Brain activation mediates the association between structural abnormality and symptom severity in schizophrenia

Thought disorder is a symptom of schizophrenia expressed as disorganized or incoherent speech. Severity of thought disorder correlates with decreased left superior temporal gyrus grey matter volume and cortical activation in posterior temporal regions during the performance of language tasks. The goal of this study was to determine whether language-related activation mediates the association between thought disorder and left superior temporal lobe grey matter volume. 12 patients with schizophrenia were assessed for thought disorder. FMRI images were acquired for each subject while they listened to English speech, along with a high resolution structural image. Thought disorder was used as a covariate in the functional analysis to identify brain regions within which activation correlated with symptom severity. Voxel based morphometry was used to calculate grey matter volume of the planum temporale. A mediation model waste-tested using a four-step multiple regression approach incorporating cortical volume, functional activation and symptom severity. Thought disorder correlated with activation in a single cluster within the left posterior middle temporal gyrus during listening to speech. Grey matter volume within the planum temporale correlated significantly with severity of thought disorder and activation within the functional cluster. Regressing thought disorder on grey matter volume and BOLD response simultaneously led to a significant reduction in the correlation between grey matter volume and thought disorder. These results support the hypothesis that the association between decreased grey matter volume in the left planum temporale and severity of thought disorder is mediated by activation in the posterior temporal lobe during language processing.     

Productive and perceptive language reorganization in temporal lobe epilepsy

The aim of this work was to determine whether productive and perceptive language functions are differentially affected in homogeneous groups of epilepsy patients with right and left temporal lobe epilepsy (TLE). Eighteen patients with left TLE, 18 with right TLE, and 17 healthy volunteers were studied using fMRI during performance of three tasks assessing the productive and perceptive aspects of language (covert semantic verbal fluency, covert sentence repetition, and story listening). Hemispheric dominance for language was calculated in the frontal and temporal regions using laterality indices (LI). Atypical lateralization was defined as a right-sided LI (LI<-0.20) in the frontal lobes during the verbal fluency task or in the temporal lobes during the story listening task. Control subjects and right TLE patients demonstrated a strong left lateralization for language in the frontal lobes during the fluency task, whereas activation was less lateralized to the left hemisphere in left TLE patients, although the difference did not reach significance. In the story listening and the repetition tasks, activation was significantly more right sided in the temporal lobes of patients with left TLE. Atypical language representation was found in 19% of TLE patients (five left and two right TLE). The shift toward the right hemisphere was significantly larger in the temporal than the frontal lobes in patients with atypical language lateralization compared to TLE patients with a typical language lateralization. Neuropsychological performances of patients with atypical language patterns were better than those of patients with typical patterns, suggesting that this reorganization may represent a compensatory mechanism.     

Left thalamo-cortical network implicated in successful speech separation and identification

The separation of concurrent sounds is paramount to human communication in everyday settings. The primary auditory cortex and the planum temporale are thought to be essential for both the separation of physical sound sources into perceptual objects and the comparison of those representations with previously learned acoustic events. To examine the role of these areas in speech separation, we measured brain activity using event-related functional Magnetic Resonance Imaging (fMRI) while participants were asked to identify two phonetically different vowels presented simultaneously. The processing of brief speech sounds (200 ms in duration) activated the thalamus and superior temporal gyrus bilaterally, left anterior temporal lobe, and left inferior temporal gyrus. A comparison of fMRI signals between trials in which participants successfully identified both vowels as opposed to when only one of the two vowels was recognized revealed enhanced activity in left thalamus, Heschl's gyrus, superior temporal gyrus, and the planum temporale. Because participants successfully identified at least one of the two vowels on each trial, the difference in fMRI signal indexes the extra computational work needed to segregate and identify successfully the other concurrently presented vowel. The results support the view that auditory cortex in or near Heschl's gyrus as well as in the planum temporale are involved in sound segregation and reveal a link between left thalamo-cortical activation and the successful separation and identification of simultaneous speech sounds.     

