Y P O Brain Network Imaging and Brain C Stimulation T O N O Michael D. Fox, MD, PhD D E Director, Laboratory for Brain Network Imaging and Visualization S Associate Director, Berenson-Allen Center for Noninvasive Brain Stimulation Associate Director, Deep Brain Stimulation Program A Beth Israel Deaconess Medical Center, Harvard Medical School E Neuroscientist, Department of Neurology and Martinos Center for Biomedical Imaging L Massachusetts General Hospital, Harvard Medical School P
Y P Disclosures O C • Intellectual property using connectivity T O imaging to guide brain stimulation (no N royalties) O D E S A E L P
Y Outline P O C • Intro to brain network imaging T • What can network imaging do for brain O stimulation? N O • What can brain stimulation do for brain D networks? E S A E L P
Y Outline P O C • Intro to brain network imaging T • What can network imaging do for brain O stimulation? N O • What can brain stimulation do for brain D networks? E S A E L P
Y P Types of Brain Network Imaging O C • Co-activation Patterns T O • Resting state functional connectivity MRI N (Rs-fcMRI) O • Diffusion tensor imaging (DTI) D E S A E L P
Y Classical Neuroimaging P O 3 C 2.5 2 % BOLD Change T Open Open Open Open 1.5 O 1 N 0.5 Closed Closed Closed Closed O 0 0 50 100 150 200 250 D -0.5 Time (s) -1 E S Open – Closed = A E L P Fox and Raichle (2007) Nat. Rev. Neuro.
Y P BOLD Data Is Very “ Noisy ” O 3 C 2.5 2 % BOLD Change T Open Open Open Open 1.5 O 1 N 0.5 Closed Closed Closed Closed O 0 0 50 100 150 200 250 D -0.5 Time (s) -1 E S Open – Closed = A E L P Fox and Raichle (2007) Nat. Rev. Neuro.
Y Spontaneous Fluctuations P O ( “ Noise ” ) in the BOLD Signal C T Left Motor Cortex 2 O N 1.5 O % BOLD Change 1 D 0.5 E 0 S 0 50 100 150 200 250 300 A -0.5 E -1 L Time (sec) P -1.5
Y Spontaneous Fluctuations are P O Specifically Correlated C T Left Motor Cortex 2 O Right Motor Cortex N 1.5 O % BOLD Change 1 D 0.5 E 0 S 0 50 100 150 200 250 300 A -0.5 E -1 L Time (sec) P -1.5 After Bharat Biswal and colleagues (1995) Magnetic Resonance in Medicine
Y Generation of Resting State P O Functional Connectivity Maps C 2 T 1.5 O % BOLD Change 1 N 0.5 0 O 0 50 100 150 200 250 300 -0.5 D -1 Time (sec) -1.5 E S A E L P Fox and Raichle (2007) Nat. Rev. Neuro.
Y Generation of Resting State P O Functional Connectivity Maps C 2 T 1.5 O % BOLD Change 1 N 0.5 0 O 0 50 100 150 200 250 300 -0.5 D -1 Time (sec) -1.5 E S A E L P Z score, fixed effects, N = 10 Fox and Raichle (2007) Nat. Rev. Neuro.
Y P O C T O N O D 1.5 E 1 % BOLD Change S 0.5 A 0 E 0 50 100 150 200 250 300 -0.5 L -1 P -1.5 Time (sec) -2
Y P O C T O N O D 1.5 E 1 % BOLD Change S 0.5 A 0 E 0 50 100 150 200 250 300 -0.5 L -1 P -1.5 Time (sec) -2
Y P O C T O N O D 1.5 E 1 % BOLD Change S 0.5 A 0 E 0 50 100 150 200 250 300 -0.5 L -1 P -1.5 Time (sec) -2
Y P O C T O N O D 1.5 E 1 % BOLD Change S 0.5 A 0 E 0 50 100 150 200 250 300 -0.5 L -1 P -1.5 Time (sec) -2 Fox et al. (2005) PNAS
Y Task-induced changes P negative positive O C T O N O D 1.5 E 1 % BOLD Change S 0.5 A 0 E 0 50 100 150 200 250 300 -0.5 L -1 P -1.5 Time (sec) -2 Fox et al. (2005) PNAS
Y Diffusion Tractography P O C T O N O D E S A E L P Fox et al. 2014 PNAS
Y Results match anatomical connectivity relevant to P DBS response O C T O N O D E S A E L P Fox et al. PNAS In Press
Y P O DTI Network Rs-fcMRI Network C T O N O D E S A E L P Honey et al. 2009 PNAS
Y P Research Applications of Rs-fcMRI O C • Trial to trial variability in behavior T O – (Fox et al. 2007 Neuron) N • Thalamic and cerebellar connections O – (Zhang et al. 2009 J. Neurophys , Buckner et al. 2011 J. Neurophys.) • Individual differences in performance D – (Hampson et al. 2006 J. Neurosci, Koyama et al. 2009 J. Neurosci.) E • Correlates of learning S A – (Lewis et al. 2009 PNAS) E L P
Y P Clinical Applications of Rs-fcMRI O C • Understanding disease pathophysiology T O • Biomarkers / Diagnosis N • Guiding treatment O D E S A E L P
Y Understanding Peduncular Hallucinosis P O C T O N O D E S A E L P Boes et al. 2015 Brain
Y Understanding Peduncular Hallucinosis P O C T O N O D E S A E L P Boes et al. 2015 Brain
