Language comprehension functionally modulates first-order relay thalamic nuclei

  1. Liu Mengxing
  2. Shiya Wang
  3. Carmen Vidaurre
  4. Sara Guediche
  5. Garikoitz Lerma-Usabiaga
  6. Pedro M Paz-Alonso

  • Curated by eLife

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    eLife Assessment

    This study presents a potentially valuable exploration of the role of thalamic nuclei in language processing. The results will be of interest to researchers interested in the neurobiology of language. However, the evidence is incomplete to support robust conclusions at this point.

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Abstract

Language, a uniquely human higher-order cognitive function, has traditionally been attributed to cortical mechanisms with limited attention given to subcortical contributions. Recent advances in non-invasive neuroimaging have revealed that thalamic activity can be modulated by attention and task demands. Moreover, lesion studies have hinted at the thalamus’s potential role in language processing. Nevertheless, the precise involvement of this structure in language remains unclear. Here, we argue that language-related modulations can occur as early as the sensory thalamic stage, challenging the conventional view of language preprocessing as a predominantly language function. Using functional MRI to image 40 human participants (both female and male) while processing linguistic and non-linguistic stimuli of three main language systems (reading, speech comprehension, and speech production), we demonstrate specific activation of first-order nuclei during targeted language system tasks: lateral geniculate (LGN) for reading, medial geniculate (MGN) for speech comprehension and ventrolateral (VLN) for speech production. Notably, we show linguistic versus non-linguistic stimuli exhibit functional modulations during comprehension tasks (reading and speech) of left MGN and, to a lesser extent, left LGN—in line with prior studies of lateralization of language processes. Multi-voxel classification analysis confirmed left-lateralized linguistic modulation in the MGN, but not in the LGN. Given the complexity of thalamic connectivity and its potential role in integrating sensory and cognitive processes, this work constitutes a relevant first step to further understand thalamic involvement and thalamocortical interactions in language function.

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  1. Version published to 10.7554/elife.109448.1 on eLife
  2. Version published to 10.7554/elife.109448 on eLife
  3. eLife

    eLife Assessment

    This study presents a potentially valuable exploration of the role of thalamic nuclei in language processing. The results will be of interest to researchers interested in the neurobiology of language. However, the evidence is incomplete to support robust conclusions at this point.

  4. eLife

    Reviewer #1 (Public review):

    Summary:

    The manuscript by Mengxing et al., reports an assessment of three first-order thalamic nuclei (auditory, visual, somatosensory) in a 3 x 2 factorial design to test for specificity of responses in first-order thalamic nuclei to linguistic processing particularly in the left hemisphere. The conditions are reading, speech production, and speech comprehension and their respective control conditions. The authors report the following results:

    (1) BOLD-response analyses: left MGB linguistic vs non-linguistic significant; left LGN linguistic vs non-linguistic significant. There is no hemisphere x stimulus interaction.

    (2) MVPA: left MGB linguistic vs. non-linguistic significant; bilateral VLN linguistic vs. non-linguistic significant; significant lateralisation in MGB (left MGB responses better classified linguistic vs. non-linguistic in contrast to right).

    (3) Functional connectivity: there is, in general, connectivity between the thalamic ROIs and the respective primary cortices independent of linguistics.

    Strengths:

    The study has a clear and comprehensive design and addresses a timely topic. First-order thalamic nuclei and their interaction with the respective cerebral cortex area are likely key to understanding how perception works in a world where one has to compute highly dynamic stimuli often in an instant. Speech is a prime example of an ecologically important, extremely dynamic, and complex stimulus. The field of the contribution of cerebral cortex-thalamic loops is wide open, and the study presents a solid approach to address their role in different speech modalities (i.e., reading, comprehension, production).

    Weaknesses:

    I see two major overall weaknesses in the manuscript in its current form:

    (1) Statistics:

    Unfortunately, I have doubts about the solidity of the statistics. In the analyses of the BOLD responses, the authors do not find significant hemisphere x stimulus interactions. In my view, such results would pre-empt doing a post-hoc t-test. Nevertheless, the authors motivate their post-hoc t-test by 'trends' in the interaction and prior hypotheses. I see two difficulties with that. First, the origin of the prior hypotheses is somewhat unclear (see also the comment below on hypotheses), and the post-hoc t-test is not corrected for multiple comparisons. I find that it is a pity that the authors did not derive more specific hypotheses grounded in the literature to guide the statistical testing, as I think these would have been available, and the response properties of the MGB and LGN also make sense in light of them. In addition, I was wondering whether the MVPA results would also need to be corrected for the three tests, i.e., the three ROIs.

