title: Abnormally persistent fMRI activation during antisaccades in schizophrenia: a neural correlate of perseveration?
abstract: OBJECTIVE
  Impaired antisaccade performance is a consistent cognitive finding in schizophrenia. Antisaccades require both response inhibition and volitional motor programming, functions that are essential to flexible responding. We investigated whether abnormal timing of hemodynamic responses (HDRs) to antisaccades might contribute to perseveration of ocular motor responses in schizophrenia. We focused on the frontal eye field (FEF), which has been implicated in the persistent effects of antisaccades on subsequent responses in healthy individuals.
  
  
  METHODS
  Eighteen chronic, medicated schizophrenia outpatients and 15 healthy controls performed antisaccades and prosaccades during functional MRI. Finite impulse response models provided unbiased estimates of event-related HDRs. We compared groups on the peak amplitude, time-to-peak, and full-width half-max of the HDRs.
  
  
  RESULTS
  In patients, HDRs in bilateral FEF were delayed and prolonged but ultimately of similar amplitude to that of controls. These abnormalities were present for antisaccades, but not prosaccades, and were not seen in a control region. More prolonged HDRs predicted slower responses in trials that followed an antisaccade. This suggests that persistent FEF activity following an antisaccade contributes to inter-trial effects on latency.
  
  
  CONCLUSIONS
  Delayed and prolonged HDRs for antisaccades in schizophrenia suggest that the functions necessary for successful antisaccade performance take longer to implement and are more persistent. If abnormally persistent neural responses on cognitively demanding tasks are a more general feature of schizophrenia, they may contribute to response perseveration, a classic behavioral abnormality. These findings also underscore the importance of evaluating the temporal dynamics of neural activity to understand cognitive dysfunction in schizophrenia.
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Kara A
authors.initials: KA
authors.lastname: Dyckman
authors.forename: Adrian K C
authors.initials: AK
authors.lastname: Lee
authors.forename: Yigal
authors.initials: Y
authors.lastname: Agam
authors.forename: Mark
authors.initials: M
authors.lastname: Vangel
authors.forename: Donald C
authors.initials: DC
authors.lastname: Goff
authors.forename: Jason J S
authors.initials: JJ
authors.lastname: Barton
authors.forename: Dara S
authors.initials: DS
authors.lastname: Manoach
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply* / Q000473:pathology; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D011930:Reaction Time / Q000502:physiology; D012438:Saccades / Q000502:physiology*; D012559:Schizophrenia / Q000473:pathology*; D013997:Time Factors
chemical_list: D010100:Oxygen