A5 -Neurocognitive Models of Behavioral Control in Obesity - The modulating effects of dynamic changes in central dopaminergic tone

The neurotransmitter dopamine (DA) plays a central role in several cognitive key domains such as (food) motivation, reinforcement learning, and memory. Our recent results point towards (a) prominent alterations in these domains in overweight and obesity and (b) a non-linear relationship between markers of obesity and the central nervous transmission efficacy of dopamine. In particular, moderately obese subjects may exhibit lower levels of dopamine compared to normal-weight subjects whereas severely obese subjects may have an abundance of central dopamine. This has important implications (1) for the assignment to experimental groups, since pooling across moderately and severely obese subjects is likely to result in a null-finding, and (2) for the expected direction of neural and behavioural changes. Due to its central role, alterations in dopaminergic transmission impact on very different behaviors, ranging from eating to decision making and learning. Moreover, opposing patterns of change in dopaminergic transmission suggest a differential pattern of cognitive alterations in moderately and severely obese subjects, giving rise to the assumption of separate subpopulations. Importantly, moderately and severely obese subjects should benefit from opposing manipulations to dopaminergic tone. In the proposed project we will test these predictions experimentally. Specifically, we will test the effects of pharmacological manipulation to central dopaminergic transmission in moderately and severely obese subjects utilizing behavioral testing, functional magnetic resonance imaging (fMRI), and neurocognitive modelling, the latter providing a direct link of behavioral and neural effects on the individual level. Further, we will investigate the interaction of ‘natural’, i.e. genetic, modulators of DA transmission with obesity- and diet-associated alterations in different brain regions.

PD Dr. Jane Neumann, Integrated Research and Treatment Center AdiposityDiseases (co-PI 2013–2016)

Abbildung 1: (A) Quadratic relationship between Positron Emission Tomography (PET) markers of dopaminergic transmission and body mass index (BMI). BP: Binding Potential of PET tracer. (B) Inverted U-shaped relationship between reward sensitivity and BMI. (C) Modulatory effect of BMI on brain activity associated with the volitional regulation of food craving. BMI is nonlinearly related to BOLD activation in clusters in left putamen, amygdala, and insula (D). (E) Inverted u-shaped relationship between BMI and BOLD effect size in the left putamen. (Colour-coding refers to t-values, p<.001 voxel level, p<.05 Family Wise Error corrected on the cluster level, whole brain).

Meemken MT, Horstmann A. Appetitive Pavlovian-to-Instrumental Transfer in Participants with Normal-Weight and Obesity. Nutrients. 2019 May 9;11(5). pii: E1037.

Mehl N, Morys F, Villringer A, Horstmann A. Unhealthy yet Avoidable-How Cognitive Bias Modification Alters Behavioral and Brain Responses to Food Cues in Individuals with Obesity. Nutrients. 2019 Apr 18;11(4).

Meemken MT, Kube J, Wickner C, Horstmann A. Keeping track of promised rewards: Obesity predicts enhanced flexibility when learning from observation. Appetite. 2018 Dec 1;131:117-124.

Morys F, Bode S, Horstmann A. Dorsolateral and medial prefrontal cortex mediate the influence of incidental priming on economic decision making in obesity. Sci Rep. 2018 Dec 4;8(1):17595.

Hellrung L, Dietrich A, Hollmann M, Pleger B, Kalberlah C, Roggenhofer E, Villringer AHorstmann A. Intermittent compared to continuous real-time fMRI neurofeedback boosts control over amygdala activation. Neuroimage. 2018 Feb 1;166:198-208.

Mehl N, Mueller-Wieland L, Mathar D, Horstmann A. Retraining automatic action tendencies in obesity. Physiol Behav. 2018 Mar 30. pii: S0031-9384(18)30154-9.

Kastner L, Kube J, Villringer A, Neumann J. Cardiac concomitants of feedback and prediction error processing in reinforcement learning. Front Neurosci. 2017;11:598

Hellrung L, Dietrich A, Hollmann M, Pleger B, Kalberlah C, Roggenhofer E, Villringer A, Horstmann A. Intermittent compared to continuous real-time fMRI neurofeedback boosts control over amygdala activation. NeuroImage. 2017;166:198-208.

Kube J, Mathar D, Horstmann A, Villringer A, Neumann J. Altered monetary loss processing and reinforcement-based learning in individuals with obesity. Brain Imaging Behav. 2017; in press.

Mathar D, Neumann J, Villringer A, Horstmann A. Failing to learn from negative prediction errors: Obesity is associated with alterations in a fundamental neural learning mechanism. Cortex.2017;95:222-37.

