Correlations between glucose metabolic rates in brain regions of healthy male adults at rest and during language stimulation

This study examines the effect of different behavioral conditions on patterns of correlation between regional cerebral metabolic rates for glucose. Cerebral glucose metabolism was determined with positron emission tomography and (11C)-deoxyglucose in 29 normal subjects between the ages of 23 and 55. Seventeen subjects were studied in an unstimulated (resting) condition and 12 subjects during a phoneme monitoring language stimulation. Partial correlation coefficients, controlling for whole brain glucose metabolism, were calculated for pairs of metabolic rates in 14 cortical and 2 subcortical regions. Both stimulated and unstimulated subjects showed statistically significant correlations between left and right hemisphere homologs. The stimulated subjects also showed significant within-hemisphere correlations between left but not right hemisphere regions. These included left perisylvian regions classically associated with language functions (left inferior frontal, left superior temporal and left transverse temporal cortical regions) as well as other regions. Significant correlations between left regions and a right superior temporal region were also found. In general, these findings show a pattern of cross-hemisphere symmetry at rest and of hemisphere asymmetry during stimulation. Moreover, the asymmetry observed during stimulation appears to be superimposed upon a pattern of cross-hemisphere symmetry similar to that observed in the unstimulated state.     

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.     

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.     

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.     

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.     

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.     

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.     

Cortical localization of finger spelling and oral language: A case study

Finger spelling of letters and words was mapped by means of the cortical stimulation procedure in a hearing patient undergoing a left dominant anterior temporal lobe resection for relief of a seizure disorder. Finger spelling was disrupted at five sites: three overlapping with one or more oral language functions at sites in the classical posterior language area, two relating only to finger spelling in the anterior temporal region. Following the resection which included these latter sites, both short- and long-term postoperative deficits in finger spelling are described. Implications for the organization of manually based communication behavior in the left hemisphere are discussed.     

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.     

Functional MRI of conventional and anomalous metaphors in Mandarin Chinese

This study looks at whether conventional and anomalous metaphors are processed in different locations in the brain while being read when compared with a literal condition in Mandarin Chinese. We find that conventional metaphors differ from the literal condition with a slight amount of increased activation in the right inferior temporal gyrus. In addition, when the anomalous metaphor condition is compared with the literal condition, increased activation occurs bilaterally in the frontal and temporal gyri. Lastly, the comparison between the anomalous and conventional metaphor conditions shows bilateral activation in the middle frontal gyrus and the precentral gyrus, and right-hemisphere activation in the superior frontal gyrus. Left hemisphere activation is found in the inferior frontal gyrus and fusiform gyrus. The left hemisphere activation in the frontal and temporal gyri point to the recruitment of traditional language-based areas for anomalous metaphor sentences, while the right-hemisphere activation found suggests that remote associations are being formed. In short, our study supports the idea that metaphors are not a homogenous type of figurative language and that distinguishing between different types of metaphors will advance theories of language comprehension.     

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.     

The angular gyrus in developmental dyslexia: task-specific differences in functional connectivity within posterior cortex

Converging evidence from neuroimaging studies of developmental dyslexia reveals dysfunction at posterior brain regions centered in and around the angular gyrus in the left hemisphere. We examined functional connectivity (covariance) between the angular gyrus and related occipital and temporal lobe sites, across a series of print tasks that systematically varied demands on phonological assembly. Results indicate that for dyslexic readers a disruption in functional connectivity in the language-dominant left hemisphere is confined to those tasks that make explicit demands on assembly. In contrast, on print tasks that do not require phonological assembly, functional connectivity is strong for both dyslexic and nonimpaired readers. The findings support the view that neurobiological anomalies in developmental dyslexia are largely confined to the phonological-processing domain. In addition, the findings suggest that right-hemisphere posterior regions serve a compensatory role in mediating phonological performance in dyslexic readers.     

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.     

