A comparison of hemispheric asymmetries in speech-related brain potentials of autistic and dysphasic children

In a previous study (G. Dawson, C. Finley, S. Phillips, & L. Galpert, 1986, Child Development, 57, 1440-1453) it was found that measures of hemispheric asymmetry during speech processing were predictive of level of language ability in autistic children. The purpose of the present study was to determine whether a similar relationship between pattern of hemispheric asymmetry and language ability exists for language-impaired children without autism. Ten autistic children (8-13 years), 10 dysphasic children (6-15 years), and 10 normal children (8-13 years) were compared in terms of their patterns of hemispheric asymmetry in the averaged cortical evoked response to a simple speech stimulus, and the relationship between pattern of hemispheric asymmetry and language ability was assessed for each clinical group. It was found that, for both the autistic and dysphasic groups, the majority of subjects showed a reversed direction of hemispheric asymmetry from that characteristic of the normal group. A strong relationship between pattern of asymmetry and level of language ability was found for autistic subjects; autistic subjects with more severe language impairments were more likely to show reversed asymmetry than subjects with less severe language impairments. In contrast, no relationship between language ability and direction of hemispheric asymmetry in the evoked response was found for dysphasic subjects. Separate analyses of right and left hemisphere evoked responses indicated that language ability was related to right hemisphere activity for autistic subjects, and to left hemisphere activity for dysphasic subjects.     

Hemodynamic and electrophysiological connectivity in the language system: Simultaneous near-infrared spectroscopy and electrocorticography recordings during cortical stimulation

We applied near-infrared spectroscopy (NIRS) and electrocorticography (ECoG) recordings during cortical stimulation to a temporal lobe epilepsy patient who underwent subdural electrode implantation. Using NIRS, changes in blood concentrations of oxyhemoglobin (HbO(2)) and deoxyhemoglobin (HbR) during cortical stimulation of the left language areas were measured in each hemisphere. NIRS revealed that 2Hz stimulation with 5mA produced no significant hemodynamic changes in either hemisphere. By contrast, 50Hz stimulation elicited significant increases in both HbO(2) and HbR at the stimulation site. Furthermore, with 50Hz stimulation of the left superior temporal gyrus, the increases in HbO(2) and HbR were observed not only at the stimulation site but also concurrently at the left inferior frontal gyrus. This suggests the existence of functional connectivity in the language system. The present study demonstrates that simultaneous NIRS and ECoG studies during cortical stimulation allow a novel analysis of cerebral connectivity.     

The specialized structure of human language cortex: pyramidal cell size asymmetries within auditory and language-associated regions of the temporal lobes

Functional lateralization of language within the cerebral cortex has long driven the search for structural asymmetries that might underlie language asymmetries. Most examinations of structural asymmetry have focused upon the gross size and shape of cortical regions in and around language areas. In the last 20 years several labs have begun to document microanatomical asymmetries in the structure of language-associated cortical regions. Such microanatomic results provide useful constraints and clues to our understanding of the biological bases of language specialization in the cortex. In a previous study we documented asymmetries in the size of a specific class of pyramidal cells in the superficial cortical layers. The present work uses a nonspecific stain for cell bodies to demonstrate the presence of an asymmetry in layer III pyramidal cell sizes within auditory, secondary auditory and language-associated regions of the temporal lobes. Specifically, the left hemisphere contains a greater number of the largest pyramidal cells, those that are thought to be the origin of long-range cortico-cortical connections. These results are discussed in the context of cortical columns and how such an asymmetry might alter cortical processing. These findings, in conjunction with other asymmetries in cortical organization that have been documented within several labs, clearly demonstrate that the columnar and connective structure of auditory and language cortex in the left hemisphere is distinct from homotopic regions in the contralateral hemisphere.     

Mechanisms of aphasia recovery after stroke and the role of noninvasive brain stimulation

One of the most frequent symptoms of unilateral stroke is aphasia, the impairment or loss of language functions. Over the past few years, behavioral and neuroimaging studies have shown that rehabilitation interventions can promote neuroplastic changes in aphasic patients that may be associated with the improvement of language functions. Following left hemisphere strokes, the functional reorganization of language in aphasic patients has been proposed to involve both intrahemispheric interactions between damaged left hemisphere and perilesional sites and transcallosal interhemispheric interactions between the lesioned left hemisphere language areas and homotopic regions in the right hemisphere. A growing body of evidence for such reorganization comes from studies using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), two safe and noninvasive procedures that can be applied clinically to modulate cortical excitability during post-stroke language recovery. We discuss a hierarchical model for the plastic changes in language representation that occur in the setting of dominant hemisphere stroke and aphasia. We further argue that TMS and tDCS are potentially promising tools for enhancing functional recovery of language and for further elucidating mechanisms of plasticity in patients with aphasia.     

