Cerebral lateralization of frontal lobe language processes and lateralization of the posterior visual word processing system

The brain areas involved in visual word processing rapidly become lateralized to the left cerebral hemisphere. It is often assumed this is because, in the vast majority of people, cortical structures underlying language production are lateralized to the left hemisphere. An alternative hypothesis, however, might be that the early stages of visual word processing are lateralized to the left hemisphere because of intrinsic hemispheric differences in processing low-level visual information as required for distinguishing fine-grained visual forms such as letters. If the alternative hypothesis was correct, we would expect posterior occipito-temporal processing stages still to be lateralized to the left hemisphere for participants with right hemisphere dominance for the frontal lobe processes involved in language production. By analyzing event-related potentials of native readers of French with either left hemisphere or right hemisphere dominance for language production (determined using a verb generation task), we were able to show that the posterior occipito-temporal areas involved in visual word processing are lateralized to the same hemisphere as language production. This finding could suggest top-down influences in the development of posterior visual word processing areas.     

Hemispheric language dominance in children demonstrated by functional magnetic resonance imaging

The objective of this study was to demonstrate hemispheric language dominance in normal children. Fifteen normal children were evaluated with functional magnetic resonance imaging (MRI) using an age-related silent word spelling paradigm. The data were analyzed with the cross-correlation method, and lateralization indices were calculated in language regions as determined by Talairach coordinates. Activation foci were detected in the left inferior frontal area and were strongly lateralized, with language lateralization indices of 0.74 +/- 0.21 (age 7-12 years, nine subjects), and 0.79 +/- 0.18 (13-18 years, six subjects). The indices were similar to those for adults (0.83 +/- 0.21, four subjects). Our study established that language is strongly lateralized to the left hemisphere in children as young as 7 years of age.     

Unsuspected atypical hemispheric dominance for language as determined by fMRI

PURPOSE: We sought to illustrate the value of functional magnetic resonance imaging (fMRI) in the presurgical assessment of hemispheric dominance for language by means of an illustrative case report. METHODS: fMRI with two language paradigms was performed in a right-handed patient without familial sinistrality suffering from a left frontal focal epilepsy. RESULTS: Both fMRI paradigms revealed unequivocally lateralized right hemispheric activation. Atypical language representation was confirmed by Wada test. The further presurgical workup could be restricted to subdural strip recordings instead of the initially intended grid implantation. After resective surgery, no language deficits were apparent. CONCLUSIONS: Hemispheric dominance for language should be assessed by fMRI in all patients before surgery in areas potentially relevant for language in either cerebral hemisphere. fMRI may influence the further diagnostic workup and should be performed before other invasive diagnostic procedures.     

Mixed lateralization of phonological assembly in developmental dyslexia

Developmental phonological dyslexia has been characterized as a deficit in phonological assembly. At a neural level, it is possible that this deficit is represented by weak connectivity between anterior and posterior language systems in the left hemisphere. This study used 3-Tesla functional magnetic resonance imaging to investigate phonological assembly in a developmental phonological dyslexic. The phonological dyslexic showed increased activation in the left hemisphere of the inferior frontal gyrus (BA 44/6) and increased activation in the right hemisphere of the parietal cortex (BA 7), occipital cortex (BA 18), and in the cerebellum, as phonological demands were systematically increased. Converging evidence suggests that the core dysfunction in phonological dyslexia resides in and around the angular gyrus of the left hemisphere. This study supports the compensatory role of posterior regions in the right hemisphere together with the left inferior frontal gyrus.     

A relationship between metabolism in frontal lobes and cerebellum in normal subjects studied with PET

Lesions of one cerebral hemisphere are associated with decreased glucose metabolism, oxygen metabolism, and blood flow in the contralateral cerebellar hemisphere. We used positron emission tomography to look for a functional relationship in cerebral metabolism between the cerebral cortex and the contralateral cerebellum in normal human subjects. Twenty-four normal subjects were scanned with [18F]fluoro-2-deoxy-D-glucose while in a resting state. Asymmetry in local CMRglu (LCMRglu) in the frontal cortex was strongly correlated with asymmetry in LCMRglu in the opposite direction in the cerebellar hemispheres (r = -0.60, p less than 0.001). Widespread subregions of the frontal cortex were found to contribute to this relationship. Considering these results together with previous studies demonstrating that frontal lesions are associated with decreased metabolism in the contralateral cerebellum, we conclude that the frontal cortex exerts a strong modulating influence on metabolism in the contralateral cerebellum in normal subjects, and that this influence may be asymmetrical.     

Specific cerebellar activation during Braille reading in blind subjects

The traditional view that the cerebellum is involved only in the control of movements has been changed recently. It has been suggested that the human cerebellum is involved in cognition and language. Likewise, besides cortical activity in sensorimotor and visual areas, an increased global activation of the cerebellum has been revealed during Braille reading in blind subjects. Our purpose was to investigate whether there is cerebellar activation during Braille reading by blind subjects other than sensorimotor activation related to finger movements. Early blind and normal sighted subjects were studied with functional magnetic resonance imaging (fMRI) during Braille reading, tactile discrimination of nonsense dots, dots forming symbols, and finger tapping. The experiments were done in block design. Echo planar imaging sequences were carried out on a 1.5-T MR scanner. All blind individuals reading Braille showed robust activation of the posterior and lateral aspects of cerebellar hemispheral lobules Crus I bilaterally but more predominately on the right side. Additionally, activation was present in the medial cerebellum within lobules IV, V, and VIIIA, predominantly on the right. Discriminating nonsense dots did not reveal any activation of Crus I, but did reveal activation within the medial part of lobules IV, V, and VIIIA, predominately on the right. Analysis of sighted subjects during reading of printed text revealed activation of the posterolateral cerebellar hemisphere in Crus I bilaterally, predominantly on the right. Tactile analysis of dots representing symbols revealed an activation in lobules IV and VIII and in right Crus II but not in Crus I. In conclusion, parts of cerebellar activation during Braille reading in blind subjects (i.e., within lobules IV, V, and VIII) overlap with the known hand representation within the cerebellum and are likely related to the sensorimotor part of the task. Cerebellar activation during Braille reading within bilateral Crus I may be due to language processes or inner speech similar to those found during text reading in normal sighted subjects. Object recognition did not account for Crus I activation.     

Paradoxical Activation in the Cerebellum During Language fMRI in Patients with Brain Tumors: Possible Explanations Based on Neurovascular Uncoupling and Functional Reorganization

The cerebellum is known for its crossed activation pattern with the contralateral cerebral hemisphere during language functional magnetic resonance imaging (fMRI) tasks in healthy patients. Crossed cerebro-cerebellar activation has been previously shown to occur in patients with brain tumors not affecting the activation areas. However, the presence of a tumor in left Broca’s area in the inferior frontal gyrus is known to disrupt cerebral activation during language tasks. This study investigated if crossed cerebro-cerebellar activation patterns for language tasks would still occur in such patients. A total of 43 right-handed patients with a glioma affecting left Broca’s area were examined for their cerebral and cerebellar activation during an fMRI language task. Only 13 of the 43 patients exhibited crossed cerebro-cerebellar activation patterns. Statistically significant differences of atypical cerebro-cerebellar activation patterns were found between cerebral right-dominant (RD) and cerebral co-dominant (CD) (p?<?0.001) as well as cerebral RD and cerebral left-dominant (LD) patients (p?<?0.01), while no differences were found when patients were divided based on cerebellar dominance (p?>?0.75) or tumor grade (p?>?0.5). No relation was found between the cerebellar and cerebral laterality index (LI) values (ρ?=???0.20; p?=?0.21). Atypical activation patterns are suspected to have been caused by the tumor, perhaps a result of contralateral reorganization in some cases and false negative activation in left Broca’s area from neurovascular uncoupling (NVU) in others. Cerebellar activation may also potentially indicate cerebral false negative behavior and future cerebral contralateral reorganization.     

Atypical hemispheric dominance for attention: functional MRI topography.

The right hemisphere is predominantly involved in tasks associated with spatial attention. However, left hemispheric dominance for spatial attention can be found in healthy individuals, and both spatial attention and language can be lateralized to the same hemisphere. Little is known about the underlying regional distribution of neural activation in these 'atypical' individuals. Previously a large number of healthy subjects were screened for hemispheric dominance of visuospatial attention and language, using functional Doppler ultrasonography. From this group, subjects were chosen who were 'atypical' for hemispheric dominance of visuospatial attention and language, and their pattern of brain activation was studied with functional magnetic resonance imaging during a task probing spatial attention. Right-handed subjects with the 'typical' pattern of brain organization served as control subjects. It was found that subjects with an inverted lateralization of language and spatial attention (language right, attention left) recruited left-hemispheric areas in the attention task, homotopic to those recruited by control subjects in the right hemisphere. Subjects with lateralization of both language and attention to the right hemisphere activated an attentional network in the right hemisphere that was comparable to control subjects. The present findings suggest that not the hemispheric side, but the intrahemispheric pattern of activation is the distinct feature for the neural processes underlying language and attention.     

Metabolic Changes of Cerebrum by Repetitive Transcranial Magnetic Stimulation over Lateral Cerebellum: A Study with FDG PET

To better understand the functional role of cerebellum within the large-scale cerebellocerebral neural network, we investigated the changes of neuronal activity elicited by cerebellar repetitive transcranial magnetic stimulation (rTMS) using (18)F-fluorodeoxyglucose (FDG) and positron emission tomography (PET). Twelve right-handed healthy volunteers were studied with brain FDG PET under two conditions: active rTMS of 1?Hz frequency over the left lateral cerebellum and sham stimulation. Compared to the sham condition, active rTMS induced decreased glucose metabolism in the stimulated left lateral cerebellum, the areas known to be involved in voluntary motor movement (supplementary motor area and posterior parietal cortex) in the right cerebral hemisphere, and the areas known to be involved in cognition and emotion (orbitofrontal, medial frontal, and anterior cingulate gyri) in the left cerebral hemisphere. Increased metabolism was found in cognition- and language-related brain regions such as the left inferior frontal gyrus including Broca's area, bilateral superior temporal gyri including Wernicke's area, and bilateral middle temporal gyri. Left cerebellar rTMS also led to increased metabolism in the left cerebellar dentate nucleus and pons. These results demonstrate that rTMS over the left lateral cerebellum modulates not only the target region excitability but also excitability of remote, but interconnected, motor-, language-, cognition-, and emotion-related cerebral regions. They provide further evidence that the cerebellum is involved not only in motor-related functions but also in higher cognitive abilities and emotion through the large-scale cerebellocereberal neural network.     

Plasticity of language networks in patients with brain tumors: a positron emission tomography activation study.

We investigated plasticity of language networks exposed to slowly evolving brain damage. Single subject 0-15-water language activation positron emission tomography studies were analyzed in 61 right-handed patients with brain tumors of the left hemisphere, and 12 normal controls. In controls, activations were found in left Brodmann's Area (BA)44 and BA45, superior posterior temporal gyrus bilaterally, and right cerebellum. Patients additionally activated left BA46, BA47, anterior insula, and left cerebellum. Superior temporal activation was less frequent, and activations in areas other than posterior temporal gyrus were found bilaterally. Frontolateral activations within the nondominant hemisphere were only seen in patients (63%) with frontal or posterior temporal lesions. Laterality indices of frontolateral cortex showed reversed language dominance in 18% of patients. Laterality indices of the cerebellum were negatively correlated with language performance. Two compensatory mechanisms in patients with slowly evolving brain lesions are described: An intrahemispheric mechanism with recruitment of left frontolateral regions other than classic language areas; and an interhemispheric compensatory mechanism with frontolateral activation in the nondominant hemisphere. The latter one was only found in patients with frontal or posterior temporal lesions, thus supporting the hypothesis that right frontolateral activations are a disinhibition phenomenon.     

