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Neurobiological mechanisms of social cognition treatment in high-functioning adults with autism spectrum disorder

  • Gabriela Rosenblau (a1) (a2) (a3), Garret O'Connell (a4), Hauke R. Heekeren (a1) (a2) (a5) and Isabel Dziobek (a1) (a2) (a4)



The promise of precision medicine for autism spectrum disorder (ASD) hinges on developing neuroscience-informed individualized interventions. Taking an important step in this direction, we investigated neuroplasticity in response to an ecologically-valid, computer-based social-cognitive training (SCOTT).


In an active control group design, 48 adults with ASD were randomly assigned to a 3-month SCOTT or non-social computer training. Participants completed behavioral tasks, a functional and structural magnetic resonance imaging session before and after the training period.


The SCOTT group showed social-cognitive improvements on close and distant generalization tasks. The improvements scaled with reductions in functional activity and increases in cortical thickness in prefrontal regions.


In sum, we provide evidence for the sensitivity of neuroscientific methods to reflect training-induced social-cognitive improvements in adults with ASD. These results encourage the use of neuroimaging data to describe and quantify treatment-related changes more broadly.


Corresponding author

Author for correspondence: Gabriela Rosenblau, E-mail:


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American Psychiatric Association (1994) Statistical Manual of Mental Disorders. Washington, DC: American Psychiatric Association.
Amodio, DM and Frith, CD (2006) Meeting of minds: the medial frontal cortex and social cognition. Nature Reviews Neuroscience 7, 268277.
Beauchamp, KG, Kahn, LE and Berkman, ET (2016) Does inhibitory control training transfer? Behavioral and neural effects on an untrained emotion regulation task. Social Cognitive and Affective Neuroscience 11, 13741382.
Behrens, TE, Hunt, LT, Woolrich, MW and Rushworth, MF (2008) Associative learning of social value. Nature 456, 245249.
Bishop-Fitzpatrick, L, Minshew, NJ and Eack, SM (2013) A systematic review of psychosocial interventions for adults with autism spectrum disorders. Journal of Autism and Developmental Disorders 43, 687694.
Bolte, S, Hubl, D, Feineis-Matthews, S, Prvulovic, D, Dierks, T and Poustka, F (2006) Facial affect recognition training in autism: Can we animate the fusiform gyrus? Behavioral Neuroscience 120, 211216.
Bolte, S, Ciaramidaro, A, Schlitt, S, Hainz, D, Kliemann, D, Beyer, A, Poustka, F, Freitag, C and Walter, H (2015) Training-induced plasticity of the social brain in autism spectrum disorder. British Journal of Psychiatry 207, 149157.
Bowler, DM (1992) ‘Theory of mind’ in Asperger's syndrome. Journal of Child Psychology and Psychiatry and Allied Disciplines 33, 877893.
Carter, CS, Barch, DM, Buchanan, RW, Bullmore, E, Krystal, JH, Cohen, J, Geyer, M, Green, M, Nuechterlein, KH, Robbins, T, Silverstein, S, Smith, EE, Strauss, M, Wykes, T and Heinssen, R (2008) Identifying cognitive mechanisms targeted for treatment development in schizophrenia: an overview of the first meeting of the cognitive neuroscience treatment research to improve cognition in schizophrenia initiative. Biological Psychiatry 64, 410.
Castelli, F, Frith, C, Happe, F and Frith, U (2002) Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes. Brain 125, 18391849.
Dapretto, M, Davies, MS, Pfeifer, JH, Scott, AA, Sigman, M, Bookheimer, SY and Iacoboni, M (2006) Understanding emotions in others: mirror neuron dysfunction in children with autism spectrum disorders. Nature Neuroscience 9, 2830.
Dziobek, I (2012) Comment: towards a more ecologically valid assessment of empathy. Emotion Review 4, 1819.