3D mapping of language networks in clinical and pre-clinical Alzheimer's disease

We investigated the associations between Boston naming and the animal fluency tests and cortical atrophy in 19 probable AD and 5 multiple domain amnestic mild cognitive impairment patients who later converted to AD. We applied a surface-based computational anatomy technique to MRI scans of the brain and then used linear regression models to detect associations between animal fluency and Boston Naming Test (BNT) performance and cortical atrophy. The global permutation-corrected significance for the maps associating BNT performance with cortical atrophy was p=.0124 for the left and p=.0196 for the right hemisphere and for the animal fluency maps p=.055 for the left and p=.073 for the right hemisphere. The degree of language impairment correlated with cortical atrophy in the left temporal and parietal lobes (BA 20, 21, 37, 39, 40, and 7), bilateral frontal lobes (BA 8, 9, and 44) and the right temporal pole (BA 38). Using a novel 3D mapping technique, we demonstrated that in AD language abilities are strongly influenced by the integrity of the perisylvian cortical regions.     

Parietal versus temporal lobe components in spatial cognition: Setting the mid‐point of a horizontal line

Recent anatomo‐clinical correlation studies have extended to the superior temporal gyrus, the right hemisphere lesion sites associated with the left unilateral spatial neglect, in addition to the traditional posterior‐inferior‐parietal localization of the responsible lesion (supramarginal gyrus, at the temporo‐parietal junction). The study aimed at teasing apart, by means of repetitive transcranial magnetic stimulation (rTMS), the contribution of the inferior parietal lobule (angular gyrus versus supramarginal gyrus) and of the superior temporal gyrus of the right hemisphere, in making judgments about the mid‐point of a horizontal line, a widely used task for detecting and investigating spatial neglect. rTMS trains at 25 Hz frequency were delivered over the inferior parietal lobule (angular gyrus and supramarginal gyrus), the superior temporal gyrus and the anterior parietal lobe of the right hemisphere, in 10 neurologically unimpaired participants, performing a line bisection judgment task. rTMS of the inferior parietal lobule at the level of the supramarginal gyrus brought about a rightward error in the bisection judgment, ipsilateral to the side of the rTMS, with stimulation over the other sites being ineffective. The neural correlates of computing the mid‐point of a horizontal segment include the right supramarginal gyrus in the inferior parietal lobule and do not extend to the angular gyrus and the superior temporal gyrus. These rTMS data in unimpaired subjects constrain the evidence from lesion studies in brain‐damaged patients, emphasizing the major role of a subset of relevant regions.     

Can small lesions induce language reorganization as large lesions do?

Shift of the cortical mechanisms of language from the usually dominant left to the non-dominant right hemisphere has been demonstrated in the presence of large brain lesions. Here, we report a similar phenomenon in a patient with a cavernoma over the anterolateral superior temporal gyrus associated with epilepsy. Language mapping was performed by two complementary procedures, magnetoencephalography, and electrocorticography. The maps, indicated right temporal lobe dominance for receptive language and left frontal lobe dominance for expressive language. These results indicate that a small lesion, associated with epilepsy, may produce selective shifting of receptive language mechanisms as large lesions have been known to produce.     

Cerebral organization of oral and signed language responses: case study evidence from amytal and cortical stimulation studies

A normally hearing left-handed patient familiar with American Sign Language (ASL) was assessed under sodium amytal conditions and with left cortical stimulation in both oral speech and signed English. Lateralization was mixed but complementary in each language mode: the right hemisphere perfusion severely disrupted motoric aspects of both types of language expression, the left hemisphere perfusion specifically disrupted features of grammatical and semantic usage in each mode of expression. Both semantic and syntactic aspects of oral and signed responses were altered during left posterior temporal-parietal stimulation. Findings are discussed in terms of the neurological organization of ASL and linguistic organization in cases of early left hemisphere damage.     