Effective connectivity analysis demonstrates involvement of premotor cortex during speech perception

Several reports of premotor cortex involvement in speech perception have been put forward. Still, the functional role of premotor cortex is under debate. In order to investigate the functional role of premotor cortex, we presented parametrically varied speech stimuli in both a behavioral and functional magnetic resonance imaging (fMRI) study. White noise was transformed over seven distinct steps into a speech sound and presented to the participants in a randomized order. As control condition served the same transformation from white noise into a music instrument sound. The fMRI data were modelled with Dynamic Causal Modeling (DCM) where the effective connectivity between Heschl's gyrus, planum temporale, superior temporal sulcus and premotor cortex were tested. The fMRI results revealed a graded increase in activation in the left superior temporal sulcus. Premotor cortex activity was only present at an intermediate step when the speech sounds became identifiable but were still distorted but was not present when the speech sounds were clearly perceivable. A Bayesian model selection procedure favored a model that contained significant interconnections between Heschl's gyrus, planum temporal, and superior temporal sulcus when processing speech sounds. In addition, bidirectional connections between premotor cortex and superior temporal sulcus and from planum temporale to premotor cortex were significant. Processing non-speech sounds initiated no significant connections to premotor cortex. Since the highest level of motor activity was observed only when processing identifiable sounds with incomplete phonological information, it is concluded that premotor cortex is not generally necessary for speech perception but may facilitate interpreting a sound as speech when the acoustic input is sparse.     

Reading, hearing, and the planum temporale

Many neuroimaging studies of single-word reading have been carried out over the last 15 years, and a consensus as to the brain regions relevant to this task has emerged. Surprisingly, the planum temporale (PT) does not appear among the catalog of consistently active regions in these investigations. Recently, however, several studies have offered evidence suggesting that the left posteromedial PT plays a role in both speech production and speech perception. It is not clear, then, why so many neuroimaging studies of single-word reading--a task requiring speech production--have tended not to find evidence of PT involvement. In the present work, we employed a high-powered rapid event-related fMRI paradigm involving both single pseudoword reading and single pseudoword listening to assess activity related to reading and speech perception in the PT as a function of the degree of spatial smoothing applied to the functional images. We show that the speech area of the PT [Sylvian-parietal-temporal (Spt)] is best identified when only a moderate (5 mm) amount of spatial smoothing is applied to the data before statistical analysis. Moreover, increasing the smoothing window to 10 mm obliterates activation in the PT, suggesting that failure to find PT activation in past studies may relate to this factor.     

Automatic analysis of cerebral asymmetry: an exploratory study of the relationship between brain torque and planum temporale asymmetry

Leftward occipital and rightward frontal lobe asymmetry (brain torque) and leftward planum temporale asymmetry have been consistently reported in postmortem and in vivo neuroimaging studies of the human brain. Here automatic image analysis techniques are applied to quantify global and local asymmetries, and investigate the relationship between brain torque and planum temporale asymmetries on T1-weighted magnetic resonance (MR) images of 30 right-handed young healthy subjects (15 male, 15 female). Previously described automatic cerebral hemisphere extraction and 3D interhemispheric reflection-based methods for studying brain asymmetry are applied with a new technique, LowD (Low Dimension), which enables automatic quantification of brain torque. LowD integrates extracted left and right cerebral hemispheres in columns orthogonal to the midsagittal plane (2D column maps), and subsequently integrates slices along the brain's anterior-posterior axis (1D slice profiles). A torque index defined as the magnitude of occipital and frontal lobe asymmetry is computed allowing exploratory investigation of relationships between this global asymmetry and local asymmetries found in the planum temporale. LowD detected significant torque in the 30 subjects with occipital and frontal components found to be highly correlated (P<0.02). Significant leftward planum temporale asymmetry was detected (P<0.05), and the torque index correlated with planum temporale asymmetry (P<0.001). However, torque and total brain volume were not correlated. Therefore, although components of cerebral asymmetry may be related, their magnitude is not influenced by total hemisphere volume. LowD provides increased sensitivity for detection and quantification of brain torque on an individual subject basis, and future studies will apply these techniques to investigate the relationship between cerebral asymmetry and functional laterality.     

