Temporal and topographical characterization of language cortices using intraoperative optical intrinsic signals

We used intraoperative optical imaging of intrinsic signals (iOIS) and electrocortical stimulation mapping (ESM) to compare functionally active brain regions in 10 awake patients undergoing neurosurgical resection. Patients performed two to four tasks, including visual and auditory naming, word discrimination, and/or orofacial movements. All iOIS maps included areas identified by ESM mapping. However, iOIS also revealed topographical specificity dependent on language task. In Broca's area, naming paradigms activated both anterior and posterior inferior frontal gyrus (IFG), while the word discrimination paradigm activated only posterior IFG. In Wernicke's area, object naming produced activations localizing over the inferior and anterior/posterior regions, while the word discrimination task activated superior and anterior cortices. These results may suggest more posterior phonological activation and more anterior semantic activations in Broca's area, and more anterior/superior phonological activation and more posterior/inferior semantic activations in Wernicke's area. Although similar response onset was observed in Broca's and Wernicke's areas, temporal differences were revealed during block paradigm (20-s) activations. In Broca's area, block paradigms yielded a boxcar temporal activation profile (in all tasks) that resembled response profiles observed in motor cortex (with orofacial movements). In contrast, activations in Wernicke's area responded with a more dynamic profile (including early and late peaks) which varied with paradigm performance. Wernicke's area profiles were very similar to response profiles observed in sensory and visual cortex. The differing temporal patterns may therefore reflect unique processing performed by receptive (Wernicke's) and productive (Broca's) language centers. This study is consistent with task-specific semantic and phonologic regions within Broca's and Wernicke's areas and also is the first report of response profile differences dependent on cortical region and language task.     

Left hemisphere plasticity and aphasia recovery

A recent study by our group revealed a strong relationship between functional brain changes in the left hemisphere and anomia treatment outcome in chronic stroke patients (N=26) with aphasia (Fridriksson, 2010). The current research represents a continuation of this work in which we have refined our methods and added data from four more patients (for a total sample size of 30) to assess where in the left hemisphere treatment-related brain changes occur. Unlike Fridriksson (2010) which only focused on changes in correct naming as a marker of treatment outcome, the current study examined the relationship between changes in left hemisphere activity and changes in correct naming, semantic paraphasias, and phonemic paraphasias following treatment. We also expanded on the work by Fridriksson by examining whether neurophysiological measures taken at baseline (defined henceforth as the time-point before the start of anomia treatment) predict treatment outcome. Our analyses revealed that changes in activation in perilesional areas predicted treatment-related increases in correct naming in individuals with chronic aphasia. This relationship was most easily observed in the left frontal lobe. A decrease in the number of semantic and phonemic paraphasias was predicted by an activation change in the temporal lobe involving cortical areas that were shown to be active during picture naming in 14 normal subjects. In contrast, a far less certain relationship was found between baseline neurophysiological measures and anomia treatment outcome. Our findings suggest that improved naming associated with behavioral anomia treatment in aphasia is associated with modulation of the left frontal lobe whereas a reduction in naming errors is mediated by left posterior regions that classically are thought to be involved in language processing.     

生物类与非生物类图片命名任务对大脑活动时空模式的影响

目的：探讨图片的语义类别对命名任务的影响，研究生物类和非生物类图片命名任务对正常大脑活动时空模式的影响。方法：入组健康成年右利手受试者10例，选取来自不同语义类别（生物类和非生物类）的图片20张，应用磁共振成像获取个体大脑结构，脑磁图（MEG）检测任务中的全脑活动。结果：在图片命名任务中，早期脑区激活从双侧枕叶开始，逐步向颞叶和顶叶扩散，最后额叶激活产生言语。在视觉相关时间窗内，生物类图片命名在右侧扣带回激活强度显著低于非生物类图片命名（P=0.0475），而生物类图片命名在双侧枕叶、左侧顶叶和左侧额叶均显著高于非生物类图片命名（均P＜0.05）。在语义相关时间窗内，生物类图片命名在双侧额叶显著高于非生物类图片命名（P＜0.05）。在语音相关时间窗内，生物类图片命名在双侧枕叶、左侧顶叶和左侧额叶均显著高于非生物类图片命名（均P＜0.05）。结论：生物类和非生物类图片命名相比，两者在颞叶的活动未见显著差异，但前者具有枕叶、顶叶和额叶优势激活。提示生物类图片可以更好地在相关时间窗内刺激相关功能脑区。     