Effective brain connectivity in children with reading difficulties during phonological processing

Using Dynamic Causal Modeling (DCM) and functional magnetic resonance imaging (fMRI), we examined effective connectivity between three left hemisphere brain regions (inferior frontal gyrus, inferior parietal lobule, fusiform gyrus) and bilateral medial frontal gyrus in 12 children with reading difficulties (M age=12.4, range: 8.11-14.10) and 12 control children (M age=12.3, range: 8.9-14.11) during rhyming judgments to visually presented words. More difficult conflicting trials either had similar orthography but different phonology (e.g. pint-mint) or similar phonology but different orthography (e.g. jazz-has). Easier non-conflicting trials had similar orthography and phonology (e.g. dime-lime) or different orthography and phonology (e.g. staff-gain). The modulatory effect from left fusiform gyrus to left inferior parietal lobule was stronger in controls than in children with reading difficulties only for conflicting trials. Modulatory effects from left fusiform gyrus and left inferior parietal lobule to left inferior frontal gyrus were stronger for conflicting trials than for non-conflicting trials only in control children but not in children with reading difficulties. Modulatory effects from left inferior frontal gyrus to inferior parietal lobule, from medial frontal gyrus to left inferior parietal lobule, and from left inferior parietal lobule to medial frontal gyrus were positively correlated with reading skill only in control children. These findings suggest that children with reading difficulties have deficits in integrating orthography and phonology utilizing left inferior parietal lobule, and in engaging phonological rehearsal/segmentation utilizing left inferior frontal gyrus possibly through the indirect pathway connecting posterior to anterior language processing regions, especially when the orthographic and phonological information is conflicting.     

Psychometric and CT scan measurements in a case of crossed aphasia in a dextral

A case of crossed aphasia with lesion deep to the right supramarginal gyrus was studied to determine (1) if this patient behaved similar to patients with the same lesion site in the left hemisphere, (2) if visuospatial deficits were present, and (3) if the CT scan asymmetries were similar to those of other right-handers. Speech and language skills were similar to those patients with similar lesions in the left hemisphere. Visuospatial and arithmetic deficits were similar to those described after right-hemisphere and left-hemisphere damage. CT scan asymmetries were atypical. These results provide behavioral and neuroradiological confirmation of atypical hemispheric dominance.     

Language localization and variability

Language localization data from 11 neurosurgical patients undergoing cortical resection for medically intractable focal epilepsy were obtained by mapping with bipolar electrical stimulation at current levels below sensory and after-discharge thresholds, during an object-naming task. The topographical extent of language cortex in an individual subject can be wider than that proposed in the classic maps. Within this zone, language is discretely localized, with different sites variably committed to language as measured by the naming function. The naming data from the left cortex of eight patients, all left-brain-dominant, were pooled to determine the variability within the primary language zone. Only a narrow band of posterior, inferior frontal lobe, immediately anterior to motor strip, showed involvement in all of the patients in whom it was sampled. This is a motor speech area; it constitutes only a small portion of the frontal language area. Other infero-frontal, parietal, and postero-temporal sites showed considerable variability, with naming involvement in only 50–80% of the patients sampled. There is a suggestion that some of these patterns of language localization may correlate with poorer verbal abilities. Data were also obtained on language localization in the left insula in a patient who was left-hemisphere-dominant for language. Mapping of the right hemisphere in a left-brain-dominant patient demonstrated no naming function. Mapping of the right hemisphere in one and the left hemisphere in another patient, both of whom were right-hemisphere-dominant for language, suggests more diffuse language representation with right hemisphere dominance.     

Transient beneficial effects of excitatory theta burst stimulation in a patient with phonological agraphia after left supramarginal gyrus infarction

We report a patient showing isolated phonological agraphia after an ischemic stroke involving the left supramarginal gyrus (SMG). In this patient, we investigated the effects of focal repetitive transcranial magnetic stimulation (rTMS) given as theta burst stimulation (TBS) over the left SMG, corresponding to the Brodmann area (BA) 40. The patient and ten control subjects performed a dictational words and nonwords writing task before, and 5 and 30 min after they received excitatory intermittent TBS (iTBS) over the left BA 40, the right hemisphere homologous to BA 40, the Wernicke’s area, or the primary visual cortex.ITBS over the left SMG lead to a brief facilitation of phonological non-words writing to dictation. This case study report illustrates that rTMS is able to influence, among other language functions, the phonological loading processes during the written language production in stroke patients.     

