Brian A. Coffman, PhD Research Instructor Department of Psychiatry University of Pittsburgh School of Medicine UPMC Western Psychiatric Hospital Pittsburgh, PA Dr. Brian Coffman is a Research Instructor of Psychiatry in the Clinical Neurophysiology Research Lab (CNRL). He earned his BS, MS, and Ph.D. in Psychology at the University of New Mexico, where his primary mentor was Dr. Vincent P. Clark. Dr. Coffman s current research program focuses on the neurophysiology of sensory and cognitive dysfunction in clinical populations such as schizophrenia, and the therapeutic effects of brain stimulation on these deficits. He has pursued interests in functional magnetic resonance imaging (fmri), electroencephalography (EEG), magnetoencephalography (MEG), transcranial direct current stimulation (tdcs), and mathematical/computational problems associated with neuroimaging data analysis. Dr. Coffman has published basic science research as well as research in various clinical populations, and he has applied multimodal neuroimaging data to complex problems in clinical diagnosis and treatment. He has published 27 research articles on these topics in peer-reviewed journals, as well as multiple chapters in edited volumes. Dr. Coffman was recently awarded a Young Investigator Award in September of 2018 for his outstanding contributions to the field as an early-career investigator. Abstract: Schizophrenia Treatment with Non-Invasive Brain Stimulation: Using Positive and Negative Currents to Treat Positive and Negative Symptoms (Intermediate) This talk will introduce the methods of transcranial magnetic stimulation and transcranial DC electric stimulation, review studies of the clinical effects of these noninvasive brain stimulation methods in schizophrenia, and present preliminary findings from Dr. Coffman s lab showing improved cognition and reduced auditory hallucinations in schizophrenia patients following DC electric stimulation paired with cognitive training. Learning Objectives By the completion of this session, participants should be able to: 1. Recognize the difference between magnetic and electrical stimulation methods 2. Recognize positive and negative symptoms of schizophrenia, including auditory hallucinations 3. Discuss noninvasive brain stimulation research studies reported in the literature References 1. Coffman BA, Clark VP, & Parasuraman R (2014). Battery powered thought: Enhancement of attention, learning, and memory in healthy adults using transcranial direct current stimulation. Neuroimage, 85(3), 895-908. 2. Brunelin, J., Mondino, M., Gassab, L., Haesebaert, F., Gaha, L., Suaud-Chagny, M.F., Saoud, M., Mechri, A. and Poulet, E., 2012. Examining transcranial direct-current stimulation (tdcs) as a treatment for hallucinations in schizophrenia. American Journal of Psychiatry, 169(7), pp.719-724. 3. Mondino, M., Haesebaert, F., Poulet, E., Suaud-Chagny, M.F. and Brunelin, J., 2015. Frontotemporal transcranial direct current stimulation (tdcs) reduces source-monitoring deficits and auditory hallucinations in patients with schizophrenia. Schizophrenia research. 83
CLINICAL NEUROPHYSIOLOGY RESEARCH University of Pittsburgh LABORATORY Schizophrenia Treatment with Non-Invasive Brain Stimulation Using Positive, Negative, and Induced Electric Fields to Treat Positive, Negative, and Cognitive Symptoms Brian A. Coffman Department of Psychiatry University of Pittsburgh School of Medicine Outline What is brain stimulation? How can brain stimulation be used therapeutically in schizophrenia? Ongoing research at UPSOM What is Brain Stimulation? Early Torpedo Fish Brain Stimulation 153 AD 19 th Century AD 84
What is Brain Stimulation? Victorian Era Electrical Stimulation Circa 1900 AD What is Brain Stimulation? What is Brain Stimulation? 85
What is Brain Stimulation? What is Brain Stimulation? What is Brain Stimulation? Electromagnetic Induction Transcranial Magnetic Stimulation 86
