Cocaine-dependence is a prevalent health problem with serious medical, psychological and societal deleterious effects. The understanding of the effects of cocaine use on the central nervous system could inform efforts towards treatment and rehabilitation of this serious disorder. Transcranial magnetic stimulation (TMS) provides a unique opportunity to non-invasively examine the inhibitory-excitatory states of the cerebral cortex in awake humans. This application is developed to examine TMS-based measures of cortical excitability in abstinent cocaine-dependent individuals. The proposed studies will also probe the physiological correlates of cocaine-induced paranoid states. Our main hypothesis is that decreased cortical excitability in cocaine-dependent subjects reflects a protective mechanism mediated mainly via increased neuronal membrane stability. We plan to demonstrate that decreased cortical excitability in cocaine-dependent subjects is mediated mainly via cellular membrane ion transport mechanisms as reflected in measurement of TMS-generated motor thresholds. In addition to a healthy control group, a healthy but at-risk for cocaine-dependence group will be examined to ascertain if genetic predisposition plays a role in the TMS findings. We further plan to demonstrate significant prolongation of the TMS-induced cortical silent period and increased intra-cortical inhibition as measured via paired-pulse stimulation techniques, in subjects with history of cocaine-induced paranoia (CIP) as compared to cocaine-dependent subjects without such a history. Our third specific aim is to examine the correlation between TMS-based measures of cortical inhibition and sensory gating measures of cerebral inhibition (also have been shown to be abnormal in this population). An additional exploratory aim is to probe the personality correlates of TMS-based cortical excitability changes in cocaine-dependent subjects.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA019055-04
Application #
7567579
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Grant, Steven J
Project Start
2006-04-01
Project End
2010-12-31
Budget Start
2009-01-01
Budget End
2010-12-31
Support Year
4
Fiscal Year
2009
Total Cost
$322,230
Indirect Cost
Name
Wayne State University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Leon-Ariza, Daniel S; Leon-Ariza, Juan S; Leon-Sarmiento, Fidias E (2015) ""Unclassical"" Combination of Smell Dysfunction, Altered Abdominal Nociception and Human Hypertension Associated ""Classical"" Adrenal-Augmentation. J Med Cases 6:527-533
Gjini, Klevest; Qazi, Aisha; Greenwald, Mark K et al. (2014) Relationships of behavioral measures of frontal lobe dysfunction with underlying electrophysiology in cocaine-dependent patients. Am J Addict 23:265-71
Leon-Sarmiento, Fidias E; Pradilla, Gustavo; Del Rosario Zambrano, Maria (2013) Primary and Reversible Pisa Syndrome in Juvenile Normal Pressure Hydrocephalus. Acta Neuropsychiatr 25:57-60
Leon-Sarmiento, Fidias E; Paez, Edwin; Hallett, Mark (2013) Nature and nurture in stuttering: a systematic review on the case of Moses. Neurol Sci 34:231-7
Gooding, Diane C; Gjini, Klevest; Burroughs, Scott A et al. (2013) The association between psychosis proneness and sensory gating in cocaine-dependent patients and healthy controls. Psychiatry Res 210:1092-100
Leon-Sarmiento, Fidias E; Rizzo-Sierra, Carlos V; Bayona, Edgardo A et al. (2013) Novel mechanisms underlying inhibitory and facilitatory transcranial magnetic stimulation abnormalities in Parkinson's disease. Arch Med Res 44:221-8
Gjini, Klevest; Ziemann, Ulf; Napier, T Celeste et al. (2012) Dysbalance of cortical inhibition and excitation in abstinent cocaine-dependent patients. J Psychiatr Res 46:248-55
Gjini, Klevest; Burroughs, Scott; Boutros, Nash N (2011) Relevance of attention in auditory sensory gating paradigms in schizophrenia A pilot study. J Psychophysiol 25:60-66
Gjini, Klevest; Arfken, Cynthia; Boutros, Nash N (2010) Relationships between sensory ""gating out"" and sensory ""gating in"" of auditory evoked potentials in schizophrenia: a pilot study. Schizophr Res 121:139-45
Leon-Sarmiento, Fidias E; Elfakhani, Mohamed; Boutros, Nash N (2009) The motor evoked potential in AIDS and HAM/TSP: state of the evidence. Arq Neuropsiquiatr 67:1157-63

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