Causal Evidence for a Mechanism of Semantic Integration in the Angular Gyrus as Revealed by High-Definition Transcranial Direct Current Stimulation

Abstract

A defining aspect of human cognition is the ability to integrate conceptual information into complex semantic combinations. For example, we can comprehend "plaid" and "jacket" as individual concepts, but we can also effortlessly combine these concepts to form the semantic representation of "plaid jacket." Many neuroanatomic models of semantic memory propose that heteromodal cortical hubs integrate distributed semantic features into coherent representations. However, little work has specifically examined these proposed integrative mechanisms and the causal role of these regions in semantic integration. Here, we test the hypothesis that the angular gyrus (AG) is critical for integrating semantic information by applying high-definition transcranial direct current stimulation (tDCS) to an fMRI-guided region-of-interest in the left AG. We found that anodal stimulation to the left AG modulated semantic integration but had no effect on a letter-string control task. Specifically, anodal stimulation to the left AG resulted in faster comprehension of semantically meaningful combinations like "tiny radish" relative to non-meaningful combinations, such as "fast blueberry," when compared to the effects observed during sham stimulation and stimulation to a right-hemisphere control brain region. Moreover, the size of the effect from brain stimulation correlated with the degree of semantic coherence between the word pairs. These findings demonstrate that the left AG plays a causal role in the integration of lexical-semantic information, and that high-definition tDCS to an associative cortical hub can selectively modulate integrative processes in semantic memory.

Significance statement: A major goal of neuroscience is to understand the neural basis of behaviors that are fundamental to human intelligence. One essential behavior is the ability to integrate conceptual knowledge from semantic memory, allowing us to construct an almost unlimited number of complex concepts from a limited set of basic constituents (e.g., "leaf" and "wet" can be combined into the more complex representation "wet leaf"). Here, we present a novel approach to studying integrative processes in semantic memory by applying focal brain stimulation to a heteromodal cortical hub implicated in semantic processing. Our findings demonstrate a causal role of the left angular gyrus in lexical-semantic integration and provide motivation for novel therapeutic applications in patients with lexical-semantic deficits.

Keywords: brain stimulation; compositionality; inferior parietal cortex; semantic integration; semantic memory; tDCS.

Figure 1.

Experimental design. A, Left angular gyrus fMRI activation in healthy adults for the processing of meaningful relative to non-meaningful word pairs (Price et al., 2015b). B, Example placement of electrodes and electrode holders for the HD-tDCS 4 × 1 configuration. C, Theoretical models of the electric-field intensity for the electrode montages targeting the left AG and right AG (HD-Explore, Soterix Medical). Coordinates are in MNI space.

Figure 2.

Behavioral tasks and example stimuli. A, In the word-pair task, participants viewed two real words whose combination was considered to be either meaningful (e.g., tiny radish) or non-meaningful (e.g., fast blueberry), as determined by the results of a norming study. On each trial, participants were asked to decide whether the word pair formed a meaningful combination or not. B, In the letter-string control task, participants viewed two letter strings that were either the same letter strings (e.g., pnqvt pnqvt) or differed by one letter (e.g., vsbsl vsbql). On each trial, participants were asked to decide whether the letter strings matched or not.

Figure 3.

Reaction time results from both tasks. A, Results from the word-pair task indicate a significant effect for the left AG stimulation session. For each session, the difference score was calculated as follows: average RT for meaningful word pairs − average RT for non-meaningful word pairs. Thus, negative values for the difference score indicate faster RT for the meaningful word-pair category relative to the non-meaningful word-pair category for that session. This reaction time difference score significantly differed between the left AG stimulation session and both the sham and right AG stimulation sessions (*p < 0.05). B, Results from the letter-string task indicate no effect between any of the stimulation conditions (all p values > 0.25). C, This plot shows the percentage change in reaction time for each word-pair category (mean ± SE) in the left AG and right AG stimulation sessions relative to sham stimulation.

Figure 4.

Results from the item analysis of individual word pairs from the meaningful word-pair category, illustrating the relationship between the size of the stimulation effect and the continuous measure of semantic coherence for the word pairs. The stimulation effect was calculated as the difference in mean reaction time between the left AG and sham stimulation sessions for word pairs of the same rank (i.e., RT for the left AG session minus RT for the sham session for each rank). The average semantic coherence values are listed below the ranks. Negative values indicate an advantage from left AG stimulation. The effect on RT from left AG stimulation strongly correlated with the degree of semantic coherence of the meaningful word pairs (r = 0.65, p < 0.001).