Recovery from wernicke's aphasia: A positron emission tomographic study

Changes in the organization of the brain after recovery from aphasia were investigated by measuring increases in regional cerebral blood flow (rCBF) during repetition of pseudowords and during verb generation. Six right-handed patients who had recovered from Wernicke's aphasia caused by an infarction destroying the left posterior perisylvian language zone were compared with 6 healthy, right-handed volunteers. In the control subjects, strong rCBF increases were found in the left hemisphere in the posterior part of the superior and middle temporal gyrus (Wernicke's area), and during the generation task in lateral prefrontal cortex (LPFC) and in inferior frontal gyrus (Broca's area). There were some weak right hemisphere increases in superior temporal gyrus and inferior premotor cortex. In the patients, rCBF increases were preserved in the frontal areas. There was clear right hemisphere activation in superior temporal gyrus and inferior premotor and lateral prefrontal cortices, homotopic to the left hemisphere language zones. Increased left frontal and right perisylvian activity in patients with persisting destruction of Wernicke's area emphasizes redistribution of activity within the framework of a preexisting, parallel processing and bilateral network as the central mechanism in functional reorganization of the language system after stroke.     

Cerebral and cerebellar motor activation abnormalities in a subject with Joubert syndrome: functional magnetic resonance imaging (MRI) study

Joubert syndrome is an autosomal recessive disorder characterized by hypotonia, ataxia, developmental delay, and a distinctive hindbrain malformation involving the cerebellum and brain stem, visualized radiographically on magnetic resonance imaging (MRI) as the "molar tooth sign." In postmortem brains from subjects with Joubert syndrome, there is an apparent absence of decussation of both corticospinal and superior cerebellar tracts, although the functional significance has not been elucidated. We sought to explore the cerebral and cerebellar activation pattern elicited by finger tapping in an adolescent with Joubert syndrome and in a normal control subject using functional MRI. In contrast to the typical highly lateralized activation seen in our control subject, the subject with Joubert syndrome demonstrated striking bilateral activation of the sensorimotor and cerebellar cortex. Although our functional MRI data do not indicate a clear absence of decussation, the abnormal activation pattern observed suggests altered brain functional organization in relation to anatomic differences. Malformation of the hindbrain could result in recruitment of alternative pathways, similar to what has been observed following ischemic injury to the developing or mature central nervous system.     

Preoperative assessment of the cerebral hemispheric dominance for language with CBF PET

This study evaluated whether cerebral blood flow positron emission tomography (CBF PET) could provide assessments of language dominance comparable to the invasive reference method, the Wada test (selective intracarotid injection of amytal with cognitive testing subsequent to the anesthesia of each hemisphere). In 9 of 11 patients with partial complex epilepsy who were operative candidates, the Wada test lateralized unequivocally; in two subjects Wasa results were indeterminate (no speech arrest following injection of either carotid). Of four brain regions selected a priori for PET analysis based on techniques developed from studies of normal volunteers, anterior frontal cortex (AFC) was most consistently detectable and lateralized. AFC laterality agreed with Wada laterality in eight of the nine subjects lateralized by Wada. In both subjects having an indeterminate Wada, PET demonstrated clear laterality. In one subject both PET and Wada lateralized, but in disagreement; anterior temporal lobectomy in the hemisphere indicated by PET as language-dominant caused long-lasting language impairment. We conclude that CBF PET: (1) provides an effective, noninvasive adjunct to the Wada test; and (2) permits assessment of language dominance in normal research volunteers. © 1993 Wiley-Liss, Inc.     

Cerebrocerebellar relationship during behavioral activation: a PET study

The effect of behavioral activation on cerebral and cerebellar glucose metabolism was studied in normal subjects when performing either a verbal memory task or a tactile somatosensory task. Each subject was also studied in a resting state control condition, either 1 h earlier or later than the activation task. Compared to the resting state, both tasks produced asymmetrical metabolic activation, which was opposite in direction within the cerebral and cerebellar hemispheres. In both tasks, the difference of activation of CMRglc in the right and left hemispheres in the cerebellum was negatively correlated with that in the sensory-motor region. This apparently coupled metabolic activation of one cerebellum and areas within the opposite cerebral hemisphere represents the inverse of the crossed cerebellar diaschisis phenomenon commonly observed when a vascular lesion affects one cerebral hemisphere and hypometabolism occurs in the opposite cerebellum. Because these correlations were selective and concordant with known anatomical connections, and were found in two different tasks, they suggest strong functional connections between these specific brain regions.     

