Modulation of the Neural Circuitry Underlying Obsessive-Compulsive Disorder

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1 BRAIN STIMULATION LABORATORY Modulation of the Neural Circuitry Underlying Obsessive-Compulsive Disorder OCD Awareness Day NOLAN WILLIAMS, M.D. Instructor Department of Psychiatry Stanford University October 14, 2017

2 Disclosures None

3 Goals of the Talk To discuss OCD as a Circuit Disorder To discuss the historical context for the assessment and treatment of circuit disorders. To discuss the known and emerging circuit abnormalities seen in OCD. To discuss novel treatment approaches being studied in OCD.

4 OCD can be Understood at Different Levels

5 OCD as a Circuit Disorder Dystonia Tourette Syndrome OCD Depression

6 Severe Circuit Disorders Require Circuit-Level Intervention

7 EXCLUSION CRITERIA HISTORICAL BACKGROUND

Jean Talairach: Obsessive-Compulsive Disorder Can Be Localized Figure

Figure 3 (right) Jean Talairach, psychiatrist and functional

al Proceedings of the 4th Congress Neurologique Internationale.

8 Jean Talairach: Obsessive-Compulsive Disorder Can Be Localized Figure 1 (left) anterior capsulotomy, Figure 2 (middle) Talairach atlas, and Figure 3 (right) Jean Talairach, psychiatrist and functional neurosurgeon. Talairach, J., et. al Proceedings of the 4th Congress Neurologique Internationale. Paris: Masson. Vol Benabid AL. Jean Talairach ( ). Stereotact Funct Neurosurg. 2008;86(1):

Mahlon Delong: Frontal-Subcortical Circuitry has a General Structure Figure 1 (left) frontal-subcortical circuitry has a general structure, is recordable and measurable.

9 Mahlon Delong: Frontal-Subcortical Circuitry has a General Structure Figure 1 (left) frontal-subcortical circuitry has a general structure, is recordable and measurable. Figure 2 (center) several corticostriatal loops, Figure 3 (right) Mahlon Delong. Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual review of neuroscience. 1986;9:

10 Transcranial Magnetic Stimulation: A Neuropsychiatric Tool for the 21 st Century

After treatment, the metabolic activity of the head of the right caudate nucleus, can be decreased. Baxter LR, Jr.

11 Obsessive-Compulsive Disorder Can Be Functionally Localized on a Circuit and Modulated with Treatment Figure 1 (left) PET for OCD, Figure 2 (right) PET pre-/post- treatment. After treatment, the metabolic activity of the head of the right caudate nucleus, can be decreased. Baxter LR, Jr., Phelps ME, Mazziotta JC, Guze BH, Schwartz JM, Selin CE. Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls. Archives of general psychiatry. 1987;44(3):

George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post

12 rtms Can Change Circuit Activity Figure 1 (left): first case of rtms to the L DLPFC with pre/post PET. Figure 2 (right): Mark George. George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rtms) improves mood in depression. Neuroreport. 1995;6(14):

13 EXCLUSION CRITERIA TOOLS FOR UNDERSTANDING CIRCUIT DISORDERS

14 The Neural Circuits Underlying OCD Can Be Imaged

activity correlates with symptoms severity and predicts

15 OCD has a Neurophysiological Signature Welter ML, et. al. Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy. Translational psychiatry. 2011;1:e5.

16 EXCLUSION CRITERIA CIRCUIT DISORDERS AND NEUROMODULATION

17 Known Brain Targets for Modulating Obsessive-Compulsive Disorder CIrcuitry Pauls DL, et. al. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nature reviews Neuroscience. 2014;15(6): International OCD Foundation July 8, 2017

18 rtms to OFC in OCD Ruffini C, et. al. Augmentation effect of repetitive transcranial magnetic stimulation over the orbitofrontal cortex in drug-resistant obsessive-compulsive disorder patients: a controlled investigation. Primary care companion to the Journal of clinical psychiatry. 2009;11(5): Nauczyciel C, et. al. Repetitive transcranial magnetic stimulation over the orbitofrontal cortex for obsessive-compulsive disorder: a double-blind, crossover study. Translational psychiatry. 2014;4:e436.

19 rtms over DMPFC/ACC for OCD Dunlop K, et. Al. Reductions in Cortico-Striatal Hyperconnectivity Accompany Successful Treatment of Obsessive-Compulsive Disorder with Dorsomedial Prefrontal rtms. Neuropsychopharmacology. 2016;41(5):

20 Implanted Cortical Stimulation of ACC for OCD De Ridder D, et. al. Anterior Cingulate Implant for Obsessive-Compulsive Disorder. World neurosurgery. 2017;97:754 e7- e16.

Different Node, Same Condition, Same Effect DBS targeted at the nucleus

activity and reduces excessive connectivity between the NAc and

Deep brain stimulation restores frontostriatal network activity in

21 Different Node, Same Condition, Same Effect DBS targeted at the nucleus accumbens (NAc) as well as rtms targeted at the DMPFC normalizes NAc activity and reduces excessive connectivity between the NAc and prefrontal cortex. Figee M, et. al. Deep brain stimulation restores frontostriatal network activity in obsessive-compulsive disorder. Nature neuroscience. 2013;16(4): Dunlop K, et. Al. Reductions in Cortico-Striatal Hyperconnectivity Accompany Successful Treatment of Obsessive-Compulsive Disorder with Dorsomedial Prefrontal rtms. Neuropsychopharmacology. 2016;41(5):

22 Thank you

23 Acknowledgement of Research Support

obsessive-compulsive disorder; OCD

9(1), 50 56, 2017 OCD OCD DBSECT tdcsrtms DBS ECT 6 tdcs rtms obsessive-compulsive disorder; OCD 2013 OCD 2012 deep brain stimulation; DBS electroconvulsive therapy; ECT transcranial direct current stimulation;