Cathodal transcranial direct current stimulation of the right Wernicke's area improves comprehension in subacute stroke patients

Previous studies have shown the appearance of right-sided language-related brain activity in right-handed patients after a stroke. Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been shown to modulate excitability in the brain. Moreover, rTMS and tDCS have been found to improve naming in non-fluent post-stroke aphasic patients. Here, we investigated the effect of tDCS on the comprehension of aphasic patients with subacute stroke. We hypothesized that tDCS applied to the left superior temporal gyrus (Wernicke’s area) or the right Wernicke’s area might be associated with recovery of comprehension ability in aphasic patients with subacute stroke. Participants included right-handed subacute stroke patients with global aphasia due to ischemic infarct of the left M1 or M2 middle cerebral artery. Patients were randomly divided into three groups: patients who received anodal tDCS applied to the left superior temporal gyrus, patients who received cathodal tDCS applied to the right superior temporal gyrus, and patients who received sham tDCS. All patients received conventional speech and language therapy during each period of tDCS application. The Korean-Western Aphasia Battery (K-WAB) was used to assess all patients before and after tDCS sessions. After intervention, all patients had significant improvements in aphasia quotients, spontaneous speech, and auditory verbal comprehension. However, auditory verbal comprehension improved significantly more in patients treated with a cathode, as compared to patients in the other groups. These results are consistent with the role of Wernicke’s area in language comprehension and the therapeutic effect that cathodal tDCS has on aphasia patients with subacute stroke, suggesting that tDCS may be an adjuvant treatment approach for aphasia rehabilitation therapy in patients in an early stage of stroke.     

Reorganization of functional and effective connectivity during real-time fMRI-BCI modulation of prosody processing

Mechanisms of cortical reorganization underlying the enhancement of speech processing have been poorly investigated. In the present study, we addressed changes in functional and effective connectivity induced in subjects who learned to deliberately increase activation in the right inferior frontal gyrus (rIFG), and improved their ability to identify emotional intonations by using a real-time fMRI Brain-Computer Interface. At the beginning of their training process, we observed a massive connectivity of the rIFG to a widespread network of frontal and temporal areas, which decreased and lateralized to the right hemisphere with practice. Volitional control of activation strengthened connectivity of this brain region to the right prefrontal cortex, whereas training increased its connectivity to bilateral precentral gyri. These findings suggest that changes of connectivity in a functionally specific manner play an important role in the enhancement of speech processing. Also, these findings support previous accounts suggesting that motor circuits play a role in the comprehension of speech.     

Neural correlates of metaphor processing: The roles of figurativeness,familiarity and difficulty

There is currently much interest in investigating the neural substrates of metaphor processing. In particular, it has been suggested that the right hemisphere plays a special role in the comprehension of figurative (non-literal) language, and in particular metaphors. However, some studies find no evidence of right hemisphere involvement in metaphor comprehension (e.g. [Lee, S. S., & Dapretto, M. (2006). Metaphorical vs. literal word meanings: fMRI evidence against a selective role of the right hemisphere. NeuroImage, 29, 536–544; Rapp, A. M., Leube, D. T., Erb, M., Grodd, W., & Kircher, T. T. J. (2004). Neural correlates of metaphor processing. Cognitive Brain Research, 20, 395–402]). We suggest that lateralization differences between literal and metaphorical language may be due to factors such as differences in familiarity ([Schmidt, G. L., DeBuse, C. J., & Seger, C. A. (2007). Right hemisphere metaphor processing? Characterizing the lateralization of semantic processes. Brain and Language, 100, 127–141]), or difficulty ([Bookheimer, S. (2002). Functional MRI of language: New approaches to understanding the cortical organization of semantic processing. Annual Review of Neuroscience, 25, 151–188; Rapp, A. M., Leube, D. T., Erb, M., Grodd, W., & Kircher, T. T. J. (2004). Neural correlates of metaphor processing. Cognitive Brain Research, 20, 395–402]) in addition to figurativeness. The purpose of this study was to separate the effects of figurativeness, familiarity, and difficulty on the recruitment of neural systems involved in language, in particular right hemisphere mechanisms. This was achieved by comparing neural activation using functional magnetic resonance imaging (fMRI) between four conditions: literal sentences, familiar and easy to understand metaphors, unfamiliar and easy to understand metaphors, and unfamiliar and difficult to understand metaphors. Metaphors recruited the right insula, left temporal pole and right inferior frontal gyrus in comparison with literal sentences. Familiar metaphors recruited the right middle frontal gyrus when contrasted with unfamiliar metaphors. Easy metaphors showed higher activation in the left middle frontal gyrus as compared to difficult metaphors, while difficult metaphors showed selective activation in the left inferior frontal gyrus as compared to easy metaphors. We conclude that the right hemisphere is involved in metaphor processing and that the factors of figurativeness, familiarity and difficulty are important in determining neural recruitment of semantic processing.