Dziobek, I, Fleck, S, Kalbe, E, Rogers, K, Hassenstab, J, Brand, M, Kessler, J, Woike, JK, Wolf, OT and Convit, A (2006) Introducing MASC: a movie for the assessment of social cognition. Journal of Autism and Developmental Disorders 36, 623636.
Dziobek, I, Rogers, K, Fleck, S, Bahnemann, M, Heekeren, HR, Wolf, OT and Convit, A (2008) Dissociation of cognitive and emotional empathy in adults with Asperger syndrome using the Multifaceted Empathy Test (MET). Journal of Autism and Developmental Disorders 38, 464473.
Dziobek, I, Bahnemann, M, Convit, A and Heekeren, HR (2010) The role of the fusiform-amygdala system in the pathophysiology of autism. Archives of General Psychiatry 67, 397405.
Erickson, KI, Colcombe, SJ, Wadhwa, R, Bherer, L, Peterson, MS, Scalf, PE, Kim, JS, Alvarado, M and Kramer, AF (2007) Training-induced functional activation changes in dual-task processing: an fMRI study. Cerebral Cortex 17, 192204.
Ethofer, T, Anders, S, Erb, M, Herbert, C, Wiethoff, S, Kissler, J, Grodd, W and Wildgruber, D (2006) Cerebral pathways in processing of affective prosody: a dynamic causal modeling study. Neuroimage 30, 580587.
Filippi, M, Ceccarelli, A, Pagani, E, Gatti, R, Rossi, A, Stefanelli, L, Falini, A, Comi, G and Rocca, MA (2010) Motor learning in healthy humans is associated to gray matter changes: a tensor-based morphometry study. Ed. PA Valdes-Sosa. PLoS ONE 5, e10198.
Frith, CD and Frith, U (2006) The neural basis of mentalizing. Neuron 50, 531534.
Frith, CD and Frith, U (2008) Implicit and explicit processes in social cognition. Neuron 60, 503510.
Garvert, MM, Moutoussis, M, Kurth-Nelson, Z, Behrens, TE and Dolan, RJ (2015) Learning-induced plasticity in medial prefrontal cortex predicts preference malleability. Neuron 85, 418428.
Golan, O and Baron-Cohen, S (2006) Systemizing empathy: teaching adults with Asperger syndrome or high-functioning autism to recognize complex emotions using interactive multimedia. Development and Psychopathology 18, 591617.
Gu, Y, Hu, X, Pan, W, Yang, C, Wang, L, Li, Y and Chen, A (2016) Neural activities underlying the feedback express salience prediction errors for appetitive and aversive stimuli. Nature Publishing Group Scientific Reports 6, 34032.
Hadjikhani, N, Joseph, RM, Snyder, J and Tager-Flusberg, H (2006) Anatomical differences in the mirror neuron system and social cognition network in autism. Cerebral Cortex 16, 12761282.
Hadwin, J, Baron-Cohen, S, Howlin, P and Hill, K (1996) Can we teach children with autism to understand emotions, belief, or pretence? Development and Psychopathology 8, 345365.
Hadwin, J, Baron-Cohen, S, Howlin, P and Hill, K (1997) Does teaching theory of mind have an effect on the ability to develop conversation in children with autism? Journal of Autism and Developmental Disorders 27, 519537.
Hall, J, Philip, RCM, Marwick, K, Whalley, HC, Romaniuk, L, McIntosh, AM, Santos, I, Sprengelmeyer, R, Johnstone, EC, Stanfield, AC, Young, AW and Lawrie, SM (2012) Social cognition, the male brain and the autism spectrum. PLoS ONE 7.
Hampton, AN, Bossaerts, P and O'Doherty, JP (2008) Neural correlates of mentalizing-related computations during strategic interactions in humans. Proceedings of the National Academy of Sciences of the USA 105, 67416746.
Joiner, J, Piva, M, Turrin, C and Chang, SWC (2017) Social learning through prediction error in the brain. npj Science of Learning 2, 8.
Jones, JA and Callan, DE (2003) Brain activity during audiovisual speech perception: an fMRI study of the McGurk effect. Neuroreport 14, 11291133.
Kelly, AMC and Garavan, H (2005) Human functional neuroimaging of brain changes associated with practice. Cerebral Cortex 15, 10891102.
