The hippocampus is a brain region critical for learning and memory, and is also implicated in several neuropsychiatric disorders that show sex differences in prevalence, symptom expression, and mean ...age of onset. On average, males have larger hippocampal volumes than females, but findings are inconclusive after adjusting for overall brain size. Although the hippocampus is a heterogenous structure, few studies have focused on sex differences in the hippocampal subfields – with little consensus on whether there are regionally specific sex differences in the hippocampus after adjusting for brain size, or whether it is important to adjust for total hippocampal volume (HPV). Here, using two young adult cohorts from the Queensland Twin IMaging study (QTIM; N = 727) and the Human Connectome Project (HCP; N = 960), we examined differences between males and females in the volumes of 12 hippocampal subfields, extracted using FreeSurfer 6.0. After adjusting the subfield volumes for either HPV or brain size (brain segmentation volume (BSV)) using four controlling methods (allometric, covariate, residual and matching), we estimated the percentage difference of the sex effect (males versus females) and Cohen’s d using hierarchical general linear models. Males had larger volumes compared to females in the parasubiculum (up to 6.04%; Cohen’s d = 0.46) and fimbria (up to 8.75%; d = 0.54) after adjusting for HPV. These sex differences were robust across the two cohorts and multiple controlling methods, though within cohort effect sizes were larger for the matched approach, due to the smaller sub-sample. Additional sex effects were identified in the HCP cohort and combined (QTIM and HCP) sample (hippocampal fissure (up to 6.79%), presubiculum (up to 3.08%), and hippocampal tail (up to −0.23%)). In contrast, no sex differences were detected for the volume of the cornu ammonis (CA)2/3, CA4, Hippocampus-Amygdala Transition Area (HATA), or the granule cell layer of the dentate gyrus (GCDG). These findings show that, independent of differences in HPV, there are regionally specific sex differences in the hippocampus, which may be most prominent in the fimbria and parasubiculum. Further, given sex differences were less consistent across cohorts after controlling for BSV, adjusting for HPV rather than BSV may benefit future studies. This work may help in disentangling sex effects, and provide a better understanding of the implications of sex differences for behaviour and neuropsychiatric disorders.
•Region-specific sex differences were found after adjusting for hippocampal volume.•Males have larger parasubiculum, fimbria, hippocampal fissure, and presubiculum.•Females show larger volumes for the hippocampal tail.•No sex differences were found in the CA2/3, CA4, HATA, or GCDG subfields.
Abstract
Quantifying the genetic architecture of the cerebral cortex is necessary for understanding disease and changes to the brain across the lifespan. Prior work shows that both surface area (SA) ...and cortical thickness (CT) are heritable. However, we do not yet understand the extent to which region-specific genetic factors (i.e., independent of global effects) play a dominant role in the regional patterning or inter-regional associations across the cortex. Using a population sample of young adult twins (N = 923), we show that the heritability of SA and CT varies widely across regions, generally independent of measurement error. When global effects are controlled for, we detected a complex pattern of genetically mediated clusters of inter-regional associations, which varied between hemispheres. There were generally weak associations between the SA of different regions, except within the occipital lobe, whereas CT was positively correlated within lobar divisions and negatively correlated across lobes, mostly due to genetic covariation. These findings were replicated in an independent sample of twins and siblings (N = 698) from the Human Connectome Project. The different genetic contributions to SA and CT across regions reveal the value of quantifying sources of covariation to appreciate the genetic complexity of cortical structures.
The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect ...genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA–DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18–85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/).
•We harmonize a DTI protocol for genetic studies of FA; protocols are made public.•Template created from 400 adults (18–85) from 4 sites with different DTI parameters•Meta-analysis of heritability from 2 sites performed voxelwise and in ROIs.•Reliable pooled heritability estimates found for most regions of the brain.•Results will help guide future studies to harmonize and combine DTI data.
