RestingState f MRI Potential Clinical Applications Michael D

Resting-State f. MRI: Potential Clinical Applications Michael D. Greicius, MD Functional Imaging in Neuropsychiatric Disorders (FIND) Lab Department of Neurology and Neurological Sciences Stanford University School of Medicine

Functional Connectivity r = 0. 80 BOLD Signal r = 0. 59 Time r = 0. 75

Exponential Growth of Resting State f. MRI Studies Disorders Studied Autism Schizophrenia Alzheimer’s Disease Parkinson’s Disease Multiple Sclerosis ADHD PTSD TBI OCD Depression/Bipolar Anxiety Disorder … Birn, Neuroimage, 2012

Potential Roles of Resting-State f. MRI in Neuropsychiatric Disorders • • • Disease mechanisms (group-level) Diagnostics (single subject-level) Prognostics (single subject-level) Treatment efficacy (single subject or group) Disease-specific roles (single subject-level) – seizure focus localization in epilepsy – pre-op cortical mapping

Presurgical Mapping Liu et al. , J Neurosurg, 2009

Epilepsy: Seizure Focus Localization Increased remote and local connectivity Stufflebeam et al. , J Neurosurg, 2011

Prognosis for Coma Recovery Vanhaudenhuyse et al. , Brain, 2010

Single-Patient Level Soddu et al. , Hum Brain Mapp, 2011

Single-Patient Level Soddu et al. , Hum Brain Mapp, 2011

The Subgenual Cingulate in Depression Mayberg et al. , Neuron, 2005

Increased Subgenual Cingulate Connectivity in Depression n = 28 n = 20 Greicius et al. , Biol Psychiatry, 2007

BA 25 Connectivity Correlates with Current Episode Duration r = 0. 49 p < 0. 05 Greicius et al. , Biol Psychiatry, 2007

Starting from BA 25 controls n = 17 age 30. 9 depressed n = 18 age 35. 9 dep > con Sheline et al. , PNAS, 2010

Early Childhood Depression n = 18 age 9 n = 21 age 9. 5 dep > con Gaffrey et al. , J Child Psychol Psychiatry, 2012

Network-Based Neurodegeneration Fire Together, Wire Together, Expire Together ” ng i t es “R LD e BO plitud am Time (sec) Single subject er tt ma y a Gr ume l vo S 1 S 2 S 3 S 4 S 5 S 6 S 7 Seeley et al. , Neuron, 2009

Inter-Network Interactions Fox et al. , PNAS, 2005 Greicius et al. , PNAS, 2003 Fransson, Hum Brain Mappp, 2005

FTD vs AD = Salience vs DMN Zhou et al. , Brain , 2010

FTD vs AD = Salience vs DMN Zhou et al. , Brain , 2010

Test-Retest Reliability Shehzad et al. , Cereb Cortex, 2009

Conclusions • Resting-state f. MRI has single-subject potential – Relatively easy for patients to undergo – Can be repeated frequently – Potentially more dynamic than other markers • More data needed – ADNI, Human Connectome Project will help • Tougher clinical questions – Specificity against disease mimics (rather than controls) – Epilepsy patients without i. EEG sources – Early scan in coma predicting long-term outcome • Test-retest reliability needs shoring up

Acknowledgments Stanford FIND Lab – – – – Stanford Lucas Center – Gary Glover Jeske Damoiseaux Anna Milazzo Matt White Heidi Jiang Will Shirer Rich Joseph Chris Hemond UCSF – Bill Seeley – Bruce Miller – Helen Zhou Funding The Dana Foundation The John Douglas French Foundation NIH: 1 RO 1 NS 073498