Effects of nicotine on hippocampal and cingulate activity during smooth pursuit eye movement in schizophrenia.
BACKGROUND
Abnormal smooth pursuit eye movement (SPEM) in schizophrenic patients is a well known phenomenon, but the neurophysiological mechanisms underlying the deficit are unknown. Nicotine temporarily improves SPEM and has been associated with reduced hippocampal hemodynamic activity in schizophrenics. Nicotine's effect on brain activity in control subjects performing SPEM has not been studied. The purpose of this work was to determine if nicotine differentially affects brain activity in schizophrenic and control subjects during pursuit eye tracking.


METHODS
16 subjects with schizophrenia and 16 control subjects underwent functional MR imaging during SPEM after receiving placebo or nicotine gum. Four brain regions were analyzed for main effects of group, drug, and interactions: hippocampus, cingulate gyrus, frontal eye fields, and area MT.


RESULTS
Nicotine reduced hippocampal activity in both groups, but the effect was greater in control subjects. A group by drug interaction was observed in the anterior cingulate gyrus, where nicotine decreased activity in control subjects and increased activity in schizophrenic subjects. There were no significant effects of group, drug, or interactions in frontal eye fields or area MT.


CONCLUSIONS
Nicotine may improve SPEM performance in people with schizophrenia through cholinergic stimulation of the hippocampus and cingulate gyrus. Potential mechanisms include improved inhibitory function and attention.
Tanabe
Jody
J
Department of Radiology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. jody.tanabe@uchsc.edu
Tregellas
Jason R
JR
Martin
Laura F
LF
Freedman
Robert
R
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005731:Ganglionic Stimulants / Q000008:administration & dosage*; D006179:Gyrus Cinguli / Q000098:blood supply / Q000187:drug effects*; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage*; D010100:Oxygen / Q000097:blood; D011698:Pursuit, Smooth / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*
D005731:Ganglionic Stimulants; D009538:Nicotine; D010100:Oxygen