Cognitive effects of nicotine in humans: an fMRI study

To elucidate the neural correlates of cognitive effects of nicotine, we examined behavioral performance and blood oxygenation level-dependent regional brain activity, using functional magnetic resonance imaging, during a parametric "n-back" task in healthy nonsmoking males after the administration of nicotine (12 microg/kg body weight) or saline. Nicotine, compared to placebo, improved accuracy (P = 0.008) in all active conditions (2%-11%), and had a load-specific effect on latency (P = 0.004; 43.78% decrease at the highest memory load). Within a network of parietal and frontal areas activated by the task (P < 0.05, corrected at the voxel level), nicotine produced an increased response (P < 0.05; uncorrected within the regions of interest) in the anterior cingulate, superior frontal cortex, and superior parietal cortex. It also produced an increased response in the midbrain tectum in all active conditions and in the parahippocampal gyrus, cerebellum, and medial occipital lobe during rest (P = 0.05; uncorrected). The present observations point to altered neuronal activity in a distributed neural network associated with on-line task monitoring and attention and arousal systems as underlying nicotine-related enhancement of attention and working memory in human subjects.

[1]  A. Vincent,et al.  Effects of tobacco smoking and gender on interhemispheric cognitive function: performance and confidence measures , 1997, Behavioural pharmacology.

[2]  Carmen Martin-Ruiz,et al.  Nicotinic receptor abnormalities in Alzheimer’s disease , 2001, Biological Psychiatry.

[3]  Richard S. J. Frackowiak,et al.  The neural correlates of the verbal component of working memory , 1993, Nature.

[4]  Agneta Nordberg,et al.  Neuronal nicotinic receptors in the human brain , 2000, Progress in Neurobiology.

[5]  Veena Kumari,et al.  Influence of cigarette smoking on prepulse inhibition of the acoustic startle response in schizophrenia , 2001, Human psychopharmacology.

[6]  Alan C. Evans,et al.  Time-Related Changes in Neural Systems Underlying Attention and Arousal During the Performance of an Auditory Vigilance Task , 1997, Journal of Cognitive Neuroscience.

[7]  Karl J. Friston,et al.  How Many Subjects Constitute a Study? , 1999, NeuroImage.

[8]  E D Levin,et al.  Development of nicotinic drug therapy for cognitive disorders. , 2000, European journal of pharmacology.

[9]  Sohee Park,et al.  Nicotine Impairs Spatial Working Memory while Leaving Spatial Attention Intact , 2000, Neuropsychopharmacology.

[10]  R G Hoffmann,et al.  Nicotine-induced limbic cortical activation in the human brain: a functional MRI study. , 1998, The American journal of psychiatry.

[11]  Jack E. Henningfield,et al.  Nicotine and Smoking: A Review of Effects on Human Performance , 1994 .

[12]  Colin Feyerabend,et al.  Non-smokers show acute tolerance to subcutaneous nicotine , 2005, Psychopharmacology.

[13]  Edward D Levin,et al.  Cognitive effects of nicotine , 2001, Biological Psychiatry.

[14]  Edward E. Smith,et al.  Working Memory: A View from Neuroimaging , 1997, Cognitive Psychology.

[15]  R. Kumar,et al.  Nicotine and smoking. , 1981, Current developments in psychopharmacology.

[16]  D. Hatsukami,et al.  The effects of varying cigarette deprivation duration on cognitive and performance tasks. , 1989, Journal of substance abuse.

[17]  Raymond E. Thornton,et al.  Smoking behaviour: Physiological and psychological influences , 1978 .

[18]  Joshua W. Brown,et al.  Monitoring and Control of Action by the Frontal Lobes , 2002, Neuron.

[19]  S. Wonnacott,et al.  Neuronal nicotinic receptors , 2001 .

[20]  R. Gray,et al.  Nicotinic Modulation of Glutamate and GABA Synaptic Transmission in Hippocampal Neurons , 1999, Annals of the New York Academy of Sciences.

[21]  J. Coull.  Neural correlates of attention and arousal: insights from electrophysiology, functional neuroimaging and psychopharmacology , 1998, Progress in Neurobiology.

[22]  S J Heishman,et al.  Effect of nicotine on brain activation during performance of a working memory task , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[23]  M. Eysenck.  Attention And Arousal, Cognition And Performance , 1982 .

[24]  Verner Knott,et al.  Transdermal Nicotine Single Dose Effects on Mood, EEG, Performance, and Event-Related Potentials , 1999, Pharmacology Biochemistry and Behavior.

[25]  R. Yerkes,et al.  The relation of strength of stimulus to rapidity of habit‐formation , 1908 .

[26]  S C Williams,et al.  Quality control for functional magnetic resonance imaging using automated data analysis and Shewhart charting , 1999, Magnetic resonance in medicine.

[27]  E. Levin,et al.  Nicotinic acetylcholine involvement in cognitive function in animals , 1998, Psychopharmacology.

[28]  D. Warburton,et al.  Improvements in performance without nicotine withdrawal , 1994, Psychopharmacology.

