Spatio-temporal cortical dynamics of phonemic and semantic fluency

Hemodynamic brain imaging and lesion studies have suggested differential involvement of expressive language-related cortical regions based on the phonemic versus semantic characteristics of verbal cues. The aims of this study were: 1) to elucidate the relative timing of the activity of inferior frontal and anterior insular versus motor and supplementary motor cortex during a fluency task and 2) to assess potential differences in the location or timing of activity in anterior and posterior language areas based on letter versus category cues. Using magnetic source imaging (MSI), we found significantly earlier onset latencies and a greater number of activity sources in motor and supplementary motor compared with inferior frontal and anterior insular regions. We also observed greater left versus right hemispheric asymmetry of activation for letter compared with category cues. This study provides new insights into cortico-cortical interactions during expressive language tasks.     

Differential cerebral activation during observation of expressive gestures and motor acts

We compared brain activation involved in the observation of isolated right hand movements (e.g. twisting a lid), body-referred movements (e.g. brushing teeth) and expressive gestures (e.g. threatening) in 20 healthy subjects by using functional magnetic resonance imaging (fMRI). Perception-related areas in the occipital and inferior temporal lobe but also the mirror neuron system in the lateral frontal (ventral premotor cortex and BA 44) and superior parietal lobe were active during all three conditions. Observation of body-referred compared to common hand actions induced increased activity in the bilateral posterior superior temporal sulcus (STS), the left temporo-parietal lobe and left BA 45. Expressive gestures involved additional areas related to social perception (bilateral STS, temporal poles, medial prefrontal lobe), emotional processing (bilateral amygdala, bilateral ventrolateral prefrontal cortex (VLPFC), speech and language processing (Broca's and Wernicke's areas) and the pre-supplementary motor area (pre-SMA). In comparison to body-referred actions, expressive gestures evoked additional activity only in the left VLPFC (BA 47). The valence-ratings for expressive gestures correlated significantly with activation intensity in the VLPFC during expressive gesture observation. Valence-ratings for negative expressive gestures correlated with right STS-activity. Our data suggest that both, the VLPFC and the STS are coding for differential emotional valence during the observation of expressive gestures.     

Neural correlates of memory organization deficits in schizophrenia. A single photon emission computed tomography study with 99mTc-ethyl-cysteinate dimer during a verbal learning task

Regional cerebral blood flow (rCBF) during a verbal learning task was measured using 99mTc-ethyl-cysteinate dimer and single photon emission computed tomography in 10 patients with schizophrenia and nine normal controls. Verbal repetition was used as a control task. The schizophrenic patients showed failure to spontaneously utilize implicit category information to learn the word lists. In the normal controls, rCBF in the left inferior frontal and left anterior cingulate regions was significantly increased during the verbal learning task, compared with the verbal repetition task. In contrast, there was no significant frontal lobe activation by the verbal learning in the schizophrenic patients. The patients had lower rCBF during the verbal learning task than the controls in the bilateral inferior frontal, left anterior cingulate, right superior frontal, and bilateral middle frontal regions. Activation in the left inferior frontal region was significantly positively correlated with categorical clustering in the task in the controls, but no such correlation was found in the patients. These results indicate that memory organization deficits in schizophrenia may be related to dysfunction in the prefrontal areas, especially in the left inferior frontal region.     

Compensatory recruitment after sleep deprivation and the relationship with performance

This study examined the effects of total sleep deprivation (TSD) on cerebral responses to a verbal learning task with two levels of word difficulty. A total of 32 subjects were studied with functional magnetic resonance imaging (FMRI) after normal sleep and following 36 h of TSD. Cerebral responses to EASY words were identical on both nights, but several brain regions showed increased activation to HARD words following TSD compared with following a normal night of sleep (NORM). These regions included bilateral inferior frontal gyrus, bilateral dorsolateral prefrontal cortex, and bilateral inferior parietal lobe. Better free recall performance on the HARD words after TSD was related to increased cerebral responses within the left inferior and superior parietal lobes and left inferior frontal gyrus. Recall was negatively related to activation within the right inferior frontal gyrus. Overall, the findings support the predictions of the compensatory recruitment hypothesis that task demands influence both the likelihood and location of increased cerebral activation during task performance following TSD, and refine that hypothesis by identifying a specific task demand that plays a role. The performance relationships suggest increased activation may be both beneficial (compensatory) and interfere with task performance, depending on the brain regions involved.     

fMRI evidence for the effect of verbal complexity on lateralisation of the neural response associated with decoding prosodic emotion