Abnormal association between reduced magnetic mismatch field to speech sounds and smaller left planum temporale volume in schizophrenia

Schizophrenia is associated with language-related dysfunction. A previous study [Schizophr. Res. 59 (2003c) 159] has shown that this abnormality is present at the level of automatic discrimination of change in speech sounds, as revealed by magnetoencephalographic recording of auditory mismatch field in response to across-category change in vowels. Here, we investigated the neuroanatomical substrate for this physiological abnormality. Thirteen patients with schizophrenia and 19 matched control subjects were examined using magnetoencephalography (MEG) and high-resolution magnetic resonance imaging (MRI) to evaluate both mismatch field strengths in response to change between vowel /a/ and /o/, and gray matter volumes of Heschl's gyrus (HG) and planum temporale (PT). The magnetic global field power of mismatch response to change in phonemes showed a bilateral reduction in patients with schizophrenia. The gray matter volume of left planum temporale, but not right planum temporale or bilateral Heschl's gyrus, was significantly smaller in patients with schizophrenia compared with that in control subjects. Furthermore, the phonetic mismatch strength in the left hemisphere was significantly correlated with left planum temporale gray matter volume in patients with schizophrenia only. These results suggest that structural abnormalities of the planum temporale may underlie the functional abnormalities of fundamental language-related processing in schizophrenia.     

A common language network for comprehension and production: a contribution to the definition of language epicenters with PET

In this paper, we report on a PET activation study designed to assess whether functional neuroimaging would help to uncover essential language areas in normal volunteers and to provide a more accurate definition of their localization. Regional cerebral blood flow was repeatedly monitored in eight right-handed male volunteers, while performing a language comprehension task (listening to factual stories) and a language production task (covert generation of verbs semantically related to heard nouns), using silent resting as a control condition. The conjunction analysis, conducted with SPM, was used to uncover the network of activations common to both task that included three left hemisphere areas, namely (1) the pars opercularis and triangularis of the inferior frontal gyrus, (2) the posterior part of the superior temporal cortex centered around the superior temporal sulcus, extending to the planum temporale posterior part but sparing the supramarginalis and angular gyri, and (3) the most anterior part of the left inferior temporal gyrus at the junction with the anterior fusiform gyrus. The inferior and lateral parts of the right cerebellar cortex were also included in the conjunction network. Each of the three cortical areas, when they are site of lesion or electrical stimulation, elicit impairment in both language comprehension and production and can thus be considered as essential to language. Accordingly, the present results provide conservative anatomofunctional definitions of the Broca, Wernicke, and basal language areas. Interestingly, contralateral homologues of Broca's and Wernicke's areas also lighted up in the conjunction analysis that could be related to the interindividual variability of hemispheric language dominance.     

On the context-dependent nature of the contribution of the ventral premotor cortex to speech perception

What is the nature of the interface between speech perception and production, where auditory and motor representations converge? One set of explanations suggests that during perception, the motor circuits involved in producing a perceived action are in some way enacting the action without actually causing movement (covert simulation) or sending along the motor information to be used to predict its sensory consequences (i.e., efference copy). Other accounts either reject entirely the involvement of motor representations in perception, or explain their role as being more supportive than integral, and not employing the identical circuits used in production. Using fMRI, we investigated whether there are brain regions that are conjointly active for both speech perception and production, and whether these regions are sensitive to articulatory (syllabic) complexity during both processes, which is predicted by a covert simulation account. A group of healthy young adults (1) observed a female speaker produce a set of familiar words (perception), and (2) observed and then repeated the words (production). There were two types of words, varying in articulatory complexity, as measured by the presence or absence of consonant clusters. The simple words contained no consonant cluster (e.g. "palace"), while the complex words contained one to three consonant clusters (e.g. "planet"). Results indicate that the left ventral premotor cortex (PMv) was significantly active during speech perception and speech production but that activation in this region was scaled to articulatory complexity only during speech production, revealing an incompletely specified efferent motor signal during speech perception. The right planum temporal (PT) was also active during speech perception and speech production, and activation in this region was scaled to articulatory complexity during both production and perception. These findings are discussed in the context of current theories of speech perception, with particular attention to accounts that include an explanatory role for mirror neurons.     