    Hypotheses:

    In my view, it is relatively unclear where the hypotheses precisely come from. For example, the paragraph on the hypotheses in the introduction (p. 6-7) is devoid of references. I also have the impression that the hypotheses are partly not taking into account previous reports on first-order thalamic nuclei involvement in linguistic vs. non-linguistic processing. For example, the authors test for lateralisation of linguistic vs. non-linguistic responses in all nuclei. However, from previous literature, one could derive the hypothesis that the lateralisation in MGB for speech might be there - previous work shows, for example, that speech recognition abilities consistently correlate with left MGB only (von Kriegstein et al., 2008 Curr Biol; Mihai et al., 2019 eLife). In addition, the involvement of the MGB in speech in noise processing is present in the left MGB (Mihai et al., 2021, J Neuroscience). Developmental dyslexia, which is supposed to be based on imprecise phonological processing (Ramus et al., 2004 TiCS), has alterations in left MGB (Diaz et al., 2012 PNAS; Galaburda et al., 1994 PNAS) and left MGB connections to planum temporale (Tschentscher et al., 2019 J Neurosci) as well as altered lateralisation (Müller-Axt et al., 2025 Brain). Conversely, in the LGN, I'm not aware of any studies showing lateralisation for speech. See, for example, Diaz et al., 2018, Neuroimage, where there are correlations of LGN task-dependent modulation with visual speech recognition behaviour in both LGNs. Thus, based on this literature, one could have predicted the result pattern displayed, for example, in Figure 3A at least for MGB and LGN.

    In summary, the motivation for the different hypotheses needs to be carved out more and couched into previous literature that is directly relevant to the topic. The above paragraph is, of course, my view on the topic, but currently, the paper lacks different literature as references to fully understand where the hypotheses are derived from.

  5. eLife

    Reviewer #2 (Public review):

    Summary:

    This study investigates the involvement of first-order thalamic nuclei in language-related tasks using task-based fMRI in a 3 × 2 design contrasting linguistic and non-linguistic versions of reading, speech comprehension, and speech production. By focusing on the LGN, MGN, and VLN and combining activation, connectivity, lateralization, and multivariate pattern analyses, the authors aim to characterize modality-specific and language-related thalamic contributions.

    Strength:

    A major strength of the work is its hypothesis-driven and multimodal analytical approach, and the modality-specific engagement of first-order thalamic nuclei is robust and consistent with known thalamocortical organization. This is a very sound study overall.

    Weaknesses:

    However, several conceptual issues complicate the interpretation of the results as evidence for linguistic modulation per se. A central concern relates to the operationalization of the linguistic versus non-linguistic contrast. In the present design, linguistic and non-linguistic stimuli differ along multiple dimensions beyond linguistic content. For example, written words and scrambled images differ in spatial frequency structure, edge composition, contrast regularities, and familiarity, while intelligible speech and acoustically scrambled sounds differ substantially in temporal and spectral statistics. This is particularly relevant given that first-order thalamic nuclei such as the LGN are known to be highly sensitive to low-level sensory properties. As a result, observed differences in thalamic responses may reflect sensitivity to stimulus properties rather than linguistic processing per se, and this limits the specificity of claims regarding linguistic modulation.

    Relatedly, although the manuscript frequently refers to effects "depending on the linguistic nature of the stimuli," the statistical evidence for linguistic versus non-linguistic modulation is uneven across analyses. Whole-brain contrasts collapse across stimulus type and primarily test modality effects. Similarly, the primary ROI analyses of activation amplitude are collapsed across linguistic and non-linguistic conditions and convincingly demonstrate modality-specific engagement of thalamic nuclei, but do not in themselves provide evidence for linguistic modulation. Linguistic effects emerge only in later, more targeted analyses focusing on hemispheric lateralization and multivariate pattern classification, and these effects are nucleus-, modality-, and analysis-specific rather than general. Taken together, these results suggest that linguistic modulation constitutes a secondary and selective finding, whereas modality-specific task engagement represents the primary and most robust outcome of the study.

    An additional interpretational issue concerns task engagement and attention. The tasks differ substantially in cognitive demands (e.g., passive reading and listening versus overt speech production), and linguistic and non-linguistic blocks may differ systematically in salience or engagement. This is particularly important given prior evidence, cited by the authors, that LGN and MGN activity can be modulated by task demands and attention. In the absence of behavioral measures indexing task engagement or compliance, it is difficult to determine whether differences between linguistic and non-linguistic conditions reflect linguistic processing per se or are mediated by attentional factors.

    Finally, while the manuscript emphasizes the novelty of evaluating thalamic involvement in language, thalamic contributions to language have been documented previously in both lesion and functional imaging studies. The contribution of the present work, therefore, lies less in establishing thalamic involvement in language per se, and more in its focus on specific first-order nuclei, its multimodal design, and its combination of univariate, connectivity, and multivariate analyses. Moderating claims of novelty would help place the findings more clearly within the existing literature.

  6. eLife

    Author response:

    We acknowledge the concerns raised by both reviewers and plan to address them in our revision:

    Regarding Reviewer #1's comments: We will strengthen the statistical framework and address the concerns about multiple comparison corrections. We will also expand our literature review to better motivate our hypotheses, particularly incorporating the work on lateralization patterns in MGN/LGN and the existing evidence on first-order thalamic nuclei in linguistic processing.

    Regarding Reviewer #2's comments: We acknowledge the valid concern that linguistic and non-linguistic stimuli differ beyond linguistic content, including some low-level sensory properties. We will elaborate on the creation and properties of these stimuli in the Methods section and upload stimuli examples to an online repository to provide transparency about differences. We will also add a discussion of this limitation in the Discussion section, acknowledging that disentangling effects of linguistic processing from low-level stimulus properties will require further testing in future research. Additionally, we will moderate part of our claims and reorganize the presentation of results as suggested, and clarify our contribution relative to existing literature.

  7. Version published to 10.1101/2025.10.30.685533 on bioRxiv