Memory deficits during electrical stimulation of the speech cortex in conscious man

Cerebral zones supporting language and recent memory were mapped by electrical stimulation during neurosurgical treatment of epileptic patients. Stimulation of sites within the left posterior temporo-parietal cortex produced transient dysphasia. Continued stimulation of this cortical region also produced a retrograde type of verbal memory disorder, indicating a failure in the mechanism responsible for retrieval of stored information. In contrast, stimulation of the anterior temporal neocortex did not produce anomia and, instead, resulted in an anterograde memory loss, apparently caused by a defect in the verbal storage mechanism. Comparable stimulation of homologous areas on the right hemisphere did not interfere with object naming or immediate verbal recall.     

Event-related brain potentials differentiate normal and disabled readers

Auditory event-related potentials (AERPs) recorded to irrelevant tone pairs while subjects performed visual, reading-related cognitive tasks differed significantly between normal and disabled readers. Disabled readers as compared with normal readers showed significantly lower amplitude right hemisphere AERP responses during tasks that involved visual-phonemic transfer of information and simple pattern recognition. Disabled readers as compared with normal readers also showed significantly higher amplitude left hemisphere responses during the visual-phonemic task. In both experimental conditions the reading-disabled subjects showed significantly lower amplitude right than left hemisphere AERP responses. Task-related strategies did not differ between groups. The pattern of AERP amplitude asymmetry found for disabled readers, which was opposite to that found for normal readers, suggests that the same reading-related tasks activated different cerebral processes in the two groups studied.     

Hemispheric Asymmetry in Transient Visual Evoked Potentials Induced by the Spatial Factor of the Stimulation

In order to enhance the effect of spatial frequency on the hemispheric asymmetry of visual evoked potentials (VEP), the response amplitudes to ON-OFF modulated gratings were compared with the responses to pattern reversal stimulation. Sinusoidal gratings of different spatial frequencies were presented to six righthanders. VEPs were recorded from temporal leads on each hemisphere. In the left hemisphere, the amplitude was constant for the two modes of presentation and independent of spatial frequency. In the right hemisphere, the response amplitude was larger to the ONSET stage of ON-OFF stimulation than to reversal and presented the characteristic spatial frequency tuning curve. This asymmetry is assumed to reflect a difference in sensitivity of the two hemispheres to the spatiotemporal characteristics of the stimulus. The relevance of these findings is discussed in relation to the other hemispheric specialization models.     

Language function and dysfunction among Chinese- and English-speaking polyglots: Cortical stimulation, Wada Testing, and clinical studies

Language functions in a group of Chinese- and English-speaking polyglots living in a multiracial society have been investigated by several methods: the effects of cortical stimulation on object-naming and reading tasks in patients who required awake craniotomy, lateralization of cerebral dominance for speech by the Wada Test, and the pattern of language loss and recovery following stroke. The data indicate that these polyglots were all left hemisphere dominant for the languages tested: no consistent evidence for increased participation by the right hemisphere for language functions was found. The cortical stimulation experiments provided data most compatible with the "differential localization" model of cerebral localization in bilingualism. The variable which most influenced performance in all of these investigations was which language was used primarily for speaking as well as reading and writing at the time of the study.     

Lesion analysis of the brain areas involved in language comprehension

The cortical regions of the brain traditionally associated with the comprehension of language are Wernicke's area and Broca's area. However, recent evidence suggests that other brain regions might also be involved in this complex process. This paper describes the opportunity to evaluate a large number of brain-injured patients to determine which lesioned brain areas might affect language comprehension. Sixty-four chronic left hemisphere stroke patients were evaluated on 11 subtests of the Curtiss-Yamada Comprehensive Language Evaluation - Receptive (CYCLE-R; Curtiss, S., & Yamada, J. (1988). Curtiss-Yamada Comprehensive Language Evaluation. Unpublished test, UCLA). Eight right hemisphere stroke patients and 15 neurologically normal older controls also participated. Patients were required to select a single line drawing from an array of three or four choices that best depicted the content of an auditorily-presented sentence. Patients' lesions obtained from structural neuroimaging were reconstructed onto templates and entered into a voxel-based lesion-symptom mapping (VLSM; Bates, E., Wilson, S., Saygin, A. P., Dick, F., Sereno, M., Knight, R. T., & Dronkers, N. F. (2003). Voxel-based lesion-symptom mapping. Nature Neuroscience, 6(5), 448-450.) analysis along with the behavioral data. VLSM is a brain-behavior mapping technique that evaluates the relationships between areas of injury and behavioral performance in all patients on a voxel-by-voxel basis, similar to the analysis of functional neuroimaging data. Results indicated that lesions to five left hemisphere brain regions affected performance on the CYCLE-R, including the posterior middle temporal gyrus and underlying white matter, the anterior superior temporal gyrus, the superior temporal sulcus and angular gyrus, mid-frontal cortex in Brodmann's area 46, and Brodmann's area 47 of the inferior frontal gyrus. Lesions to Broca's and Wernicke's areas were not found to significantly alter language comprehension on this particular measure. Further analysis suggested that the middle temporal gyrus may be more important for comprehension at the word level, while the other regions may play a greater role at the level of the sentence. These results are consistent with those seen in recent functional neuroimaging studies and offer complementary data in the effort to understand the brain areas underlying language comprehension.     

