Frontopolar cortical inefficiency may underpin reward and working memory dysfunction in bipolar disorder

Abstract Objectives. Emotional dysregulation in bipolar disorder is thought to arise from dysfunction within prefrontal cortical regions involved in cognitive control coupled with increased or aberrant activation within regions engaged in emotional processing. The aim of this study was to determine the common and distinct patterns of functional brain abnormalities during reward and working memory processing in patients with bipolar disorder. Methods. Participants were 36 euthymic bipolar disorder patients and 37 healthy comparison subjects matched for age, sex and IQ. Functional magnetic resonance imaging (fMRI) was conducted during the Iowa Gambling Task (IGT) and the n-back working memory task. Results. During both tasks, patients with bipolar disorder demonstrated a pattern of inefficient engagement within the ventral frontopolar prefrontal cortex with evidence of segregation along the medial-lateral dimension for reward and working memory processing, respectively. Moreover, patients also showed greater activation in the anterior cingulate cortex during the Iowa Gambling Task and in the insula during the n-back task. Conclusions. Our data implicate ventral frontopolar dysfunction as a core abnormality underpinning bipolar disorder and confirm that overactivation in regions involved in emotional arousal is present even in tasks that do not typically engage emotional systems.

[1]  M. Hamilton.  A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[2]  R. C. Young,et al.  A Rating Scale for Mania: Reliability, Validity and Sensitivity , 1978, British Journal of Psychiatry.

[3]  D. Wechsler.  WAIS-R manual : Wechsler adult intelligence scale-revised , 1981 .

[4]  A. Damasio,et al.  Insensitivity to future consequences following damage to human prefrontal cortex , 1994, Cognition.

[5]  R. Daroff,et al.  Clinical Handbook of Psychotropic Drugs , 1994 .

[6]  H. Damasio,et al.  Dissociation Of Working Memory from Decision Making within the Human Prefrontal Cortex , 1998, The Journal of Neuroscience.

[7]  T. Paus,et al.  Regional differences in the effects of task difficulty and motor output on blood flow response in the human anterior cingulate cortex: a review of 107 PET activation studies , 1998, Neuroreport.

[8]  R. Davidson,et al.  The functional neuroanatomy of emotion and affective style , 1999, Trends in Cognitive Sciences.

[9]  Y. Miyashita,et al.  Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI. , 1999, Brain : a journal of neurology.

[10]  S E Petersen,et al.  Direct comparison of episodic encoding and retrieval of words: an event-related fMRI study. , 1999, Memory.

[11]  Newell,et al.  A neural basis for general intelligence , 2000, American journal of ophthalmology-glaucoma.

[12]  H. Critchley,et al.  Neural Activity Relating to Generation and Representation of Galvanic Skin Conductance Responses: A Functional Magnetic Resonance Imaging Study , 2000, The Journal of Neuroscience.

[13]  Karl J. Friston,et al.  Dissociable Neural Responses in Human Reward Systems , 2000, The Journal of Neuroscience.

[14]  T. Robbins,et al.  Decision-making in mania: a PET study. , 2001, Brain : a journal of neurology.

[15]  W. Overman,et al.  Adult sex differences on a decision-making task previously shown to depend on the orbital prefrontal cortex. , 2001, Behavioral neuroscience.

[16]  J. Fuster.  The Prefrontal Cortex—An Update Time Is of the Essence , 2001, Neuron.

[17]  R. Henson,et al.  Frontal lobes and human memory: insights from functional neuroimaging. , 2001, Brain : a journal of neurology.

[18]  J B Poline,et al.  The neural system that bridges reward and cognition in humans: An fMRI study , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Gregory G. Brown,et al.  Error Rate and Outcome Predictability Affect Neural Activation in Prefrontal Cortex and Anterior Cingulate during Decision-Making , 2002, NeuroImage.

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

[21]  M. Egan,et al.  Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down. , 2003, The American journal of psychiatry.

[22]  H. Mayberg,et al.  State and trait influences on mood regulation in bipolar disorder: blood flow differences with an acute mood challenge , 2003, Biological Psychiatry.

[23]  Paul J. Laurienti,et al.  An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets , 2003, NeuroImage.

[24]  D. Yves von Cramon,et al.  Predicting events of varying probability: uncertainty investigated by fMRI , 2003, NeuroImage.

[25]  R. Murray,et al.  A functional MRI study of working memory task in euthymic bipolar disorder: evidence for task-specific dysfunction. , 2004, Bipolar disorders.

[26]  V. Menon,et al.  Anomalous prefrontal-subcortical activation in familial pediatric bipolar disorder: a functional magnetic resonance imaging investigation. , 2004, Archives of general psychiatry.

[27]  Catalina J. Hooper,et al.  Adolescents' performance on the Iowa Gambling Task: implications for the development of decision making and ventromedial prefrontal cortex. , 2004, Developmental psychology.

