RESUMEN
Repetitive transcranial magnetic stimulation (rTMS) treatment protocols targeting the right dlPFC have been effective in reducing anxiety symptoms comorbid with depression. However, the mechanism behind these effects is unclear. Further, it is unclear whether these results generalize to non-depressed individuals. We conducted a series of studies aimed at understanding the link between anxiety potentiated startle and the right dlPFC, following a previous study suggesting that continuous theta burst stimulation (cTBS) to the right dlPFC can make people more anxious. Based on these results we hypothesized that intermittent TBS (iTBS), which is thought to have opposing effects on plasticity, may reduce anxiety when targeted at the same right dlPFC region. In this double-blinded, cross-over design, 28 healthy subjects underwent 12 study visits over a 4-week period. During each of their 2 stimulation weeks, they received four 600 pulse iTBS sessions (2/day), with a post-stimulation testing session occurring 24 h following the final iTBS session. One week they received active stimulation, one week they received sham. Stimulation weeks were separated by a 1-week washout period and the order of active/sham delivery was counterbalanced across subjects. During the testing session, we induced anxiety using the threat of unpredictable shock and measured anxiety potentiated startle. Contrary to our initial hypothesis, subjects showed increased startle reactivity following active compared to sham stimulation. These results replicate work from our two previous trials suggesting that TMS to the right dlPFC increases anxiety potentiated startle, independent of both the pattern of stimulation and the timing of the post stimulation measure. Although these results confirm a mechanistic link between right dlPFC excitability and startle, capitalizing upon this link for the benefit of patients will require future exploration.
RESUMEN
BACKGROUND: Work on anxiety related attention control deficits suggests that elevated arousal impacts the ability to filter out distractors. To test this, we designed a task to look at distractor suppression during periods of threat. We administered trials of a visual short-term memory (VSTM) task, during periods of unpredictable threat, and hypothesized that threat would impair performance during trials where subjects were required to filter out large numbers of distractors. METHOD: Experiment 1 involved fifteen healthy participants who completed one study visit. They performed four runs of a VSTM task comprising 32 trials each. Participants were presented with an arrow indicating left or right, followed by an array of squares. They were instructed to remember the target side and disregard the distractors on the off-target side. A subsequent target square was shown, and participants indicated whether it matched one of the previously presented target squares. The trial conditions included 50% matches and 50% mismatches, with an equal distribution of left and right targets. The number of target and distractor squares varied systematically, with high (4 squares) and low (2 squares) target and distractor conditions. Trials alternated between periods of safety and threat, with startle responses recorded using electromyography (EMG) following white noise presentations. Experiment 2 involved twenty-seven healthy participants who completed the same VSTM task inside an MRI scanner during a single study visit. The procedure mirrored that of Experiment 1, except for the absence of white noise presentations. RESULTS: For Experiment 1, subjects showed significantly larger startle responses during threat compared to safe period, supporting the validity of the threat manipulation. However, results suggested that the white noise probes interfered with performance. For Experiment 2, we found that both accuracy was affected by threat, such that distractor load negatively impacted accuracy only in the threat condition. CONCLUSION: Overall, these findings suggest that threat affects distractor susceptibility during the short-term maintenance of visual information. The presence of threat makes it more difficult to filter out distracting information. We believe that this is related to hyperarousal of parietal cortex, which has been observed during unpredictable threat.
RESUMEN
Background: The right dorsolateral prefrontal cortex (dlPFC) has been indicated to be a key region in the cognitive regulation of emotion by many previous neuromodulation and neuroimaging studies. However, there is little direct causal evidence supporting this top-down regulation hypothesis. Furthermore, it is unclear whether contextual threat impacts this top-down regulation. By combining TMS/fMRI, this study aimed to uncover the impact of unpredictable threat on TMS-evoked BOLD response in dlPFC-regulated emotional networks. Based on the previous findings linking the dlPFC to the downregulation of emotional network activity, we hypothesized TMS pulses would deactivate activity in anxiety expression regions, and that threat would reduce this top-down regulation. Methods: 44 healthy controls (no current or history of psychiatric disorders) were recruited to take part in a broader study. Subjects completed the neutral, predictable, and unpredictable (NPU) threat task while receiving TMS pulses to either the right dlPFC or a control region. dlPFC targeting was based on data from a separate targeting session, where subjects completed the Sternberg working memory (WM) task inside the MRI scanner. Results: When compared to safe conditions, subjects reported significantly higher levels of anxiety under threat conditions. Additionally, TMS-evoked responses in the left insula (LI), right sensory/motor cortex (RSM), and a region encompassing the bilateral SMA regions (BSMA) differed significantly between safe and threat conditions. There was a significant TMS-evoked deactivation in safe periods that was significantly attenuated in threat periods across all 3 regions. Conclusions: These findings suggest that threat decreases dlPFC-regulated emotional processing by attenuating the top-down control of emotion, like the left insula. Critically, these findings provide support for the use of right dlPFC stimulation as a potential intervention in anxiety disorders.
RESUMEN
Past research has shown that the bilateral dorsolateral prefrontal cortices (dlPFC) are implicated in both emotional processing as well as cognitive processing, 1,2,3 in addition to working memory 4, 5 . Exactly how these disparate processes interact with one another within the dlPFC is less understood. To explore this, researchers designed an experiment that looked at working memory performance during fMRI under both emotional and non-emotional task conditions. Participants were asked to complete three tasks (letters, neutral images, emotional images) of the Sternberg Sorting Task under one of two trial conditions (sort or maintain). Regions of interest consisted of the left and right dlPFC as defined by brain masks based on NeuroSynth 6 . Results showed a significant main effect of the 'sort' condition on reaction speed for all three trial types, as well as a main effect of task type (letters) on accuracy. In addition, a significant interaction was found between trial type (sort) and task type (letters), but not for either of the picture tasks. These results reveal a discrepancy between BOLD signal and behavioral data, with no significant difference in BOLD activity during image trials being displayed, despite longer response times for every condition. While these results show that the dlPFC is clearly implicated in non-emotional cognitive processing, more research is needed to explain the lack of BOLD activation seen here for similar emotionally valanced tasks, possibly indicating involvement of other brain networks.
