Threat-related learning relies on distinct dorsal prefrontal cortex network connectivity

Abstract

Conditioned changes in the emotional response to threat (e.g. aversive unconditioned stimulus; UCS) are mediated in part by the prefrontal cortex (PFC). Unpredictable threats elicit large emotional responses, while the response is diminished when the threat is predictable. A better understanding of how PFC connectivity to other brain regions varies with threat predictability would provide important insights into the neural processes that mediate conditioned diminution of the emotional response to threat. The present study examined brain connectivity during predictable and unpredictable threat exposure using a fear conditioning paradigm (previously published in Wood et al., 2012) in which unconditioned functional magnetic resonance imaging data was reanalyzed to assess effective connectivity. Granger causality analysis was performed using the time series data from 15 activated regions of interest after hemodynamic deconvolution, to determine regional effective connectivity. In addition, connectivity path weights were correlated with trait anxiety measures to assess the relationship between negative affect and brain connectivity. Results indicate the dorsomedial PFC (dmPFC) serves as a neural hub that influences activity in other brain regions when threats are unpredictable. In contrast, the dorsolateral PFC (dlPFC) serves as a neural hub that influences the activity of other brain regions when threats are predictable. These findings are consistent with the view that the dmPFC coordinates brain activity to take action, perhaps in a reactive manner, when an unpredicted threat is encountered, while the dlPFC coordinates brain regions to take action, in what may be a more proactive manner, to respond to predictable threats. Further, dlPFC connectivity to other brain regions (e.g. ventromedial PFC, amygdala, and insula) varied with negative affect (i.e. trait anxiety) when the UCS was predictable, suggesting that stronger connectivity may be required for emotion regulation in individuals with higher levels of negative affect.

Forgetting the best when predicting the worst: Preliminary observations on neural circuit function in adolescent social anxiety

“…This precisely mirrored the task structure, but came at a cost: some event types had relatively few trials. Although other well-established paradigms utilize similarly sparsely-populate events (e.g., Lebron-Milad et al, 2012; Milad et al, 2013; Milad et al, 2009; Milad et al, 2007; Visser, Scholte, Beemsterboer, & Kindt, 2013; Wheelock et al, 2014), the small number of trials raises concerns about the stability of results. Research aimed at extending these findings should consider increasing the sample size, and/or implementing novel paradigms that include more trials for each event type while maintaining task complexity needed to retain external validity (Jarcho et al, 2013).…”

The impact of hemodynamic variability and signal mixing on the identifiability of effective connectivity structures in BOLD fMRI

“…In many applications, lagged methods for effective connectivity in fMRI are applied to the deconvolved BOLD time series, with an example of GC (David et al., 2008; Goodyear et al., 2016; Hutcheson et al., 2015; Ryali, Supekar, Chen, & Menon, 2011; Ryali et al., 2016; Sathian, Deshpande, & Stilla, 2013; Wheelock et al., 2014). However, as demonstrated in Figure 5b, the natural variability in the neuronal dynamics results with an upper bound on the accuracy of the lagged based methods: even assuming a perfect deconvolution (which is never the case in practice), which would allow for perfect retrieval of the neuronal time series from the BOLD time series, for the TR = 0.70 s, the accuracy rate of ∆ would be <100% (for the parameter space we are exploring in this study, this accuracy would be on the level of 90%).…”

Long-Range Neural Synchrony in Behavior

“…However, fMRI can reveal the connectivity of the amygdala with cortical structures during fear conditioning. One recent study examined large-scale network connectivity during predictable (CS paired with UCS) and unpredictable (UCS alone) threat (Wheelock et al 2014); unpredictable threat produced more intense anxiety. The authors analyzed the network activity of 15 brain regions activated by both kinds of threats.…”

“…For predictable threats, the dorso lateral prefrontal cortex formed an outward hub, communicating with the greatest number of structures, including the insular cortex, which served as a secondary hub. By contrast, for unpredictable threat, the dorso medial prefrontal cortex (dmPFC) formed the primary hub, while the amygdala comprised a secondary hub (Wheelock et al 2014). These results suggest that the dorsolateral prefrontal cortex and insular cortex provide emotional regulation during predictable stress.…”