렸거나 조절력에 문제가 생겼다는 것을 의미합니다. 반응 속도가 드리거나, 평균적인 범위를 벗어났다는 것 충동성=산만함과 유사한 개념

Isolation of Specific Interference Processing in the Stroop Task: PET Activation Studies anterior cingulate cortex (ACC) dorsolateral prefrontal cortex (DLPFC) More specifically, while both are activated when resolving conflicts and catching errors, the DLPFC assists in memory and other executive functions, while the ACC is used to select an appropriate response and allocate attentional resources Stroop JR (1935). "Studies of interference in serial verbal reactions". Journal of Experimental Psychology. 18 (6): 643–662 Taylor S et al (1997). "Isolation Of Specific Interference Processing In The Stroop Task: PET Activation Studies.". NeuroImage

impulsivity models 1 factor 1) : Reward Sensitivity 2 factor : RS + rash impulsiveness (Dawe & Loxton, 2004) 3 : Behavioral inhibition, behavioral activation, affective responses (Carver & White, 1994): 4 UPPS impulsive behaviour scale (Whiteside & Lynam, 2001): Based on 5 factor: openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism (Costa & McCrae, 1992) UPPS scales accounted for between 7% (pathological gambling) and 64% (borderline personality disorder features (Whiteside & Lynam, 2001): 5 UPPS+P (Cyders et al., 2007) 중독잘 되는 성격으로서의 인격 특성의 핵심은 “충동성” 1) Dissabandara et al., 2014; Franken & Muris, 2006; Gullo & Dawe, 2008; Kabbani & Kambouropoulos, 2013; Kambouropoulos & Staiger, 2004; Knyazev, Slobodskaya, Kharchenko, & Wilson, 2004; Loxton & Dawe, 2001; Lyvers, Czerczyk, Follent, & Lodge, 2009; Lyvers, Duff, & Hasking, 2011; O'Connor & Colder, 2005; Pardo, Aguilar, Molinuevo, & Torrubia, 2007; Smerdon & Francis, 2011)

Two factor model of impulsivity reward sensitivity: the sensitivity to signals of reward rash impulsiveness Impulsivity the tendency to engage in behavior that involves rashness, a lack of foresight or planning, or as a behavior that occurs without reflection or careful deliberation. novelty seeking, behavioral undercontrol and disinhibition clear relationship between impulsivity and substance use has been consistently found Dawe et al, Addictive Behaviors 29 (2004) 1389–1405

Gray’s theory in which two interacting systems ↑ Related structures Behavioral Inhibition System (BIS) more likely to inhibit approach behavior that is accompanied by subjective feelings of anxiety/ frustration septo-hippocampal system, comprising the hippocampus proper, dentate gyrus, entorhinal cortex, subicular area (subiculum) and the posterior cingulate cortex. Behavioral Approach System (BAS). more likely to engage in approach and active avoidance behavior and to experience greater positive affect in situations containing cues for reward mesolimbic dopaminergic pathways Gray, 1970, 1975, 1987a, 1987b; Gray & McNaughton, 2000

impulse, to approach drugs two core processes impulse, to approach drugs a reduced capacity to inhibit this approach behavior 충동적 약물이 작용하는 핵심 2가지 측면 Gullo et al. Addictive Behaviors 39 (2014) 1547–1556

Recent evidences with 2 factors Quinn and Harden (2013) found changes in (“Rash”) Impulsivity predicted alcohol, marijuana and cigarette use in adolescence/young adulthood, whereas Sensation Seeking was predictive of alcohol use only. Using a large, longitudinal dataset, Handley et al. (2011) found (Rash) Impulsivity to uniquely predict externalizing problems (ADHD and conduct disorder), while Sensation Seeking uniquely predicted substance use. Castellanos-Ryan, Rubia, and Conrod (2011) similarly found Sensation Seeking and a reward response bias were uniquely associated with binge-drinking in adolescents, whereas (Rash) Impulsivity and deficits in response inhibition were associated with conduct disorder. Gullo et al. Addictive Behaviors 39 (2014) 1547–1556

