Neuropsychiatric Complications of Alcohol Dependence Syndrome
Williams Presentation Mood-Video - Stanford...
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Modula’on of the Neural Circuitry Underlying Neuropsychiatric Disorders Nolan Williams, MD Instructor Department of Psychiatry Stanford University
Transcript of Williams Presentation Mood-Video - Stanford...
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
• The f rontopo lar ( FP -‐BA 10) and dorsolateral (DL-‐BA 9/46) prefrontal co r'ces (PFC ) p l ay d i s'nc t , ye t complementary roles in the integra'on of emo'onal and cogni've experiences (Nahas 2010).
• One or both of these two cor'cal areas appear to be central to the efficacy of deep targets (Williams 2014).
• Our study u'lized bilateral dorsolateral prefrontal and the frontopolar cortex as s'mula'on sites (Nahas 2010).
• 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 'mu l a ' o n (transcranial magne'c s'mula'on) (George 2010).
• 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).
• DLPFC has been demonstrated to be an'-‐correlated with subcallosal cingulate (SCC) (Fox 2012).
EpCS: Dorsolateral Prefrontal Cortex
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 su l'ng i n su i c ida l i dea'on and/or 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
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
BASE 7 MO 1 YR 2 YR 5 YR
BASE 7 MO 1 YR 2 YR 5 YR
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
0 5 10 15 20 25 30 35 Dura'on of accelerated
0 5 10 15 20 25 30 35
Length of tradi'onal rTMS
10 Hz Repe))ve Transcranial Magne)c S)mula)on
50 Hz Con$nuous Theta-‐Burst S)mula)on
50 Hz Intermi-ent Theta-‐Burst S)mula)on
10 Hz Repe))ve Transcranial Magne)c S)mula)on
50 Hz Con$nuous Theta-‐Burst S)mula)on
50 Hz Intermi-ent Theta-‐Burst S)mula)on
Courtesy of J Pannu
aTBS Piloted in 2 Pa'ents
0
5
10
15
20
0 10 20 30 40 50
HRSD
-‐6 Score
Days from first treatment
Pa'ent 1 Pa'ent 2
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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