Transcranial Magnetic Stimulation of Medial Prefrontal and Cingulate Cortices Reduces Cocaine Self-Administration: A Pilot Study

Background Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex may serve as a potential treatment for cocaine use disorder (CUD), which remains a public health problem that is refractory to treatment. The goal of this pilot study was to investigate the effect of rTMS on cocaine self-administration in the laboratory. In the self-administration sessions, CUD participants chose between cocaine and an alternative reinforcer (money) in order to directly measure cocaine-seeking behavior. The rTMS was delivered with the H7 coil, which provides stimulation to the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). These brain regions were targeted based on previous imaging studies demonstrating alterations in their activation and connectivity in CUD. Methods Volunteers with CUD were admitted to an inpatient unit for the entire study and assigned to one of three rTMS groups: high frequency (10 Hz), low frequency (1 Hz), and sham. Six participants were included in each group and the rTMS was delivered on weekdays for 3 weeks. The cocaine self-administration sessions were performed at three time points: at baseline (pre-TMS, session 1), after 4 days of rTMS (session 2), and after 13 days of rTMS (session 3). During each self-administration session, the outcome measure was the number of choices for cocaine. Results The results showed a significant group by time effect (p = 0.02), where the choices for cocaine decreased between sessions 2 and 3 in the high frequency group. There was no effect of rTMS on cocaine self-administration in the low frequency or sham groups. Conclusion Taken in the context of the existing literature, these results contribute to the data showing that high frequency rTMS to the prefrontal cortex may serve as a potential treatment for CUD.

[1]  A. Zangen,et al.  Clinical and electrophysiological outcomes of deep TMS over the medial prefrontal and anterior cingulate cortices in OCD patients , 2018, Brain Stimulation.

[2]  A. Bonci,et al.  Rehabilitating the addicted brain with transcranial magnetic stimulation , 2017, Nature Reviews Neuroscience.

[3]  Xiujuan Geng,et al.  Salience and default mode network dysregulation in chronic cocaine users predict treatment outcome , 2017, Brain : a journal of neurology.

[4]  A. Zangen,et al.  Add-on high frequency deep transcranial magnetic stimulation (dTMS) to bilateral prefrontal cortex reduces cocaine craving in patients with cocaine use disorder , 2016, Neuroscience Letters.

[5]  C. Gambelunghe,et al.  Bilateral Transcranial Magnetic Stimulation of the Prefrontal Cortex Reduces Cocaine Intake: A Pilot Study , 2016, Front. Psychiatry.

[6]  Logan T Dowdle,et al.  Mobilization of Medial and Lateral Frontal-Striatal Circuits in Cocaine Users and Controls: An Interleaved TMS/BOLD Functional Connectivity Study , 2016, Neuropsychopharmacology.

[7]  A. Bonci,et al.  Transcranial magnetic stimulation of dorsolateral prefrontal cortex reduces cocaine use: A pilot study , 2016, European Neuropsychopharmacology.

[8]  Logan T Dowdle,et al.  What goes up, can come down: Novel brain stimulation paradigms may attenuate craving and craving-related neural circuitry in substance dependent individuals , 2015, Brain Research.

[9]  Logan T Dowdle,et al.  A comprehensive study of sensorimotor cortex excitability in chronic cocaine users: Integrating TMS and functional MRI data. , 2015, Drug and alcohol dependence.

[10]  Ulf Ziemann,et al.  Dysbalance of cortical inhibition and excitation in abstinent cocaine-dependent patients. , 2012, Journal of psychiatric research.

[11]  Rita Z. Goldstein,et al.  Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications , 2011, Nature Reviews Neuroscience.

[12]  M. Haney,et al.  Aripiprazole maintenance increases smoked cocaine self-administration in humans , 2011, Psychopharmacology.

[13]  Gaby S. Pell,et al.  Modulation of cortical excitability induced by repetitive transcranial magnetic stimulation: Influence of timing and geometrical parameters and underlying mechanisms , 2011, Progress in Neurobiology.

[14]  R. Narendran,et al.  Dopamine D1 receptors in cocaine dependence measured with PET and the choice to self-administer cocaine , 2009, Neuropsychopharmacology.

[15]  M. Haney Self‐administration of cocaine, cannabis and heroin in the human laboratory: benefits and pitfalls , 2009, Addiction biology.

[16]  Marc N. Potenza,et al.  Pretreatment Brain Activation During Stroop Task Is Associated with Outcomes in Cocaine-Dependent Patients , 2008, Biological Psychiatry.

[17]  E. Smeraldi,et al.  Daily sessions of transcranial magnetic stimulation to the left prefrontal cortex gradually reduce cocaine craving. , 2008, The American journal on addictions.

[18]  S. Vosburg,et al.  Smoked Cocaine Self-Administration is Decreased by Modafinil , 2008, Neuropsychopharmacology.

[19]  Rita Z. Goldstein,et al.  Role of the anterior cingulate and medial orbitofrontal cortex in processing drug cues in cocaine addiction , 2007, Neuroscience.

[20]  Á. Pascual-Leone,et al.  One session of high frequency repetitive transcranial magnetic stimulation (rTMS) to the right prefrontal cortex transiently reduces cocaine craving. , 2007, Drug and alcohol dependence.

[21]  M. Hallett,et al.  Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-Coil , 2005, Clinical Neurophysiology.

[22]  Yiyun Huang,et al.  Cocaine Dependence and D2 Receptor Availability in the Functional Subdivisions of the Striatum: Relationship with Cocaine-Seeking Behavior , 2004, Neuropsychopharmacology.

[23]  Mark Hallett,et al.  A Coil Design for Transcranial Magnetic Stimulation of Deep Brain Regions , 2002, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[24]  J. Krystal,et al.  Elevated motor threshold in drug-free, cocaine-dependent patients assessed with transcranial magnetic stimulation , 2001, Biological Psychiatry.

[25]  C. Baird The pilot study. , 2000, Orthopedic nursing.

[26]  G. Pearlson,et al.  Demonstration of naturalistic methods for cocaine smoking by human volunteers. , 1990, Drug and alcohol dependence.

[27]  R. Goldstein,et al.  Functional, structural, and emotional correlates of impaired insight in cocaine addiction. , 2014, JAMA psychiatry.