The neurobiology of impulsivity and substance misuse Long-term exposure to drugs has been found to cause permanent changes to these pathways, which in turn later affect a range of brain functions including the reinforcement value of drug-related cues, hedonic drug effects, incentive motivation, drug cravings, and executive functioning (e.g., Jentsch & Taylor, 1999; Kelley & Berridge, 2002; Koob & Le Moal, 1997; Robinson & Berridge, 2003). 1. Incentive salience and the dopaminergic pathways the salience of the rewarding and/or reinforcing quality of the substance following an initial period of use. wanting and liking 2. Disinhibition and impaired functioning in the prefrontal cortex (OFC) damage to the prefrontal cortex has been implicated in the inability to inhibit impulsive behavior impulsive behavior impaired extinction of learned associations 3. Prefontal dysfunction and the implications for substance misuse risk dopamine-related reinforcement of drug effects as underpinning initial drug involvement which, with continued use compulsive drug intake loss of control The orbitofrontal cortex (OFC), in particular, is involved in disinhibited and compulsive behavior due to its involvement in regulating motivated behavior, the correcting/updating of stimulus reinforcement associations, and the extinction of such associations (Rolls, 1986; Thorpe, Rolls, & Maddison, 1983).

Studies investigating the association between impulsivity and substance misuse 충동성을 평가하기 dnlgo, novelty seeking, 행동 조절저하, 탈억게 등의 다양한 인격 검사법을 사용했지만, 물질 오남용과 충동성은 밀접한 연관이 있다. 반대로 말하면, 증가된 충동성은 이후의 sud의 하나의 위험 요인이 된다. 파랑 박스 ; 전향적 연구(나머지는 단면적 연구): 어릴때의 충동성이 이후의 물질사용장애를 예측한다는 결과

충동성을 평가하기 dnlgo, novelty seeking, 행동 조절저하, 탈억게 등의 다양한 인격 검사법을 사용했지만, Studies investigating the association between impulsivity and substance misuse 충동성을 평가하기 dnlgo, novelty seeking, 행동 조절저하, 탈억게 등의 다양한 인격 검사법을 사용했지만, 물질 오남용과 충동성은 밀접한 연관이 있다. 파랑 박스 ; 전향적 연구(나머지는 단면적 연구): 어릴때의 충동성이 이후의 물질사용장애를 예측한다는 결과 Dawe et al, Addictive Behaviors 29 (2004) 1389–1405

Impulsivity, whether measured by self-report, observer-report, or behavioral performance, is a robust predictor of current and future problems with substance use Dawe & Loxton, 2004; Jentsch & Taylor, 1999; Moeller et al., 2001; Moffitt et al., 2011; Nigg et al., 2006; Potenza, 2013; Tarter et al., 2003

4 or 5 factor model of impulsivity 4 factors 5 factors U Urgency from Negative mood: (-) urgency P (lack of) Premeditation (lack of) Perseverance, S Sensation seeking +P impulsive behavior arising from positive mood states: (+) urgency UPPS Impulsive Behavior Scale: a 45-item self-report questionnaire UPPS+P Impulsive Behavior Scale (UPPS+P) a revised version of the UPPS, including 59 items. UPPS+P short version (UPPS+Ps) 20-item scale for five facets (4 items per dimension).. Premeditation – 계획, 예측 Cyders et al, Psychological Assessment, 2007;19:107–118.

Summary of studies investigating unique relations between UPPS + P traits and substance use. Gullo et al. Addictive Behaviors 39 (2014) 1547–1556

UPPS+P를 이용한 종적, 단면 연구 결과 정리 only (Lack of) Premeditation and Negative Urgency are consistently associated with substance use. The (Lack of) Premeditation trait is most similar to the (Rash) Impulsivity/Disinhibition traits typically found in substance use studies. propensity – 나쁜 성향 Gullo et al. Addictive Behaviors 39 (2014) 1547–1556

