Handedness and its genetic influences are associated with structural asymmetries of the cerebral cortex in 31,864 individuals.

Roughly 10% of the human population is left-handed, and this rate is increased in some brain-related disorders. The neuroanatomical correlates of hand preference have remained equivocal. We resampled structural brain image data from 28,802 right-handers and 3,062 left-handers (UK Biobank population dataset) to a symmetrical surface template, and mapped asymmetries for each of 8,681 vertices across the cerebral cortex in each individual. Left-handers compared to right-handers showed average differences of surface area asymmetry within the fusiform cortex, the anterior insula, the anterior middle cingulate cortex, and the precentral cortex. Meta-analyzed functional imaging data implicated these regions in executive functions and language. Polygenic disposition to left-handedness was associated with two of these regional asymmetries, and 18 loci previously linked with left-handedness by genome-wide screening showed associations with one or more of these asymmetries. Implicated genes included six encoding microtubule-related proteins: TUBB, TUBA1B, TUBB3, TUBB4A, MAP2, and NME7-mutations in the latter can cause left to right reversal of the visceral organs. There were also two cortical regions where average thickness asymmetry was altered in left-handedness: on the postcentral gyrus and the inferior occipital cortex, functionally annotated with hand sensorimotor and visual roles. These cortical thickness asymmetries were not heritable. Heritable surface area asymmetries of language-related regions may link the etiologies of hand preference and language, whereas nonheritable asymmetries of sensorimotor cortex may manifest as consequences of hand preference.

Left-hand preference in visual artists: A pre-registered observational study on Instagram.

The notion of an increased incidence of left handers among architects and visual artists has inspired both scientific theory building and popular discussion. However, a systematic exploration of the available publications provides, at best, modest evidence for this claim. The present preregistered observational study was designed to reinvestigate the postulated association by examining hand preference of visual artists who share their artistic activities as short video clips ("reels") on the social media platform Instagram. Determining individual hand preference based on five reels for each of N = 468 artists, we identified 42 (8.97%) left handers, suggesting an incidence which is below but statistical comparable to the 10.6% expected for the general population (χ2 = 1.30; p = .25; Cohen's w = 0.05). Also, we did not find any support for the notion that the art created by left-handed artists is of higher quality than art of right handers, as no difference in public endorsement or interest were observed (reflected by the number of likes per post or account followers). Taken together, we do not find any support for difference in artistic engagement or quality between left and right handers.

Education and Income Show Heterogeneous Relationships to Lifespan Brain and Cognitive Differences Across European and US Cohorts.

Higher socio-economic status (SES) has been proposed to have facilitating and protective effects on brain and cognition. We ask whether relationships between SES, brain volumes and cognitive ability differ across cohorts, by age and national origin. European and US cohorts covering the lifespan were studied (4-97 years, N = 500 000; 54 000 w/brain imaging). There was substantial heterogeneity across cohorts for all associations. Education was positively related to intracranial (ICV) and total gray matter (GM) volume. Income was related to ICV, but not GM. We did not observe reliable differences in associations as a function of age. SES was more strongly related to brain and cognition in US than European cohorts. Sample representativity varies, and this study cannot identify mechanisms underlying differences in associations across cohorts. Differences in neuroanatomical volumes partially explained SES-cognition relationships. SES was more strongly related to ICV than to GM, implying that SES-cognition relations in adulthood are less likely grounded in neuroprotective effects on GM volume in aging. The relatively stronger SES-ICV associations rather are compatible with SES-brain volume relationships being established early in life, as ICV stabilizes in childhood. The findings underscore that SES has no uniform association with, or impact on, brain and cognition.

Laterality indices consensus initiative (LICI): A Delphi expert survey report on recommendations to record, assess, and report asymmetry in human behavioural and brain research.

Laterality indices (LIs) quantify the left-right asymmetry of brain and behavioural variables and provide a measure that is statistically convenient and seemingly easy to interpret. Substantial variability in how structural and functional asymmetries are recorded, calculated, and reported, however, suggest little agreement on the conditions required for its valid assessment. The present study aimed for consensus on general aspects in this context of laterality research, and more specifically within a particular method or technique (i.e., dichotic listening, visual half-field technique, performance asymmetries, preference bias reports, electrophysiological recording, functional MRI, structural MRI, and functional transcranial Doppler sonography). Experts in laterality research were invited to participate in an online Delphi survey to evaluate consensus and stimulate discussion. In Round 0, 106 experts generated 453 statements on what they considered good practice in their field of expertise. Statements were organised into a 295-statement survey that the experts then were asked, in Round 1, to independently assess for importance and support, which further reduced the survey to 241 statements that were presented again to the experts in Round 2. Based on the Round 2 input, we present a set of critically reviewed key recommendations to record, assess, and report laterality research for various methods.

