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Focus

Volume 20, Issue 1

Novel Neurotherapeutics

January 2022

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From the Guest Editor

January 2022

Novel Neurotherapeutics

Alexander Bystritsky, M.D., Ph.D.

Pages:1–2
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20210032

Full text
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Reviews

January 2022

The Future Is Noninvasive: A Brief Review of the Evolution and Clinical Utility of Vagus Nerve Stimulation

Bashar W. Badran, Ph.D., and
Christopher W. Austelle, M.D.

Pages:3–7
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20210023

Abstract
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Preview Abstract

Vagus nerve stimulation (VNS) is a form of neuromodulation that stimulates the vagus nerve. VNS had been suggested as an intervention in the late 1800s and was rediscovered in the late 1980s as a promising treatment for refractory epilepsy. Since then, ...

January 2022

Psychiatric Applications of Repetitive Transcranial Magnetic Stimulation

Katharine G. Marder, M.D.,
Tracy Barbour, M.D.,
Stephen Ferber, M.D.,
Olanike Idowu, A.P.R.N., P.M.H.N.P.-B.C.,
Amanda Itzkoff, M.D.

Pages:8–18
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20210021

Abstract
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Transcranial magnetic stimulation (TMS) is an increasingly popular noninvasive brain stimulation modality. In TMS, a pulsed magnetic field is used to noninvasively stimulate a targeted brain region. Repeated stimulation produces lasting changes in brain ...

January 2022

Transcranial Electrical Stimulation for Psychiatric Disorders in Adults: A Primer

Hyein Cho, Ph.D.,
Lais B. Razza, B.A.,
Lucas Borrione, M.D.,
Marom Bikson, Ph.D.,
Leigh Charvet, Ph.D.,
Tracy A. Dennis-Tiwary, Ph.D.,
Andre R. Brunoni, M.D., Ph.D.,
Pedro Sudbrack-Oliveira, M.D.

Pages:19–31
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20210020

Abstract
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Transcranial electrical stimulation (tES) comprises noninvasive neuromodulation techniques that deliver low-amplitude electrical currents to targeted brain regions with the goal of modifying neural activities. Expanding evidence from the past decade, ...

January 2022

Ultrasound as a Neurotherapeutic: A Circuit- and System-Based Interrogation

Norman M. Spivak, B.S.,
William Jamie Tyler, Ph.D.,
Ausaf A. Bari, M.D., Ph.D.,
Taylor P. Kuhn, Ph.D.

Pages:32–35
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20210022

Abstract
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Focused ultrasound is a novel brain stimulation modality that combines the noninvasiveness of repetitive transcranial magnetic stimulation and the precision of deep brain stimulation. In this review, the authors examine low-intensity focused ultrasound ...

January 2022

Brighten the Future: Photobiomodulation and Optogenetics

Li-Da Huang, Ph.D.

Pages:36–44
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20210025

Abstract
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Safe, noninvasive, and effective treatments for brain conditions are everyone’s dream. Low-level light therapy (LLLT) based on the photobiomodulation (PBM) phenomenon has recently been adopted in practice, with solid scientific evidence. Optogenetics ...

January 2022

A Systematic Approach to Neuropsychiatric Intervention: Functional Neuroanatomy Underlying Symptom Domains as Targets for Treatment

Taylor Kuhn, Ph.D.,
Jonathan Haroon, B.S.,
Norman M. Spivak, B.S.

Pages:45–54
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20210024

Abstract
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An ever-growing population experiences a wide range of psychopathologies, and there is now more than ever a need for clear differential diagnoses between disorders. Furthering this need is the fact that many psychological, psychiatric, and neurological ...

Clinical Synthesis

January 2022

Deep Brain Stimulation for Intractable Obsessive-Compulsive Disorder and Treatment-Resistant Depression

Benjamin M. Borron, B.S., and
Darin D. Dougherty, M.D., M.M.Sc.

Pages:55–63
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20210029

Abstract
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In deep brain stimulation (DBS), a neurostimulation device is implanted to generate electrical fields in targeted deep brain regions in order to affect circuits associated with neuropsychiatric illness for potential therapeutic benefit. The development of ...

January 2022

Noninvasive Delivery of Biologicals to the Brain

Sheldon Jordan, M.D., F.A.A.N.,
Margaret Zielinski, B.S.,
Marcin Kortylewski, Ph.D.,
Taylor Kuhn, Ph.D.,
Alexander Bystritsky, M.D., Ph.D.

Pages:64–70
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20210028

Abstract
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In the past, psychotherapy and neuropharmacological approaches have been the most common treatments for disordered thoughts, moods, and behaviors. One new path of brain therapeutics is in the deployment of noninvasive approaches designed to reprogram ...