What is Brain Stimulation? Thompson, 1910 Barker, 1985 Nexstim, 2015 Therapeutic Brain Stimulation A New Avenue for Clinical Translation of Neuroimaging Research? Therapeutic Brain Stimulation A New Avenue for Clinical Translation of Neuroimaging Research? Number and cost of funded proposals mentioning fmri funded through NIH, 2005-2016 (from NIH RePORTER) 14,233 projects and subprojects Total = $6,152,143,137 87
Therapeutic Brain Stimulation A New Avenue for Clinical Translation of Neuroimaging Research? Neuroimaging correlations can only be used to make inferences about causality Imaging has not provided many treatment benefits for community medicine, especially for mental health Stimulation provides new ways to apply information gained by neuroimaging Therapeutic Brain Stimulation - TMS Lasting effects of stimulus frequency TMS to motor cortex (single/ repeated pulses) EMG recording from muscle Baseline High frequency rtms increases excitability 10 Hz rtms TMS Test stimulus TMS Test stimulus MEP MEP Low frequency rtms reduces excitability 1 Hz rtms TMS Test stimulus MEP Therapeutic Brain Stimulation - TMS Choosing the right dose the MEP 88
Therapeutic Brain Stimulation - TMS ADHD Addiction Alzheimer disease Autism Bipolar Disorder Depression* Epilepsy Fibromyalgia Learning Migraine Headache* Multiple Sclerosis Parkinson's Disease PTSD Schizophrenia Stroke Recovery TBI Tinnitus Tourette s Syndrome Therapeutic Brain Stimulation - TMS Outline What is brain stimulation? How can brain stimulation be used therapeutically in schizophrenia? Ongoing research at UPSOM 89
Prevalent Lifetime prevalence: 1-5% Schizophrenia Debilitating Positive Symptoms Hallucinations Suspiciousness Delusions Negative Symptoms Diminished speech Lack of motivation Social impairment Decreased emotional Cognitive Impairments Memory Attention Motor skills Social cognition Executive skills Disorganized speech Disease Burden Top 10 Causes of Premature Mortality and/or Disability for Adults Age 15-44 years Both Sexes % Total Male % Total Female % Total HIV/AIDS 13.0 HIV/AIDS 12.1 HIV AIDS 13.9 Depressive disorders 8.6 Road traffic accidents 7.7 Depressive disorders 10.6 Road traffic accidents 4.9 Depressive disorders 6.7 Tuberculosis 3.2 Tuberculosis 3.9 Alcohol Use Disorders 5.1 Iron deficiency anemia 3.2 Alcohol Use Disorders 3.0 Tuberculosis 4.5 Schizophrenia 2.8 Self-inflicted Injuries 2.7 Violence 3.7 Obstructed labor 2.7 Iron-deficiency anemia 2.6 Self-inflicted Injuries 3.0 Bipolar disorder 2.5 Schizophrenia 2.6 Schizophrenia 2.5 Abortion 2.5 Bipolar disorder 2.5 Bipolar disorder 2.4 Self-inflicted injuries 2.4 Violence 2.3 Iron deficiency anemia 2.1 Maternal sepsis 2.1 WHO. The World Health Report 2001. Available at http://www.who.int/whr/2001/en/index.html Cloutier, et al (2016) J Clin Psychiatry 90
Course of Schizophrenia Sommer, et al. (2016) Schizophrenia Research In 25 30% of cases auditory hallucinations are not treated by traditional antipsychotic drugs. -Shergill et al (1998) Brain Stimulation in Schizophrenia Auditory Hallucinations: Overactivation of language perceptual systems in left temporoparietal junction 91
Therapeutic Brain Stimulation TMS for Auditory Hallucinations Low frequency (1 Hz, inhibitory) rtms applied to left TPJ Therapeutic Brain Stimulation TMS for Auditory Hallucinations Low frequency (1 Hz) rtms applied to left TPJ rtms and Clozapine are the only treatments with evidence of efficacy for treatment refractory psychotic symptoms Brain Stimulation in Schizophrenia Negative Symptoms: Reduced prefrontal cortex metabolism/volume r = -.70, p<.001 r = -.42, p=.002 Sanfilipo et al. (2000) Arch Gen Psychiatry 92
Therapeutic Brain Stimulation TMS for Negative Symptoms High frequency (10 Hz) rtms applied to Prefrontal Cortex SCALE SCORES 90 80 70 60 50 40 30 20 10 0 Prikryl et al. (2013) Schiz. Res. Negative Symptoms (SANS) Positive Symptoms (SAPS) Baseline Post-TMS Therapeutic Brain Stimulation TMS for Negative Symptoms High frequency (10 Hz) rtms applied to Prefrontal Cortex Ngram 93