Left hemisphere regions are critical for language in the face of early left focal brain injury.
ABSTRACT: A predominant theory regarding early stroke and its effect on language development, is that early left hemisphere lesions trigger compensatory processes that allow the right hemisphere to assume dominant language functions, and this is thought to underlie the near normal language development observed after early stroke. To test this theory, we used functional magnetic resonance imaging to examine brain activity during category fluency in participants who had sustained pre- or perinatal left hemisphere stroke (n = 25) and in neurologically normal siblings (n = 27). In typically developing children, performance of a category fluency task elicits strong involvement of left frontal and lateral temporal regions and a lesser involvement of right hemisphere structures. In our cohort of atypically developing participants with early stroke, expressive and receptive language skills correlated with activity in the same left inferior frontal regions that support language processing in neurologically normal children. This was true independent of either the amount of brain injury or the extent that the injury was located in classical cortical language processing areas. Participants with bilateral activation in left and right superior temporal-inferior parietal regions had better language function than those with either predominantly left- or right-sided unilateral activation. The advantage conferred by left inferior frontal and bilateral temporal involvement demonstrated in our study supports a strong predisposition for typical neural language organization, despite an intervening injury, and argues against models suggesting that the right hemisphere fully accommodates language function following early injury.
Project description:Acquired language disorders after stroke are strongly associated with left hemisphere damage. When language difficulties are observed in the context of right hemisphere strokes, patients are usually considered to have atypical functional anatomy. By systematically integrating behavioural and lesion data from brain damaged patients with functional MRI data from neurologically normal participants, we investigated when and why right hemisphere strokes cause language disorders. Experiment 1 studied right-handed patients with unilateral strokes that damaged the right (n = 109) or left (n = 369) hemispheres. The most frequently impaired language task was: auditory sentence-to-picture matching after right hemisphere strokes; and spoken picture description after left hemisphere strokes. For those with auditory sentence-to-picture matching impairments after right hemisphere strokes, the majority (n = 9) had normal performance on tests of perceptual (visual or auditory) and linguistic (semantic, phonological or syntactic) processing. Experiment 2 found that these nine patients had significantly more damage to dorsal parts of the superior longitudinal fasciculus and the right inferior frontal sulcus compared to 75 other patients who also had right hemisphere strokes but were not impaired on the auditory sentence-to-picture matching task. Damage to these right hemisphere regions caused long-term speech comprehension difficulties in 67% of patients. Experiments 3 and 4 used functional MRI in two groups of 25 neurologically normal individuals to show that within the regions identified by Experiment 2, the right inferior frontal sulcus was normally activated by (i) auditory sentence-to-picture matching; and (ii) one-back matching when the demands on linguistic and non-linguistic working memory were high. Together, these experiments demonstrate that the right inferior frontal cortex contributes to linguistic and non-linguistic working memory capacity (executive function) that is needed for normal speech comprehension. Our results link previously unrelated literatures on the role of the right inferior frontal cortex in executive processing and the role of executive processing in sentence comprehension; which in turn helps to explain why right inferior frontal activity has previously been reported to increase during recovery of language function after left hemisphere stroke. The clinical relevance of our findings is that the detrimental effect of right hemisphere strokes on language is (i) much greater than expected; (ii) frequently observed after damage to the right inferior frontal sulcus; (iii) task dependent; (iv) different to the type of impairments observed after left hemisphere strokes; and (v) can result in long-lasting deficits that are (vi) not the consequence of atypical language lateralization.
Project description:Aphasia is an acquired language disorder that is a common consequence of stroke. The pathogenesis of the disease is not fully understood, and as a result, current treatment options are not satisfactory. Here, we used blood oxygenation level-dependent functional magnetic resonance imaging to evaluate the activation of bilateral cortices in patients with Broca's aphasia 1 to 3 months after stroke. Our results showed that language expression was associated with multiple brain regions in which the right hemisphere participated in the generation of language. The activation areas in the left hemisphere of aphasia patients were significantly smaller compared with those in healthy adults. The activation frequency, volumes, and intensity in the regions related to language, such as the left inferior frontal gyrus (Broca's area), the left superior temporal gyrus, and the right inferior frontal gyrus (the mirror region of Broca's area), were lower in patients compared with healthy adults. In contrast, activation in the right superior temporal gyrus, the bilateral superior parietal lobule, and the left inferior temporal gyrus was stronger in patients compared with healthy controls. These results suggest that the right inferior frontal gyrus plays a role in the recovery of language function in the subacute stage of stroke-related aphasia by increasing the engagement of related brain areas.
Project description:Anterior temporal lobe resection (ATLR) controls seizures in up to 70% of patients with intractable temporal lobe epilepsy (TLE) but, in the language dominant hemisphere, may impair language function, particularly naming. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated reorganization of language in left-hemisphere-dominant patients before and after ATLR; whether preoperative functional magnetic resonance imaging (fMRI) predicts postoperative naming decline; and efficiency of postoperative language networks.We studied 44 patients with TLE due to unilateral hippocampal sclerosis (24 left) on a 3T GE-MRI scanner. All subjects performed language fMRI and neuropsychological testing preoperatively and again 4 months after left or right ATLR.Postoperatively, individuals with left TLE had greater bilateral middle/inferior frontal fMRI activation and stronger functional connectivity from the left inferior/middle frontal gyri to the contralateral frontal lobe than preoperatively, and this was not observed in individuals with right TLE. Preoperatively, in left and right TLE, better naming correlated with greater preoperative left hippocampal and left frontal activation for verbal fluency (VF). In left TLE, stronger preoperative left middle frontal activation for VF was predictive of greater decline in naming after ATLR. Postoperatively, in left TLE with clinically significant naming decline, greater right middle frontal VF activation correlated with better postoperative naming. In patients without postoperative naming decline, better naming correlated with greater activation in the remaining left posterior hippocampus. In right TLE, naming ability correlated with left hippocampal and left and right frontal VF activation postoperatively.In left TLE, early postoperative reorganization to the contralateral frontal lobe suggests multiple systems support language function. Postoperatively, ipsilateral recruitment involving the posterior hippocampal remnant is important for maintaining language, and reorganization to the contralateral hemisphere is less effective. Preoperative left middle frontal activation for VF was predictive of naming decline in left TLE after ATLR.
Project description:Verbal stimuli often induce right-hemispheric activation in patients with aphasia after left-hemispheric stroke. This right-hemispheric activation is commonly attributed to functional reorganization within the language system. Yet previous evidence suggests that functional activation in right-hemispheric homologues of classic left-hemispheric language areas may partly be due to processing nonlinguistic perceptual features of verbal stimuli. We used functional MRI (fMRI) to clarify the role of the right hemisphere in the perception of nonlinguistic word features in healthy individuals. Participants made perceptual, semantic, or phonological decisions on the same set of auditorily and visually presented word stimuli. Perceptual decisions required judgements about stimulus-inherent changes in font size (visual modality) or fundamental frequency contour (auditory modality). The semantic judgement required subjects to decide whether a stimulus is natural or man-made; the phonologic decision required a decision on whether a stimulus contains two or three syllables. Compared to phonologic or semantic decision, nonlinguistic perceptual decisions resulted in a stronger right-hemispheric activation. Specifically, the right inferior frontal gyrus (IFG), an area previously suggested to support language recovery after left-hemispheric stroke, displayed modality-independent activation during perceptual processing of word stimuli. Our findings indicate that activation of the right hemisphere during language tasks may, in some instances, be driven by a "nonlinguistic perceptual processing" mode that focuses on nonlinguistic word features. This raises the possibility that stronger activation of right inferior frontal areas during language tasks in aphasic patients with left-hemispheric stroke may at least partially reflect increased attentional focus on nonlinguistic perceptual aspects of language.
Project description:If neuroplastic changes in aphasia are consistent across studies, this would imply relatively stereotyped mechanisms of recovery which could guide the design of more efficient noninvasive brain stimulation treatments. To address this question, we performed a meta-analysis of functional neuroimaging studies of chronic aphasia after stroke.Functional neuroimaging articles using language tasks in patients with chronic aphasia after stroke (n = 105) and control subjects (n = 129) were collected. Activation likelihood estimation meta-analysis determined areas of consistent activity in each group. Functional homology between areas recruited by aphasic patients and controls was assessed by determining whether they activated under the same experimental conditions.Controls consistently activated a network of left hemisphere language areas. Aphasic patients consistently activated some spared left hemisphere language nodes, new left hemisphere areas, and right hemisphere areas homotopic to the control subjects' language network. Patients with left inferior frontal lesions recruited right inferior frontal gyrus more reliably than those without. Some areas, including right dorsal pars opercularis, were functionally homologous with corresponding control areas, while others, including right pars triangularis, were not.The network of brain areas aphasic patients recruit for language functions is largely consistent across studies. Several recruitment mechanisms occur, including persistent function in spared nodes, compensatory recruitment of alternate nodes, and recruitment of areas that may hinder recovery. These findings may guide development of brain stimulation protocols that can be applied across populations of aphasic patients who share common attributes.
Project description:The study of language network plasticity following left hemisphere stroke is foundational to the understanding of aphasia recovery and neural plasticity in general. Damage in different language nodes may influence whether local plasticity is possible and whether right hemisphere recruitment is beneficial. However, the relationships of both lesion size and location to patterns of remapping are poorly understood. In the context of a picture naming fMRI task, we tested whether lesion size and location relate to activity in surviving left hemisphere language nodes, as well as homotopic activity in the right hemisphere during covert name retrieval and overt name production. We found that lesion size was positively associated with greater right hemisphere activity during both phases of naming, a pattern that has frequently been suggested but has not previously been clearly demonstrated. During overt naming, lesions in the inferior frontal gyrus led to deactivation of contralateral frontal areas, while lesions in motor cortex led to increased right motor cortex activity. Furthermore, increased right motor activity related to better naming performance only when left motor cortex was lesioned, suggesting compensatory takeover of speech or language function by the homotopic node. These findings demonstrate that reorganization of language function, and the degree to which reorganization facilitates aphasia recovery, is dependent on the size and site of the lesion.
Project description:Language is sustained by large-scale networks in the human brain. Stroke often severely affects function and network dynamics. However, the adaptive potential of the brain to compensate for lesions is poorly understood. A key question is whether upregulation of the right hemisphere is adaptive for language recovery. Targeting the potential for short-term reorganization in the lesioned brain, we applied 'virtual lesions' over left anterior or posterior inferior frontal gyrus (IFG) in post-stroke patients with left temporo-parietal lesions prior to functional neuroimaging. Perturbation of the posterior IFG selectively delayed phonological decisions and decreased phonological activity. The individual response delay was correlated with the upregulation of the lesion homologue, likely reflecting compensation. Moreover, stronger individual tract integrity of the right superior longitudinal fascicle was associated with lesser disruption. Our results provide evidence for functional and structural underpinnings of plasticity in the lesioned language network, and a compensatory role of the right hemisphere.
Project description:Reorganization of eloquent cortex enables rescue of language functions in patients who sustain brain injury. Individuals with left-sided, early-onset focal epilepsy often show atypical (i.e. bilateral or right-sided) language dominance. Surprisingly, many patients fail to show such interhemispheric shift of language despite having major epileptogenic lesions in close proximity to eloquent cortex. Although a number of epilepsy-related factors may promote interhemispheric plasticity, it has remained unexplored if neuroanatomical asymmetries linked to human language dominance modify the likelihood of atypical lateralization. Here we examined the asymmetry of the planum temporale, one of the most striking asymmetries in the human brain, in relation to language lateralization in children with left-sided focal epilepsy. Language functional magnetic resonance imaging was performed in 51 children with focal epilepsy and left-sided lesions and 36 healthy control subjects. We examined the association of language laterality with a range of potential clinical predictors and the asymmetry of the length of the planum temporale. Using voxel-based methods, we sought to determine the effect of lesion location (in the affected left hemisphere) and grey matter density (in the unaffected right hemisphere) on language laterality. Atypical language lateralization was observed in 19 patients (38%) and in four controls (11%). Language laterality was increasingly right-sided in patients who showed atypical handedness, a left perisylvian ictal electroencephalographic focus, and a lesion in left anterior superior temporal or inferior frontal regions. Most striking was the relationship between rightward asymmetry of the planum temporale and atypical language (R = 0.70, P < 0.0001); patients with a longer planum temporale in the right (unaffected) hemisphere were more likely to have atypical language dominance. Voxel-based regression analysis confirmed that increased grey matter density in the right temporo-parietal junction was correlated with right hemisphere lateralization of language. The length of the planum temporale in the right hemisphere was the main predictor of language lateralization in the epilepsy group, accounting for 48% of variance, with handedness accounting for only a further 5%. There was no correlation between language lateralization and planum temporale asymmetry in the control group. We conclude that asymmetry of the planum temporale may be unrelated to language lateralization in healthy individuals, but the size of the right, contra-lesional planum temporale region may reflect a 'reserve capacity' for interhemispheric language reorganization in the presence of a seizure focus and lesions within left perisylvian regions.
Project description:The acquisition and evolution of speech production, discourse and communication can be negatively impacted by brain malformations. We describe, for the first time, a case of developmental dynamic dysphasia (DDD) in a right-handed adolescent boy (subject D) with cortical malformations involving language-eloquent regions (inferior frontal gyrus) in both the left and the right hemispheres. Language evaluation revealed a markedly reduced verbal output affecting phonemic and semantic fluency, phrase and sentence generation and verbal communication in everyday life. Auditory comprehension, repetition, naming, reading and spelling were relatively preserved, but executive function was impaired. Multimodal neuroimaging showed a malformed cerebral cortex with atypical configuration and placement of white matter tracts bilaterally and abnormal callosal fibers. Dichotic listening showed right hemisphere dominance for language, and functional magnetic resonance imaging (fMRI) additionally revealed dissociated hemispheric language representation with right frontal activation for phonology and bilateral dominance for semantic processing. Moreover, subject D also had congenital mirror movements (CMM), defined as involuntary movements of one side of the body that mirror intentional movements of the other side. Transcranial magnetic stimulation and fMRI during voluntary unimanual (left and right) hand movements showed bilateral motor cortex recruitment and tractography revealed a lack of decussation of bilateral corticospinal tracts. Genetic testing aimed to detect mutations that disrupt the development of commissural tracts correlating with CMM (e.g., Germline DCC mutations) was negative. Overall, our findings suggest that DDD in subject D resulted from the underdevelopment of the left inferior frontal gyrus with limited capacity for plastic reorganization by its homologous counterpart in the right hemisphere. Corpus callosum anomalies probably contributed to hinder interhemispheric connectivity necessary to compensate language and communication deficits after left frontal involvement.
Project description:Language deficits are reported in preterm born children across development. Recent neuroimaging studies have found functional alterations in large-scale brain networks underlying these language deficits, but the early childhood development of the language network has not been investigated. Here, we compared intrinsic language network connectivity in 4-year-old children born VPT and term-born controls, using defined language regions (Broca's area, Wernicke's areas, and their homologues in the right hemisphere). Resting-state functional magnetic resonance imaging (fMRI) was obtained, and the group differences in whole-brain connectivity were examined from each seed as well as correlations with language outcomes. We found significantly decreased functional connectivity in almost all language regions in children born VPT compared to their term controls. Notably, Broca's area homologue in the right hemisphere emerged as a functional hub of decreased connectivity in VPT group, specifically to bilateral inferior frontal and supramarginal gyri; connectivity strength between Broca's area homologue with the right supramarginal and the left inferior frontal gyri was associated with better language outcomes at 4 years of age. Wernicke's area and its homologue also showed decreased inter-hemispheric connections to bilateral supramarginal gyri in the VPT group. Decreased intra- and inter-hemispheric connectivity among primary language regions suggests immature and altered function in the language network in children born VPT.