Twin studies have found gross cerebellar volume to be highly heritable. However, whether fine‐grained regional volumes within the cerebellum are similarly heritable is still being determined. ...Anatomical MRI scans from two independent datasets (QTIM: Queensland Twin IMaging, N = 798, mean age 22.1 years; QTAB: Queensland Twin Adolescent Brain, N = 396, mean age 11.3 years) were combined with an optimised and automated cerebellum parcellation algorithm to segment and measure 28 cerebellar regions. We show that the heritability of regional volumetric measures varies widely across the cerebellum (h2$$ {h}^2 $$ 47%–91%). Additionally, the good to excellent test–retest reliability for a subsample of QTIM participants suggests that non‐genetic variance in cerebellar volumes is due primarily to unique environmental influences rather than measurement error. We also show a consistent pattern of strong associations between the volumes of homologous left and right hemisphere regions. Associations were predominantly driven by genetic effects shared between lobules, with only sparse contributions from environmental effects. These findings are consistent with similar studies of the cerebrum and provide a first approximation of the upper bound of heritability detectable by genome‐wide association studies.
This research reveals a wide variability in the heritability of specific cerebellar regions (47%–91%). The findings highlight the genetic underpinnings of cerebellar structure and emphasise the substantial influence of unique environmental factors on regional volumetric measures.
Most of our knowledge about the neuroanatomy of speech errors comes from lesion-symptom mapping studies in people with aphasia and laboratory paradigms designed to elicit primarily phonological ...errors in healthy adults, with comparatively little evidence from naturally occurring speech errors. In this study, we analyzed perfusion fMRI data from 24 healthy participants during a picture naming task, classifying their responses into correct and different speech error types (e.g., semantic, phonological, omission errors). Total speech errors engaged a wide set of left-lateralized frontal, parietal, and temporal regions that were almost identical to those involved during the production of correct responses. We observed significant perfusion signal decreases in the left posterior middle temporal gyrus and inferior parietal lobule (angular gyrus) for semantic errors compared to correct trials matched on various psycholinguistic variables. In addition, the left dorsal caudate nucleus showed a significant perfusion signal decrease for omission (i.e., anomic) errors compared with matched correct trials. Surprisingly, we did not observe any significant perfusion signal changes in brain regions proposed to be associated with monitoring mechanisms during speech production (e.g., ACC, superior temporal gyrus). Overall, our findings provide evidence for distinct neural correlates of semantic and omission error types, with anomic speech errors likely resulting from failures to initiate articulatory–motor processes rather than semantic knowledge impairments as often reported for people with aphasia.
Grounded or embodied cognition research has employed body-object interaction (BOI; e.g., Pexman et al., 2019) ratings to investigate sensorimotor effects during language processing. We investigated ...relationships between BOI ratings and nonarbitrary statistical mappings between words' phonological forms and their syntactic category in English; i.e., form systematicity. In Study 1, principal components analysis revealed that BOI and form systematicity measures load on a common component, indicating they convey similar information about the probability of a word belonging to a particular syntactic category. In Studies 2, 3, and 4, form systematicity measures were stronger predictors of English Lexicon Project (ELP; Balota et al., 2007), Auditory English Lexicon Project (AELP; Goh et al., 2020), and English Crowdsourcing Project (ECP; Mandera et al., 2020) performance than BOI. In Study 5, BOI was a stronger predictor of performance from the Calgary Semantic Decision Project (CSDP; Pexman et al., 2017) than form systematicity. In Study 6, only form systematicity significantly predicted performance from the LinguaPix object naming megastudy (Krautz & Keuleers, 2022). Together, these results demonstrate that nonarbitrary statistical relationships in the form of mappings between ortho-phonological information and meaning are accessed automatically during language processing; i.e., even when syntactic category is not relevant to the task, and that sensorimotor simulation mechanisms are only strongly engaged when explicitly demanded by the task. We discuss the implications of these findings for proposals of embodied or grounded cognition and interpretations of neuroimaging data from word recognition tasks.
Across spoken languages, there are some words whose acoustic features resemble the meanings of their referents by evoking perceptual imagery, i.e., they are iconic (e.g., in English, "splash" ...imitates the sound of an object hitting water). While these sound symbolic form-meaning relationships are well-studied, relatively little work has explored whether the sensory properties of English words also involve systematic (i.e., statistical) form-meaning mappings. We first test the prediction that surface form properties can predict sensory experience ratings for over 5,000 monosyllabic and disyllabic words (Juhasz & Yap, 2013), confirming they explain a significant proportion of variance. Next, we show that iconicity and sensory form typicality, a statistical measure of how well a word's form aligns with its sensory experience rating, are only weakly related to each other, indicating they are likely to be distinct constructs. To determine whether form typicality influences processing of sensory words, we conducted regression analyses using lexical decision, word recognition, naming and semantic decision tasks from behavioral megastudy data sets. Across the data sets, sensory form typicality was able to predict more variance in performance than sensory experience or iconicity ratings. Further, the effects of typicality were consistently inhibitory in comprehension (i.e., more typical forms were responded to more slowly and less accurately), whereas for production the effect was facilitatory. These findings are the first evidence that systematic form-meaning mappings in English sensory words influence their processing. We discuss how language processing models incorporating Bayesian prediction mechanisms might be able to account for form typicality in the lexicon.
