Expanding the response space in chronic schizophrenia: the relevance of left prefrontal cortex

OBJECTIVE This study probed the ability of people with chronic schizophrenia to control their behavior in time by requiring them to deliberately vary responses within the temporal domain (i.e., to avoid regular inter-response intervals). METHODS Thirteen schizophrenia patients performed single finger movements (at moments of their own choosing) in an event-related functional magnetic resonance imaging paradigm. Their performance was computed using the coefficient of variation of inter-response interval duration. RESULTS Task performance was positively correlated with activation of left lateral prefrontal cortex. Post hoc analyses revealed an inverse correlation between activation in this region and severity of attentional impairment. CONCLUSION These findings implicate left lateral prefrontal cortex in the modulation of the temporal response space in schizophrenia and imply greater attentional (executive) impairment among those who fail to modulate their behavior in time.

[1]  C. Frith,et al.  Stereotyped responding by schizophrenic patients on a two-choice guessing task , 1983, Psychological Medicine.

[2]  Nikos G. Papadakis,et al.  Approaching an ecologically valid functional anatomy of spontaneous “willed” action , 2003, NeuroImage.

[3]  L. Cipolotti,et al.  Dynamic aphasia: an inability to select between competing verbal responses? , 1998, Brain : a journal of neurology.

[4]  R. Bornstein,et al.  Neuropsychological correlates of negative, disorganized and psychotic symptoms in schizophrenia , 1998, Schizophrenia Research.

[5]  Michael D. Hunter,et al.  Spatial and temporal dissociation in prefrontal cortex during action execution , 2004, NeuroImage.

[6]  J. Fuster Frontal lobe and cognitive development , 2002, Journal of neurocytology.

[7]  J. Desmond,et al.  Dissociation of Frontal and Cerebellar Activity in a Cognitive Task: Evidence for a Distinction between Selection and Search , 1998, NeuroImage.

[8]  G. Miller Protean primates: The evolution of adaptive unpredictability in competition and courtship , 1997 .

[9]  Michael F. Green,et al.  What are the functional consequences of neurocognitive deficits in schizophrenia? , 1996, The American journal of psychiatry.

[10]  Karl J. Friston,et al.  Grey matter correlates of syndromes in schizophrenia , 1997, British Journal of Psychiatry.

[11]  Karl J. Friston,et al.  Willed action and the prefrontal cortex in man: a study with PET , 1991, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[12]  C. Frith,et al.  Towards a functional anatomy of volition , 1999 .

[13]  S. C. Strother,et al.  The Quantitative Evaluation of Functional Neuroimaging Experiments: Mutual Information Learning Curves , 2002, NeuroImage.

[14]  I. Wilkinson,et al.  Modafinil modulates anterior cingulate function in chronic schizophrenia. , 2005, The British journal of psychiatry : the journal of mental science.

[15]  J. Fuster,et al.  Prefrontal neurons in networks of executive memory , 2000, Brain Research Bulletin.

[16]  R. Byrne,et al.  Machiavellian intelligence II : extensions and evaluations , 1997 .

[17]  C. Frith,et al.  The role of dorsolateral prefrontal cortex in the selection of action as revealed by functional imaging , 2000 .

[18]  M. Jahanshahi,et al.  The left dorsolateral prefrontal cortex and random generation of responses: studies with transcranial magnetic stimulation , 1998, Neuropsychologia.

[19]  W. Prinz,et al.  Disorders of volition , 2006 .

[20]  S. M. Deban,et al.  A Novel Antipredator Mechanism in Salamanders: Rolling Escape in Hydromantes platycephalus , 1995 .

[21]  Karl J. Friston,et al.  Spatial registration and normalization of images , 1995 .

[22]  S. Rose,et al.  Deficits on self ordered tasks associated with hyperostosis frontalis interna , 1997, Journal of neurology, neurosurgery, and psychiatry.

[23]  D. A. Humphries,et al.  Protean defence by prey animals , 1970, Oecologia.

[24]  T. Shallice,et al.  Can the neuropsychological case-study approach be applied to schizophrenia? , 1991, Psychological Medicine.

[25]  Karl J. Friston,et al.  Dorsolateral prefrontal cortex dysfunction in the major psychoses; symptom or disease specificity? , 1993, Journal of neurology, neurosurgery, and psychiatry.

[26]  R. Kemp,et al.  Differences Between Fingers and Hands in Tapping Ability: Dissociation Between Speed and Regularity , 1986, Cortex.

[27]  S A Spence,et al.  Prefrontal cortex activity in people with schizophrenia and control subjects , 1998, British Journal of Psychiatry.

[28]  Alexander L. Miller,et al.  The functional significance of symptomatology and cognitive function in schizophrenia , 1997, Schizophrenia Research.

[29]  T. Shallice,et al.  “Sculpting the Response Space”—An Account of Left Prefrontal Activation at Encoding , 2000, NeuroImage.

[30]  T. Barnes A Rating Scale for Drug-Induced Akathisia , 1989, British Journal of Psychiatry.

[31]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[32]  M. Jahanshahi,et al.  Willed action and its impairments. , 1998, Cognitive neuropsychology.

[33]  M C Ridding,et al.  The effects of transcranial magnetic stimulation over the dorsolateral prefrontal cortex on suppression of habitual counting during random number generation. , 1998, Brain : a journal of neurology.

[34]  M. Lyon,et al.  Stereotyped responding by schizophrenic outpatients: cross-cultural confirmation of perseverative switching on a two-choice task. , 1986, Journal of psychiatric research.

[35]  J. Driver,et al.  Control of Cognitive Processes: Attention and Performance XVIII , 2000 .

[36]  M. Hunter,et al.  Neuroscience and the will , 2002 .

[37]  Terry M. Peters,et al.  3D statistical neuroanatomical models from 305 MRI volumes , 1993, 1993 IEEE Conference Record Nuclear Science Symposium and Medical Imaging Conference.

[38]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[39]  C. Frith,et al.  Brain regions involved in prospective memory as determined by positron emission tomography , 2001, Neuropsychologia.

[40]  ChrisD . Frith The Cognitive Neuropsychology of Schizophrenia , 1992 .

[41]  E. Perret The left frontal lobe of man and the suppression of habitual responses in verbal categorical behaviour. , 1974, Neuropsychologia.

[42]  Karl J. Friston,et al.  Patterns of Cerebral Blood Flow in Schizophrenia , 1992, British Journal of Psychiatry.

[43]  D. Brooks,et al.  A PET study of voluntary movement in schizophrenic patients experiencing passivity phenomena (delusions of alien control). , 1997, Brain : a journal of neurology.

[44]  Matthew Flatt,et al.  PsyScope: An interactive graphic system for designing and controlling experiments in the psychology laboratory using Macintosh computers , 1993 .

[45]  T. Shallice From Neuropsychology to Mental Structure: Converging Operations: Specific Syndromes and Evidence from Normal Subjects , 1988 .

[46]  Philip D. Harvey,et al.  Convergent Validity and Neuropsychological Correlates of the Schedule for the Assessment of Negative Symptoms (SANS) Attention Subscale , 2001, The Journal of nervous and mental disease.

[47]  G. Simpson,et al.  A RATING SCALE FOR EXTRAPYRAMIDAL SIDE EFFECTS , 1970, Acta psychiatrica Scandinavica. Supplementum.