The pattern of intonation accompanying an utterance provides a powerful cue as to a speaker's emotional state of mind. Most prior lesion studies have demonstrated that the nodal point for decoding these prosodic emotion cues is mediated by unimodal auditory cortex in the right posterior lateral temporal lobe. However, functional neuroimaging has brought with it increasing attention to the equivalent left hemisphere region in this role. This study used fMRI to quantitatively assess the hypothesis that involvement of the left posterior lateral temporal lobe depended on the linguistic load or verbal complexity of the prosodic emotion stimuli. BOLD contrast data was acquired on a 3T scanner whilst 16 healthy young adults identified the prosodic emotion in three conditions: 'sentences' comprised of words, a repeated monosyllable, and a single prolonged syllable (asyllabic). Whole-brain analyses were performed using SPM5 and supplemented by posterior lateral temporal lobe region of interest (ROI) analyses. The whole-brain analyses appeared to show bilateral temporal lobe activation across the conditions, however, the ROI analyses indicated a highly significant decrease in activity in the left ROI as verbal complexity decreased. Changes in right ROI activity were not statistically significant. Our results indicate that the likelihood of observing a notable left temporal lobe response in functional neuroimaging studies of emotional prosody comprehension depends on the verbal complexity of the prosodic emotion stimuli. Despite the right hemisphere dominance underlying this task, the left hemisphere region may be co-activated in its attempt to extract phonetic-segmental information from the acoustic stimuli whether or not the stimuli contain meaningful phonetic-segmental information.     

Cortical processing of tactile language in a postlingually deaf-blind subject

We compared neural activation detected by magnetoencephalography (MEG) during tactile presentation of words and non-words in a postlingually deaf-blind subject and six normal volunteers. The left postcentral gyrus, bilateral inferior frontal gyri, left posterior temporal lobe, right anterior temporal lobe, bilateral middle occipital gyri were activated when tactile words were presented to the right hand of the deaf-blind subject. This set of activated regions was not observed in the normal volunteers, although activation of several combinations of these regions was detected. Positron emission tomography confirmed the location of the MEG-activated areas in the deaf-blind subject. Our results demonstrated that the deaf-blind subject is heavily involved in interpreting tactile language by enhancing cortical activation of cognitive and semantic processing.     

Neural correlates of preparatory and regulatory control over positive and negative emotion

This study used functional magnetic resonance imaging to investigate brain activation during preparatory and regulatory control while participants (N = 24) were instructed either to simply view or decrease their emotional response to, pleasant, neutral or unpleasant pictures. A main effect of emotional valence on brain activity was found in the right precentral gyrus, with greater activation during positive than negative emotion regulation. A main effect of regulation phase was evident in the bilateral anterior prefrontal cortex (PFC), precuneus, posterior cingulate cortex, right putamen and temporal and occipital lobes, with greater activity in these regions during preparatory than regulatory control. A valence X regulation interaction was evident in regions of ventromedial PFC and anterior cingulate cortex, reflecting greater activation while regulating negative than positive emotion, but only during active emotion regulation (not preparation). Conjunction analyses revealed common brain regions involved in differing types of emotion regulation including selected areas of left lateral PFC, inferior parietal lobe, temporal lobe, right cerebellum and bilateral dorsomedial PFC. The right lateral PFC was additionally activated during the modulation of both positive and negative valence. Findings demonstrate significant modulation of brain activity during both preparation for, and active regulation of positive and negative emotional states.     

Use of functional MRI in epilepsy]

For the purpose of examining pathophysiological mechanisms of a memory function in epileptic patients or an utility of fMRI for a presurgical assessment in neurosurgical treatment of epilepsy, activated areas in fMRI during verbal or visual memory task were investigated in patient group of temporal lobe epilepsy and normal subject group. Patient group of temporal lobe epilepsy consisted of 7 cases, of which 3 and 3 cases had left and right temporal foci, respectively, except 1 case having undetermined laterality of temporal foci. Normal subjects were 16 cases. All the epileptic and normal subjects were right-handed except for 1 lefty normal subject. Verbal memory tasks were composed of covert and overt recall tasks of 10 words given auditorily, while visual ones were recall tasks of 6 figures given visually. Eventually, in normal subjects, the left side-dominant medial frontal lobes including the superior frontal and anterior cingulate gyri were mainly activated in fMRI during the covert recall tasks of verbal memory, while the left side-dominant inferior frontal and precentral gyri as the motor language areas were chiefly activated in addition to the medial frontal lobe during the overt recall tasks. Further, the bilateral occipital lobes were activated in fMRI during the recall tasks of visual memory. Also in patient groups of temporal lobe epilepsy, the activated areas in fMRI during these tasks were the same as in normal subject group, regardless of the laterality of epileptic temporal foci. These results suggest that fMRI is useful for the determination of the lateralization of the cerebral hemisphere contributing to verbal memory function and therefore for the presurgical assessment of memory function in neurosurgical treatment of epilepsy.     

A case of crossed aphasia with echolalia after the resection of tumor in the right medial frontal lobe]

We report a right-handed woman, who developed a non-fluent aphasia after resection of astrocytoma (grade III) in the right medial frontal lobe. On admission to the rehabilitation department, neurological examination revealed mild left hemiparesis, hyperreflexia on the left side and grasp reflex on the left hand. Neuropsychologically she showed general inattention, non-fluent aphasia, acalculia, constructional disability, and mild buccofacial apraxia. No other apraxia, unilateral spatial neglect or extinction phenomena were observed. An MRI demonstrated resected areas in the right superior frontal gyrus, subcortical region in the right middle frontal gyrus, anterior part of the cingulate gyrus, a part of supplementary motor area. Surrounding area in the right frontal lobe showed diffuse signal change. She demonstrated non-fluent aprosodic speech with word finding difficulty. No phonemic paraphasia, or anarthria was observed. Auditory comprehension was fair with some difficulty in comprehending complex commands. Naming was good, but verbal fluency tests for a category or phonemic cuing was severely impaired. She could repeat words but not sentences. Reading comprehension was disturbed by semantic paralexia and writing words was poor for both Kana (syllabogram) and Kanji(logogram) characters. A significant feature of her speech was mitigated echolalia. In both free conversation and examination setting, she often repeated phrases spoken to her which she used to start her speech. In addition, she repeated words spoken to others which were totally irrelevant to her conversation. She was aware of her echoing, which always embarrassed her. She described her echolalic tendency as a great nuisance. However, once echoing being forbidden, she could not initiate her speech and made incorrect responses after long delay. Thus, her compulsive echolalia helped to start her speech. Only four patients with crossed aphasia demonstrated echolalia in the literature. They showed severe aphasia with markedly decreased speech and severe comprehension deficit. A patient with a similar lesion in the right medial frontal lobe had aspontaneity in general and language function per se could not be examined properly. Echolalia related to the medial frontal lesion in the language dominant hemisphere was described as a compulsive speech response, because some other 'echoing' phenomena or compulsive behavior were also observed in these patients. On the other hand, some patients with a large lesion in the right hemisphere tended to respond to stimuli directed to other patients, so called 'response-to-next-patient-stimulation'. This behavior was explained by disinhibited shift of attention or perseveration of the set. Both compulsive speech responses and 'response-to-next-patient-stimulation' like phenomena may have contributed to the echolalia phenomena of the present case.     

Differential prefrontal and frontotemporal oxygenation patterns during phonemic and semantic verbal fluency

Movement artifacts are still considered a problematic issue for imaging research on overt language production. This motion-sensitivity can be overcome by functional near-infrared spectroscopy (fNIRS). In the present study, 50 healthy subjects performed a combined phonemic and semantic overt verbal fluency task while frontal and temporal cortex oxygenation was recorded using multi-channel fNIRS. Results showed a partial dissociation for phonemic and semantic word generation with equally increased oxygenation in frontotemporal cortices for both types of tasks whereas anterior and superior prefrontal areas were exclusively activated during phonemic fluency. Also, a general left-lateralization was found being more pronounced during semantic processing. These findings line up with earlier imaging and lesion studies emphasizing a crucial role of the temporal lobe for semantic word production, whereas phonemic processing seems to depend on intact frontal lobe function.     

Proton magnetic resonance spectroscopy of the inferior frontal gyrus and thalamus and its relationship to verbal learning task performance in patients with schizophrenia: a preliminary report

Previous research has found frontal lobe involvement in memory impairment in schizophrenia. In the present study, proton magnetic resonance spectroscopy was performed in 13 young patients with schizophrenia and 13 normal control subjects. Spectra were obtained from a voxel of 2 x 2 x 1.5 cm(3) in the bilateral inferior frontal gyrus and thalamus. Subjects were given a verbal learning task and stimulus category repetition (SCR) was calculated from the performance of the task. Significantly reduced N-acetylaspartate (NAA)/choline-containing compounds ratios were found in the left inferior frontal cortex of patients compared with controls. The total number of words recalled by patients was significantly lower than that recalled by controls. In all subjects, SCR scores were positively correlated with NAA/phosphocreatine ratios of the left inferior frontal cortex, which showed a trend towards a decrease in patients. These results support the notion of metabolic abnormalities in the left inferior frontal region related to verbal memory deficits in patients with schizophrenia.     

Inner ear hearing loss modulates ipsilateral temporal lobe activation by monaural speech stimuli

We examined cortical activation by speech in patients with moderate inner ear hearing loss using PET to investigate the response of the language network to insufficient speech input. We made two word lists, well-perceived words and poorly-perceived words, and measured rCBF during monaural presentation of these words. Well-perceived words activated bilateral temporal lobes, bilateral inferior frontal gyri (IFG) and left angular gyrus (AG) regardless of the ear stimulated, Poorly-perceived words activated contralateral temporal lobe and bilateral IFG, while little or no activation was observed in the ipsilateral temporal lobe and left AG. Insufficient activation of the temporal lobe ipsilateral to the ear stimulated might correlated with less accurate word comprehension in patients with inner ear hearing loss.     

Effects of experimentally-induced emotional states on frontal lobe cognitive task performance.

A growing body of evidence suggests that dysphoric and euphoric emotional states are associated with reliable patterns of frontal lobe activity. Specifically, dysphoric affect coincides with greater right than left frontal lobe activity, and euphoric affect tends to correspond with a converse pattern of activity. The present study examined whether cognitive outcomes associated with the left and right frontal lobes are differentially influenced by dysphoric and euphoric affect. In a completely between-groups design, 60 dextral women were administered either the positive or negative conditions of the Velten Mood Induction Procedure, and they subsequently completed either a verbal or figural fluency test. Euphoria resulted in better verbal than figural fluency performance, and dysphoria yielded better figural than verbal fluency outcomes. These findings are consistent with electrophysiological data concerning frontal lobe activity during euphoric and dysphoric affect, and they underscore the notion that affective influences upon cognition are more complicated than previously thought.     

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.     

Right hemispheric dysfunction in a case of pure progressive aphemia: fusion of multimodal neuroimaging

This article describes the unusual case of a 60-year-old woman suffering from pure progressive aphemia. The fusion of multimodal neuroimaging (MRI, perfusion SPECT) implicated the right frontal lobe, especially the inferior frontal gyrus. This area also showed the greatest functional MRI activation during the performance of a covert phonemic fluency task. Results are discussed in terms of bihemispheric language representation. The fusion of three sets of neuroimages has aided in the interpretation of the patient's cognitive brain dysfunction.     

Imaging language networks before and after anterior temporal lobe resection: results of a longitudinal fMRI study

Purpose: Anterior temporal lobe resection (ATLR) controls seizures in up to 70% of patients with intractable temporal lobe epilepsy (TLE) but, in the language dominant hemisphere, may impair language function, particularly naming. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated reorganization of language in left‐hemisphere–dominant patients before and after ATLR; whether preoperative functional magnetic resonance imaging (fMRI) predicts postoperative naming decline; and efficiency of postoperative language networks. Methods: We studied 44 patients with TLE due to unilateral hippocampal sclerosis (24 left) on a 3T GE‐MRI scanner. All subjects performed language fMRI and neuropsychological testing preoperatively and again 4 months after left or right ATLR. Key Findings: Postoperatively, individuals with left TLE had greater bilateral middle/inferior frontal fMRI activation and stronger functional connectivity from the left inferior/middle frontal gyri to the contralateral frontal lobe than preoperatively, and this was not observed in individuals with right TLE. Preoperatively, in left and right TLE, better naming correlated with greater preoperative left hippocampal and left frontal activation for verbal fluency (VF). In left TLE, stronger preoperative left middle frontal activation for VF was predictive of greater decline in naming after ATLR. Postoperatively, in left TLE with clinically significant naming decline, greater right middle frontal VF activation correlated with better postoperative naming. In patients without postoperative naming decline, better naming correlated with greater activation in the remaining left posterior hippocampus. In right TLE, naming ability correlated with left hippocampal and left and right frontal VF activation postoperatively. Significance: In left TLE, early postoperative reorganization to the contralateral frontal lobe suggests multiple systems support language function. Postoperatively, ipsilateral recruitment involving the posterior hippocampal remnant is important for maintaining language, and reorganization to the contralateral hemisphere is less effective. Preoperative left middle frontal activation for VF was predictive of naming decline in left TLE after ATLR.     