Mapping anterior temporal lobe language areas with fMRI: a multicenter normative study

Removal of the anterior temporal lobe (ATL) is an effective surgical treatment for intractable temporal lobe epilepsy but carries a risk of language and verbal memory deficits. Preoperative localization of functional zones in the ATL might help reduce these risks, yet fMRI protocols in current widespread use produce very little activation in this region. Based on recent evidence suggesting a role for the ATL in semantic integration, we designed an fMRI protocol comparing comprehension of brief narratives (Story task) with a semantically shallow control task involving serial arithmetic (Math task). The Story > Math contrast elicited strong activation throughout the ATL, lateral temporal lobe, and medial temporal lobe bilaterally in an initial cohort of 18 healthy participants. The task protocol was then implemented at 6 other imaging centers using identical methods. Data from a second cohort of participants scanned at these centers closely replicated the results from the initial cohort. The Story-Math protocol provides a reliable method for activation of surgical regions of interest in the ATL. The bilateral activation supports previous claims that conceptual processing involves both temporal lobes. Used in combination with language lateralization measures, reliable ATL activation maps may be useful for predicting cognitive outcome in ATL surgery, though the validity of this approach needs to be established in a prospective surgical series.     

Declarative memory impairments in Alzheimer's disease and semantic dementia

Semantic dementia (SD) and Alzheimer's disease (AD) are both disorders in which early pathology affects the temporal lobe yet they produce distinct syndromes of declarative memory impairment-loss of established semantic knowledge with relatively preserved episodic memory in the former and the converse in the latter. Groups with mild SD and mild AD who showed a double dissociation in these two aspects of declarative memory were studied-the SD group's episodic memory and the AD group's semantic knowledge each being comparable to controls. Positron emission tomography and volumetric magnetic resonance imaging were used to map deficits in regional cerebral metabolic rate and mesial temporal lobe (MTL) atrophy, respectively. Episodic memory impairment in AD was associated with dysfunction of an integrated network (mesial temporal lobe, mamillary bodies, dorso-mesial thalamus and posterior cingulate). Semantic memory impairment in SD was associated with bilateral rostral temporal lobe hypometabolism. The SD group had comparable MTL atrophy and hypometabolism to that found in AD but the remainder of their limbic-diencephalic network was preserved suggesting that the latter explains their ability to acquire new episodic memories. The results challenge the view that amnesia in early AD can be explained by the degree of MTL damage alone while showing that semantic impairment can occur with damage restricted to the rostral temporal lobes.     

Some neurophysiological constraints on models of word naming

The pronunciation of irregular words in deep orthographies like English cannot be specified by simple rules. On the other hand, the fact that novel letter strings can be pronounced seems to imply the existence of such rules. These facts motivate dual-route models of word naming, which postulate separate lexical (whole-word) and non-lexical (rule-based) mechanisms for accessing phonology. We used fMRI during oral naming of irregular words, regular words, and nonwords, to test this theory against a competing single-mechanism account known as the triangle model, which proposes that all words are handled by a single system containing distributed orthographic, phonological, and semantic codes rather than word codes. Two versions of the dual-route model were distinguished: an 'exclusive' version in which activation of one processing route predominates over the other, and a 'parallel' version in which both routes are equally activated by all words. The fMRI results provide no support for the exclusive dual-route model. Several frontal, insular, anterior cingulate, and parietal regions showed responses that increased with naming difficulty (nonword > irregular word > regular word) and were correlated with response time, but there was no activation consistent with the predicted response of a non-lexical, rule-based mechanism (i.e., nonword > regular word > irregular word). Several regions, including the angular gyrus and dorsal prefrontal cortex bilaterally, left ventromedial temporal lobe, and posterior cingulate gyrus, were activated more by words than nonwords, but these 'lexical route' regions were equally active for irregular and regular words. The results are compatible with both the parallel dual-route model and the triangle model. 'Lexical route' regions also showed effects of word imageability. Together with previous imaging studies using semantic task contrasts, the imageability effects are consistent with semantic processing in these brain regions, suggesting that word naming is partly semantically-mediated.     

