Neuroanatomic substrates of semantic memory impairment in Alzheimer's disease: patterns of functional MRI activation.

Impairment in semantic processing occurs early in Alzheimer's disease (AD) and differential impact on subtypes of semantic relations have been reported, yet there is little data on the neuroanatomic basis of these deficits. Patients with mild AD and healthy controls underwent 3 functional MRI auditory stimulation tasks requiring semantic or phonological decisions (match-mismatch) about word pairs (category-exemplar, category-function, pseudoword). Patients showed a significant performance deficit only on the exemplar task. On voxel-based fMRI activation analyses, controls showed a clear activation focus in the left superior temporal gyrus for the phonological task; patients showed additional foci in the left dorsolateral prefrontal and bilateral cingulate areas. On the semantic tasks, predominant activation foci were seen in the inferior and middle frontal gyrus (left greater than right) in both groups but patients showed additional activation suggesting compensatory recruitment of locally expanded foci and remote regions, for example, right frontal activation during the exemplar task. Covariance analyses indicated that exemplar task performance was strongly related to signal increase in bilateral medial prefrontal cortex. The authors conclude that fMRI can reveal similarities and differences in functional neuroanatomical processing of semantic and phonological information in mild AD compared to healthy elderly, and can help to bridge cognitive and neural investigations of the integrity of semantic networks in AD.     

Task-dependent modulation of regions in the left inferior frontal cortex during semantic processing

To distinguish areas involved in the processing of word meaning (semantics) from other regions involved in lexical processing more generally, subjects were scanned with positron emission tomography (PET) while performing lexical tasks, three of which required varying degrees of semantic analysis and one that required phonological analysis. Three closely apposed regions in the left inferior frontal cortex and one in the right cerebellum were significantly active above baseline in the semantic tasks, but not in the nonsemantic task. The activity in two of the frontal regions was modulated by the difficulty of the semantic judgment. Other regions, including some in the left temporal cortex and the cerebellum, were active across all four language tasks. Thus, in addition to a number of regions known to be active during language processing, regions in the left inferior frontal cortex were specifically recruited during semantic processing in a task-dependent manner. A region in the right cerebellum may be functionally related to those in the left inferior frontal cortex. Discussion focuses on the implications of these results for current views regarding neural substrates of semantic processing.     

汉语单字词音、义加工的脑激活模式

目的：研究汉字音、义加工的脑机制。方法：采用汉字单字词为实验材料，通过功能磁共振成像扫描执行语音和语义两种认知任务的脑区。结果：语音任务激活的脑区有，左侧顶叶下部和颞上回(BA 40／39／22，BA：Brodmann Area，即布鲁德曼分区，下同)，左侧枕中回(BA18／19)，右侧枕下回(BA18／19)，以及左中央前回(BA6)。语义任务激活的脑区有，左侧顶叶下部(BA40／39)和左侧颞上回(BA22)，左侧额下回(BA10／47)，右侧额中回和额上回(BA10／11)，以及左侧额中回(BA11)。语义任务减去语音任务激活的脑区有，左侧额下回(BA47)，左侧海马(BA36)和右侧海马旁回(BA36)。语音任务减去语义任务没有发现任何脑区的显著激活。结论：在语义任务中与语音有关的脑区得到激活；而在语音任务中与语义有关的脑区没有激活。     

Right‐hemispheric processing of non‐linguistic word features: Implications for mapping language recovery after stroke