Other studies

Impulsivity predicts problem gambling in low SES adolescent males 가설: 13-14세(n=333)의 충동성이 17세(n=168)의 도박 성향을 예측할 수 있다. Impulsivity measures teacher ratings self-reports two laboratory tasks(delay-of-gratification task and one card-playing task) Gambling: South Oaks Gambling Screen for adolescents 25. 캐나다 몬트리얼 소재의 1,034명의 유치원 생의 코호트 연구의 일부 The SOGS-RA assesses gambling severity over the past 12 months, using 12 items that are similar to those in the SOGS (Lesieur & Blume, 1987) Results of the hierarchical logistic regression using impulsivity measures to predict SOGS-RA scores after controlling for maternal occupational prestige, teacher ratings and age 13 gambling 1단계 어머니의 낮은 직업군과 13세의 갬블이 유의한 관계를 보였으며 2단계: 공격성과 불안은 연관성이 없었으며 3. 마지막으로 2가지의 충동성 검사결과도 역시 예측력이 있었다. Vitaro et al, Addiction (1999) 94(4), 565± 575

Similarities and differences among Internet gaming disorder, gambling disorder and alcohol use disorder: A focus on impulsivity and compulsivity IGD total BIS score: 72.93 (AUD = 74.15) 로 가장 높고, successful stop ratio = 0.52 (AUD= 0.51)가장 낮았다. IGD group showed a decreased proportion of successful stops on the stop-signal test compared with the HC group. IGD group scored significantly higher BIS-11 scale. Choi et al, Journal of Behavioral Addictions 3(4), pp. 246–253 (2014)

The Effect of Behavior Inhibition System on Smart-Phone Addiction : The Mediation Roll of Depression BIS와 우울, 스마트폰 중독은 유의한 정적 상관 BIS는 우울을 유의하게 설명하였으며, 스마트폰 중독도 유의하게 설명 BIS가 신경증적 경향성/우울장애와 관련이 있다는 연구 결과와 일치 Jung et al, J Korean Neuropsychiatr Assoc 2016;55(2):97-102

기타 연구 결과 The children of parents with substance use disorders constitute an alternative high-risk group, and also display markers of both impulsive action (Acheson, et al. 2011a) and impulsive choice (Acheson, et al. 2011b) the small number of existing studies also point to trait impulsivity and poor self-control from as early as 3 years of age, predicting later development of gambling problems, as well as alcohol, nicotine, and marijuana misuse (Vitaro et al, 1999; Slutske e tal, 2005; Slutske et al, 2012)

Summary: impulsivity is a core vulnerability to addictive behavior. Reward sensitivity and disinhibition play an important and unique role in addictive behavior.

Impulsivity in Addiction

Contents Impulsive Reward sensitive Loss of control addiction

1. Gambling and PG Compared to non-PG (or problem gambler), relatively diminished activation of the PFC (particularly VM, VL, OFC) subcortical regions (particularly the ventral striatum)

Diminished Frontostriatal activity during processing of monetary rewards and losses in PG 14 PG vs 14 control Monetary Incentive Delay Task Barratt Impulsiveness Scale. Brain activation changes of reward/loss prospect reward/loss anticipation reward/loss notification significantly reduced activity in the VM PFC, insula, and ventral striatum during several phases, including the prospect and anticipation phases of both gains and losses 새 참고문헌) fMRI 연구 14명 PG and 14 control Monetary Incentive Delay Task suggests consistent alterations in neurocircuitry underlying incentive valuation and loss prediction. Together with findings in alcohol dependence, these results suggest that impulsive tendencies in addictions may be reflected in diminished ventral striatal activations to reward anticipation and may represent targets for treatment development in addictions. impulsive tendencies in addictions may be reflected in diminished these area Balodis et al, BIOL PSYCHIATRY 2012;71:749–757

2. abnormal brain structure implicated in stimulant drug addiction Reduced FA in fiber tracts adjacent to the right IFG was significantly associated with poorer inhibitory control and accounted for ~6% of the variance in SSRT (Fig. 1C). - > indicating poor self control in stimulant addictors 22. SSRT: requires individuals to rapidly suppress an ongoing, well-established response whenever an auditory signal is suddenly presented 진행하다가 특정 소리가 들리면 중단해야하기까지 걸린 시간 측정 b) 파랑색 - IFG: inferior frontal gyrus Stop signal reaction time (SSRT) Ersche et al, SCIENCE VOL 2012;335:601-604

