| 1. |
- Bendtz, Katarina, 1982-, et al.
(author)
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Individual Differences in Indirect Speech Act Processing Found Outside the Language Network
- 2022
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In: Neurobiology of Language. - : MIT Press - Journals. - 2641-4368. ; 3:2, s. 287-317
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Journal article (peer-reviewed)abstract
- Face-to-face communication requires skills that go beyond core language abilities. In dialogue, we routinely make inferences beyond the literal meaning of utterances and distinguish between different speech acts based on, e.g., contextual cues. It is, however, not known whether such communicative skills potentially overlap with core language skills or other capacities, such as theory of mind (ToM). In this functional magnetic resonance imaging (fMRI) study we investigate these questions by capitalizing on individual variation in pragmatic skills in the general population. Based on behavioral data from 199 participants, we selected participants with higher vs. lower pragmatic skills for the fMRI study (N = 57). In the scanner, participants listened to dialogues including a direct or an indirect target utterance. The paradigm allowed participants at the whole group level to (passively) distinguish indirect from direct speech acts, as evidenced by a robust activity difference between these speech acts in an extended language network including ToM areas. Individual differences in pragmatic skills modulated activation in two additional regions outside the core language regions (one cluster in the left lateral parietal cortex and intraparietal sulcus and one in the precuneus). The behavioral results indicate segregation of pragmatic skill from core language and ToM. In conclusion, contextualized and multimodal communication requires a set of interrelated pragmatic processes that are neurocognitively segregated: (1) from core language and (2) partly from ToM.
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| 2. |
- Arvidsson, Caroline, et al.
(author)
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Audience design and frame of reference in adolescents' reference production
- 2021
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In: Abstracts. ; , s. 1519-1519
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Conference paper (peer-reviewed)abstract
- When participating in dialogue, speakers design their utterances to accommodate the individual needs of listeners (Bentz, et al., in prep). This feature is known as audience design (Clark & Murphy, 1982). Although audience design is central to conventional conversation, it is not known at which age speakers begin taking into account the world knowledge/frame of reference of their interlocutors. Indications from recent studies suggest that albeit preschool and first grade children engage in basic forms of perspective taking (Nadig & Sedivy, 2002), they fail to adapt their utterances in accordance with listener-specific needs in reference production (Pagmar, et al., in prep). Adult participants do however adapt their utterances, and individual differences in the adult population were not dependent on cognitive control function (Bentz, et al., in prep). The dependence on cognitive control function, e.g. switching, may be hypothesized to be greater in children. The current study aims to test the referential production of two age groups; early and mid adolescents (11;0-12;11 and 15;0-16;11), with the purpose of tracing the development of the ability to use information regarding listener-perspective during on-line referential production, and test its relation to cognitive control. The paradigm builds further on the well-established Director’s task but does not require the participants to take the visual perspective of the listener. Instead, participants are presented with a set of pictures portraying referents well-known to them, e.g. popular cartoon characters, hosts of children’s tv-shows, etc. Knowledge of the referents are controlled through post-test surveys. Furthermore, they are asked to direct listeners of two distinct groups, small children and elders, into choosing the target referent. Participants who take the frame of reference of addressees into consideration are expected to adopt different strategies when addressing the different groups, i.e., increase informativeness when denoting referents assumed to be unknown to the listener vs using less informative referential expressions (such as proper names) when denoting referents judged to be known to the listener. Cognitive control/executive function is assessed using the Wisconsin card sorting task. Results are discussed in terms of cognitive costs of switching strategies and the Gricean maxim of quantity.
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| 3. |
- Arvidsson, Caroline, et al.