Lexical learning of the English language: a PET study in healthy French subjects

To investigate the neural correlates of word learning in adults, 10 right-handed French subjects who had learned English without mastering it performed an English and a French naming task during two PET sessions, one before (PET1) and the second after (PET2) a 4-week lexical training in English. Behavioral performance was collected during the two PET exams and 2 months after (T3). At T2, performance on English naming increased in all subjects; this improvement persisted at T3, with no correlation between English performance at T2 and T3. Cerebral activation during French naming mainly showed a left frontal temporal network. The pattern specifically associated with English lexical learning included, in addition to the anterior cingulate cortex involved in attentional processing and BAs 4/6 reflecting speech output, the right cerebellum and the left insular cortex that are linked to speech gesture learning, and the right medial temporal regions, likely to reflect the involvement of episodic memory during verbal learning. Correlations between English T2/T1 performance and English T2/T1 rCBF changes reinforced the hypothesis of intervention of episodic memory since they interested right frontal, hippocampal, and lateral temporal regions. 'Predictive' correlations between English T3/T2 performance and English T2/T1 rCBF changes showed, in good reminders, increased activities in the left posterior superior temporal sulcus and middle temporal cortex probably related to efficient semantic storage of learned words.     

Thinner prefrontal cortex in veterans with posttraumatic stress disorder

Structural neuroimaging studies in posttraumatic stress disorder (PTSD) have focused primarily on structural alterations in the medial temporal lobe, and only a few have examined grey matter reductions in the cortex. Recent advances in computational analysis provide new opportunities to use semi-automatic techniques to determine cortical thickness, but these techniques have not yet been applied in PTSD. Twenty-five male veterans with PTSD and twenty-five male veterans without PTSD matched for age, year and region of deployment were recruited. All the subjects were scanned using MRI. Subjects' brains were aligned using cortex-based alignment in a region of interest based approach. Individual cortical thickness maps were calculated from the MR images. Regions of interest examined included the bilateral superior frontal gyri, bilateral middle frontal gyri, bilateral inferior frontal gyri, bilateral superior temporal gyri, and bilateral middle temporal gyri. In a large number of patients and controls, IQ scores and memory scores were also obtained. Individual cortical thickness maps were calculated from the MR images. Veterans with PTSD revealed reduced cortical thickness in the bilateral superior and middle frontal gyri, the left inferior frontal gyrus, and the left superior temporal gyrus. Veterans with PTSD performed significantly worse on memory measures compared to control veterans. Cortical thickness correlated with memory measures in the veterans without PTSD, but not in the veterans with PTSD. Cortical thinning in these regions may thus correspond to functional abnormalities observed in patients with PTSD.     

Activation reduction in anterior temporal cortices during repeated recognition of faces of personal acquaintances

Repeated recognition of the face of a familiar individual is known to show semantic repetition priming effect. In this study, normal subjects were repeatedly presented faces of their colleagues, and the effect of repetition on the regional cerebral blood flow change was measured using positron emission tomography. They repeated a set of three tasks: the familiar-face detection (F) task, the facial direction discrimination (D) task, and the perceptual control (C) task. During five repetitions of the F task, familiar faces were presented six times from different views in a pseudorandom order. Activation reduction through the repetition of the F tasks was observed in the bilateral anterior (anterolateral to the polar region) temporal cortices which are suggested to be involved in the access to the long-term memory concerning people. The bilateral amygdala, the hypothalamus, and the medial frontal cortices, were constantly activated during the F tasks, and considered to be associated with the behavioral significance of the presented familiar faces. Constant activation was also observed in the bilateral occipitotemporal regions and fusiform gyri and the right medial temporal regions during perception of the faces, and in the left medial temporal regions during the facial familiarity detection task, which are consistent with the results of previous functional brain imaging studies. The results have provided further information about the functional segregation of the anterior temporal regions in face recognition and long-term memory.     