fMRI auditory language differences between dyslexic and able reading children

During fMRI, dyslexic and control boys completed auditory language tasks (judging whether pairs of real and/or pseudo words rhymed or were real words) in 30 s 'on' conditions alternating with a 30 s 'off' condition (judging whether tone pairs were same). During phonological judgment, dyslexics had more activity than controls in right than left inferior temporal gyrus and in left precentral gyrus. During lexical judgment, dyslexics were less active than controls in bilateral middle frontal gyrus and more active than controls in left orbital frontal cortex. Individual dyslexics were reliably less active than controls in left insula and left inferior temporal gyrus. Dyslexic and control children differ in brain activation during auditory language processing skills that do not require reading.     

Reduced activation in the mirror neuron system during a virtual social cognition task in euthymic bipolar disorder

Social cognition entails both cognitive and affective processing, and impairments in both have accounted for residual symptoms of bipolar disorder (BD). However, there has been a lack of studies identifying neural substrates responsible for social cognitive difficulties in BD patients. Fourteen euthymic BD patients and 14 healthy normal controls underwent functional MRI while performing a virtual reality social cognition task, which incorporated both cognitive and emotional dimensions, simulating real-world social situations. During the scanning, subjects tried to guess (attribute) possible reasons for expressed emotion of virtual humans (avatars) while viewing their facial expressions, just after observing their verbal and nonverbal (facial) expressions which were emotionally valenced (happy, angry and neutral). BD patients compared to normal controls showed delayed reaction times in emotional conditions, with comparable response accuracy. Healthy normal controls activated the right anterior cingulate cortex, inferior frontal, and insular cortex in emotional conditions contrasted with neutral control conditions, that is, the regions that have been related to empathic processes during viewing others' emotional expression. Relative to normal controls, BD patients showed reduced activations in the ‘mirror neuron system’, including the right inferior frontal cortex, premotor cortex, and insula, mainly in angry or happy condition. These results may suggest that, even during euthymic state, BD patients have difficulties in recruiting brain regions for the utilization of emotional cues as a means for understanding others. Clinical attention should be paid to emotion-related residual symptoms to help improve social outcomes in these patients.     

Brain structure associations with phonemic and semantic fluency in typically-developing children

Verbal fluency is the ability to retrieve lexical knowledge quickly and efficiently and develops during childhood and adolescence. Few studies have investigated associations between verbal fluency performance and brain structural variation in children. Here we examined associations of verbal fluency performance with structural measures of frontal and temporal language-related brain regions and their connections in 73 typically-developing children aged 7–13 years. Tract-based spatial statistics was used to extract fractional anisotropy (FA) from the superior longitudinal fasciculus/arcuate fasciculus (SLF/AF), and the white matter underlying frontal and temporal language-related regions. FreeSurfer was used to extract cortical thickness and surface area. Better semantic and phonemic fluency performance was associated with higher right SLF/AF FA, and phonemic fluency was also modestly associated with lower left SLF/AF FA. Explorative voxelwise analyses for semantic fluency suggested associations with FA in other fiber tracts, including corpus callosum and right inferior fronto-occipital fasciculus. Overall, our results suggest that verbal fluency performance in children may rely on right hemisphere structures, possibly involving both language and executive function networks, and less on solely left hemisphere structures as often is observed in adults. Longitudinal studies are needed to clarify whether these associations are mediated by maturational processes, stable characteristics and/or experience.     

Neural basis of the non-attentional processing of briefly presented words

The neural basis of the automatic activation of words was investigated in an fMRI study. In the study, words were presented briefly (51 or 151 msec) followed by a mask. To prevent attentional processing, subjects attended to the masks and not the words, and were required to make perceptual judgment about the masks. We found that a distributed neural network (including the frontal, temporal, occipital, parietal lobes, and the cerebellum) was activated during non-attentional processing of words in both exposure durations. A significant main effect of presentation duration was found in bilateral cerebellum and the right fusiform gyrus, suggesting their role in the later (151 msec) processing of words. In addition, a significant interaction between presentation duration and word frequency was obtained. When the presentation duration was 151 msec, no significant difference in activation was found between high- and low-frequency words. Alternatively, when the presentation duration was 51 msec, high-frequency words evoked significantly greater activation in bilateral fusiform gyri, cerebellum, right inferior parietal lobe, medial frontal gyrus (BA 45/46/9), and the right temporal-occipital junction (BA 21/37). These results suggest that these regions are sensitive to word frequency, and are related to both the attentional and non-attentional access of lexical representations.