Research Interests
The abuse of drugs such as cocaine, nicotine and marijuana is a serious problem in today's society. However, little is known about their mechanisms and sites of action in the human brain. This information is necessary for the development of more effective treatment modalities. Functional magnetic resonance imaging (fMRI) is a specialized application of MRI technology that allows the study of functional activity in the brain. Localized intrinsic signal changes that correlate with increases in neuronal activity are non-invasively detected allowing the acquisition of high resolution images that are dependent on brain activity rather than anatomy. We are using fMRI to better understand the actions of abuse substances in human brain. We are also using this technology to examine the effects of adjuvant cancer chemotherapy on cognition and brain function “chemobrain” in breast cancer patients. The Laboratory has several ongoing projects.
Effects of Cigarette Smoking and Smoking Cessation on Brain Activity in Humans.
Nicotine is the second most commonly used substance of abuse. It is found in tobacco and typically administered by smoking it. It produces significant behavioral effects in man including memory facilitation, locomotor activation, mild calming and appetite suppression. In the chronic smoker, symptoms are seen when cigarette smoking is suddenly stopped. They include irritability, restlessness, difficulty concentrating, hunger, craving and a variety of other behavioral and physiological signs. The overall goal of this study is to determine alterations in cerebral activation patterns in human volunteers resulting from cigarette smoking and withdrawal from chronic nicotine self-administration (cigarette smoking). fMRI measures of blood oxygenation, and perfusion will be utilized to determine the effects of cigarette smoking and cessation on cerebral activation produced by the performance of cognitive and motor tasks. Possible functional consequences of cigarette smoking are being examined by determining changes in task-induced brain activity in current and newly abstaining, cigarette smokers. The completion of these studies will enhance our knowledge of the neurobiological consequences of chronic cigarette use and may offer insight into the development of more effective smoking cessation treatments.
Effects of Chemotherapy on Cognition and Brain Function in Breast Cancer Patients
Numerous anecdotal and research reports of cognitive deficits both during and after cancer chemotherapy are found in the literature. This phenomenon has been referred to as “chemobrain”. Breast cancer patients often receive adjuvant treatment with chemotherapy and many go on to become long-term cancer survivors. Thus it is important for us to better understand the possible immediate and chronic cognitive effects of systemic chemotherapy. This will allow both patients and health care providers to make better informed decisions about cancer treatment. We are using fMRI techniques to determine the nature of the changes in brain function that underlie the cognitive deficits that can result from chemotherapy and how long they last. This research is being carried out in women being treated for breast cancer. These women are examined while performing cognitive tasks using fMRI before, during and long after their course of chemotherapy treatment. These studies will enable us to determine what changes in brain function are associated with chemotherapy, which chemotherapy regimens are most likely to cause them and how recovery occurs. This may also give us insights into what can be done during chemotherapy to minimize effects on cognition.
Investigating cortical function in chronic cannabis users using TMS and fMRI: Combined human and rodent imaging studies. (Joint study with U. of Hawaii)
The purpose of this study is to examine, using high-field (9.4 T) fMRI, the brain responses to forepaw sensory stimulation in rats treated with THC or other cannabinoids, rats chronically treated with THC but subsequently withdrawn from treatment, rats treated with a CB1-antagonist, and drug-naïve rats Our hypothesis is that BOLD-fMRI responses of the rat brain to forepaw sensory stimulation will show characteristic changes depending on the dose of THC administered acutely, the animal’s history of administration of THC or other cannabinoids, the duration of withdrawal from THC, and treatment with a CB1-antagonist, SR141716A.
We will be the first group to use fMRI and TMS in combination to study the neurocognitive effects of cannabis use in humans, and to relate our findings to an animal model of THC administration. From these methods, we expect (a) to gain a stronger understanding about the consequences for the brain of continuing active use of cannabis, and (b) to develop testable hypotheses for future work examining long-term use and abstinence. As cannabis is widely used in the United States and elsewhere, and has potential medical benefits for some populations (e.g. glaucoma, HIV, cancer), it is a matter of utmost concern to public health to determine the consequences of chronic cannabis use. We envisage that data from this project will translate to inform issues of (a) treatment of cannabis abuse, including the development of pharmacological agents targeted at the CB1 receptor and (b) of public policy and understanding.
Recent Publications
Bloom AS, Terschner SL, Fuller SA and Stein EA: Effects of delta-9-tetrahydrocannabinol on regional cerebral blood flow in the rat. Pharmacology Biochemistry and Behavior 57:625-631, 1997.
Stein, EA,Pankiewicz, J, Harsch, HH, Cho, JK, Fuller, SA, Hoffmann, RG, Hawkins, M, Rao, SM, Bandettini, PA and Bloom, AS: Nicotine-induced limbic cortical activation in the human brain: A functional MRI study. American Journal of Psychiatry 155:1009-1015, 1998.
Bloom, A.S., Hoffmann, R.G., Fuller, S.A., Pankiewicz, J., Harsch, H.H., Stein, E.A.: The determination of drug-induced changes in functional MRI signal using a pharmacokinetic model. Human Brain Mapping, 8:235-244, 1999.
Garavan, H., Pankiewicz, J., Bloom, A., Cho-J-K, Sperry, L., Ross, T., Salmeron, B.J., Risinger, R., Kelley, D. and Stein, E.A.: Cognitive dimensions of cue-induced cocaine craving. Am. J. Psychiatry 157:1789-1798, 2000.
Risinger, R.C., Salmeron, B.J., Ross, T.J., Amen, S.L., Sanfilipo, M.J., Hoffmann, R., Bloom, A.S., Garavan, H., Stein, E.A. Neural correlates of high and craving during cocaine self-administration using BOLD fMRI. Neuroimage 26:1097-1108, 2005.
Kufahl, P., Li, Z., Risinger, R., Rainey, C., Wu, G., Bloom, A., Li, S. Neural responses to acute cocaine administration in the human brain detected by fMRI. Neuroimage 28:905-914, 2005.
Liu, H., Rainey, C., Lauer, K.K., Piacentine, L., Bloom, A., Risinger, R., Ward, D,. Stein, E., Li, S-J. Peripheral blood pressure changes induced by dobutamine do not alter BOLD signals in the human brain. Neuroimage 30:745-752, 2006.
Murphy, K., Dixon, V., LaGrave, K., Kaufman, J., Risinger, R., Bloom, A., Garavan, H. The validation of event-related fMRI comparisons between drug groups and controls. American J. Psychiatry 163:1245-1251, 2006.
Kufahl P, Li Z, Risinger R, Rainey C, Piacentine L, Wu G, Bloom A, Yang Z, Li S-J. Expectation modulates human brain responses to acute cocaine: A functional magnetic resonance imaging study. Biol Psychiatry 63:222–230, 2008.