Albrecht F, Bisenius S, Morales Schaack R, Neumann J, Schroeter ML. Disentangling the neural correlates of corticobasal syndrome and corticobasal degeneration with system and quantitative ALE meta-analyses. NPJ Parkinsons Dis. 2017;3:12.

Mehl N, Bergmann S, Klein AM, Daum M, von Klitzing K, Horstmann A. Cause or consequence? Investigating attention bias and self-regulation skills in children at risk for obesity. J Exp Child Psychol. 2017;155:113-27.

Sjoerds Z, Dietrich A, Deserno L, de Wit S, Villringer A, Heinze HJ, Schlagenhauf F, Horstmann A. Slips of action and sequential decisions: A cross-validation study of tasks assessing habitual and goal-directed action control. Front Behav Neurosci. 2016;10:234.

Schrimpf A, Kube J, Neumann JHorstmann A, Villringer A, Gaebler M. Parasympathetic cardio-regulation during social interactions in individuals with obesity - The influence of negative body image. Cogn Affect Behav Neurosci. 2017;17:330-47.

Dietrich A, de Wit S, Horstmann A. General Habit Propensity Relates to the Sensation Seeking Subdomain of Impulsivity But Not Obesity. Front Behav Neurosci. 2016;10:213.

Mathar D, Wilkinson L, Holl A,Neumann J, Deserno L, Villringer A, Jahanshahi M, Horstmann A. The role of dopamine in positive and negative prediction error utilization during incidental learning–insights from Positron Emission Tomography, Parkinson’s disease and Huntington’s disease. Cortex. 2016; Epub ahead of print.

Mühlberg C, Mathar D, Villringer A, Horstmann ANeumann J. Stopping at the sight of food - How gender and obesity impact on response inhibition. Appetite. 2016;107:663-76.

Dietrich A, De Wit S, Horstmann A. General habit propensity relates to the sensation seeking subdomain of impulsivity but not obesity. Front Behav Neurosci. 2016;10:213.

Garcia-Garcia I, Kube J, Gaebler M, Horstmann A, Villringer A,Neumann J. Neural processing of negative emotional stimuli and the influence of age, sex and task-related characteristics. Neurosci Biobehav Rev. 2016;68:773-93.

Masouleh SK, Arélin K, Horstmann A, Lampe L, Kipping JA, Luck T, Riedel-Heller SG, Schroeter ML, Stumvoll M, Villringer A, Witte AV. Higher body mass index in older adults is associated with lower gray matter volume: implications for memory performance. Neurobiol Aging. 2016;40:1-10.

Grellmann C, Neumann J, Bitzer S, Kovacs P, Tönjes A, Westlye LT, Anreassen OA, Stumvoll M, Villringer A, Horstmann A. Random projection for fast and efficient multivariate correlation analysis of high-dimensional data: A new approach. Front Genet. 2016;7:102.

Dietrich A, Hollmann M, Mathar D, Villringer A, Horstmann A. Brain regulation of food craving: Relationships with weight status & eating behavior. Int J Obes (Lond). 2016;40:982-9.

Kube J, Schrimpf A, Garcia-Garcia I, Villringer A, Neumann JHorstmann A. Differential heart rate responses to social and monetary reinforcement in women with obesity. Psychophysiology. 2016;53:868-79.

Schlögl H, Horstmann A, Villringer A, Stumvoll M. Functional neuroimaging in obesity and the potential for development of novel treatments. Lancet Diabetes Endocrinol. 2016;4:695-705.

Mathar D, Horstmann A, Pleger B, Villringer A, Neumann J. Is it worth the effort? Novel insights into obesity-associated alterations ins cost-benefit decision-making. Front Behav Neurosci. 2016;9:360.

Simmank J, Murawski C, Bode S, Horstmann A. Incidental rewarding cues influence economic decisions in people with obesity. Front Behav Neurosci. 2015;9:278.

Deserno L, Wilbertz T, Reiter A, Horstmann ANeumann J, Villringer A, Heinze HJ, Schlagenhauf F. Lateral prefrontal model-based signatures are reduced in individuals with high trait impulsivity. Transl Psychiatry. 2015;5:e659.

Löffler A, Luck T, Then FS, Sikorski C, Kovacs P, Böttcher Y, Breitfeld J, Tönjes A, Horstmann A, Löffler M, Engel C, Thiery J, Villringer A, Stumvoll M, Riedel-Heller SG. Eating Behaviour in the General Population: An Analysis of the Factor Structure of the German Version of the Three-Factor-Eating-Questionnaire (TFEQ) and Its Association with the Body Mass Index. PLoS One. 2015;10:e0133977.