Verbal stimuli often induce right‐hemispheric activation in patients with aphasia after left‐hemispheric stroke. This right‐hemispheric activation is commonly attributed to functional reorganization within the language system. Yet previous evidence suggests that functional activation in right‐hemispheric homologues of classic left‐hemispheric language areas may partly be due to processing nonlinguistic perceptual features of verbal stimuli. We used functional MRI (fMRI) to clarify the role of the right hemisphere in the perception of nonlinguistic word features in healthy individuals. Participants made perceptual, semantic, or phonological decisions on the same set of auditorily and visually presented word stimuli. Perceptual decisions required judgements about stimulus‐inherent changes in font size (visual modality) or fundamental frequency contour (auditory modality). The semantic judgement required subjects to decide whether a stimulus is natural or man‐made; the phonologic decision required a decision on whether a stimulus contains two or three syllables. Compared to phonologic or semantic decision, nonlinguistic perceptual decisions resulted in a stronger right‐hemispheric activation. Specifically, the right inferior frontal gyrus (IFG), an area previously suggested to support language recovery after left‐hemispheric stroke, displayed modality‐independent activation during perceptual processing of word stimuli. Our findings indicate that activation of the right hemisphere during language tasks may, in some instances, be driven by a “nonlinguistic perceptual processing” mode that focuses on nonlinguistic word features. This raises the possibility that stronger activation of right inferior frontal areas during language tasks in aphasic patients with left‐hemispheric stroke may at least partially reflect increased attentional focus on nonlinguistic perceptual aspects of language. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Specialization of phonological and semantic processing in Chinese word reading

The purpose of this study was to examine the neurocognitive network for processing visual word forms in native Chinese speakers using functional magnetic resonance imaging (fMRI). In order to compare the processing of phonological and semantic representations, we developed parallel rhyming and meaning association judgment tasks that required explicit access and manipulation of these representations. Subjects showed activation in left inferior/middle frontal gyri, bilateral medial frontal gyri, bilateral middle occipital/fusiform gyri, and bilateral cerebella for both the rhyming and meaning tasks. A direct comparison of the tasks revealed that the rhyming task showed more activation in the posterior dorsal region of the inferior/middle frontal gyrus (BA 9/44) and in the inferior parietal lobule (BA 40). The meaning task showed more activation in the anterior ventral region of the inferior/middle frontal gyrus (BA 47) and in the superior/middle temporal gyrus (BA 22,21). These findings are consistent with previous studies in English that suggest specialization of inferior frontal regions for the access and manipulation of phonological vs. semantic representations, but also suggest that this specialization extends to the middle frontal gyrus for Chinese. These findings are also consistent with the suggestion that the left middle temporal gyrus is involved in representing semantic information and the left inferior parietal lobule is involved in mapping between orthographic and phonological representations.     

Neural basis of single-word reading in Spanish-English bilinguals

Brain imaging studies have identified a left-lateralized network of regions that are engaged when monolinguals read. However, for individuals who are native speakers of two languages, it is unclear whether this pattern of activity is maintained across both languages or if it deviates according to language-specific properties. We used functional magnetic resonance imaging to investigate single-word processing in Spanish and in English in 12 proficient early Spanish-English bilinguals matched in skill level in both languages. Word processing in Spanish engaged the left inferior frontal and left middle temporal gyri. Word processing in English activated the left inferior frontal, middle frontal, and fusiform gyri extending to inferior temporal gyrus and the right middle temporal gyrus extending into superior temporal sulcus. The comparison of reading in Spanish greater than reading in English revealed involvement of the left middle temporal gyrus extending into the superior temporal sulcus. English greater than Spanish, however, demonstrated greater engagement of the left middle frontal gyrus extending into the superior frontal gyrus. We conclude that although word processing in either language activates classical areas associated with reading, there are language-specific differences, which can be attributed to the disparity in orthographic transparency. English, an orthographically deep language, may require greater engagement of the frontal regions for phonological coding, whereas Spanish allows increased access to semantic processing via the left middle temporal areas. Together, these results suggest that bilinguals will show adjustments to the typical neural representation of reading as necessitated by the demands of the orthography.     