[29]  E. Perez-stable,et al.  Slower metabolism and reduced intake of nicotine from cigarette smoking in Chinese-Americans. , 2002, Journal of the National Cancer Institute.

[30]  Gregory V. Simpson,et al.  Evidence for Anterior Cingulate Cortex Involvement in Monitoring Preparatory Attentional Set , 2002, NeuroImage.

[31]  P. Clarke,et al.  Nicotinic Receptors and Cholinergic Neurotransmission in the Central Nervous System , 1995, Annals of the New York Academy of Sciences.

[32]  R. Coppola,et al.  Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. , 1999, Cerebral cortex.

[33]  H. Hodges,et al.  Neurochemical mechanisms mediating the behavioral and cognitive effects of nicotine , 1994 .

[34]  Agneta Nordberg,et al.  Nicotinic receptor abnormalities of Alzheimer’s disease: therapeutic implications , 2001, Biological Psychiatry.

[35]  A Gale,et al.  Evidence of more rapid stimulus evaluation following cigarette smoking. , 1985, Addictive behaviors.

[36]  W. J. Jackson,et al.  Effects of stimulation or blockade of central nicotinic-cholinergic receptors on performance of a novel version of the rat stimulus discrimination task , 2005, Psychopharmacology.

[37]  Edward D Levin,et al.  Effects of nicotinic dimethylaminoethyl esters on working memory performance of rats in the radial-arm maze , 1995, Pharmacology Biochemistry and Behavior.

[38]  Edward D. Levin,et al.  Bridged nicotine, isonicotine, and norisonicotine effects on working memory performance of rats in the radial‐arm maze , 1999 .

[39]  Monique Ernst,et al.  Smoking History and Nicotine Effects on Cognitive Performance , 2001, Neuropsychopharmacology.

[40]  J. Cohen,et al.  Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control. , 2000, Science.

[41]  Karl J. Friston,et al.  Movement‐Related effects in fMRI time‐series , 1996, Magnetic resonance in medicine.

[42]  M. Molinari,et al.  The cerebellum in the spatial problem solving: a co-star or a guest star? , 1998, Progress in Neurobiology.

[43]  M. Botvinick,et al.  Conflict monitoring and cognitive control. , 2001, Psychological review.

[44]  Edward E. Smith,et al.  Temporal dynamics of brain activation during a working memory task , 1997, Nature.

[45]  M. Sullivan,et al.  Nicotine dependence: the role for antidepressants and anxiolytics. , 2002, Current opinion in investigational drugs.

[47]  Jeffrey A. Gray,et al.  Effect of acute subcutaneous nicotine on prepulse inhibition of the acoustic startle reflex in healthy male non-smokers , 1997, Psychopharmacology.

[48]  B. Sahakian,et al.  Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in alzheimer's disease , 2005, Psychopharmacology.

[49]  Jeffrey A. Gray,et al.  Effect of cigarette smoking on prepulse inhibition of the acoustic startle reflex in healthy male smokers , 1996, Psychopharmacology.

[50]  E. Levin,et al.  Nicotine effects on adults with attention-deficit/hyperactivity disorder , 2005, Psychopharmacology.

[51]  T. Paus.  Primate anterior cingulate cortex: Where motor control, drive and cognition interface , 2001, Nature Reviews Neuroscience.

[52]  E. Stein,et al.  Cognitive Mechanisms of Nicotine on Visual Attention , 2002, Neuron.

[53]  D. Tank,et al.  Brain magnetic resonance imaging with contrast dependent on blood oxygenation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[54]  B. Pitt.  Psychopharmacology , 1968, Mental Health.

[55]  T T Soncrant,et al.  Preferential Metabolic Activation of Subcortical Brain Areas by Acute Administration of Nicotine to Rats , 1990, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[56]  W. Parsons,et al.  Effect of smoking on caffeine clearance , 1978, Clinical pharmacology and therapeutics.

[57]  P. Newhouse,et al.  Clinical Aspects of Nicotinic Agents: Therapeutic Applications in Central Nervous System Disorders , 2000 .

[58]  S G Lomber,et al.  Role of the superior colliculus in analyses of space: Superficial and intermediate layer contributions to visual orienting, auditory orienting, and visuospatial discriminations during unilateral and bilateral deactivations , 2001, The Journal of comparative neurology.

[59]  E D Levin,et al.  Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD). , 1996, Psychopharmacology bulletin.

[60]  Edward T. Bullmore,et al.  Prolonged Reaction Time to a Verbal Working Memory Task Predicts Increased Power of Posterior Parietal Cortical Activation , 2000, NeuroImage.

[61]  Enoch Callaway,et al.  A low dose of subcutaneous nicotine improves information processing in non-smokers , 1994, Psychopharmacology.

[62]  E D Levin,et al.  Acute nicotine interactions with nicotinic and muscarinic antagonists: working and reference memory effects in the 16-arm radial maze. , 1997, Behavioural pharmacology.

[63]  E. Perez-stable,et al.  Ethnic differences in N-glucuronidation of nicotine and cotinine. , 1999, The Journal of pharmacology and experimental therapeutics.

[64]  Susan E. Gathercole,et al.  Neuropsychology and working memory: A review. , 1994 .