Kessler, D, Angstadt, M and Sripada, CS (2017) Reevaluating ‘cluster failure’ in fMRI using nonparametric control of the false discovery rate. Proceedings of the National Academy of Sciences 114, E3372E3373.
Kliemann, D, Rosenblau, G, Bölte, S, Heekeren, HR and Dziobek, I (2013) Face puzzle-two new video-based tasks for measuring explicit and implicit aspects of facial emotion recognition. Frontiers in Psychology 4.
Kühn, S, Schmiedek, F, Noack, H, Wenger, E, Bodammer, NC, Lindenberger, U and Lövden, M (2013) The dynamics of change in striatal activity following updating training. Human Brain Mapping 34, 15301541.
Lai, MC, Lombardo, MV, Ecker, C, Chakrabarti, B, Suckling, J, Bullmore, ET, Happé, F, Murphy, DGM and Baron-Cohen, S (2015) Neuroanatomy of individual differences in language in adult males with autism. Cerebral Cortex 25, 36133628.
Lai, MC, Lombardo, MV, Pasco, G, Ruigrok, AN, Wheelwright, SJ, Sadek, SA, Chakrabarti, B and Baron-Cohen, S (2011) A behavioral comparison of male and female adults with high functioning autism spectrum conditions. PLoS One 6, e20835.
Lee, H, Voss, MW, Prakash, RS, Boot, WR, Vo, LTK, Basak, C, VanPatter, M, Gratton, G, Fabiani, M and Kramer, AF (2012) Videogame training strategy-induced change in brain function during a complex visuomotor task. Behavioural Brain Research 232, 348357.
Leech, R and Sharp, DJ (2014) The role of the posterior cingulate cortex in cognition and disease. Brain 137, 1232.
Lord, C, Rutter, M, DiLavore, PC, Risi, S, Gotham, K and Bishop, S (2012) Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) Manual (Part I): Modules 1–4. Torrance, CA: Western Psychological Services.
Lord, C, Rutter, M and Le Couteur, A (1994) Autism Diagnostic interview-revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders 24, 659685.
Lord, C, Schopler, E and Revicki, D (1982) Sex differences in autism. Journal of Autism and Developmental Disorders 12, 317330.
Masi, A, DeMayo, MM, Glozier, N and Guastella, AJ (2017) An overview of autism spectrum disorder, heterogeneity and treatment options. Neuroscience Bulletin 33, 183193.
Mende-Siedlecki, P, Cai, Y and Todorov, A (2013) The neural dynamics of updating person impressions. Social Cognitive and Affective Neuroscience 8, 623631.
Metzler-Baddeley, C, Caeyenberghs, K, Foley, S and Jones, DK (2016) Task complexity and location specific changes of cortical thickness in executive and salience networks after working memory training. NeuroImage 130, 4862.
Miller, GA and Chapman, JP (2001) Misunderstanding analysis of covariance. Journal of Abnormal Psychology 110, 4048.
Montag, C, Ehrlich, A, Neuhaus, K, Dziobek, I, Heekeren, HR, Heinz, A and Gallinat, J (2010) Theory of mind impairments in euthymic bipolar patients. Journal of Affective Disorders 123, 264269.
Montag, C, Dziobek, I, Richter, IS, Neuhaus, K, Lehmann, A, Sylla, R, Heekeren, HR, Heinz, A and Gallinat, J (2011) Different aspects of theory of mind in paranoid schizophrenia: evidence from a video-based assessment. Psychiatry Research 186, 203209.
Monte, OD, Krueger, F, Solomon, JM, Schintu, S, Knutson, KM, Strenziok, M, Pardini, M, Leopold, A, Raymont, V and Grafman, J (2013) A voxel-based lesion study on facial emotion recognition after penetrating brain injury. Social Cognitive and Affective Neuroscience 8, 632639.
Mueller, S, Keeser, D, Samson, AC, Kirsch, V, Blautzik, J, Grothe, M, Erat, O, Hegenloh, M, Coates, U, Reiser, MF, Hennig-Fast, K and Meindl, T (2013) Convergent findings of altered functional and structural brain connectivity in individuals with high functioning autism: a multimodal MRI study. PLoS ONE 8, e67329.
Nichols, T, Kriegeskorte, N, Yeo, BTT, Kriegeskorte, N, Milham, MP, Poldrack, RA, Poline, J and Proal, E (2017) Best practices in data analysis and sharing in neuroimaging using MRI best practices in data analysis and sharing in neuroimaging using MRI. Nature Neuroscience 20, 299303.
