Comparing language lateralization determined by dichotic listening and fMRI activation in frontal and temporal lobes in children with epilepsy

We investigated the relationship between ear advantage scores on the Fused Dichotic Words Test (FDWT), and laterality of activation in fMRI using a verb generation paradigm in fourteen children with epilepsy. The magnitude of the laterality index (LI), based on spatial extent and magnitude of activation in classical language areas (BA 44/45, 21/22, 39) differed significantly for patients classified with unilateral left, compared to bilateral, language representation based on FDWT scores. Concordance with fMRI was higher for those classified with unilateral left, than bilateral language representation on the FDWT. Of note, asymmetry in temporal lobe, rather than frontal lobe, activation was more strongly related to the LI from the dichotic listening test. This study shows that the FDWT can provide a quick and valid estimate of lateralization in pre-surgical candidates, which can be readily adopted for other clinical or research purposes when an estimate of language dominance is desired.     

Functional connectivity in an fMRI study of semantic and phonological processes and the effect of L-Dopa

We describe an fMRI experiment examining the functional connectivity (FC) between regions of the brain associated with semantic and phonological processing. We wished to explore whether L-Dopa administration affects the interaction between language network components in semantic and phonological categorization tasks, as revealed by FC. We hypothesized that L-Dopa would decrease FC due to restriction of the semantic network. During two test sessions (placebo and L-Dopa) each participant performed two fMRI runs, involving phonological and semantic processing. A number of brain regions commonly activated by the two tasks were chosen as regions if interest: left inferior frontal, left posterior temporal and left fusiform gyri, and left parietal cortex. FC was calculated and further analyzed for effects of either the drug or task. No main effect for drug was found. A significant main effect for task was found, with a greater average correlation for the phonological task than for the semantic task. These findings suggest that language areas are activated in a more synchronous manner for phonological than for semantic tasks. This may relate to the fact that phonological processes are mediated to a greater extent within language areas, whereas semantic tasks likely require greater interaction outside of the language areas. Alternatively, this may be due to differences in the attentional requirements of the two tasks.     

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.     

Increases in language lateralization in normal children as observed using magnetoencephalography

Previous functional magnetic resonance imaging (fMRI) studies investigating hemispheric dominance for language have shown that hemispheric specialization increases with age. We employed magnetoencephalography (MEG) to investigate these effects as a function of normal development. In sum, 22 healthy children aged 7-16 years were investigated using two language tasks: a verb-generation (VG) task and a vowel-identification (VI) task. Significant hemispheric differences were found for both tasks in cerebral language areas using oscillatory MEG spectral analyses, confirming the MEG's ability to detect hemispheric specialization for language in children. Additionally, a significant increase of this lateralization as a function of age was observed for both tasks. As performance in the VI task showed no correlation with age, this increase seems to be unrelated to performance. These results confirm an increase in hemispheric specialization as a function of normal brain maturation.     

Alternative-based thresholding with application to presurgical fMRI

Functional magnetic reasonance imaging (fMRI) plays an important role in pre-surgical planning for patients with resectable brain lesions such as tumors. With appropriately designed tasks, the results of fMRI studies can guide resection, thereby preserving vital brain tissue. The mass univariate approach to fMRI data analysis consists of performing a statistical test in each voxel, which is used to classify voxels as either active or inactive—that is, related, or not, to the task of interest. In cognitive neuroscience, the focus is on controlling the rate of false positives while accounting for the severe multiple testing problem of searching the brain for activations. However, stringent control of false positives is accompanied by a risk of false negatives, which can be detrimental, particularly in clinical settings where false negatives may lead to surgical resection of vital brain tissue. Consequently, for clinical applications, we argue for a testing procedure with a stronger focus on preventing false negatives. We present a thresholding procedure that incorporates information on false positives and false negatives. We combine two measures of significance for each voxel: a classical p-value, which reflects evidence against the null hypothesis of no activation, and an alternative p-value, which reflects evidence against activation of a prespecified size. This results in a layered statistical map for the brain. One layer marks voxels exhibiting strong evidence against the traditional null hypothesis, while a second layer marks voxels where activation cannot be confidently excluded. The third layer marks voxels where the presence of activation can be rejected.     

Functional magnetic resonance imaging studies in bipolar disorder

Abnormalities in brain activation using functional magnetic resonance imaging (fMRI) during cognitive and emotional tasks have been identified in bipolar disorder patients, in frontal, subcortical and limbic regions. Several studies also indicate that mood state may be differentiated by lateralization of brain activation in fronto-limbic regions. The interpretation of fMRI studies in bipolar disorder is limited by the choice of regions of interest, medication effects, comorbidity, and task performance. These studies suggest that there is a complex alteration in regions important for neural networks underlying cognition and emotional processing in bipolar disorder. However, measuring changes in specific brain regions does not identify how these neural networks are affected. New analytical techniques of fMRI data are needed in order to resolve some of these issues and identify how changes in neural networks relate to cognitive and emotional processing in bipolar disorder.     

Functional asymmetry of human prefrontal cortex: encoding and retrieval of verbally and nonverbally coded information

There are several views about the organization of memory functions in the human prefrontal cortex. One view assumes a process-specific brain lateralization according to different memory subprocesses, that is, encoding and retrieval. An alternative view emphasizes content-specific lateralization of brain systems involved in memory processes. This study addresses this apparent inconsistency between process- and content-specific lateralization of brain activity by investigating the effects of verbal and nonverbal encoding on prefrontal activations during encoding and retrieval of environmental novel sounds using fMRI. An intentional memory task was applied in which subjects were required either to judge the sounds' loudness (nonverbal encoding task) or to indicate whether or not a sound can be verbally described (verbal encoding task). Retrieval processes were examined in a subsequent yes/no recognition test. In the study phase the right posterior dorsolateral prefrontal cortex (PFC) was activated in both tasks. During verbal encoding additional activation of the left dorsolateral PFC was obtained. Retrieval-related fMRI activity varied as a function of encoding task: For the nonverbal task we detected an activation focus in the right posterior dorsolateral PFC whereas an activation in the left dorsolateral PFC was observed for the verbal task. These findings indicate that the right dorsolateral PFC is engaged in encoding of auditory information irrespective of encoding task. The lateralization of PFC activity during retrieval was shown to depend on the availability of verbal codes, with left hemispheric involvement for verbally and right hemispheric activation for nonverbally coded information.     

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.     

Language Mapping with Verbs and Sentences in Awake Surgery: A Review

Intraoperative language mapping in awake surgery is typically conducted by asking the patient to produce automatic speech and to name objects. These tasks might not map language with sufficient accuracy, as some linguistic processes can only be triggered by tasks that use verbs and sentences. Verb and sentence processing tasks are currently used during surgery, albeit sparsely. Medline, PubMed, and Web of Science records were searched to retrieve studies focused on language mapping with verbs/sentences in awake surgery. We review the tasks reported in the published literature, spell out the language processes assessed by each task, list the cortical and subcortical regions whose stimulation inhibited language processing, and consider the types of errors elicited by stimulation in each region. We argue that using verb tasks allows a more thorough evaluation of language functions. We also argue that verb tasks are preferable to object naming tasks in the case of frontal lesions, as lesion and neuroimaging data demonstrate that these regions play a critical role in verb and sentence processing. We discuss the clinical value of these tasks and the current limitations of the procedure, and provide some guidelines for their development. Future research should aim toward a differentiated approach to language mapping – one that includes the administration of standardized and customizable tests and the use of longitudinal neurocognitive follow-up studies. Further work will allow researchers and clinicians to understand brain and language correlates and to improve the current surgical practice.     

Language comprehension vs. language production: age effects on fMRI activation

Normal language acquisition is a process that unfolds with amazing speed primarily in the first years of life. However, the refinement of linguistic proficiency is an ongoing process, extending well into childhood and adolescence. An increase in lateralization and a more focussed productive language network have been suggested to be the neural correlates of this process. However, the processes underlying the refinement of language comprehension are less clear. Using a language comprehension (Beep Stories) and a language production (Vowel Identification) task in fMRI, we studied language representation and lateralization in 36 children, adolescents, and young adults (age 6-24 years). For the language comprehension network, we found a more focal activation with age in the bilateral superior temporal gyri. No significant increase of lateralization with age could be observed, so the neural basis of language comprehension as assessed with the Beep Stories task seems to be established in a bilateral network by late childhood. For the productive network, however, we could confirm an increase with age both in focus and lateralization. Only in the language comprehension task did verbal IQ correlate with lateralization, with higher verbal IQ being associated with more right-hemispheric involvement. In some subjects (24%), language comprehension and language production were lateralized to opposite hemispheres.     

Hemispheric predominance assessment of phonology and semantics: a divided visual field experiment

The aim of the present behavioural experiment was to evaluate the most lateralized among two phonological (phoneme vs. rhyme detection) and the most lateralized among two semantic ("living" vs. "edible" categorization) tasks, within the dominant hemisphere for language. The reason of addressing this question was a practical one: to evaluate the degree of the hemispheric lateralization for several language tasks, by using the divided visual presentation of stimuli, and then choose the most lateralized semantic and phonological for mapping language in patients by using fMRI in future studies. During the divided visual field experiment by using words (semantic tasks) and pseudo-words (phonological tasks) as stimuli, thirty-nine right-handed participants were examined. Our results have shown that all tasks were significantly left hemisphere lateralized. Furthermore, the rhyme was significantly more lateralized than phoneme detection and "living" was significantly more lateralized than "edible" categorization. The rhyme decision and "living" categorization will be used in future fMRI studies for assessing hemispheric predominance and cerebral substrate for semantics and phonology in patients. Our results also suggest that the characteristics of stimuli could influence the degree of the hemispheric lateralization (i.e., the emotional charge of stimuli for words and the position of the phoneme to be detected, for pseudo-words).     

Focused and Nonfocused Attention in Verbal and Emotional Dichotic Listening: An FMRI Study

Functional magnetic resonance imaging (fMRI) was used to identify cortical regions which are involved in two dichotic listening tasks. During one task the subjects were required to allocate attention to both ears and to detect a specific target word (phonetic task), while during a second task the subjects were required to detect a specific emotional tone (emotional task). During three attentional conditions of each task, the subjects were required to focus attention to the right (FR) or left ear (FL), while during a third condition subjects were required to allocate attention to both ears simultaneously. In 11 right-handed male subjects, these dichotic listening tasks evoked strong activations in a temporofrontal network involving auditory cortices located in the temporal lobe and prefrontal brain regions. Hemodynamic responses were measured in the following regions of interest: Heschl's gyrus (HG), the planum polare (PP), the planum temporale (PT), the anterior superior temporal sulcus (aSTS), the posterior superior temporal sulcus (pSTS), and the inferior frontal gyrus region (IFG) of both hemispheres. The following findings were obtained: (1) the degree of activation in HG and PP depends on the direction of attention. In particular it was found that selectively attending to right-ear input led to increased activity specifically in the left HG and PP and attention to left ear input increased right-sided activity in these structures; (2) hemodynamic responses in the PT, aSTS, pSTS, and IFG were not modulated by the different focused-attention conditions; (3) hemodynamic responses in HG and PP in the nonforced conditions were the sum activation of the forced conditions; (4) there was no general difference between the phonetic and emotion tasks in terms of hemodynamic responses; (5) hemodynamic responses in the PT and pSTS were strongly left-lateralized, reflecting the specialization of these brain regions for language processing. These findings are discussed in the context of current theories of hemispheric specialization.     

Word and letter string processing networks in schizophrenia: evidence for anomalies and compensation

Imaging studies show that in normal language correlated activity between anterior and posterior brain regions increases as the linguistic and semantic content (i.e., from false fonts, letter strings, pseudo words, to words) of stimuli increase. In schizophrenia however, disrupted functional connectivity between frontal and posterior brain regions has been frequently reported and these disruptions may change the nature of language organization. We characterized basic linguistic operations in word and letter string processing in a region-of-interest network using structural equation modeling (SEM). Healthy volunteers and volunteers with schizophrenia performed an fMRI one-back matching task with real words and consonant letter strings. We hypothesized that left hemisphere network dysfunction in schizophrenia would be present during processes dealing with linguistic/semantic content. The modeling results suggest aberrant left hemisphere function in schizophrenia, even in tasks requiring minimal access to language. Alternative mechanisms included increases in right hemisphere involvement and increased top-down influence from frontal to posterior regions.     

The functional anatomy of inspection time: a pilot fMRI study

Seven healthy subjects underwent functional magnetic resonance imaging (fMRI) of the brain while performing an inspection time task. Employing a block-type design, the task had three difficulty levels: a control condition, an easy (200 ms stimulus duration), and a more difficult (40 ms) discrimination. Based on group results, there were widespread significant areas of difference in brain activation and deactivation when pairwise comparisons were conducted among the three task conditions. When the difficult condition was compared with the easy condition, there was relative activation in areas of the following brain regions: cingulate gyrus and some frontal and parietal lobe areas. Areas within the following regions showed relative deactivation (greater blood oxygenation level-dependent, BOLD, signal in the easy condition): frontal, temporal, and parietal lobe. There were overlaps between these areas and those found to be active while performing higher cognitive tasks in other functional brain imaging studies. These pilot data encourage future studies of the functional anatomy of inspection time and its relevance to psychometric intelligence.     

应用动态因果模型研究阅读神经网络背、腹侧通路的协作机制

在神经网络的最新取向下, 探讨阅读脑机制中背侧和腹侧通路的协作机制, 是解决语言认知神经科学多个理论问题共同面临的焦点。本项目拟通过两个脑功能成像实验, 建构汉字阅读的动态因果模型, 系统地考察汉字阅读的神经网络, 以及阅读网络中背、腹侧通路的协作机制。实验一利用快速适应实验范式的优点, 识别和考察汉字阅读涉及的认知成分所对应的功能脑区, 以及脑区联结形成的神经回路, 并建构汉字阅读的动态因果模型; 实验二进一步考察在刺激属性(语音和语义信息)和任务要求下阅读脑区的动态激活及相互作用。通过不同任务下的模型对比, 重点探讨阅读网络的脑区联结模式变化, 尤其是背、腹侧通路受刺激和任务影响时的协作机制。研究结果将为揭示阅读的神经生理模型、解决语言特异性脑区激活的争论等理论问题提供直接的证据, 还能为语言教学、阅读障碍矫治、以及临床应用提供理论基础与指导。     

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.     

Comparison of hemispheric activation during mental word and rhyme generation using transcranial Doppler sonography

The Wada test is at present the method of choice for preoperative assessment of patients who require surgery close to cortical language areas. It is, however, an invasive test with an attached morbidity risk. By now, an alternative to the Wada test is to combine a lexical word generation paradigm with non-invasive imaging techniques. However, results of this approach are still not in complete agreement with the findings of the Wada test (r = .92; Knecht, Deppe, Ebner et al., 1998). We attempted to obtain a more distinct language lateralization with the development of a phonological rhyme generation paradigm based on pseudoword stimuli. To examine the predictive value of both paradigms we performed simultaneous bilateral functional transcranial Doppler ultrasonography on 19 right-handed male native German subjects. The rhyme generation condition produced a significantly stronger lateralization to the supposed hemisphere of language dominance than the classical word generation condition. The observed differences suggest that the rhyme generation paradigm is more robust in detecting hemispheric language dominance than other neuropsychological paradigms and might be most valuable for preoperative assessment of cortical language areas.     

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.     

Age-related differences in the brain areas outside the classical language areas among adults using category decision task

Older adults perform much like younger adults on language. This similar level of performance, however, may come about through different underlying brain processes. In the present study, we evaluated age-related differences in the brain areas outside the typical language areas among adults using a category decision task. Our results showed that similar activation patterns were found in classical language processing areas across the three age groups although regional lateralization indices in Broca’s and Wernicke’s areas decreased with age. The greatest differences, however, among the three groups were found primarily in the brain areas not associated with core language functioning including the hippocampus, middle frontal gyrus, ventromedial frontal cortex, medial superior parietal cortex and posterior cingulate cortex. Therefore, the non-classical language areas may exhibit an age-related difference between three age groups while the subjects show a similar activation pattern in the core, primary language processing during a semantic decision task.