BOLD correlates of edge detection in human auditory cortex

Edges are important cues defining coherent auditory objects. As a model of auditory edges, sound on- and offset are particularly suitable to study their neural underpinnings because they contrast a specific physical input against no physical input. Change from silence to sound, that is onset, has extensively been studied and elicits transient neural responses bilaterally in auditory cortex. However, neural activity associated with sound onset is not only related to edge detection but also to novel afferent inputs. Edges at the change from sound to silence, that is offset, are not confounded by novel physical input and thus allow to examine neural activity associated with sound edges per se. In the first experiment, we used silent acquisition functional magnetic resonance imaging and found that the offset of pulsed sound activates planum temporale, superior temporal sulcus and planum polare of the right hemisphere. In the planum temporale and the superior temporal sulcus, offset response amplitudes were related to the pulse repetition rate of the preceding stimulation. In the second experiment, we found that these offset-responsive regions were also activated by single sound pulses, onset of sound pulse sequences and single sound pulse omissions within sound pulse sequences. However, they were not active during sustained sound presentation. Thus, our data show that circumscribed areas in right temporal cortex are specifically involved in identifying auditory edges. This operation is crucial for translating acoustic signal time series into coherent auditory objects.     

Anomalous sylvian fissure morphology in Williams syndrome

The unusual sensitivity and attraction to auditory stimuli in people with Williams syndrome (WS) has been hypothesized to be the consequence of atypical development of brain regions surrounding the Sylvian fissure. Planum temporale surface area, which is determined in part by Sylvian fissure patterning, was examined in 42 WS and 40 control participants to determine if anomalous Sylvian fissure morphology is present in WS. WS participants had significantly reduced leftward asymmetry of the planum temporale compared to control participants, due to a significant expansion in the size of the right planum temporale. The increased right planum temporale size was largely due to WS participants (24%) who had a right hemisphere Sylvian fissure that coursed horizontally and failed to ascend into the parietal lobe. This sulcal pattern is unusual in the right hemisphere and is more commonly found in the left hemisphere of typically developing individuals. There were no control participants with this type of right hemisphere Sylvian fissure pattern. The right hemisphere Sylvian fissure sulcal patterns were also related to a measure of cortical complexity and the amount of right hemisphere occipital lobe volume, suggesting that intrinsic genetic influences leading to anomalous visual system development in WS have widespread influences on cortical morphology that are similar in manner to extrinsic embryonic visual system lesions.     

Manual and automated measures of superior temporal gyrus asymmetry: concordant structural predictors of verbal ability in children

The planum temporale is a region on the posterior surface of the temporal lobe that exhibits robust leftward structural asymmetry, which has been linked to verbal ability in children and adults. Traditionally, structural asymmetry has been quantified with manual assessment of high resolution MRI scans. Such measures require subjective and frequently unreliable determination of highly variable anatomical boundaries. Methodological developments in automated image processing (voxel-based morphometry - VBM) offer the opportunity to obtain objective and reliable measures of structural variation. This study examined the extent to which a VBM measure of gray matter asymmetry in the posterior superior temporal gyrus (pSTG) characterized the same individual variation as a manual measure of planum temporale asymmetry in 99 healthy adults and 39 typically developing children. Planum temporale asymmetry was significantly correlated with pSTG gray matter asymmetry in the samples of adults and children. As a measure of validity we examined the extent to which the VBM measure of pSTG gray matter asymmetry predicted measures of verbal ability that were associated with the manual measure of planum temporale asymmetry in the same children. The two asymmetry measures predicted the same variance in verbal ability. The automated measure of pSTG gray matter asymmetry predicted additional significant variance in verbal ability, however. In addition, a posterior STS region was also identified that significantly predicted verbal ability. These results demonstrate significant advantages of an automated voxel-based measure over a manual measure of planum temporale asymmetry.     

Functional differentiation in the human auditory and language areas revealed by a dichotic listening task

The human auditory cortex plays a special role in speech recognition. It is therefore necessary to clarify the functional roles of individual auditory areas. We applied functional magnetic resonance imaging (fMRI) to examine cortical responses to speech sounds, which were presented under the dichotic and diotic (binaural) listening conditions. We found two different response patterns in multiple auditory areas and language-related areas. In the auditory cortex, the medial portion of the secondary auditory area (A2), as well as a part of the planum temporale (PT) and the superior temporal gyrus and sulcus (ST), showed greater responses under the dichotic condition than under the diotic condition. This dichotic selectivity may reflect acoustic differences and attention-related factors such as spatial attention and selective attention to targets. In contrast, other parts of the auditory cortex showed comparable responses to the dichotic and diotic conditions. We found similar functional differentiation in the inferior frontal (IF) cortex. These results suggest that multiple auditory and language areas may play a pivotal role in integrating the functional differentiation for speech recognition.     

