Brain Functional Organization Associated With Language Lateralization.

Although it is well-established that human language functions are mostly lateralized to the left hemisphere of the brain, little is known about the functional mechanisms underlying such hemispheric dominance. The present study investigated intrinsic organization of the whole brain at rest, by means of functional connectivity and graph theoretical analysis, with the aim to characterize brain functional organization underlying typical and atypical language dominance. We included healthy left-handers, both those with typical left-lateralized language and those with atypical right-lateralized language. Results show that 1) differences between typical and atypical language lateralization are associated with functional connectivity within the language system, particularly with weakened connectivity between left inferior frontal gyrus and several other language-related areas; and 2) for participants with atypical language dominance, the degree of lateralization is linked with multiple functional connectivities and graph theoretical metrics of whole brain organization, including local efficiency and small-worldness. This is the first study, to our knowledge, that linked the degree of language lateralization to global topology of brain networks. These results reveal that typical and atypical language dominance mainly differ in functional connectivity within the language system, and that atypical language dominance is associated with whole-brain organization.

On the other hand: including left-handers in cognitive neuroscience and neurogenetics.

Left-handers are often excluded from study cohorts in neuroscience and neurogenetics in order to reduce variance in the data. However, recent investigations have shown that the inclusion or targeted recruitment of left-handers can be informative in studies on a range of topics, such as cerebral lateralization and the genetic underpinning of asymmetrical brain development. Left-handed individuals represent a substantial portion of the human population and therefore left-handedness falls within the normal range of human diversity; thus, it is important to account for this variation in our understanding of brain functioning. We call for neuroscientists and neurogeneticists to recognize the potential of studying this often-discarded group of research subjects.

New human-specific brain landmark: the depth asymmetry of superior temporal sulcus.

Identifying potentially unique features of the human cerebral cortex is a first step to understanding how evolution has shaped the brain in our species. By analyzing MR images obtained from 177 humans and 73 chimpanzees, we observed a human-specific asymmetry in the superior temporal sulcus at the heart of the communication regions and which we have named the "superior temporal asymmetrical pit" (STAP). This 45-mm-long segment ventral to Heschl's gyrus is deeper in the right hemisphere than in the left in 95% of typical human subjects, from infanthood till adulthood, and is present, irrespective of handedness, language lateralization, and sex although it is greater in males than in females. The STAP also is seen in several groups of atypical subjects including persons with situs inversus, autistic spectrum disorder, Turner syndrome, and corpus callosum agenesis. It is explained in part by the larger number of sulcal interruptions in the left than in the right hemisphere. Its early presence in the infants of this study as well as in fetuses and premature infants suggests a strong genetic influence. Because this asymmetry is barely visible in chimpanzees, we recommend the STAP region during midgestation as an important phenotype to investigate asymmetrical variations of gene expression among the primate lineage. This genetic target may provide important insights regarding the evolution of the crucial cognitive abilities sustained by this sulcus in our species, namely communication and social cognition.

Complementary hemispheric specialization for language production and visuospatial attention.

Language production and spatial attention are the most salient lateralized cerebral functions, and their complementary specialization has been observed in the majority of the population. To investigate whether the complementary specialization has a causal origin (the lateralization of one function causes the opposite lateralization of the other) or rather is a statistical phenomenon (different functions lateralize independently), we determined the lateralization for spatial attention in a group of individuals with known atypical right hemispheric (RH) lateralization for speech production, based on a previous large-scale screening of left-handers. We show that all 13 participants with RH language dominance have left-hemispheric dominance for spatial attention, and all but one of 16 participants with left-hemispheric language dominance are RH dominant for spatial attention. Activity was observed in the dorsal fronto-parietal pathway of attention, including the inferior parietal sulcus and superior parietal lobule, the frontal eye-movement field, and the inferior frontal sulcus/gyrus, and these regions functionally colateralized in the hemisphere dominant for attention, independently of the side of lateralization. Our results clearly support the Causal hypothesis about the complementary specialization, and we speculate that it derives from a longstanding evolutionary origin. We also suggest that the conclusions about lateralization based on an unselected sample of the population and laterality assessment using coarse functional transcranial Doppler sonography should be interpreted with more caution.