Interhemispheric Integration after Callosotomy: A Meta-Analysis of Poffenberger and Redundant-Target Paradigms.

The central role of the corpus callosum in integrating perception and cognition across the cerebral hemispheres makes it highly desirable for clinical and basic research to have a repertoire of experimental paradigms assessing callosal functioning. Here, the objective was to assess the validity of two such paradigms (Poffenberger, redundant-target paradigms) by conducting single-step meta-analyses on individual case data of callosotomy patients. Studies were identified by systematic literature search (source: Pubmed and WebOfKnowledge, date: 07.03.2022) and all studies were included that reported callosotomy case data for either paradigm. Twenty-two studies (38 unique cases) provided 116 observations of the crossed-uncrossed difference (CUD) for the Poffenberger paradigm, while ten studies (22 cases, 103 observations) provided bilateral redundancy gain (bRG) measures. Using linear-mixed models with "individual" and "experiment" as random-effects variable, the mean CUD was estimated at 60.6 ms (CI95%: 45.3; 75.9) for commissurotomy, 43.5 ms (26.7; 60.2) for complete callosotomy, and 8.8 ms (1.1; 16.6) for partial anterior-medial callosotomy patients. The estimates of commissurotomy/callosotomy patients differed significantly from patients with partial callosotomy and healthy controls. The mean bRGmin (minimum unilateral reference) was estimated at 42.8 ms (27.1;58.4) for patients with complete and 30.8 ms (16.8; 44.7) for patients with partial callosotomy, both differing significantly from controls. One limitation was that different formulas for bRG were used, making it necessary to split the sample and reducing test power of some analyses. Nevertheless, the present findings suggest that both paradigms assess interhemispheric callosal integration, confirming their construct validity, but likely test distinct callosal functions.

Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium.

We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18-92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. "PSQI # 1 Subjective sleep quality" and "PSQI #5 Sleep disturbances" were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with "PSQI #5 Sleep disturbances" emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.

Meta-analysis of generalized additive models in neuroimaging studies.

Analyzing data from multiple neuroimaging studies has great potential in terms of increasing statistical power, enabling detection of effects of smaller magnitude than would be possible when analyzing each study separately and also allowing to systematically investigate between-study differences. Restrictions due to privacy or proprietary data as well as more practical concerns can make it hard to share neuroimaging datasets, such that analyzing all data in a common location might be impractical or impossible. Meta-analytic methods provide a way to overcome this issue, by combining aggregated quantities like model parameters or risk ratios. Most meta-analytic tools focus on parametric statistical models, and methods for meta-analyzing semi-parametric models like generalized additive models have not been well developed. Parametric models are often not appropriate in neuroimaging, where for instance age-brain relationships may take forms that are difficult to accurately describe using such models. In this paper we introduce meta-GAM, a method for meta-analysis of generalized additive models which does not require individual participant data, and hence is suitable for increasing statistical power while upholding privacy and other regulatory concerns. We extend previous works by enabling the analysis of multiple model terms as well as multivariate smooth functions. In addition, we show how meta-analytic p-values can be computed for smooth terms. The proposed methods are shown to perform well in simulation experiments, and are demonstrated in a real data analysis on hippocampal volume and self-reported sleep quality data from the Lifebrain consortium. We argue that application of meta-GAM is especially beneficial in lifespan neuroscience and imaging genetics. The methods are implemented in an accompanying R package metagam, which is also demonstrated.

Age-Related Differences in Functional Asymmetry During Memory Retrieval Revisited: No Evidence for Contralateral Overactivation or Compensation.

Brain asymmetry is inherent to cognitive processing and seems to reflect processing efficiency. Lower frontal asymmetry is often observed in older adults during memory retrieval, yet it is unclear whether lower asymmetry implies an age-related increase in contralateral recruitment, whether less asymmetry reflects compensation, is limited to frontal regions, or predicts neurocognitive stability or decline. We assessed age-related differences in asymmetry across the entire cerebral cortex, using functional magnetic resonance imaging data from 89 young and 76 older adults during successful retrieval, and surface-based methods allowing direct homotopic comparison of activity between cortical hemispheres . An extensive left-asymmetric network facilitated retrieval in both young and older adults, whereas diverse frontal and parietal regions exhibited lower asymmetry in older adults. However, lower asymmetry was not associated with age-related increases in contralateral recruitment but primarily reflected either less deactivation in contralateral regions reliably signaling retrieval failure in the young or lower recruitment of the dominant hemisphere-suggesting that functional deficits may drive lower asymmetry in older brains, not compensatory activity. Lower asymmetry predicted neither current memory performance nor the extent of memory change across the preceding ~ 8 years in older adults. Together, these findings are inconsistent with a compensation account for lower asymmetry during retrieval and aging.