Left and right basal ganglia and frontal activity during language generation: contributions to lexical, semantic, and phonological processes.

fMRI was used to determine the frontal, basal ganglia, and thalamic structures engaged by three facets of language generation: lexical status of generated items, the use of semantic vs. phonological information during language generation, and rate of generation. During fMRI, 21 neurologically normal subjects performed four tasks: generation of nonsense syllables given beginning and ending consonant blends, generation of words given a rhyming word, generation of words given a semantic category at a fast rate (matched to the rate of nonsense syllable generation), and generation of words given a semantic category at a slow rate (matched to the rate of generating of rhyming words). Components of a left pre-SMA-dorsal caudate nucleus-ventral anterior thalamic loop were active during word generation from rhyming or category cues but not during nonsense syllable generation. Findings indicate that this loop is involved in retrieving words from pre-existing lexical stores. Relatively diffuse activity in the right basal ganglia (caudate nucleus and putamen) also was found during word-generation tasks but not during nonsense syllable generation. Given the relative absence of right frontal activity during the word generation tasks, we suggest that the right basal ganglia activity serves to suppress right frontal activity, preventing right frontal structures from interfering with language production. Current findings establish roles for the left and the right basal ganglia in word generation. Hypotheses are discussed for future research to help refine our understanding of basal ganglia functions in language generation.     

Levels of word processing and incidental memory: dissociable mechanisms in the temporal lobe.

Word recall is facilitated when deep (e.g. semantic) processing is applied during encoding. This fact raises the question of the existence of specific brain mechanisms supporting different levels of information processing that can modulate incidental memory performance. In this study we obtained spatiotemporal brain activation profiles, using magnetic source imaging, from 10 adult volunteers as they performed a shallow (phonological) processing task and a deep (semantic) processing task. When phonological analysis of the word stimuli into their constituent phonemes was required, activation was largely restricted to the posterior portion of the left superior temporal gyrus (area 22). Conversely, when access to lexical/semantic representations was required, activation was found predominantly in the left middle temporal gyrus and medial temporal cortex. The differential engagement of each mechanism during word encoding was associated with dramatic changes in subsequent incidental memory performance.     

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.     

Developmental differences of neurocognitive networks for phonological and semantic processing in Chinese word reading

Developmental differences in the neurocognitive networks for phonological and semantic processing in Chinese word reading were examined in 13 adults and 13 children using functional magnetic resonance imaging (fMRI). Rhyming and semantic association judgments were made to two-character words that were presented sequentially in the visual modality. These lexical tasks were compared with a nonlinguistic control task involving judgment of line patterns. The first main finding was that adults showed greater activation than children in right middle occipital gyrus on both the meaning and rhyming task, suggesting adults more effectively engage right hemisphere brain regions involved in the visual-spatial analysis of Chinese characters. The second main finding was that adults showed greater activation than children in left inferior parietal lobule for the rhyming as compared with the meaning task, suggesting greater specialization of phonological processing in adults. The third main finding was that children who had better performance in the rhyming task on characters with conflicting orthographic and phonological information relative to characters with nonconflicting information showed greater activation in left middle frontal gyrus, suggesting greater engagement of brain regions involved in the integration of orthography and phonology.     

Auditory and visual word processing studied with fMRI

Brain activations associated with semantic processing of visual and auditory words were investigated using functional magnetic resonance imaging (fMRI). For each form of word presentation, subjects performed two tasks: one semantic, and one nonsemantic. The semantic task was identical for both auditory and visual presentation: single words were presented and subjects determined whether the word was concrete or abstract. In the nonsemantic task for auditory words, subjects determined whether the word had one syllable or multiple syllables. In the nonsemantic task for visual words, subjects determined whether the word was presented in lower case or upper case. There was considerable overlap in where auditory and visual word semantic processing occurred. Visual and auditory semantic tasks both activated the left inferior frontal (BA 45), bilateral anterior prefrontal (BA 10, 46), and left premotor regions (BA 6) and anterior SMA (BA 6, 8). Left posterior temporal (middle temporal and fusiform gyrus) and predominantly right‐sided cerebellar activations were observed during the auditory semantic task but were not above threshold during visual word presentation. The data, when averaged across subjects, did not show obligatory activation of left inferior frontal and temporal language areas during nonsemantic word tasks. Individual subjects showed differences in the activation of the inferior frontal region while performing the same task, even though they showed similar response latency and accuracy. Hum. Brain Mapping 7:15–28, 1999. © 1999 Wiley‐Liss, Inc.     

Distinct brain systems for processing concrete and abstract concepts

Behavioral and neurophysiological effects of word imageability and concreteness remain a topic of central interest in cognitive neuroscience and could provide essential clues for understanding how the brain processes conceptual knowledge. We examined these effects using event-related functional magnetic resonance imaging while participants identified concrete and abstract words. Relative to nonwords, concrete and abstract words both activated a left-lateralized network of multimodal association areas previously linked with verbal semantic processing. Areas in the left lateral temporal lobe were equally activated by both word types, whereas bilateral regions including the angular gyrus and the dorsal prefrontal cortex were more strongly engaged by concrete words. Relative to concrete words, abstract words activated left inferior frontal regions previously linked with phonological and verbal working memory processes. The results show overlapping but partly distinct neural systems for processing concrete and abstract concepts, with greater involvement of bilateral association areas during concrete word processing, and processing of abstract concepts almost exclusively by the left hemisphere.     

Neural correlates of semantic and morphological processing of Hebrew nouns and verbs

Neuropsychological evidence regarding grammatical category suggests that deficits affecting verbs tend to localize differently from those affecting nouns, but previous functional imaging studies on healthy subjects fail to show consistent results that correspond to the clinical dissociation. In the current imaging study, we addressed this issue by manipulating not only the grammatical category but also the processing mode, using auditory presentation of Hebrew words. Subjects were presented with verbs and nouns and were instructed to make either a semantic decision (“Does the word belong to a given semantic category?”) or a morphological decision (“Is the word inflected in plural?”). The results showed different patterns of activation across distinct regions of interest. With respect to grammatical category effects, we found increased activation for verbs in the posterior portion of the left superior temporal sulcus, left dorsal premotor area, and posterior inferior frontal gyrus. In each of these regions, the effect was sensitive to task. None of the ROIs showed noun advantage. With respect to task effects, we found a semantic advantage in left anterior inferior frontal gyrus, as well as in left posterior middle temporal gyrus. The results suggest that cerebral verb‐noun dissociation is a result of localized and subtle processes that take place in a set of left frontal and temporal regions, and that the cognitive and neural processes involved in analyzing grammatical category depend on the lexical characteristics of the stimuli, as well as on task requirements. The discrepancy between functional imaging and patient data is also discussed. Hum. Brain Mapp, 2007. © 2006 Wiley‐Liss, Inc.     

Advantages of sentence-level fMRI language tasks in presurgical language mapping for temporal lobe epilepsy

fMRI language mapping has become increasingly utilized for determining language dominance before surgical intervention for temporal lobe epilepsy (TLE). This study aimed to examine the differences between two classes of fMRI word generation tasks used in our clinic: tasks using a single word cue, referred to as simple generative tasks (SGTs), and tasks also involving sentence-level processing, referred to as sentence-level language tasks (SLTs). Specifically, we aimed to investigate the extent and laterality of activation and frontal–temporal connectivity during these language tasks and their relationship to clinical language measures. Thirty-one patients with TLE (18 patients with left TLE and 13 patients with right TLE) performed four language tasks during an fMRI scan, two SGTs and two SLTs. We found significantly greater activity for SLTs over SGTs in bilateral inferior frontal and middle temporal gyri and the left temporal pole. Sentence-level language tasks also showed greater lateralization compared with SGTs. Finally, we found that while activation extent did not correlate with clinical language tests, the degree of left frontal–temporal connectivity was significantly correlated with naming and semantic fluency performance. These correlations also were more robust for SLTs than for SGTs. Taken together, these results provide a compelling argument for including some form of SLTs in fMRI language lateralization protocols for TLE as they allow for better characterization of language networks, particularly in the temporal lobes which are at risk in surgery.     