Public Significance Statement
For over a century, language researchers have generally assumed that the relationship between the sound of a word and its meaning is entirely arbitrary. Our study shows there are systematic associations between English words referencing sensory experiences and their sound features beyond previously reported iconic relationships. We also show that these sensory sound-meaning associations influence language comprehension and production.
Abstract
Listeners can use prior knowledge to predict the content of noisy speech signals, enhancing perception. However, this process can also elicit misperceptions. For the first time, we employed ...a prime–probe paradigm and transcranial magnetic stimulation to investigate causal roles for the left and right posterior superior temporal gyri (pSTG) in the perception and misperception of degraded speech. Listeners were presented with spectrotemporally degraded probe sentences preceded by a clear prime. To produce misperceptions, we created partially mismatched pseudo-sentence probes via homophonic nonword transformations (e.g. The little girl was excited to lose her first tooth—Tha fittle girmn wam expited du roos har derst cooth). Compared to a control site (vertex), inhibitory stimulation of the left pSTG selectively disrupted priming of real but not pseudo-sentences. Conversely, inhibitory stimulation of the right pSTG enhanced priming of misperceptions with pseudo-sentences, but did not influence perception of real sentences. These results indicate qualitatively different causal roles for the left and right pSTG in perceiving degraded speech, supporting bilateral models that propose engagement of the right pSTG in sublexical processing.
A century of research has provided evidence of limited size sound symbolism in English, that is, certain vowels are non-arbitrarily associated with words denoting small versus large referents (e.g., .../i/ as in teensy and /ɑ/ as in tall). In the present study, we investigated more extensive statistical regularities between surface form properties of English words and ratings of their semantic size, that is, form typicality, and its impact on language and memory processing. Our findings provide the first evidence of significant word form typicality for semantic size. In five empirical studies using behavioural megastudy data sets of performance on written and auditory lexical decision, reading aloud, semantic decision, and recognition memory tasks, we show that form typicality for size is a stronger and more consistent predictor of lexical access during word comprehension and production than semantic size, in addition to playing a significant role in verbal memory. The empirical results demonstrate that statistical information about non-arbitrary form-size mappings is accessed automatically during language and verbal memory processing, unlike semantic size that is largely dependent on task contexts that explicitly require participants to access size knowledge. We discuss how a priori knowledge about non-arbitrary form-meaning associations in the lexicon might be incorporated in models of language processing that implement Bayesian statistical inference.
Comprehending action words often engages similar brain regions to those involved in perceiving and executing actions. This finding has been interpreted as support for grounding of conceptual ...processing in motor representations or that conceptual processing involves motor simulation. However, such demonstrations cannot confirm the nature of the mechanism(s) responsible, as word comprehension involves multiple processes (e.g., lexical, semantic, morphological, phonological). In this study, we tested whether this motor cortex engagement instead reflects processing of statistical regularities in sublexical phonological features. Specifically, we measured brain activity in healthy participants using functional magnetic resonance imaging while they performed an auditory lexical decision paradigm involving monosyllabic action words associated with specific effectors (face, arm, and leg). We show that nonwords matched to the action words in terms of their
elicit common patterns of activation. In addition, we show that a measure of the action words'
, the extent to which a word's phonology is typical of other words in the grammatical category to which it belongs (i.e., more or less verb-like), is responsible for their activating a significant portion of primary and premotor cortices. These results indicate motor cortex engagement during action word comprehension is more likely to reflect processing of statistical regularities in sublexical phonological features than conceptual processing. We discuss the implications for current neurobiological models of language, all of which implicitly or explicitly assume that the relationship between the sound of a word and its meaning is arbitrary.
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