Olumide A. Olulade, View ORCID Profile, Anna Seydell-Greenwald, Catherine E. Chambers, Peter E. Turkeltaub, Alexander W. Dromerick, View ORCID Profile, Madison M. Berl, William D. Gaillard, and Elissa L. Newport
PNAS first published September 8, 2020
- Contributed by Elissa L. Newport, July 17, 2020 (sent for review April 8, 2019; reviewed by Rachel I. Mayberry and Nicholas B. Turk-Browne)
Two types of evidence suggest different pictures of how language is represented in the brain during development. Studies of the anatomy, physiology, and fMRI activation of the two hemispheres show that language is lateralized to the left hemisphere from birth. In contrast, damage to the left versus right hemisphere in young children is equally likely to result in language impairment, suggesting that language is bilaterally represented in early development. The present study resolves this paradox by examining fMRI language activation in different ways. While group averages show LH lateralization throughout development, young children show RH language activation that declines systematically with age. Most important, this RH activation in children represents a possible mechanism for explaining language recovery following early stroke.
We have long known that language is lateralized to the left hemisphere (LH) in most neurologically healthy adults. In contrast, findings on lateralization of function during development are more complex. As in adults, anatomical, electrophysiological, and neuroimaging studies in infants and children indicate LH lateralization for language. However, in very young children, lesions to either hemisphere are equally likely to result in language deficits, suggesting that language is distributed symmetrically early in life. We address this apparent contradiction by examining patterns of functional MRI (fMRI) language activation in children (ages 4 through 13) and adults (ages 18 through 29). In contrast to previous studies, we focus not on lateralization per se but rather on patterns of left-hemisphere (LH) and right-hemisphere (RH) activation across individual participants over age. Our analyses show significant activation not only in the LH language network but also in their RH homologs in all of the youngest children (ages 4 through 6). The proportion of participants showing significant RH activation decreases over age, with over 60% of adults lacking any significant RH activation. A whole-brain correlation analysis revealed an age-related decrease in language activation only in the RH homolog of Broca’s area. This correlation was independent of task difficulty. We conclude that, while language is left-lateralized throughout life, the RH contribution to language processing is also strong early in life and decreases through childhood. Importantly, this early RH language activation may represent a developmental mechanism for recovery following early LH injury.
Based on examinations of adults with acquired brain injury, language has long been hypothesized to be lateralized to left-hemisphere (LH) inferior frontal and superior temporal areas in adults (1, 2). This notion of LH language dominance has subsequently received ample support from examinations of brain structure revealing asymmetries in the size of temporal and inferior frontal brain areas (3⇓⇓⇓–7), behavioral studies demonstrating a right ear and right visual field (thus LH) advantage for processing of language stimuli (8, 9), studies showing language impairments induced by experimental disruption of the left hemisphere (10⇓⇓–13), and electrophysiological stimulation and functional neuroimaging studies revealing left-lateralized activation during language tasks (14⇓⇓⇓⇓⇓–20). While handedness modulates language dominance to some degree (21⇓–23), it is clear that language function (especially the production and processing of syntax) is left hemisphere-dominant in the vast majority of adults.
What is less clear is whether this strong left dominance is present at birth or appears gradually during development. Here the existing bodies of evidence, each extensive, suggest apparently inconsistent findings. On one hand, clinical findings suggest that the LH and right hemisphere (RH) are equipotential and equally involved in language early in life, with gradually increasing involvement of the left hemisphere through childhood (24, 25). This generalization was initially based on observations from clinical studies of 102 individuals with early unilateral brain injuries, some of whom underwent subsequent hemispherectomies (24). As summarized by Lenneberg (25), in children whose lesions occurred prior to the onset of speech (18 to 24 mo), left- and right-hemisphere injury equally resulted in delayed or absent language development (47% of children for LH and 51% for RH). Hemispherectomy performed before age 13 resulted in permanent aphasia only for a small percentage of patients regardless of hemisphere (6% for LH and 12% for RH patients), whereas hemispherectomy in adults resulted in permanent aphasia for all LH patients and not a single RH patient. These and subsequent clinical observations (26) suggest that the adult lateralization pattern is not yet established in young children and that both hemispheres participate equally in language during early development.