Combining user logging with eye tracking for interactive and dynamic applications.

User evaluations of interactive and dynamic applications face various challenges related to the active nature of these displays. For example, users can often zoom and pan on digital products, and these interactions cause changes in the extent and/or level of detail of the stimulus. Therefore, in eye tracking studies, when a user's gaze is at a particular screen position (gaze position) over a period of time, the information contained in this particular position may have changed. Such digital activities are commonplace in modern life, yet it has been difficult to automatically compare the changing information at the viewed position, especially across many participants. Existing solutions typically involve tedious and time-consuming manual work. In this article, we propose a methodology that can overcome this problem. By combining eye tracking with user logging (mouse and keyboard actions) with cartographic products, we are able to accurately reference screen coordinates to geographic coordinates. This referencing approach allows researchers to know which geographic object (location or attribute) corresponds to the gaze coordinates at all times. We tested the proposed approach through two case studies, and discuss the advantages and disadvantages of the applied methodology. Furthermore, the applicability of the proposed approach is discussed with respect to other fields of research that use eye tracking-namely, marketing, sports and movement sciences, and experimental psychology. From these case studies and discussions, we conclude that combining eye tracking and user-logging data is an essential step forward in efficiently studying user behavior with interactive and static stimuli in multiple research fields.

Interhemispheric communication influences reading behavior.

We can read words at an amazing speed, with the left hemisphere taking the burden of the processing in most readers (i.e., over 95% of right-handers and about 75% of left-handers). Yet, it is a long-standing question whether word reading in central vision is possible without information transfer between the left and right hemispheres (LH/RH). Here we show that such communication is required by comparing word naming latencies and eye movement data of people with LH language dominance and a unique sample of healthy RH dominant people. The results reveal that individuals with LH speech dominance name words faster when they are allowed to fixate at the word beginning, whereas RH dominants are faster for fixations toward the end. In text reading, the eyes of LH dominants land more to the left than the eyes of RH dominants, making more information directly available to the dominant hemisphere. We conclude that the traditional view of bilateral projections in central vision is incorrect. In contrast, interhemispheric communication is needed in central vision, and eye movements are adjusted to optimize information uptake. Our findings therefore call into question the explanation of macular sparing in hemianopia based on a bilaterally projecting fovea. In addition, these results are in line with the increase of white matter in the splenium of the corpus callosum when people learn to read.

A surface-based analysis of language lateralization and cortical asymmetry.

Among brain functions, language is one of the most lateralized. Cortical language areas are also some of the most asymmetrical in the brain. An open question is whether the asymmetry in function is linked to the asymmetry in anatomy. To address this question, we measured anatomical asymmetry in 34 participants shown with fMRI to have language dominance of the left hemisphere (LLD) and 21 participants shown to have atypical right hemisphere dominance (RLD). All participants were healthy and left-handed, and most (80%) were female. Gray matter (GM) volume asymmetry was measured using an automated surface-based technique in both ROIs and exploratory analyses. In the ROI analysis, a significant difference between LLD and RLD was found in the insula. No differences were found in planum temporale (PT), pars opercularis (POp), pars triangularis (PTr), or Heschl's gyrus (HG). The PT, POp, insula, and HG were all significantly left lateralized in both LLD and RLD participants. Both the positive and negative ROI findings replicate a previous study using manually labeled ROIs in a different cohort [Keller, S. S., Roberts, N., Garcia-Finana, M., Mohammadi, S., Ringelstein, E. B., Knecht, S., et al. Can the language-dominant hemisphere be predicted by brain anatomy? Journal of Cognitive Neuroscience, 23, 2013-2029, 2011]. The exploratory analysis was accomplished using a new surface-based registration that aligns cortical folding patterns across both subject and hemisphere. A small but significant cluster was found in the superior temporal gyrus that overlapped with the PT. A cluster was also found in the ventral occipitotemporal cortex corresponding to the visual word recognition area. The surface-based analysis also makes it possible to disentangle the effects of GM volume, thickness, and surface area while removing the effects of curvature. For both the ROI and exploratory analyses, the difference between LLD and RLD volume laterality was most strongly driven by differences in surface area and not cortical thickness. Overall, there were surprisingly few differences in GM volume asymmetry between LLD and RLD indicating that gross morphometric asymmetry is only subtly related to functional language laterality.