(author)
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Conversational production and comprehension: fMRI-evidence reminiscent of but deviant from the classical Broca–Wernicke model
- 2024
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In: Cerebral Cortex. - 1047-3211 .- 1460-2199. ; 34:3
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Journal article (peer-reviewed)abstract
- A key question in research on the neurobiology of language is to which extent the language production and comprehension systems share neural infrastructure, but this question has not been addressed in the context of conversation. We utilized a public fMRI dataset where 24 participants engaged in unscripted conversations with a confederate outside the scanner, via an audio-video link. We provide evidence indicating that the two systems share neural infrastructure in the left-lateralized perisylvian language network, but diverge regarding the level of activation in regions within the network. Activity in the left inferior frontal gyrus was stronger in production compared to comprehension, while comprehension showed stronger recruitment of the left anterior middle temporal gyrus and superior temporal sulcus, compared to production. Although our results are reminiscent of the classical Broca–Wernicke model, the anterior (rather than posterior) temporal activation is a notable difference from that model. This is one of the findings that may be a consequence of the conversational setting, another being that conversational production activated what we interpret as higher-level socio-pragmatic processes. In conclusion, we present evidence for partial overlap and functional asymmetry of the neural infrastructure of production and comprehension, in the above-mentioned frontal vs temporal regions during conversation.
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| 4. |
- Arvidsson, Caroline, et al.
(author)
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Conversational production and comprehension: fMRI-evidence reminiscent of the classic Broca-Wernicke model
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Other publication (other academic/artistic)abstract
- A key question in neurolinguistics is whether language production and comprehension share neural infrastructure, but this question has not been addressed in the context of actual conversation. We utilized a public fMRI dataset where participants (N=24) engaged in unscripted conversations with a confederate outside the scanner via an audio-video link. We provide evidence indicating that production and comprehension, in a conversational setting, diverge with respect to how they modulate the recruitment of regions in the left-lateralized perisylvian language network. Activity in the left inferior frontal gyrus was stronger in production than in comprehension. Compared to production, comprehension showed stronger recruitment of the left anterior middle temporal gyrus and superior temporal sulcus, but this was not the case for the posterior aspect of these loci. Although our results are reminiscent of the classic Broca-Wernicke model, the anterior temporal activation is a notable difference from that model. This is one of the findings which may be a consequence of the conversational setting, another being that conversational production activated what we interpret as higher-level socio-pragmatic processes. In conclusion, we present evidence supporting that the above-mentioned frontal vs temporal regions in the language network are functionally segregated during conversation.
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| 5. |
- Arvidsson, Caroline, et al.
(author)
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The Brain in Conversation : Mapping Turn-taking, Production and Comprehension with fMRI
- 2022
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Conference paper (peer-reviewed)abstract
- INTRODUCTION: Conversation is the most ubiquitous form of language use. A hallmark of conversation is turn-taking, in which speakers rapidly alternate between speaker and listener roles without conscious effort, while simultaneously planning their upcoming turn. Since previous neurolinguistic studies have mainly investigated single or few linguistic processes in isolated environments that lack resemblance to real-world language use, the neurobiology of turntaking, production, and comprehension during real-time conversation is currently under-explored. In this fMRI investigation, we asked whether turn initiations would activate areas outside the classical perisylvian core language network and whether we would observe differences in activation during conversational production vs. conversational comprehension. METHODS: We utilized a publicly available fMRI dataset in which participants (N = 23) engaged in unscripted conversations via an audio-video link with a confederate outside the scanner. Each conversation (24 per participant) lasted for one minute. Conversational events were defined from the participant’s perspective. These events included turn initiations, defined as a 600 ms time window whose offset coincided with the onset of the participant’s turn. The duration of turn initiations was based on the reported minimum latency of speech preparation. The other events investigated in this study were production (defined as participant speech), and comprehension (defined as confederate speech). RESULTS: Turn initiations were associated with frontal regions outside of the classical perisylvian core language network. One cluster (2796 voxels, significant with FWE-correction used throughout) was observed in the medial prefrontal cortex bilaterally, spanning from the dorsal portion to the most ventral anterior cingulate cortex. Activation during turn initiations was also observed in the left middle frontal gyrus. Furthermore, both production and comprehension during conversation were associated with core language regions in the bilateral temporal lobes, but activation in the left inferior frontal gyrus (LIFG) was only present for production. Moreover, larger parts of the occipital cortex, and specifically the fusiform face area, were activated in comprehension than in production. DISCUSSION: We suggest that the observed frontal activation during turn initiations reflects sociopragmatic processes involved in intention processing and attentional control – processes that have not previously been localized outside the core perisylvian language network but have been hypothesized to play a crucial role in speech preparation during interaction. Furthermore, we interpret the fusiform face area activation during comprehension as an indication that listeners are aided by their interlocutor’s facial gestures specifically when comprehending speech input during real-time conversation. Finally, LIFG activation in conversational production but not comprehension may reflect the syntactic and semantic heuristics at play in conversational comprehension, minimizing the need for a full syntactic parse. The utilization of such heuristics may be a possible prerequisite for consistently meeting the expectations of timing in turn-taking.