[28]  V. Schmithorst,et al.  Changes in neuronal activation in patients with bipolar disorder during performance of a working memory task. , 2004, Bipolar disorders.

[29]  S. Strakowski,et al.  The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings , 2005, Molecular Psychiatry.

[30]  M. Platt,et al.  Risk-sensitive neurons in macaque posterior cingulate cortex , 2005, Nature Neuroscience.

[31]  Kathryn M. McMillan,et al.  N‐back working memory paradigm: A meta‐analysis of normative functional neuroimaging studies , 2005, Human brain mapping.

[32]  O. Turnbull,et al.  Emotion-based learning and central executive resources: An investigation of intuition and the Iowa Gambling Task , 2005, Brain and Cognition.

[33]  Takashi Hanakawa,et al.  Functional activity related to risk anticipation during performance of the Iowa gambling task , 2005, NeuroImage.

[34]  A. Bechara.  Decision making, impulse control and loss of willpower to resist drugs: a neurocognitive perspective , 2005, Nature Neuroscience.

[35]  Joshua W. Brown,et al.  Learned Predictions of Error Likelihood in the Anterior Cingulate Cortex , 2005, Science.

[36]  M. Farah,et al.  Different underlying impairments in decision-making following ventromedial and dorsolateral frontal lobe damage in humans. , 2004, Cerebral cortex.

[37]  M. Paulus,et al.  Neurobiology of Decision Making: A Selective Review from a Neurocognitive and Clinical Perspective , 2005, Biological Psychiatry.

[38]  Peter Boesiger,et al.  Affective judgment and beneficial decision making: Ventromedial prefrontal activity correlates with performance in the Iowa Gambling Task , 2006, Human brain mapping.

[39]  Peter Fransson,et al.  Sustained and Transient Neural Modulations in Prefrontal Cortex Related to Declarative Long-Term Memory, Working Memory, and Attention , 2007, Cortex.

[40]  E. Koechlin,et al.  Anterior Prefrontal Function and the Limits of Human Decision-Making , 2007, Science.

[41]  Theo G. M. van Erp,et al.  The relationship between performance and fMRI signal during working memory in patients with schizophrenia, unaffected co-twins, and control subjects , 2007, Schizophrenia Research.

[42]  I. Torres,et al.  Neuropsychological functioning in euthymic bipolar disorder: a meta‐analysis , 2007, Acta psychiatrica Scandinavica. Supplementum.

[43]  D. Pandya,et al.  Efferent Association Pathways from the Rostral Prefrontal Cortex in the Macaque Monkey , 2007, The Journal of Neuroscience.

[44]  Melissa J. Green,et al.  The cognitive and neurophysiological basis of emotion dysregulation in bipolar disorder. , 2007, Journal of affective disorders.

[45]  Vanessa Raymont,et al.  Examining ventral and dorsal prefrontal function in bipolar disorder: A functional magnetic resonance imaging study , 2008, European Psychiatry.

[46]  Jonathan D. Cohen,et al.  Functional Imaging of Decision Conflict , 2008, The Journal of Neuroscience.

[47]  E. Rolls,et al.  The orbitofrontal cortex and beyond: From affect to decision-making , 2008, Progress in Neurobiology.

[48]  M L Phillips,et al.  Neural systems underlying voluntary and automatic emotion regulation: toward a neural model of bipolar disorder , 2008, Molecular Psychiatry.

[49]  D. Kupfer,et al.  Medication effects in neuroimaging studies of bipolar disorder. , 2008, The American journal of psychiatry.

[50]  M. Phillips,et al.  A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder , 2008, Molecular Psychiatry.

[51]  R. Murray,et al.  Genetic Liability for Bipolar Disorder Is Characterized by Excess Frontal Activation in Response to a Working Memory Task , 2008, Biological Psychiatry.

[52]  Sabine Landau,et al.  Cognitive functioning in patients with affective disorders and schizophrenia: A meta-analysis , 2009, International review of psychiatry.

[53]  S. Frangou.  Risk and resilience in bipolar disorder: rationale and design of the Vulnerability to Bipolar Disorders Study (VIBES). , 2009, Biochemical Society transactions.

[54]  D. Collier,et al.  Dissociable Brain Structural Changes Associated with Predisposition, Resilience, and Disease Expression in Bipolar Disorder , 2009, The Journal of Neuroscience.

[55]  Fernando Zelaya,et al.  Distinct roles of prefrontal cortical subregions in the Iowa Gambling Task. , 2009, Cerebral cortex.

[56]  N. Makris,et al.  An fMRI study of working memory in persons with bipolar disorder or at genetic risk for bipolar disorder , 2009, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[57]  V. Calhoun,et al.  Working memory circuitry in schizophrenia shows widespread cortical inefficiency and compensation , 2010, Schizophrenia Research.

[58]  E. Walker,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[59]  Janet B W Williams,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .