Functional MRI of Language in Aphasia: A Review of the Literature and the Methodological Challenges

Animal analogue studies show that damaged adult brains reorganize to accommodate compromised functions. In the human arena, functional magnetic resonance imaging (fMRI) and other functional neuroimaging techniques have been used to study reorganization of language substrates in aphasia. The resulting controversy regarding whether the right or the left hemisphere supports language recovery and treatment progress must be reframed. A more appropriate question is when left-hemisphere mechanisms and when right-hemisphere mechanisms support recovery of language functions. Small lesions generally lead to good recoveries supported by left-hemisphere mechanisms. However, when too much language eloquent cortex is damaged, right-hemisphere structures may provide the better substrate for recovery of language. Some studies suggest that recovery is particularly supported by homologues of damaged left-hemisphere structures. Evidence also suggests that under some circumstances, activity in both the left and right hemispheres can interfere with recovery of function. Further research will be needed to address these issues. However, daunting methodological problems must be managed to maximize the yield of future fMRI research in aphasia, especially in the area of language production. In this review, we cover six challenges for imaging language functions in aphasia with fMRI, with an emphasis on language production: (1) selection of a baseline task, (2) structure of language production trials, (3) mitigation of motion-related artifacts, (4) the use of stimulus onset versus response onset in fMRI analyses, (5) use of trials with correct responses and errors in analyses, and (6) reliability and stability of fMRI images across sessions. However, this list of methodological challenges is not exhaustive. Once methodology is advanced, knowledge from conceptually driven fMRI studies can be used to develop theoretically driven, mechanism-based treatments that will result in more effective therapy and to identify the best patient candidates for specific treatments. While the promise of fMRI in the study of aphasia is great, there is much work to be done before this technique will be a useful clinical tool.     

Pre-Surgical Language Mapping with Functional Magnetic Resonance Imaging

Patients with lesions in or near eloquent cortex typically undergo one of several invasive techniques to prevent loss of function following surgery. One of the most promising potential clinical applications of functional magnetic resonance imaging (fMRI) is to map these functions as part of the pre-surgical work-up to identify patients at-risk, guide the surgical entry, or tailor the surgical procedure to prevent deficits. While motor and sensory mapping are relatively straightforward, language mapping is far more complex. The language system is variable in location across individuals and in many cases may reorganize partially or completely to the contralateral hemisphere. In addition, multiple regions of the brain contribute to language functioning including essential regions that must not be removed in surgery, and contributory regions that may result in transient or insignificant impairments post-surgery. Despite these challenges, an increasing number of studies have supported the use of fMRI for pre-surgical language mapping in a variety of disorders. This article reviews the literature from three disorders for which patients benefit from preoperative language mapping: epilepsy, brain tumors, and arteriovenous malformations. Each disorder presents unique challenges to language mapping. Specific case studies are presented highlighting the both the potential benefits of preclinical fMRI for language mapping as well as the potential risks and pitfalls.     

Two functional magnetic resonance imaging f(MRI) tasks that may replace the gold standard, Wada testing, for language lateralization while giving additional localization information

Two tasks were used to lateralize and localize language functions noninvasively, using functional magnetic resonance (fMRI BOLD sequences). fMRI images produced during comprehension of the gist of a tale derived from an ordered series of inferential questions were used to lateralize and locate the center of and margins within language dominant hemisphere near posterior temporal-parietal-occipital (TPO) cortical area(s), e.g., Wernicke's. A silent noun-generating task was used to lateralize and localize naming functions within and along superior temporal gyrus (STG) and/or the basal temporal language area (BTLA) in fusiform gyrus. Used within a series of tasks, their purpose was to investigate the reliability and validity of replacing the invasive gold standard for language lateralization, Wada test, with a noninvasive test, BOLD fMRI.     

Where and how does grammatically geared processing take place-and why is Broca's area often involved. A coordinated fMRI/ERBP study of language processing

We address the possibility of combining the results from hemodynamic and electrophysiological methods for the study of cognitive processing of language. The hemodynamic method we use is Event-Related fMRI, and the electrophysiological method measures Event-Related Band Power (ERBP) of the EEG signal. The experimental technique allows us to approach the relation between cortical structure and cognitive function in a sophisticated way. In particular, we can formulate original working hypotheses about the language-induced changes in the ongoing brain dynamics. We show, on the basis of electrophysiological data collected in an experiment on language production, that synchronized cortical networks code cognitive processes induced by language in form of power modulations of specific frequency bands. The hemodynamic (fMRI) data collected in the same task point to the existence of a central processor for the phrase structure assignment. We conceptualize such a central processor as a frequency scanner, a cortical device designed to pick up synchronized brain activity over a specific range of frequencies. We discuss the experimental designs which result from this set of hypotheses and show their relevance for the models of language processing.     

fMRI of developmental stuttering: a pilot study

The purpose of this investigation was to explore the feasibility of fMRI in the study of developmental stuttering. Speech contrasts (loud versus silent reading) and language contrasts (reading of semantically meaningful text versus nonsense words) of six developmental stutterers and six nonstutterers were compared using a commercial 1 Tesla MR-Scanner (Siemens Expert). Results indicate that mapping cortical function in persons who stutter is indeed feasible, even with a 1TMR-system. Compared to normals the stutterers seemed to employ different and particularly less differentiated auditory and motor feedback strategies in speech. They apparently rely on auditory processing and on cerebellar contribution as much during silent reading as during reading aloud. Moreover, they showed a greater involvement of the right hemisphere in language processing, activating not only the typical language areas on the left but also and with equal magnitude the right side homologues of these areas. In spite of the promising results, at present several practical problems such as possible movement artifacts and possible masking through scanner noise still hamper a more straightforward use of fMRI in the study of developmental stuttering.     

fMRI and cognitive dysfunction in schizophrenia

Despite being one of the most prevalent psychiatric conditions, SCHIZOPHRENIA is still poorly understood, with no clear objective biological marker. The advent of neuroimaging has enabled in vivo investigations to complement older techniques, and has revealed important insights. fMRI provides a means to assess the neurobiological theory that schizophrenia is caused by abnormal fronto-temporal lobe connections. In studies of language abnormalities, fMRI can explicitly assess the hypothesis that the normal lateralization of language is reversed in schizophrenia. Longitudinal fMRI studies, and studies examining the effects of medication, suggest that the technique has further potential to advance our understanding of this complex disorder.     

Should Psychology Ignore the Language of the Brain?

ABSTRACT— Claims that neuroscientific data do not contribute to our understanding of psychological functions have been made recently. Here I argue that these criticisms are solely based on an analysis of functional magnetic resonance imaging (fMRI) studies. However, fMRI is only one of the methods in the toolkit of cognitive neuroscience. I provide examples from research on event-related brain potentials (ERPs) that have contributed to our understanding of the cognitive architecture of human language functions. In addition, I provide evidence of (possible) contributions from fMRI measurements to our understanding of the functional architecture of language processing. Finally, I argue that a neurobiology of human language that integrates information about the necessary genetic and neural infrastructures will allow us to answer certain questions that are not answerable if all we have is evidence from behavior.     

Language difficulties in children adopted internationally: Neuropsychological and functional neural correlates

Children who have experienced deprivation as a result of orphanage care during early development are at increased risk for a number of cognitive, emotional, and social difficulties (MacLean, 2003). This study examined the neuropsychological and behavioral profile of internationally adopted children with language difficulties, one of the most common cognitive challenges (Behen et al., 2008). In addition to neuropsychological testing, fMRI was utilized to examine activation patterns during expressive fluency and receptive language tasks. In comparison to internationally adopted children without language difficulties and nonadopted controls, participants with language difficulty had worse performance on tasks of verbal memory and reasoning, academic skills, and working memory. Behaviorally, all internationally adopted participants, regardless of language ability, had more parent-reported hyperactivity and impulsivity compared with controls. The fMRI tasks revealed reduced activation in traditional language areas in participants with language difficulty. The impact of early adverse experience on later development is discussed.     

