Modeling anxiety in healthy humans: a key intermediate bridge between basic and clinical sciences

Grillon, Christian; Robinson, Oliver J.; Cornwell, Brian R.; Ernst, Monique

doi:10.1038/s41386-019-0445-1

Cited by 62 publications

(58 citation statements)

References 188 publications

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“…The current manipulation, threat of predictable and unpredictable shock, can induce robust increases in physiological arousal 15,16 , impairments in performance on tasks that require working memory processes 57,58 , and improvements in tasks that require sustained attention 59 . Accordingly, it is clear that instructed threat impacts behavior across multiple domains important for anxiety symptomatology 60 . However, the benefit of TMS as an intervention is that one can potentially selectively target distinct symptom domains at the individual level.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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

et al. 2020

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“…Importantly, this physiological measure allowed us to measure the objective effect of the active stimulation protocol on anxiety [53], independent of the subjective placebo effects induced by both the active and sham stimulation. This is an important step because anxiety is highly dimensional, so this healthy volunteer approach employing APS could be used from proof-of-concept in the development of novel rTMS treatment strategies [54]. Although it is out of the scope of the current work to directly test the predictive validity of APS as predictive of clinical outcomes, there is ample evidence to suggest that APS is influenced by many of the same therapeutic interventions as clinical anxiety [18,55], and is elevated in women, who are known to suffer from anxiety disorders at higher rates than men [56].…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Mechanistic link between right prefrontal cortical activity and anxious arousal revealed using transcranial magnetic stimulation in healthy subjects

Balderston

Beydler

Roberts

et al. 2019

Neuropsychopharmacol.

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Much of the mechanistic research on anxiety focuses on subcortical structures such as the amygdala; however, less is known about the distributed cortical circuit that also contributes to anxiety expression. One way to learn about this circuit is to probe candidate regions using transcranial magnetic stimulation (TMS). In this study, we tested the involvement of the dorsolateral prefrontal cortex (dlPFC), in anxiety expression using 10 Hz repetitive TMS (rTMS). In a within-subject, crossover experiment, the study measured anxiety in healthy subjects before and after a session of 10 Hz rTMS to the right dorsolateral prefrontal cortex (dlPFC). It used threat of predictable and unpredictable shock to induce anxiety and anxiety potentiated startle to assess anxiety. Counter to our hypotheses, results showed an increase in anxiety-potentiated startle following active but not sham rTMS. These results suggest a mechanistic link between right dlPFC activity and physiological anxiety expression. This result supports current models of prefrontal asymmetry in affect, and lays the groundwork for further exploration into the cortical mechanisms mediating anxiety, which may lead to novel anxiety treatments.

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“…While anxiety disorders constitute a major global health burden 10 , anxiety is also a normative adaptive function that varies across the population. Studying anxiety in healthy human subjects can thus help bridge the gap between animal models of anxiety and clinical applications for patients with anxiety disorders 11,12 . Myriad studies have suggested that a wide range of cognitive functions are modulated by anxiety levels (see 13 for a review): sensory processing and gating [14][15][16] , attentional biases toward negative emotional stimuli 17,18 , decreased emotion regulation 19,20 , deficits in attentional control 21 , reduced working memory performance 22,23 , impairments during reinforcement learning 24,25 and increased risk avoidance during decision-making [26][27][28] .…”

Section: Introductionmentioning

confidence: 99%

How representative are neuroimaging samples? Large-scale evidence for trait anxiety differences between fMRI and behaviour-only research participants.

Charpentier¹,

Faulkner²,

Pool³

et al. 2020

Preprint

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Over the past three decades, MRI has become a key tool to study how cognitive processes are implemented in the human brain. However, the question of whether participants recruited into MRI studies differ from participants recruited into other study contexts has received little to no attention. This is particularly pertinent when effects fail to generalize across study contexts: for example, if a behavioural effect discovered in a non-imaging context does not replicate in a neuroimaging environment. Here, we tested the hypothesis, motivated by preliminary findings (n=272), that MRI study participants differ from behaviour-only study participants on one fundamental individual difference variable: trait anxiety. Analysing a large-scale dataset drawn from multiple institutions (n=3317) and controlling for possible confounding variables, we found robust support for lower trait anxiety in MRI study participants, consistent with a sampling bias. Distributions of trait anxiety scores differed most markedly when psychiatric screening was minimal. Our findings highlight the need for surveying trait anxiety at recruitment and for appropriate screening procedures, in an attempt to mitigate this bias.

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Modeling anxiety in healthy humans: a key intermediate bridge between basic and clinical sciences

Cited by 62 publications

References 188 publications

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

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

Mechanistic link between right prefrontal cortical activity and anxious arousal revealed using transcranial magnetic stimulation in healthy subjects

How representative are neuroimaging samples? Large-scale evidence for trait anxiety differences between fMRI and behaviour-only research participants.

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