and Neurostimulation: Going inside the black box

Benzi M. Kluger M.D., M.S.

Director, Movement Disorders Center Associate Professor of Neurology & Psychiatry University of Colorado OUTLINE

I. What is neuroimaging and neurostimulation? II. Brief history of neuroimaging and neurostimulation in Parkinson’s? III. Why is this important? IV. What’s in the research pipeline? V. What else is happening at the University of Colorado? The Black Box

I. What is neuroimaging and neurostimulation? Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the nervous system. Neuroimaging

What can we see inside the head?

• Structure • Molecules • Flow • Metabolic/Chemicals Activity • Electrical Activity Neuroimaging

• Computed Tomography (CT) Scan • Positron Emission Tomography (PET) and Single photon emission computed tomography (SPECT) Scans (e.g. DAT Scan) • Magnetic resonance imaging (MRI) • Megnetoencephalography (MEG) and (EEG) • Near Infrared spectroscopy (NIRS) CT, PET and SPECT DAT Scan MRI MEG/EEG NIRS Neurostimulation is a therapeutic activation of part of the nervous system using various techniques.

Neurostimulation

• Deep Brain Stimulation (DBS) • Transcranial Magnetic Stimulation (TMS) • Transcranial direct current stimulation (tDCS) • Gene Therapy • Cell Transplantation/Stem Cells • (Ultrasound) DBS TMS tDCS Gene Therapy Stem Cells IIa. Brief History of Neuroimaging History of Neuroimaging Neuroimaging and Parkinson’s • There is no brain scan that can diagnose PD • There is nothing that can be seen on an MRI • DAT scan can assist in detecting a loss of dopamine • PET scans have found patterns of brain activity associated with both motor and nonmotor symptoms • MRI scans have found changes in both grey matter and white matter IIb. Brief History of Neurostimulation History of Neurostimulation History of Neurostimulation & PD

. Surgery in PD has a long history . First use of DBS for tremor was in 1987 . DBS rapidly became the surgical treatment of choice with targets in STN, GPI and thalamus . PD is most widely used indication for DBS with over 100,000 implanted patients III. Why is this important? Neuroimaging: Mechanism Neuroimaging: Biomarker

• A biomarker, or biological marker, generally refers to a measurable indicator of some biological state or condition • Diagnostic • Predictive • Monitor Disease progression IV. What’s in the research pipeline? Optogenetics Biomarkers

• Imaging alpha-synuclein • Connectivity – Structural – Functional 7 Tesla MRI Deep Brain Stimulation

• Paramedian Pontine Nucleus (PPN) • Stimulation for depression and • Neuroprotection? • Smarter stimulators Gene Therapy and Stem Cells

• All trials have been negative to date • Dopamine replacement • Neurotransmitter replacement • Growth factors Transcranial Magnetic Stimulation Transcranial Direct Current Stimulation V. Research at the University of Colorado Getting Patients Involved

• Parkinson’s Advocates in Research (PAIR) Grant • Patient Centered Outcomes Research Institute (PCORI) Marijuana

• Used by 5-10% of our patients • Most helpful for non-motor symptoms • New Grant from state of Colorado on CBD for tremor • Also looking at memory and driving Complementary and Alternative • Acupuncture • Massage • Yoga • Meditation Exercise

• Different forms of exercise have different benefits • SPARX study is looking into the question of what is the right dose • Neuroprotective? Neuroimaging

• fMRI and PD phenotypes • MEG and cognitive symptoms • MRS and cognitive symptoms • MEG and the benefits of rhythm on movement Nonmotor Symptoms

• Palliative Care • Fatigue • Cognitive Impairment – TMS treatment Genetics

• PROGENI study • More on the way Neuroprotection

• Curt Freed and phenylbutyrate • Margaret Schenkman and Exercise • Katherine James and pesticides • CoQ10 • Creatine Medications

• Long acting amantadine • Botox for drooling • Low dose azilect/mirapex