Towards robust functional neuroimaging genetics of cognition

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. SIGNIFICANCE STATEMENT A pervasive idea in neuroscience is that neuroimaging-based measures of brain function, being closer to underlying neurobiology, are more amenable for uncovering links to genetics. This is a core assumption of prominent studies that associate common DNA variants with altered activations in task-based fMRI, despite using samples (10–100 people) that lack power for detecting the tiny effect sizes typical of genetically complex traits. Here, we test central findings from one of the most influential prior studies. Using matching paradigms and substantially larger samples, coupled to power calculations and formal Bayesian statistics, our data strongly refute the original findings. We demonstrate that neuroimaging genetics with task-based fMRI should be subject to the same rigorous standards as studies of other complex traits

The language network is recruited but not required for nonverbal event semantics

The ability to combine individual concepts of objects, properties, and actions into complex representations of the world is often associated with language. Yet combinatorial event-level representations can also be constructed from nonverbal input, such as visual scenes. Here, we test whether the language network in the human brain is involved in and necessary for semantic processing of events presented nonverbally. In Experiment 1, we scanned participants with fMRI while they performed a semantic plausibility judgment task versus a difficult perceptual control task on sentences and line drawings that describe/depict simple agent–patient interactions. We found that the language network responded robustly during the semantic task performed on both sentences and pictures (although its response to sentences was stronger). Thus, language regions in healthy adults are engaged during a semantic task performed on pictorial depictions of events. But is this engagement necessary? In Experiment 2, we tested two individuals with global aphasia, who have sustained massive damage to perisylvian language areas and display severe language difficulties, against a group of age-matched control participants. Individuals with aphasia were severely impaired on the task of matching sentences to pictures. However, they performed close to controls in assessing the plausibility of pictorial depictions of agent–patient interactions. Overall, our results indicate that the left frontotemporal language network is recruited but not necessary for semantic processing of nonverbally presented events

Tracking Colisteners’ Knowledge States During Language Comprehension

When we receive information in the presence of other people, are we sensitive to what they do or do not understand? In two event-related-potential experiments, participants read implausible sentences (e.g., “The girl had a little beak”) in contexts that rendered them plausible (e.g., “The girl dressed up as a canary for Halloween”). No semantic-processing difficulty (no N400 effect) ensued when they read the sentences while alone in the room. However, when a confederate was present who did not receive the contexts so that the critical sentences were implausible for him or her, participants exhibited processing difficulty: the social-N400 effect. This effect was obtained when participants were instructed to adopt the confederate’s perspective—and critically, even without such instructions—but not when performing a demanding comprehension task. Thus, unless mental resources are limited, comprehenders engage in modeling the minds not only of those individuals with whom they directly interact but also of those individuals who are merely present during the linguistic exchange