Cerebral specialization for speech production in persons with Down syndrome.

The study of cerebral specialization in persons with Down syndrome (DS) has revealed an anomalous pattern of organization. Specifically, dichotic listening studies (e.g., Elliott & Weeks, 1993) have suggested a left ear/right hemisphere dominance for speech perception for persons with DS. In the current investigation, the cerebral dominance for speech production was examined using the mouth asymmetry technique. In right-handed, nonhandicapped subjects, mouth asymmetry methodology has shown that during speech, the right side of the mouth opens sooner and to a larger degree then the left side (Graves, Goodglass, & Landis, 1982). The phenomenon of right mouth asymmetry (RMA) is believed to reflect the direct access that the musculature on the right side of the face has to the left hemisphere's speech production systems. This direct access may facilitate the transfer of innervatory patterns to the muscles on the right side of the face. In the present study, the lateralization for speech production was investigated in 10 right-handed participants with DS and 10 nonhandicapped subjects. A RMA at the initiation and end of speech production occurred for subjects in both groups. Surprisingly, the degree of asymmetry between groups did not differ, suggesting that the lateralization of speech production is similar for persons with and persons without DS. These results support the biological dissociation model (Elliott, Weeks, & Elliott, 1987), which holds that persons with DS display a unique dissociation between speech perception (right hemisphere) and speech production (left hemisphere).     

Neural Systems Mediating American Sign Language: Effects of Sensory Experience and Age of Acquisition

ERPs were recorded from deaf and hearing native signers and from hearing subjects who acquired ASL late or not at all as they viewed ASL signs that formed sentences. The results were compared across these groups and with those from hearing subjects reading English sentences. The results suggest that there are constraints on the organization of the neural systems that mediate formal languages and that these are independent of the modality through which language is acquired. These include different specializations of anterior and posterior cortical regions in aspects of grammatical and semantic processing and a bias for the left hemisphere to mediate aspects of mnemonic functions in language. Additionally, the results suggest that the nature and timing of sensory and language experience significantly impact the development of the language systems of the brain. Effects of the early acquisition of ASL include an increased role for the right hemisphere and for parietal cortex and this occurs in both hearing and deaf native signers. An increased role of posterior temporal and occipital areas occurs in deaf native signers only and thus may be attributable to auditory deprivation.     

The Use of Non-invasive Brain Stimulation Techniques to Facilitate Recovery from Post-stroke Aphasia

Aphasia is a common symptom after left hemispheric stroke. Neuroimaging techniques over the last 10–15 years have described two general trends: Patients with small left hemisphere strokes tend to recruit perilesional areas, while patients with large left hemisphere lesions recruit mainly homotopic regions in the right hemisphere. Non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have been employed to facilitate recovery by stimulating lesional and contralesional regions. The majority of these brain stimulation studies have attempted to block homotopic regions in the right posterior inferior frontal gyrus (IFG) to affect a presumed disinhibited right IFG (triangular portion). Other studies have used anodal or excitatory tDCS to stimulate the contralesional (right) fronto-temporal region or parts of the intact left IFG and perilesional regions to improve speech-motor output. It remains unclear whether the interhemispheric disinhibition model, which is the basis for motor cortex stimulation studies, also applies to the language system. Future studies could address a number of issues, including: the effect of lesion location on current density distribution, timing of the intervention with regard to stroke onset, whether brain stimulation should be combined with behavioral therapy, and whether multiple brain sites should be stimulated. A better understanding of the predictors of recovery from natural outcome studies would also help to inform study design, and the selection of clinically meaningful outcome measures in future studies.     