Impact of modality and linguistic complexity during reading and listening tasks

Reading and understanding speech are usually considered as different manifestations of a single cognitive ability, that of language. In this study, we were interested in characterizing the specific contributions of input modality and linguistic complexity on the neural networks involved when subjects understand language. We conducted an fMRI study during which 10 right-handed male subjects had to read and listen to words, sentences and texts in different runs. By comparing reading to listening tasks, we were able to show that the cerebral regions specifically recruited by a given modality were circumscribed to unimodal and associative unimodal cortices associated with the task, indicating that higher cognitive processes required by the task may be common to both modalities. Such cognitive processes involved a common phonological network as well as lexico-semantic activations as revealed by the conjunction between all reading and listening tasks. The restriction of modality-specific regions to their corresponding unimodal cortices was replicated when looking at brain areas showing a greater increase during the comprehension of more complex linguistic units than words (such as sentences and texts) for each modality. Finally, we discuss the possible roles of regions showing pure effect of linguistic complexity, such as the anterior part of the superior temporal gyrus and the ventro-posterior part of the middle temporal gyrus that were activated for sentences and texts but not for isolated words, as well as a text-specific region found in the left posterior STS.     

Controlling for individual differences in fMRI brain activation to tones, syllables, and words

Previous neuroimaging studies have consistently reported bilateral activation to speech stimuli in the superior temporal gyrus (STG) and have identified an anteroventral stream of speech processing along the superior temporal sulcus (STS). However, little attention has been devoted to the possible confound of individual differences in hemispheric dominance for speech. The present study was designed to test for speech-selective activation while controlling for inter-individual variance in auditory laterality, by using only subjects with at least 10% right ear advantage (REA) on the dichotic listening test. Eighteen right-handed, healthy male volunteers (median age 26) participated in the study. The stimuli were words, syllables, and sine wave tones (220-2600 Hz), presented in a block design. Comparing words > tones and syllables > tones yielded activation in the left posterior MTG and the lateral STG (upper bank of STS). In the right temporal lobe, the activation was located in the MTG/STS (lower bank). Comparing left and right temporal lobe cluster sizes from the words > tones and syllables > tones contrasts on single-subject level demonstrated a statistically significant left lateralization for speech sound processing in the STS/MTG area. The asymmetry analyses suggest that dichotic listening may be a suitable method for selecting a homogenous group of subjects with respect to left hemisphere language dominance.     

Processing of location and pattern changes of natural sounds in the human auditory cortex

Parallel cortical pathways have been proposed for the processing of auditory pattern and spatial information, respectively. We tested this segregation with human functional magnetic resonance imaging (fMRI) and separate electroencephalographic (EEG) recordings in the same subjects who listened passively to four sequences of repetitive spatial animal vocalizations in an event-related paradigm. Transitions between sequences constituted either a change of auditory pattern, location, or both pattern+location. This procedure allowed us to investigate the cortical correlates of natural auditory "what" and "where" changes independent of differences in the individual stimuli. For pattern changes, we observed significantly increased fMRI responses along the bilateral anterior superior temporal gyrus and superior temporal sulcus, the planum polare, lateral Heschl's gyrus and anterior planum temporale. For location changes, significant increases of fMRI responses were observed in bilateral posterior superior temporal gyrus and planum temporale. An overlap of these two types of changes occurred in the lateral anterior planum temporale and posterior superior temporal gyrus. The analysis of source event-related potentials (ERPs) revealed faster processing of location than pattern changes. Thus, our data suggest that passive processing of auditory spatial and pattern changes is dissociated both temporally and anatomically in the human brain. The predominant role of more anterior aspects of the superior temporal lobe in sound identity processing supports the role of this area as part of the auditory pattern processing stream, while spatial processing of auditory stimuli appears to be mediated by the more posterior parts of the superior temporal lobe.     