3. Internet gaming

Liking wanting Preoccupation & craving 배외측 전두엽: 목적 지향적 활동을 기획하는 곳 배외측 전두엽: 목적 지향적 활동을 기획하는 곳 - 작업 기억 – 온라인 게임에 몰두하게 한다. - 이전의 긍정적 경험(보상, 강화물)을 떠올리며 게임 하기를 결정 내측 전두 피질: 게임하기, 갈망 우측 안와 전두피질: 결과를 예측하면서 적절한 동기에 부합되는 목적 지향적 행동을 관장 한다. (Rolls, 2000). Preoccupation & craving 앞쪽 대상피질: 게임 욕구과 갈망, 특히 게임 관련 단서를 주었을 때 갈망하기와 관련이 있으며, 보상을 갈구하는 행동을 조절하는 역할을 한다.(Chiamulera, 2005; Risinger et al., 2005). 본문: 206번 토론부분 정리 Mesolimbic-accumbens-amygdaloid complex는 연두색 영역으로 주로 dopaminergic and opioidergic pathway로 연결되어 있으며ventral tegmental area에서 nucleus accumbens 그리고 bed nucleus of stria terminalis 및 amygdala로 이어지는 extended amygdala를 구성한다. 이는 addictive drug에 의해 직접적으로 영향을 받는 곳으로 알려져 있으며 Neural input과 output이 서로 긴밀하게 연관되어 있고 태생학적으로도 유사한 발달과정을 밟아 나아가는 구조적인 공통점이 있다. Brain stress system 는 Hypothalamic-pituitary-adrenal brain stress system과 extra hypothalamic CRF brain stress system로 크게 나눌 수 있으며, Stress가 있는 경우 homeostasis를 유지하기 위한 bodily demand에 반응하기 위해 adaptive autonomic nervous system과 behavior change가 일어나는데 기여한다. Striatal-pallidal-thalamic circuitry는 최는 단순한 운동 기능의 조절 만이 아니라 Motor-learning, reinforcer evaluation, stimulus-reward association등에 중요한 구조로 생각되고 있으며, Cognitive functioning, active inhibitory central mechanism, drive and impulsive repetitive behavior 등에 전반적인 영향을 미친다. 이러한 구조들이 addictive drug의 섭취 이후 중독에 이르는 과정에서 allostasis가 일어나는 데 영향을 준다. Liking 보상회로 측좌핵: 동기 증진 선조체: 습관 형성 wanting Ko et al, Journal of Psychiatric Research 2009:739–747

The neurobiology of impulsivity and substance misuse Long-term exposure to drugs has been found to cause permanent changes to these pathways, which in turn later affect a range of brain functions including the reinforcement value of drug-related cues, hedonic drug effects, incentive motivation, drug cravings, and executive functioning (e.g., Jentsch & Taylor, 1999; Kelley & Berridge, 2002; Koob & Le Moal, 1997; Robinson & Berridge, 2003). 1. Incentive salience and the dopaminergic pathways the salience of the rewarding and/or reinforcing quality of the substance following an initial period of use. wanting and liking 2. Disinhibition and impaired functioning in the prefrontal cortex (OFC) damage to the prefrontal cortex has been implicated in the inability to inhibit impulsive behavior impulsive behavior impaired exticntion of learned associations 3. Prefontal dysfunction and the implications for substance misuse risk dopamine-related reinforcement of drug effects as underpinning initial drug involvement which, with continued use compulsive drug intake loss of control The orbitofrontal cortex (OFC), in particular, is involved in disinhibited and compulsive behavior due to its involvement in regulating motivated behavior, the correcting/updating of stimulus reinforcement associations, and the extinction of such associations (Rolls, 1986; Thorpe, Rolls, & Maddison, 1983). 결국 같은 설명

Conclusion: trait and state-dependent Impulsive Reward sensitive Loss of control Reward seeking addiction