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| 6. |
- Arvidsson, Caroline, et al.
(author)
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When did you stop speaking to yourself? : Age-related differences in adolescents' world knowledge-based audience design
- 2022
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In: Royal Society Open Science. - : Royal Society. - 2054-5703. ; 9:11
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Journal article (peer-reviewed)abstract
- The ability to adapt utterances to the world knowledge of one’s addressee is undeniably ubiquitous in human social cognition, but its development and association with other cognitive mechanisms during adolescence have not been studied. In an online production task, we measured the ability of children entering adolescence (ages 11–12, M = 11.8, N=29, 17 girls) and adolescents (ages 15–16, M = 15.9, N=29, 17 girls) to tailor referential expressions in accordance with the inferred world knowledge of their addressee—an ability we refer to as world knowledge-based audience design (AD). A post-test survey showed that both age groups held similar assumptions about the addressees’ knowledge of referents, but the younger age group did not consistently adapt their utterances in accordance with these assumptions during online production, resulting in a significantly improved AD behaviour across age groups. We also investigated the reliance of AD on executive functions (EF). Executive functioning (as reflected by performance on the Wisconsin card sorting task) increased significantly with age, but did not explain the age-related increase in AD performance. We thus provide evidence in support of an adolescent development of world knowledge-based AD over and above development of EF.
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| 7. |
- Arvidsson, Caroline, et al.
(author)
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Why the GPT task of predicting the next word does not suffice to describe human language production : A conversational fMRI-study
- 2023
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In: Program Pdf of The 15th Annual Meeting of the Society for the Neurobiology of Language.
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Conference paper (peer-reviewed)abstract
- Interest is surging around the ”next-word-predictability” task that allowed large language models to reach their current capacity. It is sometimes claimed that prediction is enough to model language production. We set out to study predictability in an interactive setting. The current fMRI study used the information-theoretic measure of surprisal – the negative log-probability of a word occurring given the preceding linguistic context, estimated by a pre-trained language model (GPT-2). Surprisal has been shown to correlate with bottom-up processing located in the bilateral middle and superior temporal gyri (MTG/STG) during narrative comprehension (Willems et al., 2016). Still, surprisal has never been used to investigate conversational comprehension or any kind of language production. We hypothesized that previous results on surprisal in narrative comprehension would be replicated with conversational comprehension and that next-word- predictability would not encompass language production processes. We utilized a publicly available fMRI dataset in which participants (N=24) engaged in unscripted conversations (12 min/participant) via an audio- video link with a confederate outside the scanner. The conversational events Production, Comprehension, and Silence were modeled in a whole-brain analysis. Two parametric modulations of production and comprehension were added: (1) log-transformed context-independent word frequency (control regressor) and (2) surprisal. Production-surprisal and Comprehension-surprisal were respectively contrasted against the implicit baseline. These contrasts were compared with the contrasts Production and Comprehension vs implicit baseline. If surprisal merely indexed part of the activity in the latter, broader contrasts, this provides a handle on production and comprehension processes beyond next-word-predictability. For surprisal in conversational production, we observed statistically signi�cant clusters in the left inferior frontal gyrus (LIFG), the medial frontal gyrus, and the motor cortex. Importantly, Production vs implicit baseline showed bilateral STG activation while STG was not parametrically modulated by surprisal. Moreover, the bilateral MTG/STG were the only clusters active for Comprehension vs implicit baseline and they were also modulated by surprisal. For comprehension, we thus replicated the previous narrative comprehension study (Willems et al.,2016), showing that unpredictable words activate the bilateral MTG/STG also in conversational settings. Next- word-predictability is thus so far a good model for conversational comprehension. For production, however, the next-word-predictability task helped to hone in on what is sometimes considered core production machinery in LIFG. Several functional interpretations of the STG recruitment during production are possible (such as monitoring for speech errors), but the current results point in the direction of two important conclusions: (1) a functional division of the frontal and temporal cortices during production, where the frontal component is prediction-related, and (2) that language processing during production is more than prediction, at least at the word-level. We provide a functional handle on such extra-predictive processes.