Differences in unity: The go/no-go and stop signal tasks rely on different mechanisms.

Response inhibition refers to the suppression of prepared or initiated actions. Typically, the go/no-go task (GNGT) or the stop signal task (SST) are used interchangeably to capture individual differences in response inhibition. On the one hand, factor analytic and conjunction neuroimaging studies support the association of both tasks with a single inhibition construct. On the other hand, studies that directly compare the two tasks indicate distinct mechanisms, corresponding to action restraint and cancellation in the GNGT and SST, respectively. We addressed these contradictory findings with the aim to identify the core differences in the temporal dynamics of the functional networks that are recruited in both tasks. We extracted the time-courses of sensory, motor, attentional, and cognitive control networks by group independent component (G-ICA) analysis of electroencephalography (EEG) data from both tasks. Additionally, electromyography (EMG) from the responding effector muscles was recorded to detect the timing of response inhibition. The results indicated that inhibitory performance in the GNGT may be comparable to response selection mechanisms, reaching peripheral muscles at around 316 â€‹ms. In contrast, inhibitory performance in the SST is achieved via biasing of the sensorimotor system in preparation for stopping, followed by fast sensory, motor and frontal integration during outright stopping. Inhibition can be detected at the peripheral level at 140 â€‹ms after stop stimulus presentation. The GNGT and the SST therefore seem to recruit widely different neural dynamics, implying that the interchangeable use of superficially similar inhibition tasks in both basic and clinical research is unwarranted.

Continuity and Discontinuity in Human Cortical Development and Change From Embryonic Stages to Old Age.

The human cerebral cortex is highly regionalized, and this feature emerges from morphometric gradients in the cerebral vesicles during embryonic development. We tested if this principle of regionalization could be traced from the embryonic development to the human life span. Data-driven fuzzy clustering was used to identify regions of coordinated longitudinal development of cortical surface area (SA) and thickness (CT) (n = 301, 4-12 years). The principal divide for the developmental SA clusters extended from the inferior-posterior to the superior-anterior cortex, corresponding to the major embryonic morphometric anterior-posterior (AP) gradient. Embryonic factors showing a clear AP gradient were identified, and we found significant differences in gene expression of these factors between the anterior and posterior clusters. Further, each identified developmental SA and CT clusters showed distinguishable life span trajectories in a larger longitudinal dataset (4-88 years, 1633 observations), and the SA and CT clusters showed differential relationships to cognitive functions. This means that regions that developed together in childhood also changed together throughout life, demonstrating continuity in regionalization of cortical changes. The AP divide in SA development also characterized genetic patterning obtained in an adult twin sample. In conclusion, the development of cortical regionalization is a continuous process from the embryonic stage throughout life.

From observed laterality to latent hemispheric differences: Revisiting the inference problem.

Researchers interested in hemispheric dominance frequently aim to infer latent functional differences between the hemispheres from observed lateral behavioural or brain-activation differences. To be valid, these inferences may not only rely on the observed laterality measures but also need to account for the antecedent probabilities of the studied latent classes. This fact is frequently ignored in the literature, leading to misclassifications especially when considering low probability classes as, for example, "atypical" right hemispheric language dominance. In the present paper, we revisit this inference problem (a) by outlining a general Bayesian framework for the inferential process and (b) by exemplarily applying this framework on the inference of hemispheric dominance for speech processing from dichotic-listening laterality scores. Utilizing large-scale empirical data sets as well as simulation studies, we show that valid inferences also regarding low probable latent classes can be drawn applying the present framework, although within certain boundaries. We further illustrate that repeated laterality measures of the same person may be used to improve the classification outcome. The article additionally provides R package and Shiny app implementations of the suggested Bayesian framework, which allow to explore the boundaries of valid inference for the present and other examples.

A primer on dichotic listening as a paradigm for the assessment of hemispheric asymmetry.

Dichotic listening is a well-established method to non-invasively assess hemispheric specialization for processing of speech and other auditory stimuli. However, almost six decades of research also have revealed a series of experimental variables with systematic modulatory effects on task performance. These variables are a source of systematic error variance in the data and, when uncontrolled, affect the reliability and validity of the obtained laterality measures. The present review provides a comprehensive overview of these modulatory variables and offers both guiding principles as well as concrete suggestions on how to account for possible confounding effects and avoid common pitfalls. The review additionally provides guidance for the evaluation of past studies and help for resolving inconsistencies in the available literature.