Neural substrates of emotion as revealed by functional magnetic resonance imaging.

OBJECTIVES: To examine the brain circuitry involved in emotional experience and determine whether the cerebral hemispheres are specialized for positive and negative emotional experience. BACKGROUND: Recent research has provided a preliminary sketch of the neurologic underpinnings of emotional processing involving specialized contributions of limbic and cortical brain regions. Electrophysiologic, functional imaging, and Wada test data have suggested positive, approach-related emotions are associated with left cerebral hemisphere regions, whereas negative, withdrawal-related emotions appear to be more aligned with right hemisphere mechanisms. METHOD: These emotional-neural associations were investigated using functional magnetic resonance imaging in 10 healthy controls with 20 positively and 20 negatively valenced pictures from the International Affective Picture System in a counterbalanced order. Pictures were viewed within a 1.5 Telsa scanner through computerized video goggles. RESULTS: Emotional pictures resulted in significantly increased blood flow bilaterally in the mesial frontal lobe/anterior cingulate gyrus, dorsolateral frontal lobe, amygdala/anterior temporal regions, and cerebellum. Negative emotional pictures resulted in greater activation of the right hemisphere, and positive pictures caused greater activation of the left hemisphere. CONCLUSIONS: Results are consistent with theories emphasizing the importance of circuitry linking subcortical structures with mesial temporal, anterior cingulate, and frontal lobe regions in emotion and with the valence model of emotion that posits lateralized cerebral specialization for positive and negative emotional experience.     

Widespread and lateralized social brain activity for processing dynamic facial expressions

Dynamic facial expressions of emotions constitute natural and powerful means of social communication in daily life. A number of previous neuroimaging studies have explored the neural mechanisms underlying the processing of dynamic facial expressions, and indicated the activation of certain social brain regions (e.g., the amygdala) during such tasks. However, the activated brain regions were inconsistent across studies, and their laterality was rarely evaluated. To investigate these issues, we measured brain activity using functional magnetic resonance imaging in a relatively large sample (n = 51) during the observation of dynamic facial expressions of anger and happiness and their corresponding dynamic mosaic images. The observation of dynamic facial expressions, compared with dynamic mosaics, elicited stronger activity in the bilateral posterior cortices, including the inferior occipital gyri, fusiform gyri, and superior temporal sulci. The dynamic facial expressions also activated bilateral limbic regions, including the amygdalae and ventromedial prefrontal cortices, more strongly versus mosaics. In the same manner, activation was found in the right inferior frontal gyrus (IFG) and left cerebellum. Laterality analyses comparing original and flipped images revealed right hemispheric dominance in the superior temporal sulcus and IFG and left hemispheric dominance in the cerebellum. These results indicated that the neural mechanisms underlying processing of dynamic facial expressions include widespread social brain regions associated with perceptual, emotional, and motor functions, and include a clearly lateralized (right cortical and left cerebellar) network like that involved in language processing.     

Speech activation SPECT and plasticity of language networks

Neuronal activity might be measured by regional cerebral blood flow (rCBF) Single Photon Emission Computed Tomography (SPECT) as there is a close relationship between neuronal activity and rCBF changes. In order to study the hemispheric dominance for language and the plasticity of language networks by measuring the rCBF rest and language activation SPECT studies were performed in the presurgical evaluation of ten right-handed and two left handed patients with brain lesions of the dominant hemisphere. A special group of hemisphere-specific neuropsychologic tasks were used for activation, after a proper psychologic conditioning. The rCBF results were calculated by comparing the rest and activation SPECT data using a special regions of interest program and asymmetry index (AI). We compared the results of speech-activation to the results of clinical, morphological (MRI), and postoperative data. In controls, significant activation was found in Brodmann's area 44 and 45, contralateral cerebellum, superior middle and posterior temporal gyrus. In patients, additional regions of activation were seen in contralateral frontal and temporal regions, and in ipsilateral temporal region. AIs of the cerebellum demonstrated a negative correlation with hemispheric dominance for language. In conclusion, significant changes in rCBF in or adjacent to the eloquent areas with various patterns of rCBF changes of the additional regions demonstrate the close relationship between neuronal activity and cerebral blood flow, that can be measured by SPECT.     