功能磁共振成像观察左颞前部在汉语听觉词加工中的机制

目的 探讨左侧颞前部在汉语听觉信息加工中的作用机制。方法 应用3.0T磁共振成像系统与标准头线圈对15名健康志愿者(男5名,女10名)进行功能磁共振成像(fMRI)。要求受试者完成听觉复述任务和听觉语义危险判断任务。应用软件包AFNI分析两种听觉任务在左颞前部的任务功能定位及其差异。结果 正常成人听觉语义判断任务相比听觉复述任务更多激活左侧颞中回及颞下回前部,而听觉语音复述任务相比听觉语义判断任务更多激活左侧颞上回前部。结论 脑内存在左颞前部对汉语听觉语音语义信息加工的分离,颞上前部对语音分析更强,颞前中下部对语义分析更强。     

Differential temporo-parietal cortical networks that support relational and item-based recency judgments

There is a growing interest in the parietal cortical role for episodic memory retrieval. Previous functional magnetic resonance imaging (fMRI) studies of recency judgments, judgments of the relative temporal order of two studied items, have highlighted the involvement of the lateral prefrontal and medial temporal regions. However, the parietal cortical contribution to recency judgments has rarely been highlighted. To examine the parietal involvement, in this study, we conducted a re-analysis to increase the statistical power using three data sets (N = 73) from our previous fMRI studies of recency judgments. Recency judgments can be achieved by at least two mechanisms, relational and item-based ones. It has been revealed that the left hippocampus/parahippocampal region is related to relational recency judgments, and that the right anterior temporal region is related to item-based recency judgments. We examined whether the parietal cortex is involved in these two types of recency judgments. Significant brain activity related to relational recency judgments was observed in the left ventral parietal region and, as reported previously, the left parahippocampal region. On the other hand, significant brain activity related to item-based recency judgments was observed in the left dorsal parietal region and, as reported previously, the right anterior temporal region. Furthermore, correlation analyses of resting-state BOLD signals detected significant correlations between the ventral parietal region and the parahippocampal region, as well as between the dorsal parietal region and anterior temporal region. These results suggest that the two temporo-parietal networks differentially contribute to relational and item-based recency judgments.     

The contribution of the study of neurodegenerative disorders to the understanding of human memory

Memory impairment is one of the most common complaints affecting patients with neurodegenerative disorders, and its investigation has provided insights into the function and properties of human memory. The study of Alzheimer's disease has indicated the importance of mesial temporal structures and the hippocampus in episodic memory. In progressive supranuclear palsy, frontotemporal dementias, Parkinson's disease and Huntington's disease fronto-striatal networks are involved in working memory and higher level cognition. The study of semantic dementia, where there is lobar atrophy of the temporal lobe, has shown that the temporal neocortex has an important function in semantic memory. The investigation of human memory in neurodegenerative disorders suggests that the interaction of networks subserving episodic memory, semantic memory, and working memory contributes to higher level cognition and results in the fundamental homeostatic processes of recall and learning.     

Traces of vocabulary acquisition in the brain: Evidence from covert object naming

One of the strongest predictors of the speed with which adults can name a pictured object is the age at which the object and its name are first learned. Age of acquisition also predicts the retention or loss of individual words following brain damage in conditions like aphasia and Alzheimer's disease. Functional Magnetic Resonance Imaging (fMRI) was used to reveal brain areas differentially involved in naming objects with early or late acquired names. A baseline task involved passive viewing of non-objects. The comparison between the silent object naming conditions (early and late) with baseline showed significant activation in frontal, parietal and mediotemporal regions bilaterally and in the lingual and fusiform gyri on the left. Direct comparison of early and late items identified clusters with significantly greater activation for early acquired items at the occipital poles (in the posterior parts of the middle occipital gyri) and at the left temporal pole. In contrast, the left middle occipital and fusiform gyri showed significantly greater activation for late than early acquired items. We propose that greater activation to early than late objects at the occipital poles and at the left temporal pole reflects the more detailed visual and semantic representations of early than late acquired items. We propose that greater activation to late than early objects in the left middle occipital and fusiform gyri occurs because those areas are involved in mapping visual onto semantic representations, which is more difficult, and demands more resource, for late than for early items.     

Cortical thickness is associated with gait disturbances in cerebral small vessel disease

Although gait disturbances are present in a substantial portion of patients with cerebral small vessel disease (SVD), their pathogenesis has not been clarified as they are not entirely explained by the white matter lesions (WMLs) and lacunar infarcts. The role of cortical thickness in these patients remains largely unknown. We aimed to assess the regions of cortical thickness associated with distinct gait parameters in patients with SVD, and whether these associations were dependent on WMLs and lacunar infarcts. MRI data were obtained from 415 subjects with SVD, aged between 50 and 85 years. We assessed cortical thickness using surface-based cortical thickness analysis, and gait performance using the GAITRite system. Cortical thickness of predominantly the orbitofrontal and ventrolateral prefrontal cortex, the inferior parietal lobe, cingulate areas and visual association cortices was positively related to stride length. Thickness of the primary and supplementary motor cortices and the cingulate cortex was positively related to cadence, while thickness of the orbitofrontal and ventrolateral prefrontal cortex, anterior cingulate cortex and especially the inferior parietal lobe and superior temporal gyrus was negatively related to stride width. The associations with stride length and width were partially explained by the subcortical WMLs and lacunar infarcts. Cortical thickness may therefore be important in gait disturbances in individuals with SVD, with different cortical patterns for specific gait parameters. We suggest that cortical atrophy is part of the disease processes in patients with SVD.     

Semantic memory involvement in the default mode network: a functional neuroimaging study using independent component analysis

The Default Mode Network (DMN) is a higher order functional neural network that displays activation during passive rest and deactivation during many types of cognitive tasks. Accordingly, the DMN is viewed to represent the neural correlate of internally-generated self-referential cognition. This hypothesis implies that the DMN requires the involvement of cognitive processes, like declarative memory. The present study thus examines the spatial and functional convergence of the DMN and the semantic memory system. Using an active block-design functional Magnetic Resonance Imaging (fMRI) paradigm and Independent Component Analysis (ICA), we trace the DMN and fMRI signal changes evoked by semantic, phonological and perceptual decision tasks upon visually-presented words. Our findings show less deactivation during semantic compared to the two non-semantic tasks for the entire DMN unit and within left-hemispheric DMN regions, i.e., the dorsal medial prefrontal cortex, the anterior cingulate cortex, the retrosplenial cortex, the angular gyrus, the middle temporal gyrus and the anterior temporal region, as well as the right cerebellum. These results demonstrate that well-known semantic regions are spatially and functionally involved in the DMN. The present study further supports the hypothesis of the DMN as an internal mentation system that involves declarative memory functions.     

Neural systems for word meaning modulated by semantic ambiguity

One important issue in neuroimaging research on language is how the brain processes and represents lexical semantics. Past studies with various paradigms reveal that the left inferior prefrontal and mid-superior temporal regions play a crucial role in semantic processing. Those studies, however, typically utilize words having a precise and dominant meaning as stimuli and have not manipulated lexico-semantic ambiguity, a key feature of human language, as an experimental variable. Here, we used a word generation paradigm to examine whether neuroanatomical networks for meaning are modulated by lexical ambiguity. We found that, compared with semantically precise words, semantically ambiguous words were mediated by strong brain activations in the left dorsal-lateral frontal areas, the anterior cingulate, and the right inferior parietal lobe. Semantically precise words, instead, were associated with the left inferior prefrontal and mid-superior temporal sites. These findings indicate that semantic analysis of written words is a dynamic process involving coordination of widely distributed neural subsystems, which are weighted by semantic ambiguity.     

Three distinct ventral occipitotemporal regions for reading and object naming.

This study investigates word and object processing during naming and viewing tasks and identifies three distinct regions in the left ventral occipitotemporal cortex. Irrespective of task, words and objects (relative to meaningless visual controls) activated the medial surface of the left anterior fusiform gyrus, a region that has previously been associated with semantic knowledge. A more lateral region was differentially active for naming words and objects relative to viewing the same stimuli and a more posterior region was differentially active for objects relative to words irrespective of task. In addition, we found that word processing resulted in greater activation than object processing on the dorsal surface of the left superior temporal gyrus and the left supramarginal gyrus. These regions appear to be important for converting orthography into phonology; their response to words irrespective of task is consistent with established psychological evidence that implicit phonological processing is stronger for words than objects.     

Dissociating intentional learning from relative novelty responses in the medial temporal lobe

The establishment of a role for medial temporal lobe (MTL) structures in episodic memory has led to an investigative focus on the specific contributions and interactions between constituent MTL regions, including the hippocampus and surrounding medial temporal cortices. By dissociating an intentional stimulus-category learning condition from a passive viewing condition, we demonstrate, using fMRI, that novelty- and familiarity-driven responses in human anterior and posterior hippocampus, respectively, only occur during intentional learning. With increasing familiarity of stimulus-category associations, there is a shift in neuronal responses from anterior to posterior hippocampal regions. This anterior/posterior response gradient may reflect a weighting of functional hippocampal architecture related to encoding of novel and retrieval of familiar information. By contrast, perirhinal cortex is engaged by novel stimuli irrespective of task, highlighting this region as a component of a generic familiarity discrimination system. By introducing distinct stimulus types, we further demonstrate that these MTL responses are independent of stimulus complexity. Different patterns of activity for intentional learning vs. passive viewing indicate that intentional encoding/retrieval of stimulus-category associations and automatic novelty/familiarity assessment of stimuli are processed in anatomically dissociable neuronal ensembles within the MTL memory system.     

Cortical lateralization during verb generation: a combined ERP and fMRI study

Lateralization of scalp-recorded event-related potentials (ERPs) and functional MRI (fMRI) activation was investigated using a verb generation task in 10 healthy right-handed adults. ERPs showed an early transient positivity in the left inferior temporal region (500-1250 ms) following auditory presentation of the stimulus noun. A sustained slow cortical negativity of later onset (1250-3000 ms) was then recorded, most pronounced over left inferior frontal regions. fMRI data were in agreement with both ERP effects, showing left lateralized activation in inferior and superior temporal as well as inferior frontal cortices. Lateralized ERP effects occurred during the verb generation task but not during passive word listening or during word- and nonword repetition. Thus, ERPs and fMRI provided convergent evidence regarding language lateralization, with ERPs revealing the temporal sequence of posterior to anterior cortical activation during semantic retrieval.     

Time-dependent neural activations related to recognition of people's names in emotional and neutral face-name associative learning: an fMRI study

Previous data have indicated that the left anterior temporal lobe contributes to the retrieval of familiar people's names, and that the extended network including the bilateral anterior temporal lobe plays an important role in the retrieval of newly learned people's names. However, there has been no direct evidence for time-dependent change in brain activation in face-name associations. In addition, previous studies have demonstrated that emotional information such as emotional faces may contribute to the organization of long-lasting episodic memory. In the present study, we investigated the activations related to the recognition of people's names in the context of emotional and neutral face-name associative learning. Before fMRI scanning, subjects learned face-name associations that included emotionally positive and neutral facial expressions. In immediate (5 min later) and delayed (2 weeks later) recognition with fMRI scanning, subjects were presented with studied faces with two names, and were asked to choose the correct associative name learned previously. Recognition-related activations were identified in the anterior part of bilateral temporal lobe for immediate recognition and only in the left temporal lobe for delayed recognition. Further analysis confirmed the time-dependent change in activation of the right anterior temporal lobe. Activation related to the processing of faces with positive expressions were observed in the left periamygdaloid area and temporal pole, although emotional information did not have an influence on task performance in this study. These findings suggest that the neural network involving the bilateral temporal lobe contributes to the retrieval of newly learned people's names, and that the left temporal lobe has a crucial and stable role in retrieval of people's names from faces, whereas the role of the right temporal lobe in retrieval of people's names may decrease with the time course.