How to get a left-ear advantage: A technical review of assessing brain asymmetry with dichotic listening.

The dichotic-listening paradigm with verbal stimuli is a widely employed behavioral task for the assessment of hemispheric asymmetry for speech and language processing. Participants with assumed left-hemispheric dominance report the right-ear stimulus with higher probability than the left-ear stimulus. However, there is substantial between-subject and trial-to-trial variability observed in the paradigm, motivating scrutiny of the task set-up and theoretical models. Here, we give an in-depth discussion of specific features of stimulus material and experimental parameters, as well as the conditions of stimulus/response selection, which explain a significant proportion of intra- and inter-individual variability. Carefully considering these factors should be at the heart of any experimental planning when using the dichotic-listening paradigm to achieve an optimal testing situation for measuring laterality and avoid confounds in between-subject and between-group comparisons.

Premises of plasticity - And the loneliness of the medial temporal lobe.

In this perspective paper, we examine possible premises of plasticity in the neural substrates underlying cognitive change. We take the special role of the medial temporal lobe as an anchoring point, but also investigate characteristics throughout the cortex. Specifically, we examine the dimensions of evolutionary expansion, heritability, variability of morphometric change, and inter-individual variance in myelination with respect to the plastic potential of different brain regions. We argue that areas showing less evolutionary expansion, lower heritability, greater variability of cortical thickness change through the lifespan, and greater inter-individual differences in intracortical myelin content have a great extent of plasticity. While different regions of the brain show these features to varying extent, analyses converge on the medial temporal lobe including the hippocampi as the target of all these premises. We discuss implications for effects of training on brain structures, and conditions under which plasticity may be evoked.

Selective increase in posterior corpus callosum thickness between the age of 4 and 11years.

Establishing an efficient functional and structural connectivity between the two cerebral hemispheres is an important developmental task during childhood, and alterations in this development have accordingly been linked to a series of neurodevelopmental and pediatric disorders. The corpus callosum, the major white-matter structure connecting the hemispheres, has been shown to increase in size throughout the three first decades of life. However, behavioral studies indicate that adult-like performance levels of functional hemispheric interaction are already reached during middle and late childhood. Thus, here we specifically examine the structural development of the corpus callosum during the functionally relevant time period by for the first time (a) selectively addressing prospective childhood development and (b) analyzing a sample in which also younger children are well represented. Corpus callosum anatomy was assessed from 732 T1-weighted MRI datasets acquired from 428 children (213 boys, 215 girls) aged of 4.1 and 10.9years, of which 304 were scanned at two time points. Regional callosal thickness was determined from an outline-based segmentation of the mid-sagittal cross-sectional surface area. Linear-mixed model analyses revealed a significant increase in thickness with age (effect size: up to 15% explained variance) equivalent to a growth in callosal thickness of up to 0.19mm per year in the posterior corpus callosum. The age effect was found to be stronger in posterior segments (i.e., splenium) than in other callosal subregions. Also, the age effect was found to be comparable between boys and girls, and was detected irrespective of whether developmental or individual differences in overall brain size where accounted for or not. Our results demonstrate a selective increase in posterior corpus-callosum thickness during middle and late childhood. Since axons crossing the midline in the splenium mainly connect occipital and parietal cortices, the accentuated posterior growth might reflect the onset of a posterior-to-anterior moving maturation wave in cortical development known to take place in the same time period.

Investigating heritability of laterality and cognitive control in speech perception.

Several studies analyzing the ontogenetic origin of cerebral lateralization provide evidences for a genetic foundation of handedness in humans that is modulated by environmental influences. Since other forms of behavioral lateralization are less investigated, it is unclear as to how far different functions display similar heritability. But deeper knowledge is necessary to understand if and how developmental coupling of different functions is based on a shared genetic background or on the impact of environmental influences. Here, we investigated the heritability of language lateralization assessed with the dichotic listening task, as well as the heritability of cognitive control processes modulating performance in this task. Overall, 103 families consisting of both parents and offspring were tested with the non-forced, as well as the forced-right and forced-left condition of the forced attention dichotic listening task, implemented in the iDichotic smartphone app, developed at the University of Bergen, Norway. The results indicate that the typical right ear advantage in the dichotic listening task shows weak and non-significant heritability (h2=0.003; p=0.98). In contrast, cognitive factors, like attention focus (forced right condition: h2=0.36; p<0.01; forced left condition: h2=0.28; p<0.05) and cognitive control (Gain forced right: h2=0.39; p<0.01; Gain forced left: h2=0.49; p<0.01) showed stronger and significant heritability. These findings indicate a variable dependence of different aspects of a cognitive function on heritability and implicate a major contribution of non-genetic influences to individual language lateralization.

