Neural predictors of treatment response to brain stimulation and psychological therapy in depression: a double-blind randomized controlled trial

Nord, Camilla L.; Halahakoon, D. Chamith; Limbachya, Tarun; Charpentier, Caroline J.; Lally, Níall; Walsh, Vincent; Leibowitz, Judy; Pilling, Stephen; Roiser, Jonathan P.

doi:10.1038/s41386-019-0401-0

Cited by 59 publications

(49 citation statements)

References 41 publications

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“…Consistent with this hypothesis, stimulation to the IPS, which shows strong prefrontal connections, lead to impairments on a stop signal task compared to stimulation of the tempoparietal junction, an area not connected to the prefrontal cortex 74 . Also consistent with this network hypothesis of TMS effects, recent work has shown that prefrontal stimulation alters parietal activity 75 , and that the therapeutic effects of prefrontal stimulation may be mediated in part through these changes in parietal activity 76 .…”

Section: Discussionmentioning

confidence: 60%

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

et al. 2020

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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 (anxietypotentiated 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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Section: Discussionmentioning

confidence: 60%

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

et al. 2020

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“…However, in a previous study, euthymic MDD patients showed comparable lateral prefrontal activation during working memory to healthy controls ( Schöning et al., 2009 ), and pharmacological ( Brody et al., 2001 ; Fales et al., 2009 ), psychological ( Brody et al., 2001 ; Goldapple et al., 2004 ), and somatic treatments for depression ( Perrin et al., 2012 ) have all been found to normalise DLPFC activation. Similarly, most non-invasive brain stimulation treatments for depression target the DLPFC ( Blumberger et al., 2018 ; George et al., 2000 ; Loo et al., 2012 ; Nord et al., 2019 ; Nord and Roiser, 2015 ), and there is preliminary evidence that DLPFC activation may be a ‘biomarker’ for treatment response to these interventions ( Nord et al., 2019 ; Weiduschat and Dubin, 2013 ).…”

Section: Resultsmentioning

confidence: 99%

“…Improving executive function might represent one way of treating or preventing depression, through top-down control of emotional processing regions: several trials found (unexpectedly) that cognitive training in dementia improved depressive symptoms ( Sitzer et al., 2006 ). An alternative approach involves directly targeting prefrontal mechanisms in depression with non-invasive brain stimulation: transcranial magnetic stimulation ( George et al., 2000 ) and transcranial direct current stimulation ( Loo et al., 2012 ; Nord and Roiser, 2015 ) have both shown efficacy at treating depression; the latter in particular may target executive function mechanisms ( Nord et al., 2017a , 2019 ). Future work needs to better clarify the interaction between dorsal prefrontal and ventral prefrontal/subcortical responses in individuals at a familial risk for depression, with the view to preventing at-risk populations from developing depression, and better treating those who do.…”

Section: Discussionmentioning

confidence: 99%

“…Non-invasive brain stimulation interventions for depression almost all target the DLPFC ( Blumberger et al., 2018 ; George et al., 2000 ; Loo et al., 2012 ; Nord et al., 2019 ; Nord and Roiser, 2015 ), though with mixed results. However, some studies suggest that individual differences in DLPFC activation predict treatment response to interventions directly targeting this region ( Nord et al., 2019 ; Weiduschat and Dubin, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

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The neural basis of hot and cold cognition in depressed patients, unaffected relatives, and low-risk healthy controls: An fMRI investigation

Nord

Lally

et al. 2020

Journal of Affective Disorders

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Highlights Depressed patients show decreased prefrontal cortex activation compared to controls. First-degree relatives without depression show intact prefrontal cortex activation. The prefrontal cortex may be involved in resilience to depression. This could also provide preliminary support for targeting this region in treatment.

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“…Nord [124], 2019 Anodal tDCS is significantly superior to sham in individuals with high left prefrontal cortex BOLD activation at baseline during the performance of an n-back task (86% accuracy in predicting clinical response using this measure)…”

Section: Resultsmentioning

confidence: 99%

Transcranial Magnetic and Direct Current Stimulation in the Treatment of Depression: Basic Mechanisms and Challenges of Two Commonly Used Brain Stimulation Methods in Interventional Psychiatry

et al. 2019

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Noninvasive neuromodulation, including repetitive transcranial magnetic stimulation (rTMS) and direct current stimulation (tDCS), provides researchers and health care professionals with the ability to gain unique insights into brain functions and treat several neurological and psychiatric conditions. Undeniably, the number of published research and clinical papers on this topic is increasing exponentially. In parallel, several methodological and scientific caveats have emerged in the transcranial stimulation field; these include less robust and reliable effects as well as contradictory clinical findings. These inconsistencies are maybe due to the fact that research exploring the relationship between the methodological aspects and clinical efficacy of rTMS and tDCS is far from conclusive. Hence, additional work is needed to understand the mechanisms underlying the effects of magnetic stimulation and low-intensity transcranial electrical stimulation (TES) in order to optimize dosing, methodological designs, and safety aspects.

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Neural predictors of treatment response to brain stimulation and psychological therapy in depression: a double-blind randomized controlled trial

Cited by 59 publications

References 41 publications

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

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

The neural basis of hot and cold cognition in depressed patients, unaffected relatives, and low-risk healthy controls: An fMRI investigation

Transcranial Magnetic and Direct Current Stimulation in the Treatment of Depression: Basic Mechanisms and Challenges of Two Commonly Used Brain Stimulation Methods in Interventional Psychiatry

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