Neurocognitive models of behavioral control in obesity
PD Dr. Jane Neumann and Dr. Annette Horstmann, Integrated Research and Treatment Center AdiposityDiseases
An emerging insight from recent research is that obesity is not merely a problem of food intake, but a complex cognitive, emotional and motivational syndrome that needs to be addressed from different perspectives. One of the crucial problems concerns the integrity of executive functioning. It is hypothesized that cognitive control over behavior is deficient in obesity, although the exact mechanisms are not known to date. Identifying the nature of obesity-specific alterations of brain networks supporting cognitive control processes, such as response inhibition and outcome processing (i.e. the evaluation of reward and punishment), is vital to a deeper understanding of this disorder and to derive suitable targets for obesity therapy.
The overall goal of this project is to understand the interdependence between alterations in cognitive control over behavior and the development of obesity. Most of the previous research on this topic is confined to food-related contexts. Our research targets more fundamental mechanisms of behavioral and cognitive control, namely the ability to flexibly adapt one's behavior in the pursuit of an internal goal. This way we will be able to elucidate general alterations in obesity, whose influence in the development of obesity might have been overlooked so far.
In a series of behavioral and event-related fMRI experiments, we investigate key features of efficient cognitive control over behavior such as outcome processing, response inhibition and the effort subjects are willing to invest in pursuing a reward. Based on experimental data we establish comprehensive models capturing the different aspects of cognitive control, and identify the obesity-specific layout of its neural substrates. Data is analyzed in a multimodal approach, linking functional imaging, meta-analyses and behavioral assessments to computational and connectivity modeling, and taking into account gender and genotype as important modulating factors for the prevalence of obesity. Using these combined research approaches and analyses will allow us to provide targets for the development of optimal integrated behavioral therapy in obesity.
Figure 1. Obesity is associated with profound, gender-dependent structural alterations within brain regions involved in reward processing, cognitive, and homeostatic control.
The volume of posterior medial orbitofrontal cortex (OFC), nucleus accumbens (NAcc), and hypothalamus increases significantly with BMI and leptin, a more direct measure of the degree of obesity than BMI, in both genders (a, purple). For women, an additional association between gray matter volume and BMI/leptin can be observed in the left putamen (a, red). We found a significant negative association between leptin and GMV restricted to women in the right lateral prefrontal cortex (b). All GMV values are mean standardized and corrected for age, total gray and white matter.
Lean and obese women differ in their ability to adjust choice behavior to match long-term goals on the Iowa Gambling Task. (c) Preference for deck B over all trials correlates with BMI within the group of women. Gray line: linear regression. (d) Difference between lean and obese women in choice behavior during learning. Lean women learn to gradually select fewer cards from deck B. In contrast, obese women continue to select cards from deck B. Each block consists of five trials. (e) No difference between lean and obese men in choice behavior is observable during learning. Each block consists of five trials. (cf. Horstmann A et al., Frontiers in Human Neuroscience (2011)).
- 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; Epub ahead of print.
- 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; Epub ahead of print.
- 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; Epub ahead of print.
- Kube J, Schrimpf A, Garcia-Garcia I, Villringer A, Neumann J, Horstmann A. Differential heart rate responses to social and monetary reinforcement in women with obesity. Psychophysiology. 2016; Epub ahead of print.
- Schlögl H, Horstmann A, Villringer A, Stumvoll M. Functional neuroimaging in obesity and the potential for development of novel treatments. Lancet Diabetes Endocrinol. 2016; Epub ahead of print.
- 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.
- Deserno L, Wilbertz T, Reiter A, Horstmann A, Neumann 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.
- 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.
- 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 A, Horstmann 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 A, Neumann J. Reward processing in obesity, substance addiction and non-substance addiction. Obes Rev. 2014;15:853-69.
- Wilbertz T, Deserno L, Horstmann A, Neumann J, Villringer 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 A, Stumvoll M, Kovacs 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 A, Neumann 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, Villringer A, Horstmann A. Neural correlates of the volitional regulation of the desire for 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, Stumvoll 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.
* contributed equally