Ethics Commentary

January 2022

Ethical Issues in Vagus Nerve Stimulation and Deep Brain Stimulation

Reuben Heyman-Kantor, M.D., and
Richard G. Cockerill, M.D., MBE

Pages:71–75
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20210031

First Page
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Influential Publications

January 2022

Pages:76–78
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20107

First Page
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January 2022

Page:79
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20108

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January 2022

Neurophysiologic Effects of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) via Electrical Stimulation of the Tragus: A Concurrent taVNS/fMRI Study and Review

Bashar W. Badran,
Logan T. Dowdle
Oliver J. Mithoefer,
Nicholas T. LaBate,
James Coatsworth,
Joshua C. Brown,
William H. DeVries,
Christopher W. Austelle,
Lisa M. McTeague,
Mark S. George

Pages:80–89
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20110

Abstract
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Background: Electrical stimulation of the auricular branch of the vagus nerve (ABVN) via transcutaneous auricular vagus nerve stimulation (taVNS) may influence afferent vagal networks. There have been 5 prior taVNS/fMRI studies, with inconsistent ...

January 2022

Sonication of the Anterior Thalamus With MRI-Guided Transcranial Focused Ultrasound (tFUS) Alters Pain Thresholds in Healthy Adults: A Double-Blind, Sham-Controlled Study

Bashar W. Badran,
Kevin A. Caulfield,
Sasha Stomberg-Firestein,
Philipp M. Summers,
Logan T. Dowdle,
Matt Savoca,
Xingbao Li,
Christopher W. Austelle,
E. Baron Short,
Jeffrey J. Borckardt,
Norman Spivak,
Alexander Bystritsky,
Mark S. George

Pages:90–99
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20109

Abstract
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Background: Transcranial focused ultrasound (tFUS) is a noninvasive brain stimulation method that may modulate deep brain structures. This study investigates whether sonication of the right anterior thalamus would modulate thermal pain thresholds in ...

January 2022

Neutrophil Recruitment and Leukocyte Response Following Focused Ultrasound and Microbubble Mediated Blood-Brain Barrier Treatments

Charissa Poon,
Carly Pellow, and
Kullervo Hynynen

Pages:100–116
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20104

Abstract
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Rationale: Delivery of therapeutic agents to the brain is limited by the presence of the blood-brain barrier (BBB). An emerging strategy to temporarily and locally increase the permeability of the BBB is the use of transcranial focused ultrasound (FUS) ...

January 2022

Review of Current Strategies for Delivering Alzheimer's Disease Drugs Across the Blood-Brain Barrier

Ka Hong Wong,
Muhammad Kashif Riaz,
Yuning Xie,
Xue Zhang,
Qiang Liu,
Huoji Chen,
Zhaoxiang Bian,
Xiaoyu Chen,
Aiping Lu and
Zhijun Yang

Pages:117–136
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20106

Abstract
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Effective therapy for Alzheimer's disease is a major challenge in the pharmaceutical sciences. There are six FDA approved drugs (e.g., donepezil, memantine) that show some effectiveness; however, they only relieve symptoms. Two factors hamper research. ...

January 2022

Treating Refractory Mental Illness With Closed-Loop Brain Stimulation: Progress Towards a Patient-Specific Transdiagnostic Approach

Alik S. Widge,
Kristen K. Ellard,
Angelique C. Paulk,
Ishita Basu,
Ali Yousefi,
Samuel Zorowitz,
Anna Gilmour,
Afsana Afzal,
Thilo Deckersbach,
Sydney S. Cash,
Mark A. Kramer,
Uri T. Eden,
Darin D. Dougherty,
Emad N. Eskandar

Pages:137–151
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20102

Abstract
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Mental disorders are a leading cause of disability, morbidity, and mortality among civilian and military populations. Most available treatments have limited efficacy, particularly in disorders where symptoms vary over relatively short time scales. ...

January 2022

Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial

Lior Carmi, Ph.D.,
Aron Tendler, M.D.,
Alexander Bystritsky, M.D.,
Eric Hollander, M.D.,
Daniel M. Blumberger, M.D.,
Jeff Daskalakis, M.D.,
Herbert Ward, M.D.,
Kyle Lapidus, M.D.,
Wayne Goodman, M.D.,
Leah Casuto, M.D.,
David Feifel, M.D.,
Noam Barnea-Ygael, Ph.D.,
Yiftach Roth, Ph.D.,
Abraham Zangen, Ph.D.,
Joseph Zohar, M.D.

Pages:152–159
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20103

Abstract
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Objective: Obsessive-compulsive disorder (OCD) is a chronic and disabling condition that often responds unsatisfactorily to pharmacological and psychological treatments. Converging evidence suggests a dysfunction of the cortical-striatal-thalamic-...

January 2022

A Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder: Clinical and Imaging Evidence for Dissociable Effects

Himanshu Tyagi,
Annemieke M. Apergis-Schoute,
Harith Akram,
Tom Foltynie,
Patricia Limousin,
Lynne M. Drummond,
Naomi A. Fineberg,
Keith Matthews,
Marjan Jahanshahi,
Trevor W. Robbins,
Barbara J. Sahakian,
Ludvic Zrinzo,
Marwan Hariz, and
Eileen M. Joyce

Pages:160–169
Published Online:25 January 2022

https://doi.org/10.1176/appi.focus.20105

Abstract
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Background: Deep brain stimulation (DBS) is an emerging treatment for severe obsessive-compulsive disorder (OCD). We compared the efficacy of ventral capsule/ventral striatal (VC/VS) and anteromedial subthalamic nucleus (amSTN) DBS in the same patients ...

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