Disease/Condition References Findings Y Alzheimer ’ s (Allen et al. 2007; Greicius et al. 2004; Li et al. 2002; Supekar Decreased correlations within the default mode network including hippocampi and et al. 2008; Wang et al. 2006a; Wang et al. 2007; Wang et al. decreased anticorrelations between the DMN and TPN P 2006b) PIB positive (Hedden et al. 2009; Sheline et al. 2009) Decreased correlations within the default mode network O Mild Cognitive Impairment (Li et al. 2002; Sorg et al. 2007) Decreased correlations within the default mode network and decreased anticorrelations between the DMN and TPN C Fronto-Temporal Dementia (Seeley et al. 2007a; Seeley et al. 2008) Decreased correlations within the salience network Healthy Aging (Andrews-Hanna et al. 2007; Damoiseaux et al. 2007) Decreased correlations within the default mode network Multiple Sclerosis (De Luca et al. 2005; Lowe et al. 2002) Decreased correlations within the somatomotor network T ALS (Mohammadi et al. 2009) Decreased connectivity in DMN and premotor cortex Depression (Anand et al. 2009; Anand et al. 2005a; b; Bluhm et al. 2009a; O Variable: Decreased connectivity between dACC and limbic regions (amygdala, medial Greicius et al. 2007) thalamus, pallidostriatum) increased connectivity within the DMN (esp. subgenual prefrontal cortex), decreased connectivity between DMN and caudate N Bipolar (Anand et al. 2009) Decreased corticolimbic connectivity PTSD (Bluhm et al. 2009c) Decreased connectivity in the DMN Schizophrenia Variable: Decreased or increased DMN connectivity (Bluhm et al. 2007; Bluhm et al. 2009b; Jafri et al. 2008; Liang O et al. 2006; Liu et al. 2006; Liu et al. 2008; Salvador et al. 2007; Whitfield-Gabrieli et al. 2009; Zhou et al. 2007) D Schizophrenia 1 relatives (Whitfield-Gabrieli et al. 2009) Increased connectivity in the DMN ADHD (Cao et al. 2006; Castellanos et al. 2008; Tian et al. 2006; Variable: reduced connectivity within the DMN, reduced anticorrelations, increased connectivity in salience Wang et al. 2008; Zang et al. 2007; Zhu et al. 2008; Zhu et al. E 2005) Autism (Cherkassky et al. 2006; Kennedy and Courchesne 2008; Monk Decreased connectivity within the DMN (although hippocampus is variable and et al. 2009; Weng et al. 2009) S connectivity may be increased in younger patients) Tourette Syndrome (Church et al. 2009) Delayed maturation of task-control and cingulo-opercular networks A Epilepsy (Bettus et al. 2009; Lui et al. 2008; Waites et al. 2006; Zhang et Variable: decreased connectivity in mult. networks including medial temporal lobe, al. 2009a; Zhang et al. 2009b) decreased connectivity in DMN with generalized seizure E Blindness (Liu et al. 2007; Yu et al. 2008) decreased connectivity within the visual cortices and between visual cortices and somatosensory, frontal motor and temporal multisensory cortices L Chronic Pain (Cauda et al. 2009a; Cauda et al. 2009c; Cauda et al. 2009d; Variable: Increased/decreased connectivity within the salience network, decreased P Greicius et al. 2008) connectivity in attention networks Neglect (He et al. 2007) Decreased connectivity within the dorsal and ventral attention networks Vegetative State (Boly et al. 2009; Cauda et al. 2009b) Progressively decreased DMN connectivity with progressive states of impaired consciousness Fox and Greicius (2010) Frontiers Sys Neurosci
Y Outline P O C • Intro to brain network imaging T • What can network imaging do for brain O stimulation? N O • What can brain stimulation do for brain D networks? E S A E L P
Y Therapeutic Brain Stimulation P O Deep Brain Stimulation (DBS) Transcranial Magnetic Stimulation (TMS) C T O N O D E • Implanted by Neurosurgeon • Noninvasive S • Constant stimulation • Repeated sessions of stimulation A • 130-180 Hz • 10 Hz (excitatory), 1Hz (inhibitory) E • FDA approved for Parkinson’s, • FDA approved for depression L essential tremor, dystonia, OCD P
Y Therapeutic Brain Stimulation P O Deep Brain Stimulation (DBS) Transcranial Magnetic Stimulation (TMS) C T O N O D E S A Both are showing early signs of utility in many of the same disorders E L P
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