Neural correlates of creative writing: An fMRI Study

Cerebral activations involved in actual writing of a new story and the associated correlates with creative performance are still unexplored. To investigate the different aspects of the creative writing process, we used functional magnetic resonance imaging while 28 healthy participants performed a new paradigm related to creative writing: “brainstorming” (planning a story) and “creative writing” (writing a new and creative continuation of a given literary text), as well as an additional control paradigm of “reading” and “copying.” Individual verbal creativity was assessed with a verbal creativity test and creative performance with a qualitative rating of the creative products. “brainstorming” engaged cognitive, linguistic, and creative brain functions mainly represented in a parieto‐frontal‐temporal network, as well as writing preparation, and visual and imaginative processing. “creative writing” activated motor and visual brain areas for handwriting and additionally, cognitive and linguistic areas. Episodic memory retrieval, free‐associative and spontaneous cognition, and semantic integration were observed in a right lateralized activation pattern in bilateral hippocampi, bilateral temporal poles (BA 38), and bilateral posterior cingulate cortex in a “creative writing” minus “copying” comparison. A correlation analysis of “creative writing” minus “copying” with the creativity index revealed activation in the left inferior frontal gyrus (BA 45) and the left temporal pole (BA 38). Thus, verbal creativity during “creative writing” is associated with verbal and semantic memory as well as semantic integration. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Increased functional connectivity in the ventral and dorsal streams during retrieval of novel words in professional musicians

Current models of speech and language processing postulate the involvement of two parallel processing streams (the dual stream model): a ventral stream involved in mapping sensory and phonological representations onto lexical and conceptual representations and a dorsal stream contributing to sound‐to‐motor mapping, articulation, and to how verbal information is encoded and manipulated in memory. Based on previous evidence showing that music training has an influence on language processing, cognitive functions, and word learning, we examined EEG‐based intracranial functional connectivity in the ventral and dorsal streams while musicians and nonmusicians learned the meaning of novel words through picture–word associations. In accordance with the dual stream model, word learning was generally associated with increased beta functional connectivity in the ventral stream compared to the dorsal stream. In addition, in the linguistically most demanding “semantic task,” musicians outperformed nonmusicians, and this behavioral advantage was accompanied by increased left‐hemispheric theta connectivity in both streams. Moreover, theta coherence in the left dorsal pathway was positively correlated with the number of years of music training. These results provide evidence for a complex interplay within a network of brain regions involved in semantic processing and verbal memory functions, and suggest that intensive music training can modify its functional architecture leading to advantages in novel word learning.     

Cognitive processing in Chinese literate and illiterate subjects: an fMRI study

Functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) were used to map brain activation during language tasks. While previous studies have compared performance between alphabetic literate and illiterate subjects, there have been no such data in Chinese-speaking individuals. In this study, we used fMRI to examine the effects of education on neural activation associated with silent word recognition and silent picture-naming tasks in 24 healthy right-handed Chinese subjects (12 illiterates and 12 literates). There were 30 single Chinese characters in the silent word recognition task and 30 meaningful road-signs in the silent picture-naming task. When we compared literate and illiterate subjects, we observed education-related differences in activation patterns in the left inferior/middle frontal gyrus and both sides of the superior temporal gyrus for the silent word recognition task and in the bilateral inferior/middle frontal gyrus and left limbic cingulated gyrus for the silent picture-naming task. These results indicate that the patterns of neural activation associated with language tasks are strongly influenced by education. Education appears to have enhanced cognitive processing efficiency in language tasks.     