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| 8. |
- Ekaterina, Torubarova, et al.
(author)
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Investigating Conversational Dynamics in Human-Robot Interaction with fMRI
- 2023
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In: Proceedings of the 45th Annual Conference of the Cognitive Science.
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Conference paper (peer-reviewed)abstract
- We investigated how verbal communication with a robot differs from talking to a human in terms of brain activity by analysing an open-source fMRI dataset. We focused on modeling conversational dynamics rather than conversation as a whole, by analysing fine-grained events, in particular turn initiation. The results indicate that turn initiation in a conversation with a human involves higher activation in auditory and visual cortex than turn initiation with a robot. Conversely, listening to the robot showed higher engagement of auditory cortex than listening to a human. We suggest that verbal and non-verbal turn-taking cues provided by the human agent engage more cognitive processing for picking up the turn. On the other hand, listening to a robot agent requires more processing than listening to a human. Both findings suggest that the accurate simulation of appropriate turn-taking cues and behaviors will help robots to establish more natural conversation dynamics and that the use of brain imaging can provide valuable objective measurements for assessing user states in human-robot interaction.
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| 9. |
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| 10. |
- Pagmar, David, 1983-, et al.
(author)
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Conversations between ages five and seven : Connections to executive functions and implicature comprehension
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Other publication (other academic/artistic)abstract
- A language user must rely on several different abilities to carry out a conversation, e.g. the ability to acknowledge the conversational contributions of others, to respond appropriately, to stay on topic, etc. There are many aspects of the development of conversational conduct that are yet unknown. In this study, the longitudinal development of conversational conduct, as in acknowledging one’s interlocutor’s previous turn, were traced from age 5;0 to 7;2. We also investigated whether conversational conduct was predicted by core language skill, executive functions, and specific pragmatic abilities. Previous findings of productive morpho- syntactic accuracy were replicated, while findings concerning longitudinal receptive vocabulary were not. We also found connections between childrens’ conversational responses and executive functions, working memory, and the comprehension of conversational implicatures. The results suggest that conversational conduct is dependent on both inferring communicative intentions, as well as being able to keep track of others' contributions and how they relate to previous turns.
