Modula'on of the Neural Circuitry Underlying Neuropsychiatric Disorders Nolan Williams, MD Instructor Department of Psychiatry Stanford University
Classic Neuropsychiatrist: Trained as Both a Neurologist and a Psychiatrist
Theodor Meynert
Joseph Babinski
Jean-‐Mar'n Charcot
Objec'ves • Introduce the Concept of Modula'ng Psychiatric Symptoms at the Level of the Circuit • Discuss Some of the Currently U'lized Approaches • Discuss Some of the Emerging Interven'onal Techniques
2014
The Way in Which We Conceptualize Psychiatric Disorders Dictates the Treatment Advances
Neuropsychiatric Disorders are Disorders of Distributed Neural Networks
Neurology: • Parkinson’s Disease • ToureTe’s syndrome
Psychiatry: • Obsessive-‐ Compulsive Disorder • Depression • BPAD
Brain Interven'ons Start In Neurology and Transi'on to Psychiatry
Lancet, 1985
Interven'onal Tools
Deep Brain S'mula'on (DBS) • Video
Motor Disorders Can Be Observed • Video
Brain Circuits Can Be Modulated Effec'vely with Neurotechnology • Video
Psychiatric Symptoms Can Be Recorded in the Brain • Video
S'mula'on-‐Induced Mood Change
Haq, 2011
Mood Can Be Turned Up Exogenously • Video
EpCS for TRD
EpCS
Hot Off the Press
Sample Demographics
EpCS: Two Cor'cal S'mula'on Sites •
T h e f r o n t o p o l a r ( F P -‐ B A 1 0 ) a n d dorsolateral (DL-‐BA 9/46) prefrontal c o r ' c e s ( P F C ) p l a y d i s ' n c t , y e t complementary roles in the integra'on of emo'onal and cogni've experiences (Nahas 2010).
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One or both of these two cor'cal areas appear to be central to the efficacy of deep targets (Williams 2014).
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Our study u'lized bilateral dorsolateral prefrontal and the frontopolar cortex as s'mula'on sites (Nahas 2010).
EpCS: Dorsolateral Prefrontal Cortex •
Established cor'cal s'mula'on site for n o n -‐ i n v a s i v e b r a i n s ' m u l a ' o n (transcranial magne'c s'mula'on) (George 2010).
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In TRD, L DLPFC hypoac'vity is associated with nega've emo'onal judgment and right DLPFC hyperac'vity is linked to aTen'onal modula'on (Grimm 2008).
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DLPFC has been demonstrated to be an'-‐ correlated with subcallosal cingulate (SCC) (Fox 2012).
EpCS: Frontopolar Cortex • The medial prefrontal cortex has been implicated in animal (Covington 2010) and human studies (Downar 2013) as playing a central role in the pathogenesis of depression as well as in its recovery. • There is a consistent finding of increased res'ng-‐ state ac'vity in the frontopolar cortex (FPC) in pa'ents with depression (Fitzgerald 2008). • Effec've SCC DBS requires func'onal connec'on to the FPC (Riva Posse 2014).
Modified Mayberg Target
Riva-‐Posse 2014
Epidural Prefrontal Cor'cal S'mula'on • We implanted five adults with four s'mula'on paddles over dura (between dura and skull) covering FP and DLPFC. • These five individuals had failed an average of 5.8 an'depressants prior to implant with three who had failed VNS and four who had failed or were unable to tolerate ECT.
• All subjects received ongoing clinical assessments at baseline, seven-‐month (7mo), one-‐year (1yr), two-‐year (2yr), and five-‐year (5yr) 'me points.
Epidural Prefrontal Cor'cal S'mula'on • All pa'ents have con'nued to tolerate the therapy. • There were five serious adverse events: one paddle infec'on and four device malfunc'ons, all r e s u l ' n g i n s u i c i d a l i d e a ' o n a n d / o r hospitaliza'on with three involving the baTery (2-‐drain, 1-‐turned off) and one involving connectors.
• Three of five (60%) subjects con'nued to be in remission at 5yr. • One of the non-‐responders converted to a responder (80%) once a technical error was discovered.
Average HAMD Scores
Average HAMD Scores
The First Circuit-‐Level Interven'on for a Neuropsychiatric Disorder
Transcranial Magne'c S'mula'on • Transcranial magne'c s'mula'on (TMS) is a non-‐invasive procedure that uses magne'c fields to s'mulate cor'cal neurons. • In 2008, the FDA approved rTMS as a treatment for adults with MDD who “have not responded to a single an'depressant medica'on in the current episode.”
Transcranial S'mula'on • Video
rTMS Effects on Brain Circuits
Importance of Accelera'ng and Compressing rTMS Treatment
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Length of tradi'onal rTMS
35
Dura'on of accelerated
Courtesy of J Pannu
aTBS Piloted in 2 Pa'ents
HRSD-‐6 Score
20 15 10
Pa'ent 1 Pa'ent 2
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10 20 30 40 Days from first treatment
50 Courtesy of J Pannu
Accelerated TMS Effects on SCC
Δ in HDRS to Δ in SCC Ac'vity
Acknowledgements • Stanford Brain S'mula'on Lab • Depression Research Clinic • MUSC Brain S'mula'on Lab • PAN Lab • The Bernert Lab Contact: brains'mula'
[email protected]
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