A visual joke fMRI investigation into Theory of Mind and enhanced risk of schizophrenia

Theory of Mind (ToM) or mentalizing is the ability of individuals to determine the intentions and behavior of others. This ability is known to be compromised in schizophrenia and has been shown to fluctuate with symptom severity. Neuropsychological investigations into relatives of individuals with schizophrenia have shown that some relatives also show a deficit in this area of social cognition. In order to address this state and trait issue, we investigated the performance of high-risk relatives of individuals with schizophrenia to those of a matched control group (n = 13) on a blocked design visual joke fMRI paradigm. The task involved looking at two sets of cartoon jokes, one set which required mentalizing abilities to understand the jokes and another set that did not require such abilities. Relatives were divided into two groups based on the presence (HR+, n = 12) or absence (HR-, n = 12) of positive symptoms. The task provided robust activations across the groups in areas previously associated with mentalizing abilities, such as the PFC, precuneus, and temporal lobes. Significant between-group activations were observed in the PFC (primarily BA6, 8, and 9) with the HR- activating significantly greater than the HR+ in these regions. Both a secondary state-specific analysis and a third post hoc analysis further investigating state effects showed significant PFC between-group differences. This study is the first time relatives of individuals with schizophrenia have been imaged using a ToM paradigm, and the results provide evidence of both a state and state-mediated trait effect.

[1]  René S. Kahn,et al.  Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis , 2004, Schizophrenia Research.

[2]  D. Braus,et al.  [Functional magnetic resonance imaging and antipsychotics. Overview and own data]. , 2005, Der Radiologe.

[3]  Edward E. Smith,et al.  Neuroimaging studies of working memory: , 2003, Cognitive, affective & behavioral neuroscience.

[4]  D. Yves von Cramon,et al.  Variants of uncertainty in decision-making and their neural correlates , 2005, Brain Research Bulletin.

[5]  C. Frith,et al.  Schizophrenia, symptomatology and social inference: Investigating “theory of mind” in people with schizophrenia , 1995, Schizophrenia Research.

[6]  C. Frith,et al.  Functional imaging of ‘theory of mind’ , 2003, Trends in Cognitive Sciences.

[7]  Richard S. J. Frackowiak,et al.  ‘Theory of mind’ in the brain. Evidence from a PET scan study of Asperger syndrome , 1996, Neuroreport.

[8]  J. Decety,et al.  A PET Investigation of the Attribution of Intentions with a Nonverbal Task , 2000, NeuroImage.

[9]  Jordan Henry Grafman,et al.  Social contracts and precautions activate different neurological systems: An fMRI investigation of deontic reasoning , 2005, NeuroImage.

[10]  Evelyn C. Ferstl,et al.  The Anterior Frontomedian Cortex and Evaluative Judgment: An fMRI Study , 2002, NeuroImage.

[11]  Yaakov Stern,et al.  An event-related fMRI study of the neural networks underlying the encoding, maintenance, and retrieval phase in a delayed-match-to-sample task. , 2005, Brain research. Cognitive brain research.

[12]  Philip Robbins,et al.  Knowing Me, Knowing You Theory of Mind and the Machinery of Introspection , 2005 .

[13]  Klaus P. Ebmeier,et al.  fMRI correlates of state and trait effects in subjects at genetically enhanced risk of schizophrenia. , 2003, Brain : a journal of neurology.

[14]  A. Abu-Akel.  A neurobiological mapping of theory of mind , 2003, Brain Research Reviews.

[15]  M. Egan,et al.  Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia. , 2003, The American journal of psychiatry.

[16]  M. Hallett,et al.  Modeling other minds , 1995, Neuroreport.

[17]  M. Siegal,et al.  Neural systems involved in 'theory of mind' , 2002, Nature Reviews Neuroscience.

[18]  E. Bullmore,et al.  Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Marcia K. Johnson,et al.  Prefrontal activity associated with working memory and episodic long-term memory , 2003, Neuropsychologia.

[20]  C. Frith,et al.  Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes. , 2002, Brain : a journal of neurology.

[21]  Beatriz Luna,et al.  A preliminary functional magnetic resonance imaging study in offspring of schizophrenic parents , 2002, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[22]  M. Brüne.  "Theory of mind" in schizophrenia: a review of the literature. , 2005, Schizophrenia bulletin.

[23]  Uta Frith,et al.  Theory of mind , 2001, Current Biology.

[24]  C. Frith,et al.  Reading the mind in cartoons and stories: an fMRI study of ‘theory of mind’ in verbal and nonverbal tasks , 2000, Neuropsychologia.

[25]  F. Happé,et al.  Theory of mind: Independence of executive function and the role of the frontal cortex in acquired brain injury , 2000 .

[26]  Eve C. Johnstone,et al.  A neuropsychological investigation into ‘Theory of Mind’ and enhanced risk of schizophrenia , 2006, Psychiatry Research.

[27]  D. Manoach.  Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings , 2003, Schizophrenia Research.

[28]  S. Kéri,et al.  No evidence for impaired ‘theory of mind’ in unaffected first‐degree relatives of schizophrenia patients , 2004, Acta psychiatrica Scandinavica.

[29]  C. Frith,et al.  Development and neurophysiology of mentalizing. , 2003, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[30]  Eiman Azim,et al.  Sex differences in brain activation elicited by humor. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[31]  S. Lawrie,et al.  Voxel-based morphometry of grey matter densities in subjects at high risk of schizophrenia , 2003, Schizophrenia Research.

[32]  Stephen Lawrie,et al.  BMC Psychiatry BioMed Central , 2005 .

[33]  W. Grodd,et al.  Neural correlates of laughter and humour. , 2003, Brain : a journal of neurology.

[34]  Eve C. Johnstone,et al.  Declarative memory in unaffected adult relatives of patients with schizophrenia: A systematic review and meta-analysis , 2005, Schizophrenia Research.

[35]  Kenneth Mark Colby,et al.  Clinical artificial intelligence , 1981, Behavioral and Brain Sciences.

[36]  John K. Wing,et al.  Measurement and Classification of Psychiatric Symptoms: An Instruction Manual for the PSE and Catego Program , 1974 .

[37]  Eve C. Johnstone,et al.  Grey matter changes over time in high risk subjects developing schizophrenia , 2005, NeuroImage.

[38]  Lisa T. Eyler,et al.  Review of longitudinal functional neuroimaging studies of drug treatments in patients with schizophrenia , 2005, Schizophrenia Research.

[39]  Richard S. J. Frackowiak,et al.  Other minds in the brain: a functional imaging study of “theory of mind” in story comprehension , 1995, Cognition.

[40]  D. Premack,et al.  Does the chimpanzee have a theory of mind? , 1978, Behavioral and Brain Sciences.

[41]  M J Brammer,et al.  Exploring the social brain in schizophrenia: left prefrontal underactivation during mental state attribution. , 2000, The American journal of psychiatry.

[42]  Klaus P. Ebmeier,et al.  Predicting schizophrenia: findings from the Edinburgh High-Risk Study , 2005, British Journal of Psychiatry.

[43]  Jim van Os,et al.  Alterations in theory of mind in patients with schizophrenia and non‐psychotic relatives , 2003, Acta psychiatrica Scandinavica.

[44]  M Petrides,et al.  Monitoring of selections of visual stimuli and the primate frontal cortex , 1991, Proceedings of the Royal Society of London. Series B: Biological Sciences.