Brain network interactions in auditory, visual and linguistic processing

In the paper, we discuss the importance of network interactions between brain regions in mediating performance of sensorimotor and cognitive tasks, including those associated with language processing. Functional neuroimaging, especially PET and fMRI, provide data that are obtained essentially simultaneously from much of the brain, and thus are ideal for enabling one to assess interregional functional interactions. Two ways to use these types of data to assess network interactions are presented. First, using PET, we demonstrate that anterior and posterior perisylvian language areas have stronger functional connectivity during spontaneous narrative production than during other less linguistically demanding production tasks. Second, we show how one can use large-scale neural network modeling to relate neural activity to the hemodynamically-based data generated by fMRI and PET. We review two versions of a model of object processing - one for visual and one for auditory objects. The regions comprising the models include primary and secondary sensory cortex, association cortex in the temporal lobe, and prefrontal cortex. Each model incorporates specific assumptions about how neurons in each of these areas function, and how neurons in the different areas are interconnected with each other. Each model is able to perform a delayed match-to-sample task for simple objects (simple shapes for the visual model; tonal contours for the auditory model). We find that the simulated electrical activities in each region are similar to those observed in nonhuman primates performing analogous tasks, and the absolute values of the simulated integrated synaptic activity in each brain region match human fMRI/PET data. Thus, this type of modeling provides a way to understand the neural bases for the sensorimotor and cognitive tasks of interest.     

White-matter microstructure and language lateralization in left-handers: A whole-brain MRI analysis

Most people are left-hemisphere dominant for language. However the neuroanatomy of language lateralization is not fully understood. By combining functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), we studied whether language lateralization is associated with cerebral white-matter (WM) microstructure. Sixteen healthy, left-handed women aged 20–25 were included in the study. Left-handers were targeted in order to increase the chances of involving subjects with atypical language lateralization. Language lateralization was determined by fMRI using a verbal fluency paradigm. Tract-based spatial statistics analysis of DTI data was applied to test for WM microstructural correlates of language lateralization across the whole brain. Fractional anisotropy and mean diffusivity were used as indicators of WM microstructural organization. Right-hemispheric language dominance was associated with reduced microstructural integrity of the left superior longitudinal fasciculus and left-sided parietal lobe WM. In left-handed women, reduced integrity of the left-sided language related tracts may be closely linked to the development of right hemispheric language dominance. Our results may offer new insights into language lateralization and structure–function relationships in human language system.     

The bimodal bilingual brain: effects of sign language experience

Bimodal bilinguals are hearing individuals who know both a signed and a spoken language. Effects of bimodal bilingualism on behavior and brain organization are reviewed, and an fMRI investigation of the recognition of facial expressions by ASL-English bilinguals is reported. The fMRI results reveal separate effects of sign language and spoken language experience on activation patterns within the superior temporal sulcus. In addition, the strong left-lateralized activation for facial expression recognition previously observed for deaf signers was not observed for hearing signers. We conclude that both sign language experience and deafness can affect the neural organization for recognizing facial expressions, and we argue that bimodal bilinguals provide a unique window into the neurocognitive changes that occur with the acquisition of two languages.     

Using fMRI to study recovery from acquired dysphasia

We have used functional magnetic resonance imaging (fMRI) to characterize brain activations associated with two distinct language tasks performed by a 28-year-old woman after partial recovery from dysphasia due to a left frontal hemispheric ischemic stroke. MRI showed that her ischemic lesion extended posteriorly from the left inferior frontal to the perisylvian cortex. fMRI scans of both language tasks revealed substantial differences in activation pattern relative to controls. The nature of this difference was task-specific. During performance of a verbal semantic decision task, the patient, in contrast to controls, activated a network of brain areas that excluded the inferior frontal gyrus (in either hemisphere). A second task involving rhyme judgment was designed to place a heavier cognitive load on language production processes and activated the left inferior frontal gyrus (Broca's area) strongly in normal controls. During this task, the most prominent frontal activation in the patient occurred in the right homologue of Broca's area. Subsequent analysis of this data by methods able to deal with responses of changing amplitude revealed additional, less sustained recruitment by the patient of cortex adjacent to the infarct in the region inferior to Broca's area during rhyming. These results suggest that in addition to changes in cognitive strategy, recovery from dysphasia could be mediated by both the preservation of neuronal networks in and around the infarct and the use of homologous regions in the contralateral hemisphere.     