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| 11. |
- Pagmar, David, 1983-
(author)
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The Development of Conversational Contingency : and Selected Pragmatic Abilities
- 2023
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Doctoral thesis (other academic/artistic)abstract
- The aim of this thesis was to examine children’s development as language users, with a focus on their development as conversationalists. Conversational development was measured through conversational contingency, i.e. how conversational turns are connected to each other, either in topic or time. The thesis introduces a conversational contingency hierarchy, including basic conversational contingency (turns that in any way acknowledges the topic of the previous turn), which constitutes the main outcomes measure in the conducted studies. The thesis consists of four papers. Paper I-III were conducted with Swedish speaking children from the longitudinal MINT project (n=40; n=50; n=63). The first paper investigated which factors, internal and external to the child, that best predicted conversational contingency of children age five. The studies included linguistic and cognitive measures, environmental factors, as well as social and cognitive measures in early development. Results showed that receptive vocabulary (but not morphosyntactic accuracy) was related to positive conversational measures, as was later preschool entry. A suggested explanation is that a child needs to reach a specific level of lexical knowledge to start to understand conversational conventions. Paper II investigated the development of conversational behaviour at age seven. Conversational measures were analysed with measures of core language, executive functions (EF), and specific pragmatic abilities. Results showed that the conversational measures at age seven were no longer predicted by receptive vocabulary. Instead there were correlations to working memory, cognitive flexibility, and comprehension of conversational implicatures. A key finding was that measures of basic conversational contingency increased substantially from age five to seven. The results indicate that certain abilities affect conversational development during certain stages of development. Paper II also shows that basic conversational contingency develops gradually towards the adult conversational norm. Paper III examined the size, velocity, and acceleration of the parental reported productive vocabulary and if these measures predicted later core language and language use/pragmatic skill. Parental reports of productive vocabulary informed later language ability (receptive vocabulary and morphosyntactic accuracy), but not to the same extent as in previous research. The results indicate that the early lexicon does not inform later language use. Paper IV investigated older children, ages 11–12, 15–16, and the development of audience design (AD). We measured the ability to tailor referential expressions in accordance with the inferred world knowledge of an addressee. Measures of EF were also obtained. Results showed that AD develops during adolescence, and provided indications for a separation of world knowledge-based AD from EF. Additionally, the study shows that aspects of pragmatic competence are still under development well into adolescence. In sum, the thesis concludes that the relationship between conversational development and other developmental factors is dynamic and multifaceted. The ability to acknowledge the turns of others develops in tandem with several other abilities. Specific phases during conversational development connect to core language, executive functions, and comprehension of implicatures.
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| 12. |
- Schoffelen, Jan-Mathijs, et al.
(author)
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A 204-subject multimodal neuroimaging dataset to study language processing
- 2019
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In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 6
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Journal article (peer-reviewed)abstract
- This dataset, colloquially known as the Mother Of Unification Studies (MOUS) dataset, contains multimodal neuroimaging data that has been acquired from 204 healthy human subjects. The neuroimaging protocol consisted of magnetic resonance imaging (MRI) to derive information at high spatial resolution about brain anatomy and structural connections, and functional data during task, and at rest. In addition, magnetoencephalography (MEG) was used to obtain high temporal resolution electrophysiological measurements during task, and at rest. All subjects performed a language task, during which they processed linguistic utterances that either consisted of normal or scrambled sentences. Half of the subjects were reading the stimuli, the other half listened to the stimuli. The resting state measurements consisted of 5 minutes eyes-open for the MEG and 7 minutes eyes-closed for fMRI. The neuroimaging data, as well as the information about the experimental events are shared according to the Brain Imaging Data Structure (BIDS) format. This unprecedented neuroimaging language data collection allows for the investigation of various aspects of the neurobiological correlates of language.
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| 13. |
- Seyfried, Friederike, et al.
(author)
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Phonotactics and syntax : investigating functional specialisation during structured sequence processing
- 2023
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In: Language, Cognition and Neuroscience. - : Taylor & Francis Group. - 2327-3798 .- 2327-3801. ; 38:3, s. 346-358
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Journal article (peer-reviewed)abstract
- Frontal lobe organisation displays a functional gradient, with overarching processing goals located in parts anterior to more subordinate goals, processed more posteriorly. Functional specialisation for syntax and phonology within language relevant areas has been supported by meta-analyses and reviews, but never directly tested experimentally. We tested for organised functional specialisation by manipulating syntactic case and phonotactics, creating violations at the end of otherwise matched and predictable sentences. Both violations led to increased activation in expected language regions. We observe the clearest signs of a functional gradient for language processing in the medial frontal cortex, where syntactic violations activated a more anterior portion compared to the phonotactic violations. A large overlap of syntactic and phonotactic processing in the left inferior frontal gyrus (LIFG) supports the view that general structured sequence processes are located in this area. These findings are relevant for understanding how sentence processing is implemented in hierarchically organised processing steps in the frontal lobe.