On the other hand, anatomical and functional evidence in healthy children suggests that left dominance is present even in infants and neonates. For example, the above-mentioned anatomical asymmetries have been observed in infant brains as well (4, 27, 28), and language-evoked brain activation measured using electroencephalography (EEG) evoked potentials, near-infrared spectroscopy (NIRS), and functional MRI (fMRI) is left-lateralized early in life (15, 29⇓⇓⇓⇓⇓⇓⇓⇓–38). While some studies have found that language is somewhat less lateralized in children and that left lateralization increases from childhood to adulthood (31⇓–33, 35), others have found no differences in lateralization between children and adults (34, 39) and, among those who did, there is disagreement about whether the increase in left lateralization is driven by a decrease of RH activation or an increase of LH activation. Either way, the common finding of left lateralization of language early in life is seemingly at odds with the clinical observation that early damage to either hemisphere is equally likely to result in language deficits.
This apparent conflict may at least partly be caused by the way laterality data from functional imaging studies are traditionally analyzed. The vast majority of studies to date have investigated language lateralization using a laterality index (LI) comparing LH and RH activation. While the precise method for quantifying LH and RH activation and computing the LI differs across studies (40, 41), the LI in general compares the difference between LH and RH activation with the total activation. LIs near 0 indicate bilateral and equal activation in the two hemispheres, whereas positive LIs indicate left lateralization. This measure allows quantification of lateralization regardless of absolute activation levels, which may be influenced by age or other factors that may differ over age, such as stimulus complexity, effort, and task difficulty (17, 42⇓⇓–45). However, because the LI is a difference score, potentially important information may be lost. An increase in LI with age could reflect a decrease of RH activation, an increase of LH activation, or both; the extent to which the LH and the RH are each involved in language processing is not directly reflected in LI scores. Activation maps presented along with LI data usually show group data, averaged across participants. Lower RH activation in these group maps does not necessarily reflect lower RH activation in individual participants; it could simply indicate that RH activation is not as consistent across individuals as LH activation.
For these reasons, the present fMRI study focuses on activation patterns in each hemisphere rather than on lateralization per se, and on analyses of individual activation maps rather than group averages, through childhood to young adults. Doing this requires a task that activates the brain strongly and reliably enough to compute activation maps for individuals and also requires that task difficulty be kept fairly stable over age.
We examined brain activation in 39 children (ages in years;months from 4;6 through 13;0) and 14 adults (ages 18;5 through 29;2) during a well-studied and highly reliable language-comprehension task called the Auditory Description Decision Task (ADDT) (37, 46). All participants were right-handed, neurologically healthy native speakers of English and had IQs in the normal or above-normal range. During forward-speech blocks, participants heard sentences defining a noun and pushed a button if the sentence was correct (e.g., “a big gray animal is an elephant”). During the reverse-speech control condition, participants heard the same audio files played backward and pushed a button if they heard a beep at the end of the file. To equate task difficulty across ages, all target words were selected from the 5,000 most common words in print; within this range, the word frequency of the target nouns was varied across the three child age groups, based on norms from age-appropriate reading materials [targets were chosen from the 2,500 most frequent words for the youngest age group, from the 3,500 most frequent words for the middle age group, and from the 5,000 most frequent words for the oldest group (47)], while leaving the syntactic frame of the sentences the same. Response accuracy was high and did not differ significantly between the child age groups (Table 1), suggesting that this manipulation matched task difficulty fairly well. Adults received the same stimuli as the oldest children.
Several analyses contrasting the fMRI response to forward vs. reverse speech were performed. For comparability with other studies, we first did a random-effects group analysis to generate and compare language activation maps for our four age groups: young (4;6 through 6;8, n = 10), middle (7;4 through 9;10, n = 14), and oldest (10;0 through 13;0, n = 15) children and adults (18;5 through 29;2, n = 14). We then turned to individual activation maps in order to determine significant activation for each individual participant in LH language areas and their RH homologs. To examine the consistency of these activation patterns across individuals in each group, we generated penetrance maps showing the percentage of subjects in each group who showed significant activation in each brain voxel and determined the percentage of subjects with significant activation in anatomically defined regions of interest (ROIs) in left and right inferior frontal and superior temporal cortex. Finally, we performed a whole-brain analysis across all participants to identify brain areas in which language activation was correlated with age. While the first of these analyses is frequently performed on imaging data, the other analyses are less common and are designed to illuminate the patterns of activation that appear in substantial numbers of children and that may change systematically over age but may not appear in a traditional mean activation analysis.