The neural correlates of sex differences in left-right confusion.

Difficulties in left-right discrimination (LRD) are commonly experienced in everyday life situations. Here we investigate the neurocognitive mechanisms of LRD and the specific role of left angular gyrus. Given that previous behavioral research reported women to be more susceptible to left-right confusion, the current study focuses particularly on the neural basis of sex differences in LRD while controlling for potential menstrual cycle effects (repeated measures design). 16 women and 15 men were presented pictures of pointing hands in various orientations (rotated versus non-rotated) and were asked to identify them as left or right hands. Results revealed that LRD was particularly associated with activation in inferior parietal regions, extending into the right angular gyrus. Irrespective of menstrual cycle phase, women, relative to men, recruited more prefrontal areas, suggesting higher top-down control in LRD. For the subset of rotated stimuli as compared to the non-rotated, we found leftward asymmetry for both men and women, although women scored significantly lower. We conclude that there are sex differences in the neurocognitive mechanisms underlying LRD. Although the angular gyrus is involved in LRD, several other parietal areas are at least as critical. Moreover, the hypothesis that more left-right confusion is due to more bilateral activation (in women) can be rejected.

Electrophysiological correlates of adult age differences in attentional control of auditory processing.

In addition to sensory decline, age-related losses in auditory perception also reflect impairments in attentional modulation of perceptual saliency. Using an attention and intensity-modulated dichotic listening paradigm, we investigated electrophysiological correlates of processing conflicts between attentional focus and perceptual saliency in 25 younger and 26 older adults. Participants were instructed to attend to the right or left ear, and perceptual saliency was manipulated by varying the intensities of both ears. Attentional control demand was higher in conditions when attentional focus and perceptual saliency favored opposing ears than in conditions without such conflicts. Relative to younger adults, older adults modulated their attention less flexibly and were more influenced by perceptual saliency. Our results show, for the first time, that in younger adults a late negativity in the event-related potential (ERP) at fronto-central and parietal electrodes was sensitive to perceptual-attentional conflicts during auditory processing (N450 modulation effect). Crucially, the magnitude of the N450 modulation effect correlated positively with task performance. In line with lower attentional flexibility, the ERP waveforms of older adults showed absence of the late negativity and the modulation effect. This suggests that aging compromises the activation of the fronto-parietal attentional network when processing the competing and conflicting auditory information.

Resting-state glutamate level in the anterior cingulate predicts blood-oxygen level-dependent response to cognitive control.

The dorsal anterior cingulate cortex (dACC) is a core structure for the governing of cognitive control, and recent studies have shown that interindividual differences in dACC anatomy are associated with corresponding differences in the ability for cognitive control. However, individuals differ not only in anatomical features of dACC, but also exhibit substantial variability regarding the biochemical characteristics of the dACC. In this study, we combined magnetic resonance spectroscopy ((1)H-MRS) and functional magnetic resonance imaging (fMRI), finding that interindividual differences of glutamate levels in the dACC during resting-state predict the strength of the blood-oxygen level-dependent (BOLD) response to a task requiring cognitive control. This relationship was observed in the retrosplenial cortex, the orbitofrontal cortex, the inferior parietal lobe, and the basal ganglia. More specifically, individuals with low resting-state glutamate levels in the dACC showed an increased BOLD response when the task demands were high, whereas high-glutamate individuals showed the opposite pattern of an increased BOLD response when the task demands were low. Thus, we show here that individual variability of glutamate levels is directly related to how the brain implements cognitive control.

Laterality across languages: Results from a global dichotic listening study using a smartphone application.

Left-hemispheric language dominance has been suggested by observations in patients with brain damages as early as the 19th century, and has since been confirmed by modern behavioural and brain imaging techniques. Nevertheless, most of these studies have been conducted in small samples with predominantly Anglo-American background, thus limiting generalization and possible differences between cultural and linguistic backgrounds may be obscured. To overcome this limitation, we conducted a global dichotic listening experiment using a smartphone application for remote data collection. The results from over 4,000 participants with more than 60 different language backgrounds showed that left-hemispheric language dominance is indeed a general phenomenon. However, the degree of lateralization appears to be modulated by linguistic background. These results suggest that more emphasis should be placed on cultural/linguistic specificities of psychological phenomena and on the need to collect more diverse samples.