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| 14. |
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| 15. |
- Uddén, Julia, et al.
(author)
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Artifical Grammar Learning and its Neurobiology in Relation to Language Processing and Development
- 2018. - 2
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In: The Oxford Handbook of Psycholinguistics. - Oxford : Oxford University Press. - 9780198786825 ; , s. 755-783
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Book chapter (peer-reviewed)abstract
- The artificial grammar learning (AGL) paradigm enables systematic investigation of the acquisition of linguistically relevant structures. It is a paradigm of interest for language processing research, interfacing with theoretical linguistics, and for comparative research on language acquisition and evolution. This chapter presents a key for understanding major variants of the paradigm. An unbiased summary of neuroimaging findings of AGL is presented, using meta-analytic methods, pointing to the crucial involvement of the bilateral frontal operculum and regions in the right lateral hemisphere. Against a background of robust posterior temporal cortex involvement in processing complex syntax, the evidence for involvement of the posterior temporal cortex in AGL is reviewed. Infant AGL studies testing for neural substrates are reviewed, covering the acquisition of adjacent and non-adjacent dependencies as well as algebraic rules. The language acquisition data suggest that comparisons of learnability of complex grammars performed with adults may now also be possible with children.
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| 16. |
- Uddén, Julia, et al.
(author)
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Hierarchical Structure in Sequence Processing : How to Measure It and Determine Its Neural Implementation
- 2020
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In: Topics in Cognitive Science. - : Wiley. - 1756-8757 .- 1756-8765. ; 12:3, s. 910-924
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Journal article (peer-reviewed)abstract
- In many domains of human cognition, hierarchically structured representations are thought to play a key role. In this paper, we start with some foundational definitions of key phenomena like “sequence” and “hierarchy," and then outline potential signatures of hierarchical structure that can be observed in behavioral and neuroimaging data. Appropriate behavioral methods include classic ones from psycholinguistics along with some from the more recent artificial grammar learning and sentence processing literature. We then turn to neuroimaging evidence for hierarchical structure with a focus on the functional MRI literature. We conclude that, although a broad consensus exists about a role for a neural circuit incorporating the inferior frontal gyrus, the superior temporal sulcus, and the arcuate fasciculus, considerable uncertainty remains about the precise computational function(s) of this circuitry. An explicit theoretical framework, combined with an empirical approach focusing on distinguishing between plausible alternative hypotheses, will be necessary for further progress.
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| 17. |
- Uddén, Julia
(author)
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Language as structured sequences : a causal role of Broca's region in sequence processing
- 2012
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Doctoral thesis (other academic/artistic)abstract
- In this thesis I approach language as a neurobiological system. I defend a sequence processing perspective on language and on the function of Broca's region in the left inferior frontal gyrus (LIFG). This perspective provides a way to express common structural aspects of language, music and action, which all engage the LIFG. It also facilitates the comparison of human language and structured sequence processing in animals. Research on infants, song-birds and non-human primates suggests an interesting role for non-adjacent dependencies in language acquisition and the evolution of language. In a series of experimental studies using a sequence processing paradigm called artificial grammar learning (AGL), we have investigated sequences with adjacent and non-adjacent dependencies. Our behavioral and transcranial magnetic stimulation (TMS) studies show that healthy subjects successfully discriminate between grammatical and non-grammatical sequences after having acquired aspects of a grammar with nested or crossed non-adjacent dependencies implicitly. There were no indications of separate acquisition/processing mechanisms for sequence processing of adjacent and non-adjacent dependencies, although acquisition of non-adjacent dependencies takes more time. In addition, we studied the causal role of Broca‟s region in processing artificial syntax. Although syntactic processing has already been robustly correlated with activity in Broca's region, the causal role of Broca's region in syntactic processing, in particular syntactic comprehension has been unclear. Previous lesion studies have shown that a lesion in Broca's region is neither a necessary nor sufficient condition to induce e.g. syntactic deficits. Subsequent to transcranial magnetic stimulation of Broca‟s region, discrimination of grammatical sequences with non-adjacent dependencies from non-grammatical sequences was impaired, compared to when a language irrelevant control region (vertex) was stimulated. Two additional experiments show perturbation of discrimination performance for grammars with adjacent dependencies after stimulation of Broca's region. Together, these results support the view that Broca‟s region plays a causal role in implicit structured sequence processing.