Neuroimaging studies of the cerebellum: language, learning and memory

During the decade following a functional neuroimaging study of language that showed cerebellar involvement in a cognitive task, PET and fMRI studies have continued to provide evidence that the role of the cerebellum extends beyond that of motor control and that this structure contributes in some way to cognitive operations. In this review, we describe neuroimaging evidence for cerebellar involvement in working memory, implicit and explicit learning and memory, and language, and we discuss some of the problems and limitations faced by researchers who use neuroimaging to investigate cerebellar function. We also raise a set of outstanding questions that need to be addressed through further neuroimaging and behavioral experiments before differing functional accounts of cerebellar involvement in cognition can be resolved.     

Brain-behavior relationships in reading acquisition are modulated by socioeconomic factors

Functional neuroimaging may provide insights into the achievement gap in reading skill commonly observed across socioeconomic status (SES). Brain activation during reading tasks is known to be associated with individual differences in children's phonological language skills. By selecting children of equivalent phonological skill, yet diverse socioeconomic backgrounds, we use functional magnetic resonance imaging (fMRI) to demonstrate that a child's experience, as operationalized by SES, can systematically modulate the relationship between phonological language skills and reading-related brain activity in left fusiform and perisylvian regions. Specifically, at lower socioeconomic levels, individual differences in skill result in large differences in brain activation. In contrast, as SES increases, this relationship between phonological language skill and activation is attenuated. Socioeconomic background factors are thus found to modulate brain-behavior relationships in reading, indicating that cognitive, social, and neurobiological influences on reading development are fundamentally intertwined.     

The contribution of functional near-infrared spectroscopy (fNIRS) to the presurgical assessment of language function in children

Before performing neurosurgery, an exhaustive presurgical assessment is required, usually including an investigation of language cerebral lateralization. Among the available procedures, the intracarotid amobarbital test (IAT) was formerly the most widely used. However, this procedure has many limitations: it is invasive and potentially traumatic, especially for children. To overcome these limitations, neuroimaging techniques such as functional magnetic resonance imaging (fMRI) have been used. Again, these methods are difficult to use with children, who must remain motionless during data acquisition. Functional near-infrared spectroscopy (fNIRS) is a noninvasive functional imaging technique that is easily applied to pediatric and cognitively limited patients. It has been used recently in epileptic children for presurgical assessment of expressive and receptive language brain lateralization. The aim of this review is to present the contribution of fNIRS to the presurgical assessment of language function in children with neurological diseases.     

Test-retest reliability of fMRI during nonverbal semantic decisions in moderate-severe nonfluent aphasia patients

Cortical reorganization in poststroke aphasia is not well understood. Few studies have investigated neural mechanisms underlying language recovery in severe aphasia patients, who are typically viewed as having a poor prognosis for language recovery. Although test-retest reliability is routinely demonstrated during collection of language data in single-subject aphasia research, this is rarely examined in fMRI studies investigating the underlying neural mechanisms in aphasia recovery. The purpose of this study was to acquire fMRI test-retest data examining semantic decisions both within and between two aphasia patients. Functional MRI was utilized to image individuals with chronic, moderate-severe nonfluent aphasia during nonverbal, yes/no button-box semantic judgments of iconic sentences presented in the Computer-assisted Visual Communication (C-ViC) program. We investigated the critical issue of intra-subject reliability by exploring similarities and differences in regions of activation during participants' performance of identical tasks twice on the same day. Each participant demonstrated high intra-subject reliability, with response decrements typical of task familiarity. Differences between participants included greater left hemisphere perilesional activation in the individual with better response to C-ViC training. This study provides fMRI reliability in chronic nonfluent aphasia, and adds to evidence supporting differences in individual cortical reorganization in aphasia recovery.     

