Clinical Neuroscience Research Unit
Nicotinic Research and Therapeutics Program
Our laboratory has had a major focus on understanding the role of central nervous system (CNS) nicotinic cholinergic receptors in normal and abnormal human cognition for over 15 years. Nicotinic receptors are ligand-gated ion channels that occur on the surface of neurons (nerve cells) in the brain and serve to modulate neuronal transmission. Nicotinic receptors bind the naturally occurring neurotransmitter acetylcholine and of course nicotine. Research from this laboratory and others has shown that nicotinic receptors appear to be important in regulating learning and memory, anxiety, and motor performance as well as attention and impulsivity.
Our research has investigated the role of nicotinic receptor functioning in learning and memory both in normal individuals and those with neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease as well as neurodevelopmental disorders like Attention-Deficit/Hyperactivity Disorder. We have also tested the effects of novel nicotinic drugs in humans, designed to produce the positive effects of nicotinic stimulation without some of the liabilities of nicotine itself.
Current research focuses on the importance of nicotinic systems in therapeutic drug development for early memory loss and for impulsivity symptoms associated with Attention-Deficit/Hyperactivity Disorder (ADHD), schizophrenia, and Parkinson's disease.
Faculty associated with these projects include:
Nicotine and ADHD
Adolescents who suffer from Attention-Deficit/Hyperactivity Disorder (ADHD) become cigarette smokers and tobacco users at twice the rate of non-ADHD adolescents. While ADHD first appears in childhood the symptoms persist into adolescence and adulthood for up to 80% of people who are diagnosed as children. Similarly, the high rate of tobacco use continues into adulthood. The reasons for this vulnerability of people with ADHD to tobacco are poorly understood.
One possible reason is that nicotine, the psychoactive component of tobacco, may produce positive effects on attentional performance in ADHD adolescents. ADHD produces specific attentional difficulties which are partially ameliorated by medications that enhance dopaminergic functioning in the brain. Extensive studies of nicotine over several decades from our laboratory and others have demonstrated that nicotine has significant attentional and cognitive-enhancing effects even in clinical populations with neuropsychiatric disorders. It is therefore possible that tobacco use in adolescents serves as a form of self-selected medication to improve some of the cognitive difficulties associated with ADHD.
We are examining whether nicotine, the psychoactive constituent of tobacco, may have positive effects on cognitive and motor processes involving attention that appear to be impaired in many adolescents and young adults with ADHD. The primary aim of these studies is to examine the effects of acute nicotinic stimulation on a measure of behavioral inhibition, decision-making, and motor performance in adolescents and adults with ADHD. These results should provide significant information as to some of the reasons for the vulnerability of the ADHD population to high rates of tobacco use, and may help in the future development of better and safer alternative treatments for ADHD.
- Nicotine Brain Study: The goal of this study is to use functional MRI to examine how nicotine improves impulse control and working memory in young adults (18-25) who either have or do not have ADHD. This study will look at patterns of brain activation associated with nicotine and methylphenidate (Ritalin, a common treatment for ADHD) to help understand how the differences in the brain functioning of people who have ADHD may affect their behavior. We are looking for 24 non-smoking young adults (18-25) who have, and 24 who do not have, ADHD. The volunteers will complete three 6-hour study visits in which they will receive nicotine alone, methylphenidate alone, or placebo and then be asked to perform computer tasks in the fMRI.
Nicotine and Schizophrenia
Schizophrenia is a chronic mental illness that affects approximately 1% of the population. People with schizophrenia smoke at drastically higher rates than the general population. Extensive studies of nicotine over several decades from our laboratory and others have demonstrated that nicotine has significant cognitive-enhancing effects, even in clinical populations with neuropsychiatric disorders. It is therefore possible that tobacco use serves as a form of self-selected medication to improve some of the cognitive difficulties associated with schizophrenia.
- Study of Nicotinic Blockade and Social Information Processing: A symptom of schizophrenia that develops before diagnosis is difficulty with relationships and understanding social information such as people's facial expressions. The goal of this study is to determine how social information is processed differently from other types of information. We believe that a certain naturally occurring chemical in the brain, acetylcholine, is important in processing non-social information, may also be related to how social information is processed. We will look at how the brain processes information differently in people who do versus people who don't have difficulty understanding social information. We will use functional magnetic imaging to identify the areas involved in processing social information in the presence and absence of a chemical called Mecamylamine that temporarily lowers the brain's ability to use acetylcholine. This study will consist of men and women between the ages of 18-25 who have a family member or close relative with schizophrenia, or who have trouble interpreting social information. This is a four-visit study (5-6 hours each) in which participants will receive a free physical, cognitive screening, and monetary compensation.
Nicotine and Parkinson's Disease
In recent years, a group of behavior changes collectively called impulse control disorders have been identified in Parkinson's disease (PD). Acetylcholine is a chemical in the brain which works to regulate the effects of dopamine. It has been known for many years that nicotine imitates many of the actions of acetylcholine. In preliminary studies, nicotine has been shown to reduce impulsive behavior in Attention Deficit Hyperactivity Disorder. By administering nicotine across the skin using a patch, we hope to better understand whether nicotine may act to improve impulse control disorders in PD without needing to reduce or stop PD medications.
- Nicotine Treatment of Impulsivity in Parkinson's Disease: The study will examine whether treatment with nicotine (delivered through the skin via a patch) improves computer-based laboratory and clinical measures of impulsive and compulsive behaviors in those with Parkinson's disease who have recently experienced an impulse control disorder (ICD).
The principal investigator of this Parkinson's disease trial is James Boyd, MD.