Blinking predicts enhanced cognitive control.

Recent models have suggested an important role for neuromodulation in explaining trial-to-trial adaptations in cognitive control. The adaptation-by-binding model (Verguts & Notebaert, Psychological review, 115(2), 518-525, 2008), for instance, suggests that increased cognitive control in response to conflict (e.g., incongruent flanker stimulus) is the result of stronger binding of stimulus, action, and context representations, mediated by neuromodulators like dopamine (DA) and/or norepinephrine (NE). We presented a flanker task and used the Gratton effect (smaller congruency effect following incongruent trials) as an index of cognitive control. We investigated the Gratton effect in relation to eye blinks (DA related) and pupil dilation (NE related). The results for pupil dilation were not unequivocal, but eye blinks clearly modulated the Gratton effect: The Gratton effect was enhanced after a blink trial, relative to after a no-blink trial, even when controlling for correlated variables. The latter suggests an important role for DA in cognitive control on a trial-to-trial basis.

Towards a unified understanding of lateralized vision: A large-scale study investigating principles governing patterns of lateralization using a heterogeneous sample.

While functional lateralization of the human brain has been a widely studied topic in the past decades, few studies to date have gone further than investigating lateralization of single, isolated processes. With the present study, we aimed to arrive at a more unified view by investigating lateralization patterns in face and word processing, and associated lower-level visual processing. We tested a large and heterogeneous participant group, and used a number of tasks that had been shown to produce replicable indices of lateralized processing of visual information of different types and complexity. Following Bayesian statistics, group-level analyses showed the expected right hemisphere (RH) lateralization for face, global form, low spatial frequency processing, and spatial attention, and left hemisphere (LH) lateralization for visual word and local feature processing. Compared to right-handed individuals, lateralization patterns of left-handed and especially those who are RH-dominant for language deviated from this 'typical' pattern. Our results support the notion that face and word processes come to be lateralized to homologue areas of the two hemispheres, under influence of the RH- and LH-specializations in global form, local feature, and low and high spatial frequency processing. As such, we present a more unified understanding of lateralized vision, providing evidence for the input asymmetry and causal complementarity principles of lateralized visual information processing. The absence of correlations between spatial attention and lateralization of the other processes supports the notion of their independent lateralization, conform the statistical complementarity principle.

Laterality for recognizing written words and faces in the fusiform gyrus covaries with language dominance.

Recognizing words and faces engages highly specialized sites within the middle fusiform gyrus, known as the visual word form area (VWFA) and fusiform face area (FFA) respectively. The VWFA and FFA have clear but opposite population-level asymmetries, with the VWFA typically being lateralized to the left and the FFA to the right hemisphere. The present study investigates how language dominance may relate to these asymmetries. We hypothesize that individuals with left hemisphere dominance for word production (i.e., left language dominance, LLD) will have typical lateralization for word and face recognition in the fusiform gyrus, whereas participants with right language dominance (RLD) will demonstrate 'atypical' rightward laterality for words and leftward dominance for faces. To test this hypothesis, we recruited twenty-seven left-handers who had previously been identified as being LLD or RLD based on a visual half field task. Using fMRI, hemisphere dominance was determined for language (Broca's region) as well as for word and face recognition in the middle fusiform gyrus for each participant. The direction of asymmetry correlated significantly between language and recognizing words (ρ = .648, p < .001) as well as between language and face recognition (ρ = -.620, p = .001). Moreover, most LLD-participants were typically lateralized for faces and written words, while both functions tended to be reversed in individuals with RLD. However, segregation between language and face recognition was less clear in participants with RLD, as many of them lacked an obvious asymmetry for faces. Although our results thus suggest there is no one-on-one relationship between asymmetries for language, written word and face recognition, they also argue against a complete independence of their lateralization.

