title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Cognitive Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and amyroseprice@gmail.com roy.hamilton@uphs.upenn.edu.
authors.forename: Amy Rose
authors.identifier: http://orcid.org/0000-0002-3560-6294
authors.initials: AR
authors.lastname: Price
authors.affiliation: Department of Otolaryngology, Washington University in St Louis, St Louis, Missouri 63110.
authors.forename: Jonathan E
authors.identifier: http://orcid.org/0000-0001-9194-854X
authors.initials: JE
authors.lastname: Peelle
authors.affiliation: Center for Cognitive Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Michael F
authors.identifier: http://orcid.org/0000-0002-4992-674X
authors.initials: MF
authors.lastname: Bonner
authors.affiliation: Center for Cognitive Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and.
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
authors.affiliation: Center for Cognitive Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and amyroseprice@gmail.com roy.hamilton@uphs.upenn.edu.
authors.forename: Roy H
authors.initials: RH
authors.lastname: Hamilton
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001245:Association Learning / Q000502:physiology; D001931:Brain Mapping; D003210:Concept Formation / Q000502:physiology; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D010296:Parietal Lobe / Q000098:blood supply / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology; D012660:Semantics; D065908:Transcranial Direct Current Stimulation; D014825:Vocabulary; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: brain stimulation; compositionality; inferior parietal cortex; semantic integration; semantic memory; tDCS