Low-frequency parietal repetitive transcranial magnetic stimulation reduces fear and anxiety

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Abstract

Anxiety disorders are the most prevalent mental disorders, with few effective neuropharmacological treatments, making treatments development critical. While noninvasive neuromodulation can successfully treat depression, few treatment targets have been identified specifically for anxiety disorders. Previously, we showed that shock threat increases excitability and connectivity of the intraparietal sulcus (IPS). Here we tested the hypothesis that inhibitory repetitive transcranial magnetic stimulation (rTMS) targeting this region would reduce induced anxiety. Subjects were exposed to neutral, predictable, and unpredictable shock threat, while receiving double-blinded, 1 Hz active or sham IPS rTMS. We used global brain connectivity and electric-field modelling to define the single-subject targets. We assessed subjective anxiety with online ratings and physiological arousal with the startle reflex. Startle stimuli (103 dB white noise) probed fear and anxiety during the predictable (fear-potentiated startle, FPS) and unpredictable (anxiety-potentiated startle, APS) conditions. Active rTMS reduced both FPS and APS relative to both the sham and no stimulation conditions. However, the online anxiety ratings showed no difference between the stimulation conditions. These results were not dependent on the laterality of the stimulation, or the subjects’ perception of the stimulation (i.e. active vs. sham). Results suggest that reducing IPS excitability during shock threat is sufficient to reduce physiological arousal related to both fear and anxiety, and are consistent with our previous research showing hyperexcitability in this region during threat. By extension, these results suggest that 1 Hz parietal stimulation may be an effective treatment for clinical anxiety, warranting future work in anxiety patients.

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Most cited references 73

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We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.

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A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition.

Paul B. Fitzgerald, Sarah Fountain, Zafiris Daskalakis (2006)

Repetitive transcranial magnetic stimulation (rTMS) procedures are being widely applied in therapeutic and investigative studies. Numerous studies have investigated the effects of rTMS on cortical excitability and inhibition, yielding somewhat contradictory results. The purpose of this study was to comprehensively review this literature to guide the selection of methodology in therapeutic studies. We conducted a comprehensive review of all identified studies that investigated effects of low and/or high frequency rTMS on motor cortical excitability or inhibition. Low frequency rTMS appears to produce a transient reduction in cortical excitability as assessed by motor evoked potential (MEP) size and produces no substantial effect on cortical inhibition. High frequency rTMS appears to produce a persistent increase in MEP size and a reduction in cortical inhibition measured with paired pulse methods although few studies have investigated frequencies greater than 5Hz. A number of novel stimulation paradigms have significant potential for altering cortical excitability but require further investigation. Although commonly applied forms of rTMS have effects on cortical excitability, more substantial effects may be obtained through the use of novel stimulation paradigms or innovative approaches to the stimulation of areas connected to a potential target site. Further research is required, however, before these paradigms can be more widely adopted.

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Author and article information

Contributors

Nicholas L. Balderston:

ORCID: http://orcid.org/0000-0002-8565-1544

nicholas.balderston@pennmedicine.upenn.edu

Journal

Journal ID (nlm-ta): Transl Psychiatry

Journal ID (iso-abbrev): Transl Psychiatry

Title: Translational Psychiatry

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2158-3188

Publication date (Electronic): 17 February 2020

Publication date PMC-release: 17 February 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 68

Affiliations

[1 ]ISNI 0000 0004 0464 0574, GRID grid.416868.5, Section on Neurobiology of Fear and Anxiety, , National Institute of Mental Health, National Institutes of Health Bethesda, ; Bethesda, MD USA

[2 ]ISNI 0000 0004 1936 8972, GRID grid.25879.31, Center for Neuromodulation in Depression and Stress, Department of Psychiatry, , University of Pennsylvania Philadelphia, ; Philadelphia, PA USA

[3 ]ISNI 0000 0004 0464 0574, GRID grid.416868.5, Noninvasive Neuromodulation Unit, , National Institute of Mental Health, National Institutes of Health Bethesda, ; Bethesda, MD USA

Author information

Nicholas L. Balderston http://orcid.org/0000-0002-8565-1544

Article

Publisher ID: 751

DOI: 10.1038/s41398-020-0751-8

PMC ID: 7026136

PubMed ID: 32066739

SO-VID: 02d5947e-2839-42f3-8f70-961826fb3843

License:

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