Garcia-Garcia I, Jurado MA, Garolera M, Marques-Iturria I, Horstmann A, Segura B, Pueyo R, Sender-Palacios MJ, Vernet-Vernet M, Villringer A, Junque C, Margulies DS, Neumann J. Functional network centrality in obesity: A resting-state and task fMRI study. Psychiatry Res. 2015;233:3331-8.

Mueller K, Möller HE, Horstmann A, Busse-Voigt FP, Lepsien J, Blüher M, Stumvoll M, Villringer A, Pleger B. Physical exercise in overweight to obese individuals induces metabolic- and neurotrophic-related structural brain plasticity. Front Hum Neurosci. 2015;9:372.

Horstmann A, Fenske WK, Hankir MK. Argument for a non-linear relationship between severity of human obesity and dopaminergic tone. Obes Rev. 2015;16:821-30.

Löffler A, Luck T, Then FS, Luppa M, Sikorski C, Kovacs P, Tönjes A, Böttcher Y, Breitfeld J, Horstmann A, Löffler M, Engel C, Thiery J, Stumvoll M, Riedel-Heller SG. Age- and gender-specific norms for the German version of the Three-Factor Eating-Questionnaire (TFEQ). Appetite. 2015;91:241-7.

Hankir MK, Ashrafian H, Hesse S, Horstmann A, Fenske WK. Distinctive striatal dopamine signaling after dieting and gastric bypass. Trends Endocrinol Metab. 2015;26:223-30.

Rohde K, Federbusch M, Horstmann A, Keller M, Villringer A, Stumvoll M, Tönjes A, Kovacs P, Böttcher Y. Genetic variants in AKR1B10 associate with human eating behavior. BMC Genet. 2015;16:31.

Hellrung L, Hollmann M, Zscheyge O, Schlumm T, Kalberlah C, Roggenhofer E, Okon-Singer H, Villringer A, Horstmann A. Flexible adaptive paradigms for fMRI using a novel software package 'Brain Analysis in Real-Time' (BART). PLoS One. 2015;10:e0118890.

Rohde K, Keller M, Horstmann A, Liu X, Eichelmann F, Stumvoll M, Villringer A, Kovacs P, Tönjes A, Böttcher Y. Role of genetic variants in ADIPOQ in human eating behavior. Genes Nutr. 2015;10:449.

Grellmann C, Bitzer S, Neumann J, Westlye LT, Andreassen OA, Villringer A, Horstmann A. Comparison of variants of canonical correlation analysis and partial least squares for combined analysis of MRI and genetic data. Neuroimage. 2015;107:289-310.

Mueller K*, Horstmann A*, Möller HE, Anwander A, Lepsien J, Schroeter ML, Villringer A, Pleger B. Obesity associated cerebral gray and white matter alterations are interrelated in the female brain. PLoS One. 2014;9:e114206.

Horstmann A, Dietrich A, Mathar D, Pössel M, Villringer A, Neumann J. Slave to habit? Obesity is associated with decreased behavioural sensitivity to reward devaluation. Appetite. 2014;87C:175-83.

Dietrich A*, Federbusch MG*, Grellmann C, Villringer AHorstmann A. Body weight status, eating behavior, sensitivity to reward/punishment, and geder: relationships and interdependencies. Front Psychol. 2014;5:1073

Garcia-Garcia I, Horstmann A, Jurado MA, Garolera M, Chaudhry SJ, Margulies DS, Villringer ANeumann J. Reward processing in obesity, substance addiction and non-substance addiction. Obes Rev. 2014;15:853-69.

Wilbertz T, Deserno L, Horstmann ANeumann JVillringer A, Heinze HJ, Boehler CN, Schlagenhauf F. Response inhibition and its relation to multidimensional impulsivity. Neuroimage. 2014;103:241-8.

Gast MT, Tönjes A, Keller M, Horstmann A, Steinle N, Scholz M, Müller I, Villringer AStumvoll MKovacs P, Böttcher Y. The role of rs2237781 within GRM8 in eating behavior. Brain Behav. 2013;3:495-502.

Machann J, Horstmann A, Born M, Hesse S, Hirsch FW. Diagnostic imaging in obesity. Best Pract Res Clin Endocrinol Metab. 2013;27:261-77.

Horstmann A, Kovacs P, Kabisch S, Boettcher Y, Schloegl H, Toenjes A, Stumvoll M, Pleger B, Villringer A. Common genetic variation near MC4R has a sex-specific impact on human brain structure and brain behavior. PLoS One. 2013;8:e74362.