Both frontal and temporal cortex exhibit phonological and semantic specialization during spoken language processing in 7‐ to 8‐year‐old children

A previous functional magnetic resonance imaging (fMRI) study by Weiss et al. (Weiss et al., Human Brain Mapping, 2018, 39, 4334–4348) examined brain specialization for phonological and semantic processing of spoken words in young children who were 5 to 6 years old and found evidence for specialization in the temporal but not the frontal lobe. According to a prominent neurocognitive model of language development (Skeide & Friederici, Nature Reviews Neuroscience, 2016, 17, 323–332), the frontal lobe matures later than the temporal lobe. Thus, the current study aimed to examine if brain specialization in the frontal lobe can be observed in a slightly older cohort of children aged 7 to 8 years old using the same experimental and analytical approach as in Weiss et al. (Weiss et al., Human Brain Mapping, 2018, 39, 4334–4348). One hundred and ten typically developing children were recruited and were asked to perform a sound judgment task, tapping into phonological processing, and a meaning judgment task, tapping into semantic processing, while in the MRI scanner. Direct task comparisons showed that these children exhibited language specialization in both the temporal and the frontal lobes, with the left posterior dorsal inferior frontal gyrus (IFG) showing greater activation for the sound than the meaning judgment task, and the left anterior ventral IFG and the left posterior middle temporal gyrus (MTG) showing greater activation for the meaning than the sound judgment task. These findings demonstrate that 7‐ to 8‐year‐old children have already begun to develop a language‐related specialization in the frontal lobe, suggesting that early elementary schoolers rely on both specialized linguistic manipulation and representation mechanisms to perform language tasks.     

“Are there lexicons?” A study of lexical and semantic processing in word-meaning deafness suggests “yes”

A controversial issue in the cognitive neuroscience of language is the question whether independent lexical representations need to be included in cognitive models. Recent models claim to account for the available data without including phonological or orthographic lexicons. These models base their lexical decision (“Is it a word or not?”) either on familiarity of the input string or alternatively, on semantic information. These two alternatives were evaluated in a series of experiments with an individual suffering from word-meaning deafness. This is a rare disorder of auditory word comprehension which affects mapping of a word’s phonology to its meaning. The participant, BB, was unaffected by the ‘word-likeness’ of nonwords with comparable accuracy for plausible and abstruse nonwords. She was further able to make lexical decisions despite her severe impairment in comprehending the word’s meaning. Lexical and semantic processing were assessed on an item-specific basis providing a methodological advancement over previous studies. The comprehension tasks involved word-picture matching as well as definition tasks. The results suggest that BB’s lexical decisions are based neither on familiarity of the input string nor on semantic information, which was largely unavailable. The only alternative are lexical representations on which she could base her decisions.     

Attenuated frontal activation in schizophrenia may be task dependent

Functional magnetic resonance imaging was used to examine the neural correlates of two linguistic tasks in schizophrenia. METHOD: Five dextral male schizophrenic patients and five volunteers matched for demographic variables and task performance participated. Echoplanar images were acquired over 5 min at 1.5 T while subjects performed two paced, covert tasks; (1) verbal fluency: silent generation of words beginning with an aurally presented cue letter, contrasted with silent repetition of the aurally presented word 'rest'; (2) semantic decision: deciding whether a visually presented cue word was 'living or non-living' and silently articulating the response, contrasted with rest. Both tasks entailed language processing; only verbal fluency requires the intrinsic generation of verbal material. Between-group differences in the mean power of experimental response to the semantic decision task were identified by a one-way analysis of covariance (ANCOVA), with a measure of stimulus-correlated motion as a covariate. Voxels demonstrating a significant interaction between task and group were identified using a two-way ANCOVA. RESULTS: In controls, both tasks were associated with activation of prefrontal cortex. In patients with schizophrenia there was a significantly reduced power of response in several prefrontal regions during verbal fluency relative to controls, a difference that was not evident for the semantic decision task. There was a significant group x task interaction in the left inferior frontal gyrus, left dorsolateral prefrontal cortex and the supplementary motor area at voxel and regional levels of analysis. CONCLUSIONS: Attenuation of frontal activation during cognitive task performance in schizophrenia does not represent a fixed deficit in frontal function, but may depend on the specific cognitive demands of the experimental task employed.