Reproducibility of fMRI-determined language lateralization in individual subjects

This study investigated within-subject test-retest reproducibility (i.e., reliability) of language lateralization obtained with fMRI. Nine healthy subjects performed the same set of three different language tasks during two fMRI sessions on separate days (verb generation, antonym generation, and picture naming). A fourth task analysis was added in which the three tasks were analyzed conjointly (combined task analysis, CTA). The CTA targets brain areas that are commonly used in different language tasks, aiming more selectively at language-critical structures. The number of active voxels (i.e., robustness) and calculated lateralization index (LI) were compared across sessions, tasks, subjects, and two a priori defined volumes of interest (classical language regions versus whole hemisphere) for a wide range of statistical thresholds. Robustness and reliability strongly varied between task analyses. The CTA was a robust detector of language-related brain activity, in contrast to the single task approaches. The CTA and verb generation task allowed for reliable calculation of the LI. Higher thresholds yielded a clear increase in left lateralization, which was largest when calculated from active voxels in classical language regions.     

Dual language use in sign-speech bimodal bilinguals: fNIRS brain-imaging evidence

The brain basis of bilinguals’ ability to use two languages at the same time has been a hotly debated topic. On the one hand, behavioral research has suggested that bilingual dual language use involves complex and highly principled linguistic processes. On the other hand, brain-imaging research has revealed that bilingual language switching involves neural activations in brain areas dedicated to general executive functions not specific to language processing, such as general task maintenance. Here we address the involvement of language-specific versus cognitive-general brain mechanisms for bilingual language processing. We study a unique population, bimodal bilinguals proficient in signed and spoken languages, and we use an innovative brain-imaging technology, functional Near-Infrared Spectroscopy (fNIRS; Hitachi ETG-4000). Like fMRI, the fNIRS technology measures hemodynamic change, but it is also advanced in permitting movement for unconstrained speech and sign production. Participant groups included (i) hearing ASL–English bilinguals, (ii) ASL monolinguals, and (iii) English monolinguals. Imaging tasks included picture naming in “Monolingual mode” (using one language at a time) and in “Bilingual mode” (using both languages either simultaneously or in rapid alternation). Behavioral results revealed that accuracy was similar among groups and conditions. By contrast, neuroimaging results revealed that bilinguals in Bilingual mode showed greater signal intensity within posterior temporal regions (“Wernicke’s area”) than in Monolingual mode. Significance: Bilinguals’ ability to use two languages effortlessly and without confusion involves the use of language-specific posterior temporal brain regions. This research with both fNIRS and bimodal bilinguals sheds new light on the extent and variability of brain tissue that underlies language processing, and addresses the tantalizing questions of how language modality, sign and speech, impact language representation in the 7brain.     

Structural and functional imaging in children with partial epilepsy

Imaging plays an increasingly important role in the evaluation of children with complex partial seizures. Most partial epilepsy, especially of temporal lobe origin, begins during childhood. Structural imaging with high-resolution MRI can help identify the etiology of partial seizure disorders in many children. MRI studies also show the more widespread effect of seizures on brain structure. Progressive volume loss of the hippocampal formation in some patients with temporal lobe epilepsy provides evidence that continued seizures may be associated with progressive neuronal injury. FDG-PET studies show regional decreases in glucose consumption in the cortical zone from which seizures arise. Functional abnormalities often are more extensive than the seizure focus. Studies in children with recent-onset epilepsy show that metabolic abnormalities are considerably less common than in adults with partial epilepsy, supporting the notion that in some patients there may be progressive metabolic changes that occur with continued seizures. Functional MRI may be used to identify language areas in children with partial epilepsy. fMRI language tasks reliably identify the dominant hemisphere for language dominance when compared to the intracarotid amytal procedure. Tests of verbal fluency and semantic decision identify frontal lobe language areas, while reading text paradigms and auditory passage paradigms are better for identifying temporal language areas. A panel of paradigms is best used to identify language areas in children being considered for epilepsy surgery. fMRI is a valuable tool for elucidating the impact of chronic neurologic disease states on the functional organization of language networks during development.