Schloegl H*, Kabisch S*Horstmann A, Lohmann G, Mueller K, Lepsien J, Busse-Voigt FP, Kratzsch J, Pleger B, Villringer A, Stumvoll M. Exenatide-induced reduction in energy intake is associated with increase in hypothalamic connectivity. Diabetes Care. 2013;36:1933-40.

Hollmann M, Pleger B, Villringer A, Horstmann A. Brain imaging in the context of food perception and eating. Curr Opin Lipidol. 2013;24:18-24.

Lohmann G, Stelzer J, Neumann J, Ay N, Turner R. "More is different'' in fMRI: a review of recent data analysis techniques. Brain Connect. 2013;3:223-39.

Sacher J, Neumann J, Okon-Singer H, Gotowiec S, Villringer A. Sexual dimorphism in the human brain: evidence from neuroimaging. Magn Reson Imaging. 2013;31:366-74.

Steingroever H, Wetzels R,Horstmann ANeumann J, Wagenmakers EJ. Performance of Healthy Participants on the Iowa Gambling Task. Psychol Assess. 2012;25:180-93.

Horstmann A, Villringer A,Neumann J. Iowa Gambling Task: There is More to Consider than Long-Term Outcome. Using a Linear Equation Model to Disentangle the Impact of Outcome and Frequency of Gains and Losses. Front Neurosci. 2012;6:61.

Hollmann M, Hellrung L, Pleger B, Schlögl H, Kabisch S, Stumvoll M, Vill ringer A,Horstmann A. Neural correlates of the volitional regulation of the desire food. Int J Obes (Lond). 2012;36:648-55.

Forstmann BU, Keuken MC, Jahfari S, Bazin PL, Neumann J, Schäfer A, Anwander A, Turner R. Cortico-subthalamic white matter tract strength predicts interindividual efficacy in stopping a motor response.Neuroimage. 2012;60:370-5.

Horstmann A, Busse FP,  Mathar D, Müller K, Lepsien J, Schlögl H, Kabisch S, Kratzsch J,Neumann J, Stumvoll M, Villringer A, Pleger B. Obesity-Related Differences between Women and Men in Brain Structure and Goal-Directed Behavior.Front Hum Neurosci. 2011;5:58.

Müller K, Anwander A, Möller HE, Horstmann A, Lepsien J, Busse F, Mohammadi S, Schroeter ML, Stumvoll M, Villringer A, Pleger B. Sex-dependent influences of obesity on cerebral white matter investigated by diffusion-tensor imaging.PLoS One. 2011;6:e18544.

Schlögl H, Percik R,Horstmann A, Villringer A, Stum voll M. Peptide hormones regulating appetite - focus on neuroimaging studies in humans. Diabetes Metab Res Rev. 2011;27:104-12.

Lizier JT, Heinzle J, Horstmann A, Haynes JD, Prokopenko M. Multivariate information-theoretic measures reveal directed information structure and task relevant changes in fMRI connectivity. J Comput Neurosci. 2011;30:85-107.

Neumann J, Fox PT, Turner R, Lohmann G. Learning partially directed functional networks from meta-analysis imaging data. Neuroimage. 2010;49:1372-84.

Taubert M, Draganski B, Anwander A, Müller K, Horstmann A, Villringer A, Ragert P. Dynamic properties of human brain structure: learning-related changes in cortical areas and associated fiber connections. J Neurosci. 2010;30:11670-7.

Lohmann G, Margulies DS, Horstmann A, Pleger B, Lepsien J, Goldhahn D, Schloegl H, Stumvoll M, Villringer A, Turner R. Eigenvector centrality mapping for analyzing connectivity patterns in fMRI data of the human brain. PLoS One. 2010;5:e10232.

Jocham G, Neumann J, Klein TA, Danielmeier C, Ullsperger M. Adaptive coding of action values in the human rostral cingulate zone. J Neurosci. 2009;29:7489-96.

Neumann J, von Cramon DY, Lohmann G. Model-based clustering of meta-analytic functional imaging data. Hum Brain Mapp. 2008;29:177-92.

Forstmann BU, Wolfensteller U, Derrfuss J, Neumann J, Brass M, Ridderinkhof KR, von Cramon DY. When the choice is ours: context and agency modulate the neural bases of decision-making. PLoS One. 2008;3:e1899.

Klein TA, Endrass T, Kathmann N, Neumann J, von Cramon DY, Ullsperger M. Neural correlates of error awareness. Neuroimage. 2007;34:1774-81.

Klein TA, Neumann J, Reuter M, Hennig J, von Cramon DY, Ullsperger M. Genetically determined differences in learning from errors. Science. 2007;318:1642-5.



Filip Morys, Phd student

Henrik Hartmann, Phd student

Kathleen Wiencke, PhD student