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| 18. |
- Uddén, Julia, et al.
(author)
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Supramodal Sentence Processing in the Human Brain : fMRI Evidence for the Influence of Syntactic Complexity in More Than 200 Participants
- 2022
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In: Neurobiology of Language. - : MIT Press. - 2641-4368. ; 3:4, s. 575-598
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Journal article (peer-reviewed)abstract
- This study investigated two questions. One is: To what degree is sentence processing beyond single words independent of the input modality (speech vs. reading)? The second question is: Which parts of the network recruited by both modalities is sensitive to syntactic complexity? These questions were investigated by having more than 200 participants read or listen to well-formed sentences or series of unconnected words. A largely left-hemisphere frontotemporoparietal network was found to be supramodal in nature, i.e., independent of input modality. In addition, the left inferior frontal gyrus (LIFG) and the left posterior middle temporal gyrus (LpMTG) were most clearly associated with left-branching complexity. The left anterior temporal lobe showed the greatest sensitivity to sentences that differed in right-branching complexity. Moreover, activity in LIFG and LpMTG increased from sentence onset to end, in parallel with an increase of the left-branching complexity. While LIFG, bilateral anterior temporal lobe, posterior MTG, and left inferior parietal lobe all contribute to the supramodal unification processes, the results suggest that these regions differ in their respective contributions to syntactic complexity related processing. The consequences of these findings for neurobiological models of language processing are discussed.
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| 19. |
- Uddén, Julia, et al.
(author)
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Toward Robust Functional Neuroimaging Genetics of Cognition
- 2019
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In: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 39:44, s. 8778-8787
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Journal article (peer-reviewed)abstract
- A commonly held assumption in cognitive neuroscience is that, because measures of human brain function are closer to underlying biology than distal indices of behavior/cognition, they hold more promise for uncovering genetic pathways. Supporting this view is an influential fMRI-based study of sentence reading/listening by Pinel et al. (2012), who reported that common DNA variants in specific candidate genes were associated with altered neural activation in language-related regions of healthy individuals that carried them. In particular, different single-nucleotide polymorphisms (SNPs) of FOXP2 correlated with variation in task-based activation in left inferior frontal and precentral gyri, whereas a SNP at the KIAA0319/TTRAP/THEM2 locus was associated with variable functional asymmetry of the superior temporal sulcus. Here, we directly test each claim using a closely matched neuroimaging genetics approach in independent cohorts comprising 427 participants, four times larger than the original study of 94 participants. Despite demonstrating power to detect associations with substantially smaller effect sizes than those of the original report, we do not replicate any of the reported associations. Moreover, formal Bayesian analyses reveal substantial to strong evidence in support of the null hypothesis (no effect). We highlight key aspects of the original investigation, common to functional neuroimaging genetics studies, which could have yielded elevated false-positive rates. Genetic accounts of individual differences in cognitive functional neuroimaging are likely to be as complex as behavioral/ cognitive tests, involving many common genetic variants, each of tiny effect. Reliable identification of true biological signals requires large sample sizes, power calculations, and validation in independent cohorts with equivalent paradigms.
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