Interference of left and right cerebellar rTMS with procedural learning

Increasing evidence suggests cerebellar involvement in procedural learning. To further analyze its role and to assess whether it has a lateralized influence, in the present study we used a repetitive transcranial magnetic stimulation interference approach in a group of normal subjects performing a serial reaction time task. We studied 36 normal volunteers: 13 subjects underwent repetitive transcranial magnetic stimulation on the left cerebellum and performed the task with the right (6 subjects) or left (7 subjects) hand; 10 subjects underwent repetitive transcranial magnetic stimulation on the right cerebellum and performed the task with the hand ipsilateral (5 subjects) or contralateral (5 subjects) to the stimulation; another 13 subjects served as controls and were not submitted to repetitive transcranial magnetic stimulation; 7 of them performed the task with the right hand and 6 with the left hand. The main results show that interference with the activity of the lateral cerebellum induces a significant decrease of procedural learning: Interference with the right cerebellar hemisphere activity induces a significant decrease in procedural learning regardless of the hand used to perform the serial reaction time task, whereas left cerebellar hemisphere activity seems more linked with procedural learning through the ipsilateral hand. In conclusion, the present study shows for the first time that a transient interference with the functions of the cerebellar cortex results in an impairment of procedural learning in normal subjects and it provides new evidences for interhemispheric differences in the lateral cerebellum.     

The effects of gender on the neural substrates of pitch memory

Imaging studies have indicated that males and females differ anatomically in brain regions thought to underlie language functions. Functional studies have corroborated this difference by showing gender differences in terms of language processing with females relying on less lateralized processing strategies than males. Gender differences in musical functions might show similar differences in functional asymmetries, although no detailed study has been performed. The current study employed a pitch memory task while acquiring functional magnetic resonance images to investigate possible differences in hemispheric processing between males and females. Gender differences were found in the time course of activation (during the first four imaging time points after the end of the auditory stimulus-"perceptual phase"-and the subsequent three imaging time points after the end of the auditory stimulus-"memory phase") in both anterior and posterior perisylvian regions. Male subjects had greater lateralized activations (left > right) in anterior and posterior perisylvian regions during the "perceptual" as well as during the "memory" phase. There was a trend for males to have more cerebellar activation than females. Females showed more prominently posterior cingulate/retrosplenial cortex activation compared to males. Although activation patterns differed, there was no difference in the behavioral performance between both genders. These data indicate that similar to language studies, males rely more on left lateralized hemispheric processing even for basic pitch tasks.     

Cerebral lateralization of language in normal left-handed people studied by functional MRI

OBJECTIVE: To use functional MRI (fMRI) to further define the occurrence of left-hemisphere, bilateral, and right-hemisphere language in a normal left-handed population. METHODS: A total of 100 healthy volunteers, consisting of 50 left-handed subjects and a reference group of 50 right-handed subjects, were studied by fMRI of the frontal cortex during silent word generation. RESULTS: Ninety-six percent of right-handed subjects showed fMRI changes lateralized to the left hemisphere, whereas 4% showed a bilateral activation pattern. In contrast, left-hemisphere lateralization occurred in 76% of left-handers, bilateral activation in 14%, and right-hemisphere lateralization in the remaining 10%. The predominance of right-hemisphere activation, however, was weak in these cases; only a single left-handed subject (2%) showed complete right-hemisphere lateralization. CONCLUSIONS: Silent word generation lateralizes to the left cerebral hemisphere in both handedness groups, but right-hemisphere participation is frequent in normal left-handed subjects. Exclusive right-hemisphere activation rarely occurred in the frontal lobe region studied.