Genome sequencing for rightward hemispheric language dominance.

Most people have left-hemisphere dominance for various aspects of language processing, but only roughly 1% of the adult population has atypically reversed, rightward hemispheric language dominance (RHLD). The genetic-developmental program that underlies leftward language laterality is unknown, as are the causes of atypical variation. We performed an exploratory whole-genome-sequencing study, with the hypothesis that strongly penetrant, rare genetic mutations might sometimes be involved in RHLD. This was by analogy with situs inversus of the visceral organs (left-right mirror reversal of the heart, lungs and so on), which is sometimes due to monogenic mutations. The genomes of 33 subjects with RHLD were sequenced and analyzed with reference to large population-genetic data sets, as well as 34 subjects (14 left-handed) with typical language laterality. The sample was powered to detect rare, highly penetrant, monogenic effects if they would be present in at least 10 of the 33 RHLD cases and no controls, but no individual genes had mutations in more than five RHLD cases while being un-mutated in controls. A hypothesis derived from invertebrate mechanisms of left-right axis formation led to the detection of an increased mutation load, in RHLD subjects, within genes involved with the actin cytoskeleton. The latter finding offers a first, tentative insight into molecular genetic influences on hemispheric language dominance.

Language lateralisation measured across linguistic and national boundaries.

The visual half-field technique has been shown to be a reliable and valid neuropsychological measurement of language lateralisation, typically showing higher accuracy and faster correct responses for linguistic stimuli presented in the right visual field (RVF) than left visual field (LVF). The RVF advantage corresponds to the well-known dominance of the left hemisphere (LH) in processing language(s). However, clinical and experimental neuroscientists around the globe use different variations of the visual half-field paradigm, making direct comparisons difficult. The current study used a word/non-word visual half-field paradigm with translingual stimuli. In total, 496 participants from seven European countries were investigated: Belgium (64), England (49), Germany (85), Italy (34), The Netherlands (87), Norway (51), and Switzerland (126), covering six international languages (Dutch, English, French, German, Italian, Norwegian). All language groups revealed a significant RVF/LH advantage in accuracy and reaction times that accounted for up to 26.1% of the total variance in performance. We found some variation in the degree of the RVF/LH advantage across language groups, accounting for a maximum of 3.7% of the total variance in performance. The RVF/LH advantage did not differ between subsamples speaking English, French or German as first or second languages or between monolingual and early/late bi/multilinguals. The findings suggest that the translingual lexical decision task (TLDT) is a simple but reliable measurement of language lateralisation that can be applied clinically and experimentally across linguistic and national boundaries.

The relationship between behavioral language laterality, face laterality and language performance in left-handers.

Left-handers provide unique information about the relationship between cognitive functions because of their larger variability in hemispheric dominance. This study presents the laterality distribution of, correlations between and test-retest reliability of behavioral lateralized language tasks (speech production, reading and speech perception), face recognition tasks, handedness measures and language performance tests based on data from 98 left-handers. The results show that a behavioral test battery leads to percentages of (a)typical dominance that are similar to those found in neuropsychological studies even though the incidence of clear atypical lateralization (about 20%) may be overestimated at the group level. Significant correlations were found between the language tasks for both reaction time and accuracy lateralization indices. The degree of language laterality could however not be linked to face laterality, handedness or language performance. Finally, individuals were classified less consistently than expected as being typical, bilateral or atypical across all tasks. This may be due to the often good (speech production and perception tasks) but sometimes weak (reading and face tasks) test-retest reliabilities. The lack of highly reliable and valid test protocols for functions unrelated to speech remains one of the largest impediments for individual analysis and cross-task investigations in laterality research.