Ochsner, KN, Knierim, K, Ludlow, DH, Hanelin, J, Ramachandran, T, Glover, G and Mackey, SC (2004) Reflecting upon feelings: an fMRI study of neural systems supporting the attribution of emotion to self and other. Journal of Cognitive Neuroscience 16, 17461772.
Pelphrey, KA and Carter, EJ (2008) Brain mechanisms for social perception: lessons from autism and typical development. Annals of the New York Academy of Sciences 1145, 283299.
Pike, N (2011) Using false discovery rates for multiple comparisons in ecology and evolution. Methods in Ecology and Evolution 2, 278282.
Preissler, S, Dziobek, I, Ritter, K, Heekeren, HR and Roepke, S (2010) Social cognition in borderline personality disorder: evidence for disturbed recognition of the emotions, thoughts, and intentions of others. Frontiers in Behavioral Neuroscience 4, 182.
Rochon, E, Leonard, C, Burianova, H, Laird, L, Soros, P, Graham, S and Grady, C (2010) Neural changes after phonological treatment for anomia: an fMRI study. Brain and Language 114, 164179.
Rosenblau, G, Kliemann, D, Heekeren, HR and Dziobek, I (2015) Approximating implicit and explicit mentalizing with two naturalistic video-based tasks in typical development and autism spectrum disorder. Journal of Autism and Developmental Disorders 45, 953965.
Rosenblau, G, Kliemann, D, Dziobek, I and Heekeren, HR (2017) Emotional prosody processing in autism spectrum disorder. Social Cognitive and Affective Neuroscience 12, 224239.
Rosenblau, G, Kliemann, D, Lemme, B, Walter, H, Heekeren, HR and Dziobek, I (2016) The role of the amygdala in naturalistic mentalising in typical development and in autism spectrum disorder. British Journal of Psychiatry 208, 556564.
Rosenblau, G, Korn, CW and Pelphrey, KA, Rosenblau, G, Korn, CW and Pelphrey, KA (2018). A computational account of optimizing social predictions reveals that adolescents are conservative learners in social contexts. The Journal of Neuroscience 38, 974988.
Sabatinelli, D, Fortune, EE, Li, Q, Siddiqui, A, Krafft, C, Oliver, WT, Beck, S and Jeffries, J (2011) Emotional perception: meta-analyses of face and natural scene processing. NeuroImage 54, 25242533.
Sakia, RM (1992) The Box-Cox transformation technique: a review. The Statistician 41, 169.
Sato, W, Kochiyama, T, Uono, S, Yoshimura, S, Kubota, Y, Sawada, R, Sakihama, M and Toichi, M (2017) Reduced gray matter volume in the social brain network in adults with autism spectrum disorder. Frontiers in Human Neuroscience 11, 395.
Schiller, D, Freeman, JB, Mitchell, JP, Uleman, JS and Phelps, EA (2009) A neural mechanism of first impressions. Nature Neuroscience 12, 508514.
Seid-Fatemi, A and Tobler, PN (2015) Efficient learning mechanisms hold in the social domain and are implemented in the medial prefrontal cortex. Social Cognitive and Affective Neuroscience 10, 735743.
Storey, JD (2002) A direct approach to false discovery rates. Journal of the Royal Statistical Society. Series B: Statistical Methodology 64, 479498.
Sukhodolsky, DG, Vander Wyk, BC, Eilbott, JA, McCauley, SA, Ibrahim, K, Crowley, MJ and Pelphrey, KA (2016) Neural mechanisms of cognitive-behavioral therapy for aggression in children and adolescents: design of a randomized controlled trial within the National Institute for Mental Health Research Domain Criteria Construct of Frustrative Non-Reward. Journal of Child and Adolescent Psychopharmacology 26, 3848.
Szycik, GR, Jansma, H and Münte, TF (2009) Audiovisual integration during speech comprehension: an fMRI study comparing ROI-based and whole brain analyses. Human Brain Mapping 30, 19901999.
Takahashi, H, Yahata, N, Koeda, M, Matsuda, T, Asai, K and Okubo, Y (2004) Brain activation associated with evaluative processes of guilt and embarrassment: an fMRI study. Neuroimage 23, 967974.