Neuroanatomic overlap of working memory and spatial attention networks: a functional MRI comparison within subjects

Frontal and posterior parietal activations have been reported in numerous studies of working memory and visuospatial attention. To directly compare the brain regions engaged by these two cognitive functions, the same set of subjects consecutively participated in tasks of working memory and spatial attention while undergoing functional MRI (fMRI). The working memory task required the subject to maintain an on-line representation of foveally displayed letters against a background of distracters. The spatial attention task required the subject to shift visual attention covertly in response to a centrally presented directional cue. The spatial attention task had no working memory requirement, and the working memory task had no covert spatial attention requirement. Subjects' ability to maintain central fixation was confirmed outside the MRI scanner using infrared oculography. According to cognitive conjunction analysis, the set of activations common to both tasks included the intraparietal sulcus, ventral precentral sulcus, supplementary motor area, frontal eye fields, thalamus, cerebellum, left temporal neocortex, and right insula. Double-subtraction analyses yielded additional activations attributable to verbal working memory in premotor cortex, left inferior prefrontal cortex, right inferior parietal lobule, precuneus, and right cerebellum. Additional activations attributable to covert spatial attention included the occipitotemporal junction and extrastriate cortex. The use of two different tasks in the same set of subjects allowed us to provide an unequivocal demonstration that the neural networks subserving spatial attention and working memory intersect at several frontoparietal sites. These findings support the view that major cognitive domains are represented by partially overlapping large-scale neural networks. The presence of this overlap also suggests that spatial attention and working memory share common cognitive features related to the dynamic shifting of attentional resources.     

Shared and distinct neural correlates of singing and speaking

Using a modified sparse temporal sampling fMRI technique, we examined both shared and distinct neural correlates of singing and speaking. In the experimental conditions, 10 right-handed subjects were asked to repeat intoned ("sung") and non-intoned ("spoken") bisyllabic words/phrases that were contrasted with conditions controlling for pitch ("humming") and the basic motor processes associated with vocalization ("vowel production"). Areas of activation common to all tasks included the inferior pre- and post-central gyrus, superior temporal gyrus (STG), and superior temporal sulcus (STS) bilaterally, indicating a large shared network for motor preparation and execution as well as sensory feedback/control for vocal production. The speaking more than vowel-production contrast revealed activation in the inferior frontal gyrus most likely related to motor planning and preparation, in the primary sensorimotor cortex related to motor execution, and the middle and posterior STG/STS related to sensory feedback. The singing more than speaking contrast revealed additional activation in the mid-portions of the STG (more strongly on the right than left) and the most inferior and middle portions of the primary sensorimotor cortex. Our results suggest a bihemispheric network for vocal production regardless of whether the words/phrases were intoned or spoken. Furthermore, singing more than humming ("intoned speaking") showed additional right-lateralized activation of the superior temporal gyrus, inferior central operculum, and inferior frontal gyrus which may offer an explanation for the clinical observation that patients with non-fluent aphasia due to left hemisphere lesions are able to sing the text of a song while they are unable to speak the same words.     

Mapping an intrinsic MR property of gray matter in auditory cortex of living humans: a possible marker for primary cortex and hemispheric differences

Recently, magnetic resonance properties of cerebral gray matter have been spatially mapped--in vivo--over the cortical surface. In one of the first neuroscientific applications of this approach, this study explores what can be learned about auditory cortex in living humans by mapping longitudinal relaxation rate (R1), a property related to myelin content. Gray matter R1 (and thickness) showed repeatable trends, including the following: (1) Regions of high R1 were always found overlapping posteromedial Heschl's gyrus. They also sometimes occurred in planum temporale and never in other parts of the superior temporal lobe. We hypothesize that the high R1 overlapping Heschl's gyrus (which likely indicates dense gray matter myelination) reflects auditory koniocortex (i.e., primary cortex), a heavily myelinated area that shows comparable overlap with the gyrus. High R1 overlapping Heschl's gyrus was identified in every instance suggesting that R1 may ultimately provide a marker for koniocortex in individuals. Such a marker would be significant for auditory neuroimaging, which has no standard means (anatomic or physiologic) for localizing cortical areas in individual subjects. (2) Inter-hemispheric comparisons revealed greater R1 on the left on Heschl's gyrus, planum temporale, superior temporal gyrus and superior temporal sulcus. This asymmetry suggests greater gray matter myelination in left auditory cortex, which may be a substrate for the left hemisphere's specialized processing of speech, language, and rapid acoustic changes. These results indicate that in vivo R1 mapping can provide new insights into the structure of human cortical gray matter and its relation to function.