Laterality and unilateral deafness: Patients with congenital right ear deafness do not develop atypical language dominance.

Auditory speech perception, speech production and reading lateralize to the left hemisphere in the majority of healthy right-handers. In this study, we investigated to what extent sensory input underlies the side of language dominance. We measured the lateralization of the three core subprocesses of language in patients who had profound hearing loss in the right ear from birth and in matched control subjects. They took part in a semantic decision listening task involving speech and sound stimuli (auditory perception), a word generation task (speech production) and a passive reading task (reading). The results show that a lack of sensory auditory input on the right side, which is strongly connected to the contralateral left hemisphere, does not lead to atypical lateralization of speech perception. Speech production and reading were also typically left lateralized in all but one patient, contradicting previous small scale studies. Other factors such as genetic constraints presumably overrule the role of sensory input in the development of (a)typical language lateralization.

What can atypical language hemispheric specialization tell us about cognitive functions?

Recent studies have made substantial progress in understanding the interactions between cognitive functions, from language to cognitive control, attention, and memory. However, dissociating these functions has been hampered by the close proximity of regions involved, as in the case in the prefrontal and parietal cortex. In this article, we review a series of studies that investigated the relationship between language and other cognitive functions in an alternative way - by examining their functional (co-)lateralization. We argue that research on the hemispheric lateralization of language and its link with handedness can offer an appropriate starting-point to shed light on the relationships between different functions. Besides functional interactions, anatomical asymmetries in non-human primates and those underlying language in humans can provide unique information about cortical organization. Finally, some open questions and criteria are raised for an ideal theoretical model of the cortex based on hemispheric specialization.

Speech dominance is a better predictor of functional brain asymmetry than handedness: a combined fMRI word generation and behavioral dichotic listening study.

An unresolved issue in behavioral studies of hemispheric asymmetry is why both left-handers and right-handers show a right ear advantage at the group level. In the present study we screened left-handers for left- versus right-hemisphere speech dominance with fMRI by comparing right versus left hemisphere frontal lobe activity (in Broca's area) in a silent word generation task. A left hemisphere dominant right-handed control group was included as well. All participants took part in a dichotic listening task with consonant-vowel syllables. The results showed that left-handers and right-handers with left-hemisphere speech dominance showed a right ear advantage. However, the left-handers with right hemisphere speech dominance had a left ear advantage. Thus, at the group level the direction of the ear advantage in dichotic listening was predicted by language dominance but not by hand preference. At the individual level, the dichotic task we used showed more variability than the fMRI results. Further research will have to indicate whether this is a feature inherent to dichotic listening, or whether the variability is due to alternative explanations such as a more bilateral representation of speech perception compared to speech production.

Symmetry detection in typically and atypically speech lateralized individuals: a visual half-field study.

Visuospatial functions are typically lateralized to the right cerebral hemisphere, giving rise to a left visual field advantage in visual half-field tasks. In a first study we investigated whether this is also true for symmetry detection off fixation. Twenty right-handed participants with left hemisphere speech dominance took part in a visual half-field experiment requiring them to judge the symmetry of 2-dimensional figures made by joining rectangles in symmetrical or asymmetrical ways. As expected, a significant left visual field advantage was observed for the symmetrical figures. In a second study, we replicated the study with 37 left-handed participants and left hemisphere speech dominance. We again found a left visual field advantage. Finally, in a third study, we included 17 participants with known right hemisphere dominance for speech (speech dominance had been identified with fMRI in an earlier study; Van der Haegen, Cai, Seurinck, & Brysbaert, 2011). Around half of these individuals showed a reversed pattern, i.e. a right visual half-field advantage for symmetric figures while the other half replicated the left visual-field advantage. These findings suggest that symmetry detection is indeed a cognitive function lateralized to the right hemisphere for the majority of the population. The data of the participants with atypical speech dominance are more in line with the idea that language and visuospatial functions are lateralized in opposite brain hemispheres than with the idea that different functions lateralize independently, although there seems to be more variability in this group.

