Nicotine effects on brain function and functional connectivity in schizophrenia.
BACKGROUND
Nicotine in tobacco smoke can improve functioning in multiple cognitive domains. High rates of smoking among schizophrenic patients may reflect an effort to remediate cognitive dysfunction. Our primary aim was to determine whether nicotine improves cognitive function by facilitating activation of brain regions mediating task performance or by facilitating functional connectivity.


METHODS
Thirteen smokers with schizophrenia and 13 smokers with no mental illness were withdrawn from tobacco and underwent functional magnetic resonance imaging (fMRI) scanning twice, once after placement of a placebo patch and once after placement of a nicotine patch. During scanning, subjects performed an n-back task with two levels of working memory load and of selective attention load.


RESULTS
During the most difficult (dichotic 2-back) task condition, nicotine improved performance of schizophrenic subjects and worsened performance of control subjects. Nicotine also enhanced activation of a network of regions, including anterior cingulate cortex and bilateral thalamus, and modulated thalamocortical functional connectivity to a greater degree in schizophrenic than in control subjects during dichotic 2-back task performance.


CONCLUSIONS
In tasks that tax working memory and selective attention, nicotine may improve performance in schizophrenia patients by enhancing activation of and functional connectivity between brain regions that mediate task performance.
Jacobsen
Leslie K
LK
Department of Psychiatry, Yale University School of Medicine, 100 York Street #28, West Haven, CT 06511, USA.
D'Souza
D Cyril
DC
Mencl
W Einar
WE
Pugh
Kenneth R
KR
Skudlarski
Pawel
P
Krystal
John H
JH
D000328:Adult; D000704:Analysis of Variance; D001288:Attention / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001931:Brain Mapping; D010054:Brief Psychiatric Rating Scale; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D008875:Middle Aged; D009483:Neuropsychological Tests; D009538:Nicotine / Q000097:blood / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000097:blood / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D012044:Regression Analysis; D012559:Schizophrenia / Q000473:pathology / Q000503:physiopathology*; D012906:Smoke; D013647:Task Performance and Analysis; D014706:Verbal Learning / Q000187:drug effects*
D018722:Nicotinic Agonists; D012906:Smoke; D009538:Nicotine