Neural inhibition enables selection during language processing

Abstract

Whether grocery shopping or choosing words to express a thought, selecting between options can be challenging, especially for people with anxiety. We investigate the neural mechanisms supporting selection during language processing and its breakdown in anxiety. Our neural network simulations demonstrate a critical role for competitive, inhibitory dynamics supported by GABAergic interneurons. As predicted by our model, we find that anxiety (associated with reduced neural inhibition) impairs selection among options and associated prefrontal cortical activity, even in a simple, nonaffective verb-generation task, and the GABA agonist midazolam (which increases neural inhibition) improves selection, whereas retrieval from semantic memory is unaffected when selection demands are low. Neural inhibition is key to choosing our words.

Fig. 1.

Design and basic behavioral findings for the verb generation task. (A) Selection demands (high vs. low competition) are crossed with retrieval demands (high vs. low association strength) (SI Methods 2.1). (B) Participants take longer to generate a response when retrieval demands are high and when selection demands are high. (C) Selection costs (RT difference between high and low selection demand conditions) are greater when retrieval demands are low than when they are high. All error bars are SEs.

Fig. 2.

Neural network model. (A) Network architecture. (B) Model simulates human performance, showing independent effects of selection demand (driven by competition between active representations) and retrieval demand (driven by synaptic weight strength). (C) Model simulates interaction between selection and retrieval (driven by benefit of spreading activation when retrieval demands are high). All error bars are SEs.

Fig. 3.

Effects of reduced neural inhibition (A) Model predictions: Reduced competitive neural inhibition in the VLPFC layer, simulating increasing anxiety, impairs selection (i.e., increases selection cost) under high and low retrieval demands, and suggests that effects of anxiety on selection may be most robust under low retrieval demands. (B) Empirical results. Higher anxiety participants show impaired selection under high and low retrieval demands (model fit is further discussed in Results). All error bars are SEs.

Fig. 4.

Effect of increased neural inhibition. (A) Model predictions. Increased neural inhibition (simulating GABA agonist drugs) improves selection (i.e., reduces selection cost) only when retrieval demands are low. (B) Empirical results. Midazolam improves selection only when retrieval demands are low. RTs are z transformed to remove baseline differences between conditions. All error bars are SEs.

Fig. 5.

Engagement of left VLPFC during selection, as a function of anxiety. (A) Anatomically defined region of interest (mid and anterior left VLPFC, shown in blue) was chosen based on prior work establishing its role in selection. Engagement of this region during selection was computed for each participant as the difference in fMRI activation between the high and low selection demand conditions. (B) Higher anxiety participants showed reduced engagement of left VLPFC during selection under low retrieval demands, which may reflect reduced activity of GABAergic interneurons (SI Discussion).