Takeuchi, H, Taki, Y, Sassa, Y, Hashizume, H, Sekiguchi, A, Fukushima, A and Kawashima, R (2011) Working memory training using mental calculation impacts regional gray matter of the frontal and parietal regions. Ed. G Chapouthier PLoS ONE 6, e23175.
Tavares, RM, Mendelsohn, A, Grossman, Y, Williams, CH, Shapiro, M, Trope, Y and Schiller, D (2015) A map for social navigation in the human brain. Neuron 87, 231243.
Tomasi, D, Ernst, T, Caparelli, EC and Chang, L (2004) Practice-induced changes of brain function during visual attention: a parametric fMRI study at 4 Tesla. NeuroImage 23, 14141421.
Uono, S, Sato, W, Kochiyama, T, Sawada, R, Kubota, Y, Yoshimura, S and Toichi, M (2016). Neural substrates of the ability to recognize facial expressions: a voxel-based morphometry study. Social Cognitive and Affective Neuroscience. 12, 487495.
Valkanova, V, Eguia Rodriguez, R and Ebmeier, KP (2014) Mind over matter – what do we know about neuroplasticity in adults? International Psychogeriatrics 26, 891909.
van Raalten, TR, Ramsey, NF, Duyn, J and Jansma, JM (2008) Practice induces function-specific changes in brain activity. Ed. J Lauwereyns. PLoS ONE 3, e3270.
Ventola, P, Friedman, HE, Anderson, LC, Wolf, JM, Oosting, D, Foss-Feig, J, McDonald, N, Volkmar, F and Pelphrey, KA (2014) Improvements in social and adaptive functioning following short-duration PRT program: a clinical replication. Journal of Autism and Developmental Disorders 44, 28622870.
Ventola, P, Yang, DY, Friedman, HE, Oosting, D, Wolf, J, Sukhodolsky, DG and Pelphrey, KA (2015) Heterogeneity of neural mechanisms of response to pivotal response treatment. Brain Imaging and Behavior 9, 7488.
Wallace, GL, Eisenberg, IW, Robustelli, B, Dankner, N, Kenworthy, L, Giedd, JN and Martin, A (2015) Longitudinal cortical development during adolescence and young adulthood in autism spectrum disorder: increased cortical thinning but comparable surface area changes. Journal of the American Academy of Child and Adolescent Psychiatry 54, 464469.
Walter, H, Adenzato, M, Ciaramidaro, A, Enrici, I, Pia, L and Bara, BG (2004) Understanding intentions in social interaction: the role of the anterior paracingulate cortex. Journal of Cognitive Neuroscience 16, 18541863.
Wilson, SM, Molnar-Szakacs, I and Iacoboni, M (2008) Beyond superior temporal cortex: intersubject correlations in narrative speech comprehension. Cerebral Cortex 18, 230242.
Wolf, I, Dziobek, I and Heekeren, HR (2010) Neural correlates of social cognition in naturalistic settings: a model-free analysis approach. Neuroimage 49, 894904.
Woollett, K and Maguire, EA (2011) Acquiring ‘the knowledge’ of London's layout drives structural brain changes. Current Biology 21, 21092114.
Yang, DY-J, Rosenblau, G, Keifer, C and Pelphrey, KA (2015) An integrative neural model of social perception, action observation, and theory of mind. Neuroscience and Biobehavioral Reviews 51, 263275.
Yang, YJD, Allen, T, Abdullahi, SM, Pelphrey, KA, Volkmar, FR and Chapman, SB (2018) Neural mechanisms of behavioral change in young adults with high-functioning autism receiving virtual reality social cognition training: a pilot study. pp. 113.
Zaki, J and Ochsner, K (2009) The need for a cognitive neuroscience of naturalistic social cognition. Annals of the New York Academy of Sciences 1167, 1630.


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Neurobiological mechanisms of social cognition treatment in high-functioning adults with autism spectrum disorder

  • Gabriela Rosenblau (a1) (a2) (a3), Garret O'Connell (a4), Hauke R. Heekeren (a1) (a2) (a5) and Isabel Dziobek (a1) (a2) (a4)


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