FMRI activation in language areas correlates with verb generation performance in children

Functional MRI mapping of language areas in children frequently employs a covert verb generation task. Because responses are not monitored, the relationship between fMRI activation and task performance is unknown. We compared fMRI activation during covert and overt verb generation to performance during the overt task. 15 children, ages 11-13 years, listened to concrete nouns and responded with related verbs covertly and overtly. A clustered fMRI acquisition allowed for recording of overt responses without motion artifacts. Region of interest analysis was also performed in areas that exhibited correlation between activation and performance during overt verb generation in left inferior frontal and left superior temporal gyri (along with their right hemisphere homologues). Regression analysis determined that during both covert and overt generation, left hemisphere regions showed positive correlations with average counts of verbs generated during the overt task. These results suggest that increased verb generation performance leads to increased activation. In addition, overt performance may be used as an estimator of covert performance.     

Left-hemisphere processing of emotional connotation during word generation

Areas of the brain's left hemisphere involved in retrieving words with emotional connotations were studied with fMRI. Participants silently generated words from different semantic categories which evoked either words with emotional connotations or emotionally neutral words. Participants repeated emotionally neutral words as a control task. Compared with generation of emotionally neutral words, generation of words with emotional connotations engaged cortices near the left frontal and temporal poles which are connected to the limbic system. Thus, emotional connotations of words are processed in or near cortices with access to emotional experience.     

Norwegian norms and factor-structure of phonemic and semantic word list generation

Word list generation (WLG) tasks are used world wide as measures of executive function, although the tests are sensitive also to deficits in other cognitive functions. Norms derived from English-speaking samples are often used in Norway, even though the consequences of language differences are not yet been assessed. The reliability of WLG testing in Norway is increased by the norms presented in the first part of the study. The validity of WLG tests as measures of executive function is addressed in the second part, by performing a factor-analysis of neuropsychological performance in a mixed psychiatric sample. Education contributed most to performance. There were no sex-differences in overall performance. Factor analysis indicated that phonemic WLG is a more specific measure of executive function than semantic WLG. Semantic WLG correlated higher with basal processing speed, thus being more sensitive to aging. In conclusion the clinical neuropsychologist is advised to control for reduction in basal processing speed before interpreting WLG scores as specific deficits in executive function. The Norwegian norms correspond well with most comparable studies in other languages, thus failing to show any language specific effects.     

Estimating verbal intelligence in unipolar depression: Comparison of word definition and word recognition

Depression is known to be associated with deficits in effortful processing and word fluency. Automatic processes, instead, appear largely intact in depressed patients. It was investigated whether active word definition could be a less appropriate method than passive word recognition as a measure of verbal intelligence in depression. The valid assessment of premorbid IQ is important for correct comparison with current cognitive efficiency of depressed individuals, since premorbid IQ serves as baseline or control parameter to estimate the extent and severity of acquired cognitive impairments, both in the clinical and the research context. Two vocabulary tests were administered to 90 patients (31 women) with unipolar depression and 30 control subjects (15 women): a word definition task [the vocabulary subtest of the Wechsler Adult Intelligence Scale (WAIS-R)] and a word recognition task [the Multiple choice vocabulary test (MWT)]. In the depressed sample, scores of the MWT tended to be higher than WAIS-R scores. For depressed women, the MWT score was significantly higher than the WAIS-R score. In the control sample, no differences between MWT and WAIS-R scores were observed. Our findings indicate that word definition tasks could underestimate verbal intelligence especially in depressed women. For depressed women, it could be more appropriate to administer word recognition than word definition as an estimate of premorbid or verbal intelligence.     

ERP nonword rhyming effects in children and adults

In a simple prime-target auditory rhyming event-related potential (ERP) paradigm with adults and 6-, 7-, and 8-year-old children, nonword stimuli (e.g., nin-rin, ked-voo) were used to investigate neurocognitive systems involved in rhyming and their development across the early school years. Even absent semantic content, the typical CNV to primes and late rhyming effect (RE) to targets were evident in all age groups. The RE consisted of a more negative response to nonrhyming targets as compared to rhyming targets over posterior sites, with a reversal of this pattern at lateral anterior sites. The hypothesis that the CNV indexes phonological memory processes was not well supported by correlation analyses conducted with the ERP measures and scores on standardized behavioral tests. However, the onset of the rhyming effect was later in those scoring lower on phonological awareness measures.     

Imagined viewer and object rotations dissociated with event-related FMRI

Human spatial reasoning may depend in part on two dissociable types of mental image transformations: object-based transformations, in which an object is imagined to move in space relative to the viewer and the environment, and perspective transformations, in which the viewer imagines the scene from a different vantage point. This study measured local brain activity with event-related fMRI while participants were instructed to either imagine an array of objects rotating (an object-based transformation) or imagine themselves rotating around the array (a perspective transformation). Object-based transformations led to selective increases in right parietal cortex and decreases in left parietal cortex, whereas perspective transformations led to selective increases in left temporal cortex. These results argue against the view that mental image transformations are performed by a unitary neural processing system, and they suggest that different overlapping systems are engaged for different image transformations.     

Altered hemispheric functional dominance during word generation in negative schizophrenia

Functional brain imaging studies have reported decreased frontal activations in schizophrenia, but hemispheric dominance for language has rarely been assessed. To investigate regional activation and lateralization during word production, we determined normalized regional cerebral blood flow (rCBF) variations with positron emission tomography (PET) and H2(15)O (water labeled with the isotope oxygen 15) in 14 negative schizophrenia patients and 14 volunteers. Subjects were scanned during two trials of three conditions: rest, vocalized verbal fluency, and spontaneous word production. Images were analyzed using an anatomical volumes of interest method, and the two groups' changes were compared, using rest as a baseline. Differences in the lateralization of changes were detected in homologous frontal and inferior parietal regions. The lateralization effects in patients arose from lower activations in the left frontal regions, abnormal right inferior frontal activations, and weaker right inferior parietal deactivation, during the word production tasks. The right hemisphere changes correlated negatively with the performance in verbal fluency. Thus in negative schizophrenia patients, while the activations were less focused on the left hemisphere regions usually engaged in word generation, rCBF changes in the right hemisphere might reflect a compensatory functional pattern.     

Frontal lobe activation during word generation studied by functional MRI

Aims – To further delimit the specific verbal operations occurring in the dorsolateral frontal cortex during the generation of words, methods – different verbal fluency tasks guided by distinct specifications (phonological, semantic, or automatic production of words) were used in a functional magnetic resonance study. The study group comprised 10 right-handed normal subjects ranging in age from 23 to 27 years. Functional magnetic resonance images were obtained in a 1.5-Tesla magnet using a spoiled GRASS sequence. Results – Noticeable activation was found during the word generation tasks in the dorsolateral frontal cortex. The region showing the most prominent activation was the posterior part of the left middle frontal gyrus. Nevertheless, the different tasks each had a different activation effect. The phonologically guided generation of words produced the most consistent activation of the middle frontal gyrus, which mainly involved the premotor cortex. Conclusion – The results suggest that operations concerned with the generation of sound sequences, rather than the amount of produced words or their semantics, are responsible for sustained focal activity observed in the frontal lobes during verbal fluency tasks.     

The cerebellum and its role in word generation: a cTBS study

The purpose of this study was to investigate the role of the cerebellum in the executive control of word generation using a phonemic and semantic fluency task. Phonemic fluency tasks require novel strategy to organize verbal output, and are more effortful than semantic fluency tasks. The number of category switches made between subcategories of words is a measure of mental flexibility, and is greatest during the early phase of the task (first 15 sec). Both tasks were tested on healthy participants, before and after the application of transcranial magnetic stimulation using continuous theta burst stimulation (cTBS) applied over the left or the right posterior/lateral cerebellar cortex in separate groups. We hypothesized that the number of category switches and number of words produced within the first 15 sec would be reduced after cTBS to the right, posterior-lateral cerebellum during phonemic fluency tasks. The results from the study were consistent with the hypothesis. Within the first 15 sec of each trial, right cTBS participants displayed significantly lower switching scores (p = .05) after stimulation. Previous studies have illustrated similar impairments in switching between categories during phonemic fluency performance in patients with damage to the left frontal cortex. Our findings support the general hypothesis of cerebellar involvement in executive control through connections to the frontal cortex.     

Visual event-related potentials of dyslexic children to rhyming and nonrhyming stimuli

Abstract

In a visual event-related potential (ERP) study, children diagnosed as dyslexic in terms of both age and IQ discrepancy criteria were compared with two contrast groups: poor for age (SLOW) readers and normal reading children with Attention Deficit Disorder (ADD). The children viewed 200 stimulus pairs and judged whether the second stimulus of each pair rhymed with the first. The first stimulus was always a three-letter word, while half of the second stimuli were pronounceable nonsense words and half were real words. Rhyme probability was 50%. The ERP waveforms of the dyslexics were significantly different from those of the ADD group in showing less late negativity. The SLOW group's waveforms more closely paralleled those of the ADD group. The major anomalous feature of the dyslexics' waveform was a pronounced late positive peak (P500), which followed an attenuated N450 peak. Over all groups, the N450 peak was sensitive to the rhyme manipulation, as has been found in adults (Rugg, 1984a, 1984b). Real words and nonsense words produced similar waveforms. Hemispheric effects were found but did not interact with group. Results suggest non-automatic visual cognitive processing of rhyme in dyslexics.     

Asymmetries in mouth opening during word generation in male stuttering and non-stuttering participants

We examined lateral asymmetries in mouth opening in right-handed male stuttering (N = 11) and non-stuttering (N = 14) participants. Lateral asymmetries in mouth opening were video-recorded and analysed in participants while they generated words beginning with the bilabial phones /b, p, m/. Non-stuttering participants showed an expected preference for right mouth opening during the task, whereas a group of stuttering participants who were matched for sex and age produced a left or bilateral pattern of mouth opening. Analysis of variance revealed the difference between the groups to be significant (p < .001). However, there was more variability in the lateral mouth asymmetries in the stuttering participants. We interpret this finding as adding some support for the hypothesis that aberrant hemispheric control for speech is involved in stuttering. Asymmetric mouth openings appear to have no direct linguistic function, and we discuss the possible implications of the phenomenon for models of speech planning and programming.     

Asymmetries in mouth opening during word generation in male stuttering and non-stuttering participants

We examined lateral asymmetries in mouth opening in right-handed male stuttering (N = 11) and non-stuttering (N = 14) participants. Lateral asymmetries in mouth opening were video-recorded and analysed in participants while they generated words beginning with the bilabial phones /b, p, m/. Non-stuttering participants showed an expected preference for right mouth opening during the task, whereas a group of stuttering participants who were matched for sex and age produced a left or bilateral pattern of mouth opening. Analysis of variance revealed the difference between the groups to be significant (p &lt; .001). However, there was more variability in the lateral mouth asymmetries in the stuttering participants. We interpret this finding as adding some support for the hypothesis that aberrant hemispheric control for speech is involved in stuttering. Asymmetric mouth openings appear to have no direct linguistic function, and we discuss the possible implications of the phenomenon for models of speech planning and programming.     

Analysis and use of FMRI response delays

In this study, we implemented a new method for measuring the temporal delay of functional magnetic resonance imaging (fMRI) responses and then estimated the statistical distribution of response delays evoked by visual stimuli (checkered annuli) within and across voxels in human visual cortex. We assessed delay variability among different cortical sites and between parenchyma and blood vessels. Overall, 81% of all responsive voxels showed activation in phase with the stimulus while the remaining voxels showed antiphase, suppressive responses. Mean delays for activated and suppressed voxels were not significantly different (P < 0.001). Cortical flat maps showed that the pattern of activated and suppressed voxels was dynamically induced and depended on stimulus size. Mean delays for blood vessels were 0.7-2.4 sec longer than for parenchyma (P < 0.01). However, both parenchyma and blood vessels produced responses with long delays. We developed a model to identify and quantify different components contributing to variability in the empirical delay measurements. Within-voxel changes in delay over time were fully accounted for by the effects of empirically measured fMRI noise with virtually no measurable variability associated with the stimulus-induced response itself. Across voxels, as much as 47% of the delay variance was also the result of fMRI noise, with the remaining variance reflecting fixed differences in response delay among brain sites. In all cases, the contribution of fMRI noise to the delay variance depended on the noise power at the stimulus frequency. White noise models significantly underestimated the fMRI noise effects.     

FMRI lateralization of expressive language in children with cerebral lesions

PURPOSE: Lateralization of language function is crucial to the planning of surgery in children with frontal or temporal lobe lesions. We examined the utility of functional magnetic resonance imaging (fMRI) as a determinant of lateralization of expressive language in children with cerebral lesions. METHODS: fMRI language lateralization was attempted in 35 children (29 with epilepsy) aged 8-18 years with frontal or temporal lobe lesions (28 left hemisphere, five right hemisphere, two bilateral). Axial and coronal fMRI scans through the frontal and temporal lobes were acquired at 1.5 Tesla by using a block-design, covert word-generation paradigm. Activation maps were lateralized by blinded visual inspection and quantitative asymmetry indices (hemispheric and inferior frontal regions of interest, at p<0.001 uncorrected and p<0.05 Bonferroni corrected). RESULTS: Thirty children showed significant activation in the inferior frontal gyrus. Lateralization by visual inspection was left in 21, right in six, and bilateral in three, and concordant with hemispheric and inferior frontal quantitative lateralization in 93% of cases. Developmental tumors and dysplasias involving the inferior left frontal lobe had activation overlying or abutting the lesion in five of six cases. fMRI language lateralization was corroborated in six children by frontal cortex stimulation or intracarotid amytal testing and indirectly supported by aphasiology in a further six cases. In two children, fMRI language lateralization was bilateral, and corroborative methods of language lateralization were left. Neither lesion lateralization, patient handedness, nor developmental versus acquired nature of the lesion was associated with language lateralization. Involvement of the left inferior or middle frontal gyri increased the likelihood of atypical language lateralization. CONCLUSIONS: fMRI lateralizes language in children with cerebral lesions, although caution is needed in interpretation of individual results.     

An fMRI study comparing brain activation between word generation and electrical stimulation of language-implicated acupoints

We compared the brain activation on functional magnetic resonance imaging (MRI) during word generation with the activation during electrical stimulation of two language-implicated acupoints in 17 healthy, Mandarin-speaking, Chinese male volunteers (age 19-26 years). All subjects were strongly right handed according to a handedness inventory. Using a standard functional MRI procedure and a word-generation paradigm, significant activation was seen in the left and right inferior frontal gyri (BA 44, 45) as well as the left superior temporal gyrus (BA 22, 42). Stronger activation with a larger volume was seen in the left hemisphere. Electrical stimulation of either one of the two language-implicated acupoints, SJ 8 (11 subjects) and Du 15 (6 subjects), without the word-generation paradigm in the same cohort, produced significant activation in the right inferior frontal gyrus (BA 44, 46) and in the left and right superior temporal gyri (BA 22, 42), respectively. Nevertheless, no activation was seen in the left inferior frontal gyrus. In addition, electrical stimulation of the adjacent non-acupoints did not produce any significant brain activation. Although our results support the notion of acupoint-brain activation, applying acupuncture at SJ 8 or Du 15 does not activate the typical language areas in the left inferior frontal cortex.     

Semantic category and rhyming processing in the left and right cerebral hemisphere

In this study, the question of hemispheric abilities in processing explicit semantic and phonological information was addressed by measuring response latencies and performances in two judgement tasks. In the semantic task, word pairs were sequentially presented to the left or right visual field and subjects were asked to judge whether these words were categorically related or not. In the phonological task, the same subjects were asked to decide whether pairs of orthographically dissimilar words rhymed or not. Statistical analysis showed that reaction times (RT) were significantly shorter in both tasks when words were presented to the right visual field. Furthermore, in the semantic task, faster responses were observed in both visual fields when the words were related than when they were unrelated. This response facilitation tended to be stronger when words were presented to the left visual field. This result is in accordance with other results obtained by lexical decision studies showing that priming in the right hemisphere is due to controlled processing. By contrast, RT differences between rhyming and non-rhyming word pairs in the phonological task did not reach significance. This supports previous findings showing that phonological facilitation cannot occur when orthographic and phonological indices are in conflict.     

An FMRI study of syntactic adaptation

It is easier to produce and comprehend a series of sentences when they have similar syntactic structures. This "syntactic priming" effect was investigated during silent sentence reading using (i) blood oxygenation level-dependent (BOLD) response as a physiological measure in an f MRI study and (ii) reading time as a behavioral measure in a complementary self paced reading paradigm. We found that reading time and left anterior temporal activation were decreased when subjects read sentences with similar relative to dissimilar syntactic forms. Thus, syntactic adaptation during sentence comprehension is demonstrated in a neural area that has previously been linked to both lexical semantic and sentence processing.     

Effect of retrieval effort and switching demand on fMRI activation during semantic word generation in schizophrenia

Verbal fluency deficits in schizophrenia are difficult to interpret because the tasks are multi-factorial and groups differ in total words generated. We manipulated retrieval and switching demands by requiring alternation between over-learned sequences in which retrieval is relatively automatic (OS) and semantic categories requiring increased retrieval effort (SC). Controlled processing was also manipulated by including switching and non-switching conditions, and formal thought disorder (FTD) was assessed with the communication disorders index (CDI). The OS/SC semantic fluency paradigm was administered during fMRI to 13 patients with schizophrenia and 14 matched controls. Images were acquired on a 3 Tesla Siemens scanner using compressed image acquisition to allow for cued overt word production. Subjects alternated between OS, SC, OS-switch, SC-switch, and baseline blocks. Images were pre-processed in SPM-2, and a two-stage random effects analysis tested within and between group contrasts. There were no group performance differences. fMRI analysis did not reveal any group differences during the OS non-switching condition. Both groups produced expected activation in bilateral prefrontal and inferior parietal regions. However, during the SC condition patients had greater activation than controls in left prefrontal, right anterior cingulate, right superior temporal, bilateral thalamus, and left parietal regions. There was also evidence of patient over-activation in prefrontal, superior temporal, superior parietal, and visual association areas when a switching component was added. FTD was negatively correlated with BOLD response in the right anterior cingulate, cuneus and superior frontal gyrus during increased retrieval demand, and positively correlated with fMRI activation in the left lingual gyrus, right fusiform gyrus and left superior parietal lobule during increased switching demand. These results indicate that patients are able to successfully perform effortful semantic fluency tasks during non-speeded conditions. When retrieval is relatively automatic there does not appear to be an effect of schizophrenia on fMRI response. However, when retrieval and controlled processing demands increase, patients have greater activation than controls despite unimpaired task performance. This inefficient BOLD response may explain why patients are slower and less accurate on standard self-paced fluency tasks.