From the left to the right: How the brain compensates progressive loss of language function

In normal right-handed subjects language production usually is a function oft the left brain hemisphere. Patients with aphasia following brain damage to the left hemisphere have a considerable potential to compensate for the loss of this function. Sometimes, but not always, areas of the right hemisphere which are homologous to language areas of the left hemisphere in normal subjects are successfully employed for compensation but this integration process may need time to develop. We investigated right-handed patients with left hemisphere brain tumors as a model of continuously progressive brain damage to left hemisphere language areas using functional neuroimaging and transcranial magnetic stimulation (TMS) to identify factors which determine successful compensation of lost language function. Only patients with slowly progressing brain lesions recovered right-sided language function as detected by TMS. In patients with rapidly progressive lesions no right-sided language function was found and language performance was linearly correlated with the lateralization of language related brain activation to the left hemisphere. It can thus be concluded that time is the factor which determines successful integration of the right hemisphere into the language network for compensation of lost left hemisphere language function.     

Visual field asymmetries for motion processing in deaf and hearing signers

Recently, we reported a strong right visual field/left hemisphere advantage for motion processing in deaf signers and a slight reverse asymmetry in hearing nonsigners (Bosworth & Dobkins, 1999). This visual field asymmetry in deaf signers may be due to auditory deprivation or to experience with a visual-manual language, American Sign Language (ASL). In order to separate these two possible sources, in this study we added a third group, hearing native signers, who have normal hearing and have learned ASL from their deaf parents. As in our previous study, subjects performed a direction-of-motion discrimination task at different locations across the visual field. In addition to investigating differences in left vs right visual field asymmetries across subject groups, we also asked whether performance differences exist for superior vs inferior visual fields and peripheral vs central visual fields. Replicating our previous study, a robust right visual field advantage was observed in deaf signers, but not in hearing nonsigners. Like deaf signers, hearing signers also exhibited a strong right visual field advantage, suggesting that this effect is related to experience with sign language. These results suggest that perceptual processes required for the acquisition and comprehension of language (motion processing in the case of ASL) are recruited by the left, language-dominant, hemisphere. Deaf subjects also exhibited an inferior visual field advantage that was significantly larger than that observed in either hearing group. In addition, there was a trend for deaf subjects to perform relatively better on peripheral than on central stimuli, while both hearing groups showed the reverse pattern. Because deaf signers differed from hearing signers and nonsigners along these domains, the inferior and peripheral visual field advantages observed in deaf subjects is presumably related to auditory deprivation. Finally, these visual field asymmetries were not modulated by attention for any subject group, suggesting they are a result of sensory, and not attentional, factors.     

Semantic categorization in the human brain: spatiotemporal dynamics revealed by magnetoencephalography

We examined the cortical representation of semantic categorization using magnetic source imaging in a task that revealed both dissociations among superordinate categories and associations among different base-level concepts within these categories. Around 200 ms after stimulus onset, the spatiotemporal correlation of brain activity elicited by base-level concepts was greater within than across superordinate categories in the right temporal lobe. Unsupervised clustering of data showed similar categorization between 210 and 450 ms mainly in the left hemisphere. This pattern suggests that well-defined semantic categories are represented in spatially distinct, macroscopically separable neural networks, independent of physical stimulus properties. In contrast, a broader, task-required categorization (natural/man-made) was not evident in our data. The perceptual dynamics of the categorization process is initially evident in the extrastriate areas of the right hemisphere; this activation is followed by higher-level activity along the ventral processing stream, implicating primarily the left temporal lobe.     

The effect of word length on hemispheric word recognition: evidence from unilateral and bilateral-redundant presentations

Visual half field studies have repeatedly demonstrated the left hemisphere's superiority for language processing. Previous studies examined the effect of word length on bilateral and unilateral performance by comparing foveal and parafoveal presentations. The present study removed the potential confound of acuity by using parafoveal presentations for both unilateral and bilateral trials. Twenty participants named 3-, 4-, 5-, and 6-letter words. The results supported previous findings, with right hemisphere performance being particularly degraded with increases in word length. There was no difference between left hemisphere and bihemispheric performance in terms of speed or accuracy, suggesting that bihemispheric performance is reliant upon the strategy of the hemisphere superior for language processing. Overall, the pattern of results supports the notion that the left hemisphere's superior linguistic capacity results from a more parallel processing strategy, while the right hemisphere is reliant upon a more sequential mechanism.