Praxis and language are linked: evidence from co-lateralization in individuals with atypical language dominance.

We determined the neural correlates of word generation and tool use pantomiming in healthy subjects with typical (n=10) or atypical (n=10) language dominance to investigate similarities in response pattern and hemispheric specialization between language and praxis. All typical language dominant volunteers also revealed left hemisphere changes during tool use pantomiming in prefrontal, premotor, and posterior parietal regions. All atypical language dominant participants displayed right hemisphere engagement for tool use. Co-lateralization of the language and praxis networks was observed on group and individual level, regardless of the participant's handedness. Activation maps of the word generation and tool use pantomiming contrasts displayed overlap in five cortical regions: supplementary motor area, dorsal and ventral premotor cortex, dorsolateral prefrontal cortex, and posterior parietal cortex. Individual lateralization indices were calculated for each region and revealed significant positive group correlations between .51 and .95 with every other region within the paradigms. Positive cross-task correlations ranged between .72 (supplementary motor complex) and .97 (dorsal premotor cortex) and illustrate that the strength of hemispheric specialization of one task significantly predicts the side and degree of lateralization of the other task, suggesting a functional and topographic link between language and praxis. These findings support models that link gestures and speech to explain the evolution of human language. We argue that the existence of a common and co-lateralized network underlying the production of complex learned movement, whether it be speech or tool use, may represent the evolutionary remnant of a neural system out of which proto-sign and proto-speech co-evolved.

Colateralization of Broca's area and the visual word form area in left-handers: fMRI evidence.

Language production has been found to be lateralized in the left hemisphere (LH) for 95% of right-handed people and about 75% of left-handers. The prevalence of atypical right hemispheric (RH) or bilateral lateralization for reading and colateralization of production with word reading laterality has never been tested in a large sample. In this study, we scanned 57 left-handers who had previously been identified as being clearly left (N=30), bilateral (N=7) or clearly right (N=20) dominant for speech on the basis of fMRI activity in the inferior frontal gyrus (pars opercularis/pars triangularis) during a silent word generation task. They were asked to perform a lexical decision task, in which words were contrasted against checkerboards, to test the lateralization of reading in the ventral occipitotemporal region. Lateralization indices for both tasks correlated significantly (r=0.59). The majority of subjects showed most activity during lexical decision in the hemisphere that was identified as their word production dominant hemisphere. However, more than half of the sample (N=31) had bilateral activity for the lexical decision task without a clear dominant role for either the LH or RH, and three showed a crossed frontotemporal lateralization pattern. These findings have consequences for neurobiological models relating phonological and orthographic processes, and for lateralization measurements for clinical purposes.

The mechanisms underlying the interhemispheric integration of information in foveal word recognition: evidence for transcortical inhibition.

Words are processed as units. This is not as evident as it seems, given the division of the human cerebral cortex in two hemispheres and the partial decussation of the optic tract. In two experiments, we investigated what underlies the unity of foveally presented words: A bilateral projection of visual input in foveal vision, or interhemispheric inhibition and integration as proposed by the SERIOL model of visual word recognition. Experiment 1 made use of pairs of words and nonwords with a length of four letters each. Participants had to name the word and ignore the nonword. The visual field in which the word was presented and the distance between the word and the nonword were manipulated. The results showed that the typical right visual field advantage was observed only when the word and the nonword were clearly separated. When the distance between them became smaller, the right visual field advantage turned into a left visual field advantage, in line with the interhemispheric inhibition mechanism postulated by the SERIOL model. Experiment 2, using 5-letters stimuli, confirmed that this result was not due to the eccentricity of the word relative to the fixation location but to the distance between the word and the nonword.