Threat of shock increases excitability and connectivity of the intraparietal sulcus

Balderston, Nicholas L.; Hale, Elizabeth; Hsiung, Abigail; Torrisi, Salvatore; Holroyd, Tom; Carver, Frederick W.; Coppola, Richard; Ernst, Monique; Grillon, Christian

doi:10.7554/elife.23608

Cited by 41 publications

(43 citation statements)

References 150 publications

(250 reference statements)

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“…Previous studies using electroencephalography (EEG) have demonstrated hyperactivity in the parietal cortex as a function of arousal in anxious patients 12 , suggesting a potential link between parietal hyperactivity and attention control deficits 13 . Consistent with these results, our previous work used unbiased data-driven approaches in a multimodal (MEG/fMRI) neuroimaging study of effects of threat-of-shock-induced anxiety on cortical excitability (alpha desynchronization) and global brain connectivity 14 .…”

Section: Introductionsupporting

confidence: 60%

“…We based our target choice on group data from Balderston et al (see Fig. 2a) 14,16 , which found increases in global connectivity in the intraparietal sulcus during threat-of-shock, suggesting that this region may be a connectivity hub mediating anxiety expression. Accordingly, the goal of the present work was to extract the location within this region with the highest global connectivity.…”

Section: Target Localizationmentioning

confidence: 99%

“…To localize the optimal IPS target, we drew 10 mm spheres around the MNI coordinates reported in Balderston et al 14,16 . We then calculated global connectivity from the denoised resting-state EPI scan using the AFNI tool 3dTCorrMap.…”

Section: Fmri-guided Target Selectionmentioning

confidence: 99%

“…Finally, we extracted the voxel with the highest global connectivity, and used the coordinates as the TMS target. Importantly, because the Balderston et al 14,16 finding was bilateral, we did not constrain our search to a specific hemisphere. Therefore, we had roughly equal numbers of people receiving left (N = 9) and right (N = 10) IPS stimulation.…”

Section: Fmri-guided Target Selectionmentioning

confidence: 99%

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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: Introductionsupporting

confidence: 60%

Section: Target Localizationmentioning

confidence: 99%

Section: Fmri-guided Target Selectionmentioning

confidence: 99%

Section: Fmri-guided Target Selectionmentioning

confidence: 99%

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

et al. 2020

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“…To calculate APS, we subtracted the response during the neutral ITI from the response during the unpredictable ITI. This approach has been traditionally used by our group and was chosen because it allows a direct comparison to other non-NPU threat studies where neutral and predictable blocks are presented without cues (e.g [1,31]). Another benefit to this approach is that the APS measurement is not contaminated by the cue presentation, which can potentiate the startle response even though it does not carry any predictive information about the shock in the U condition [6].…”

Section: Electromyographymentioning

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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Striatal responsiveness to reward under threat‐of‐shock and working memory load: A preliminary study

et al. 2019

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Introduction Reward and stress are important determinants of motivated behaviors. Striatal regions play a crucial role in both motivation and hedonic processes. So far, little is known on how cognitive effort interacts with stress to modulate reward processes. This study examines how cognitive effort (load) interacts with an unpredictable acute stressor (threat‐of‐shock) to modulate motivational and hedonic processes in healthy adults. Materials and Methods A reward task, involving stress with unpredictable mild electric shocks, was conducted in 23 healthy adults aged 20–37 (mean age: 24.7 ± 0.9; 14 females) during functional magnetic resonance imaging (fMRI). Manipulation included the use of (a) monetary reward for reinforcement, (b) threat‐of‐shock as the stressor, and (c) a spatial working memory task with two levels of difficulty (low and high load) for cognitive load. Reward‐related activation was investigated in a priori three regions of interest, the nucleus accumbens (NAcc), caudate nucleus, and putamen. Results During anticipation, threat‐of‐shock or cognitive load did not affect striatal responsiveness to reward. Anticipated reward increased activation in the ventral and dorsal striatum. During feedback delivery, both threat‐of‐shock and cognitive effort modulated striatal activation. Higher working memory load blunted NAcc responsiveness to reward delivery, while stress strengthened caudate nucleus reactivity regardless reinforcement or load. Conclusions These findings provide initial evidence that both stress and cognitive load modulate striatal responsiveness during feedback delivery but not during anticipation in healthy adults. Of clinical importance, sustained stress exposure might go along with dysregulated arousal, increasing therefore the risk for the development of maladaptive incentive‐triggered motivation. This study brings new insight that might help to build a framework to understand common stress‐related disorders, given that these psychiatric disorders involve disturbances of the reward system, cognitive deficits, and abnormal stress reactivity.

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Threat of shock increases excitability and connectivity of the intraparietal sulcus

Cited by 41 publications

References 150 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

Striatal responsiveness to reward under threat‐of‐shock and working memory load: A preliminary study

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