6D dynamic tractography visualizes the effective connectivity supporting specific linguistic stages in the developing brain

During a verbal conversation, as individuals listen and respond, the human brain moves through a series of complex linguistic processing stages: decoding of speech sounds, semantic comprehension, retrieval of semantically coherent words, and finally, overt production of speech outputs. Each process is thought to be supported by a cortical network consisting of local and long-range connections bridging between major cortical areas. Both temporal and extratemporal lobe regions are suggested to have functional compartments responsible for distinct language domains, including the perception and production of phonological and semantic components. This study provides quantitative evidence of how directly connected, inter-lobar neocortical networks support distinct linguistic stages of linguistic processing across brain development. A novel six-dimensional tractography animation technique was used to intuitively visualize the strength and temporal dynamics of direct inter-lobar effective connectivity between cortical areas activated during distinct linguistic processing stages. This study analyzed 3,401 non-epileptic intracranial electrode sites from 37 children with focal epilepsy (age: 5–20 years) who underwent extraoperative electrocorticography recording. We used a principal component analysis of high-gamma modulations during an auditory naming task to determine the relative involvement of each cortical area during each linguistic processing stage. To quantify direct effective connectivity, we delivered single-pulse electrical stimulation to 488 temporal lobe sites and 1,581 extratemporal lobe sites and measured the early cortico-cortical spectral responses at distant electrodes. Mixed model analyses determined the effects of naming-related high-gamma co-augmentation between connecting regions, age, and cerebral hemisphere on the strength of effective connectivity independent of epilepsy-related factors. Direct effective connectivity was strongest between temporal and extratemporal lobe site pairs which were simultaneously activated during the period between sentence offset and verbal response onset (i.e., semantic retrieval period); this connectivity was approximately twice more robust than that with temporal lobe sites activated during stimulus listening or overt response. Conversely, extratemporal lobe sites activated during overt response were equally connected with temporal lobe language sites. Older age was associated with the increased strength of inter-lobar effective connectivity between those activated during semantic retrieval. The arcuate fasciculus supported approximately two-thirds of the direct effective connectivity pathways from temporal to extratemporal auditory language-related areas but only up to half of those in the opposite direction. The uncinate fasciculus consisted of only less than 2% of those in the temporal-to-extratemporal direction and up to 6% of those in the opposite direction. Our multimodal study quantified and animated the direct inter-lobar networks toward and from temporal lobe regions supporting distinct stages of auditory language processing. Additionally, age-dependent strengthening of connectivity after age five may preferentially occur between language areas supporting semantic retrieval.