Title:

Right Neural Substrates of Language and Music Processing Left Out: Activation Likelihood Estimation (ALE) & Meta-Analytic Connectivity Modelling (MACM)

Introduction: Language and music processing are frequently investigated in cognitive neuroimaging experiments as they both are complex, representational systems unique to humans. However, regions of covariance and their intrinsic functional connectivity remain elusive secondary to independent methodologies employing various paradigms, tasks, and response modalities. Identifying normative covariance and connectivity within language and music processing can provide clinicians with a normative model to identify neural substrates that may be impacted at the level of impairment. Aim: (a) Mitigate the influence of various methodologies by identifying areas that coactivate when processing predetermined stimuli and or response type(s) (language processing or music processing); (b) Determine a functionally connected intra- and interhemispheric brain network consisting of language and music processing studies across various tasks and paradigms. Hypotheses: (a) Expect areas of significant coactivation in the inferior frontal gyri and auditory cortices with convergence involving affective-related regions, namely the insula, cingulate gyrus, and cerebellum; (b) Observe significant functional connectivity involving the inferior frontal gyri, superior temporal gyri, left dominant Heschl’s gyrus, planum temporale, insula, cingulate gyrus, and cerebellum within the subsequent network as compared to other networks in the whole brain analysis. Methods: Following PRISMA guidelines, the present coordinate-based meta-analysis analyzed 65 functional magnetic resonance imaging (fMRI) studies which investigated language processing (35 studies), music processing (30 studies) in healthy adult subjects via BrainMap software and ancillary tools. We conducted activation likelihood estimates (ALE) across (1) language processing, (2) music processing, and (3) language processing + music processing (Omnibus) contexts. Using nodes identified via Omnibus ALE, we then identify immanent functional connectivity and directionality using meta-analytic connectivity modelling (MACM). Paradigm Class (PC) and Behavioral Domain (BD) analyses were conducted for each node to aid the functional interpretation of MACM. Results: Omnibus ALE revealed 10 significant peak activation clusters: bilateral inferior frontal gyri, left medial frontal gyrus, right superior temporal gyrus, left Heschl’s gyrus, bilateral claustra, left superior parietal lobule, right precentral gyrus, and right anterior culmen. MACM revealed a coactivated, interconnected functional network with directionality amongst each of the ten nodes. PC analyses identified each node to have associations with 44 BrainMap PCs, in which and eight out of ten node associations were significant (z-score > 3.00). BD analyses identified each node to have associations with 32 BrainMap BDs, in which eight out of ten node associations were significant (z-score > 3.00). Discussion: Findings demonstrate intra- and interhemispheric functional connectivity among Omnibus areas of covariance. ALE outcomes partially supported our hypothesized areas of activation by having fewer affective-related regions than anticipated. Subsequently, network connectivity analyses partially supported our hypotheses given fewer affective-related intrinsic functional connections; however, each node revealed multiple significant connections either depicting one-way or two-way covariance. PC and BD analyses further depicted congruent nodal associations to respective functional association(s). These results deepen neuroscientific knowledge of higher cognitive domains, such as normal language and music processing, and conclude the importance of identifying the level of impairment to target ipsilateral and contralateral hemispheric functional connectivity as opposed to right hemisphere homologous regions when implementing music therapy in populations with acquired language disorders.

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