Using a large cohort of healthy adults with high-quality multimodal MRI data and highly accurate PT determination, the present study shows clear associations between structural and functional asymmetries in the PT. Crucially, most effects were observed for asymmetries in microstructural features of the PT, such as myelin content, neurite density, or neurite orientation dispersion. This highlights that microstructural asymmetries are likely more relevant for functional asymmetries than macrostructural asymmetries. For the left or right PT per se, its functional activation of speech perception and comprehension also correlated with its myelin content, neurite density, and neurite orientation dispersion, both selectively and hemisphere-dependently. Among the observed PT functional-structural associations, only those between speech comprehension activation and myelin content showed interaction with the HG gyrification pattern. Finally, these observed functional-structural associations are highly specific to the within-PT functional activation of auditory-language processing.
As one of the most prominent structural asymmetries across the entire human brain, PT structural asymmetries have been well recognized and widely believed to play a critical role in human auditory or language processing 8,19,21,30, 43–45. In concordance, anomalies of PT asymmetries in surface area or thickness have been reported in various brain disorders with auditory or language deficits, e.g., dyslexia, autism, and schizophrenia 17,21, 46–52. To understand the role of PT structural asymmetries in language, it is critical to determine how they relate to functional patterns of language-related processing, e.g., language-related functional asymmetries. Some evidence has demonstrated an association of PT structural asymmetry with language-related functional asymmetries, but these functional asymmetries were not measured directly from the PT 16,27,28,53. For instance, PT asymmetry in surface area was correlated with regional asymmetries of language-related functional activation around the Sylvian fissure but not the activation of the PT 16.
Our present study provides the first empirical evidence of interindividual associations between functional and structural asymmetries within the PT, implying a functional pathway from PT structural asymmetry to PT functional asymmetry to effective speech processing. A large sample size and accurate PT localization based on well-trained manual operation were crucial in obtaining these results. For other PT-related studies with large sample sizes, however, it is difficult to apply such a labor-intensive manual PT labeling approach, and therefore, an accurate automatic labeling approach should be developed. Notably, our observed PT structural-functional associations were across healthy right-handed young adults, and it is unclear whether these associations could be extrapolated to children, left-handed adults, or patients. Therefore, future studies are required to evaluate the functional-structural association of PT asymmetries in other populations, which should provide insight into the modulating factor of functional-structural associations of PT.
In the context of brain asymmetries, our currently observed functional-structural coupling of PT asymmetries at the individual level empirically proves the role of structural gray matter asymmetries in the functional laterization of the same brain area, supporting the compelling hypothesis that “functional lateralization is guided by structural asymmetry” 3. For a specific brain area, however, its gray matter asymmetries are unlikely to be the only determinant for its functional lateralization. The relevant corpus callosum (interhemispheric connection) and structural white matter asymmetries should also play important roles in its functional lateralization, and integrating the three factors is encouraged for detangling structural mechanisms underlying functional lateralization 2, 54–57.
The observed functional-structural coupling of PT asymmetries strongly depends on functional and structural measures. On the functional side, only PT functional activation of auditory speech processing showed such coupling with PT structural asymmetries, indicating the functional and spatial specificity of PT asymmetry in auditory-language processing 8,13,58,59. Speech perception and comprehension also showed functional-structural coupling with different structural measures, compatible with the dissociation of these two speech-processing components 15,60. It is possible that hemispheric asymmetries of different functional processing are generally related to distinct structural mechanisms. On the structural side, the observed functional-structural coupling of PT asymmetries mainly involves microstructural measures, e.g., myelin content, neurite density, and neurite orientation dispersion, except for the association of speech comprehension with surface area. These microstructural measures represent specific aspects of cortical composition on the level of axons or dendrites 61,62, therefore implying a dominant role of within-PT microconnectional or microcircuitry asymmetries in functional asymmetries of PT. Specific microstructural asymmetry between bilateral PTs might cause less recruitment of the nondominant hemisphere in particular speech processing, therefore resulting in more pronounced functional lateralization 16,44,53.
Compatibly with the functional-structural coupling of PT asymmetries, only microstructural measures, including myelin content, neurite density, and neurite orientation dispersion, showed an association with speech-related activation for the left or right PT per se. Similar functional-structural associations have been observed in other non-PT cortical areas, e.g., between myelin content and task-evoked activities 63–68. These findings together indicate an important contribution of intracortical microcircuits to functional activity: cortical areas with greater intracortical fiber density and more complex dendritic structures are likely accompanied by stronger local activation during the task. Intriguingly, within-hemispheric PT functional-structural coupling could be asymmetric, e.g., existing only in one hemisphere but not in the other. For instance, EEG-measured neurophysiological processing of speech perception correlated with neurite density of the left PT but not the right PT, as recently revealed by Ocklenburg and colleagues 30. Consistent with this, within-hemispheric PT functional-structural coupling of neurite density was also asymmetric in our study: only in the right PT but not in the left PT. These particular asymmetries highlight the distinct role of PT neurite density in speech processing between the two hemispheres, but computational implementation for such hemisphere-dependent functional-structural association warrants further investigation.
The functional-structural coupling of PT asymmetries should relate to the asymmetry of within-hemispheric functional-structural coupling between the left or right PT per se but in a complex manner. The coupling of PT asymmetries could be accompanied by either asymmetric (e.g., speech perception vs. neurite density) or nonasymmetric within-hemispheric functional-structural couplings (e.g., speech perception vs. myelin content or neurite orientation dispersion). On the other hand, asymmetric within-hemispheric structure-function association does not necessarily lead to a coupling of PT asymmetries (e.g., speech comprehension activation vs. neurite density). Finally, PT functional and structural asymmetries could be associated, even though there was no within-hemispheric functional-structural coupling for both left and right PTs (e.g., surface area vs. speech comprehension activation). This implied that PT asymmetries and their functional-structural coupling might represent unique structural and functional information, independent of within-hemispheric PT measures per se. Overall, there was no simple causal relationship between these functional-structural couplings, and they likely capture distinct aspects of PT functional-structural associations and therefore should be investigated separately.
In line with previous observations, HG duplication occurred considerably in healthy adults in the present study and induced significant changes in both PT functional and structural measures as well as their asymmetries 33,41. However, the vast majority of functional-structural coupling of both PT asymmetries and within-hemispheric PT measures were not significantly affected by the HG gyrification pattern. Therefore, HG duplication-induced individual changes in PT measures or their asymmetry do not necessarily lead to changes in the interindividual association between these measures or asymmetries, suggesting the robustness of these PT functional-structural couplings. Notably, the left HG duplication did show a significant impact on the coupling of speech comprehension activation and myelin content of the left PT as well as on their asymmetry coupling. This could be related to functional reorganization of the left PT when a left duplication of HG occurs, but this speculation should be empirically tested in future studies. Given these observed influences of the duplication of HG as well as its substantial incidence in healthy adults, more attention should be given to this phenomenon, particularly when studying HG or PT and its asymmetry.
In conclusion, the association between specific PT functional and microstructural asymmetries provides direct empirical support for the contribution of structural asymmetry to functional lateralization of the same cortical area. Moreover, the findings highlight a critical role of microstructural PT asymmetries in auditory-language processing.