Diffusion tensor imaging depicting damage to the arcuate fasciculus in patients with conduction aphasia: a study of the Wernicke–Geschwind model

Abstract

Objectives: In contrast with disorders of comprehension and spontaneous expression, conduction aphasia is characterized by poor repetition, which is a hallmark of the syndrome. There are many theories on the repetition impairment of conduction aphasia. The disconnection theory suggests that a damaged in the arcuate fasciculus, which connects Broca's and Wernicke's area, is the cause of conduction aphasia. In this study, we examined the disconnection theory.

Methods: We enrolled ten individuals with conduction aphasia and ten volunteers, and analysed their arcuate fasciculus using diffusion tensor imaging (DTI) and obtained fractional anisotropy (FA) values. Then, the results of the left hemisphere were compared with those of the right hemisphere, and the results of the conduction aphasia cases were compared with those of the volunteers.

Results: There were significant differences in the FA values between the left and right hemispheres of volunteers and conduction cases. In volunteers, there was an increase in fiber in the left hemisphere compared with the right hemisphere, whereas there was an increase in fiber in the right hemisphere compared with the left hemisphere in conduction aphasia patients. The results of diffusion tensor tractography suggested that the configuration of the arcuate fasciculus was different between conduction aphasia patients and volunteers, suggesting that there was damage to the arcuate fasciculus of conduction aphasia cases.

Conclusions: The damage seen in the arcuate fasciculus of conduction aphasia cases in this study supports the Wernicke–Geschwind disconnection theory. A disconnection between Broca's area and Wernicke's area is likely to be one mechanism of conduction aphasia repetition impairment.     

Double dissociation of letter and category fluency following left frontal and temporal lobe lesions

Background: A number of studies have suggested that temporal cortex is critical for the ability to generate exemplars belonging to a particular semantic category (i.e., category fluency), while frontal cortex is critical for generating words beginning with a particular letter (i.e., letter or phonemic fluency). However, previous studies have often focused on relative, quantitative differences in performance across groups of patients and primarily in the oral domain.

Aims: The current study analysed verbal fluency data from two individuals with chronic aphasia, one with a large left temporal lobe lesion and a severe Wernicke's aphasia, and a second individual with a large left frontal lobe lesion and a moderately severe non-fluent aphasia. The goal of the study was to do both qualitative and quantitative analyses of letter and category fluency performance in these two individuals across oral and written fluency domains.

Methods & Procedures: Participants were administered both oral and written versions of letter fluency (FAS) and category fluency conditions (fruits, animals, and supermarket items). Participants were given 90 seconds to generate as many items as possible, and their responses were scored for both overall output, as well as qualitative structure using a clustering analysis.

Outcomes & Results: The individual with an extensive temporal lobe lesion generated a large number of exemplars on the letter fluency task. Some of these items were neologisms (e.g., frest, anth, and swink), but remarkably all adhered to the phonological constraints of the task. However, this individual was very poor at generating items belonging to semantic categories. In contrast, the individual with a large frontal lesion generated many exemplars on the category fluency task but only two items on the letter fluency task. The same pattern was replicated in the written domain in both individuals, and results from the clustering analysis paralleled these quantitative findings.

Conclusions: This report describes two individuals with aphasia who exhibited a double dissociation between letter and category fluency performance in both oral and written domains. The current findings provide further evidence for the notion that left frontal cortex is critical for word retrieval based on phonology, while left temporal cortex is critical for word retrieval based on semantics. The findings have implications for the types of strategies that may be most effective in individuals with lesions to these brain regions critical for word retrieval.     

The role of speech production in auditory-verbal short-term memory: evidence from progressive fluent aphasia

We report investigations of auditory-verbal short-term memory (AVSTM) in a patient with progressive fluent anomic aphasia. Despite having apparently normal AVSTM as measured by digital span, FM was significantly impaired in immediate serial recall of short sequences of familiar words, and even in reproducing a single word after a filled delay of just a few seconds. In both tasks, unlike normal subjects, she produced numerous phonological errors, often consisting of phonological segments from the intended target word concatenated with segments from other words in the stimulus sequence. Her success in these tasks was modulated (i) consistently by word frequency (high > low), (ii) inconsistently by word imageability (high > low), and (iii) most dramatically by 'nameability': that is, FM was much more likely to reproduce a word correctly in AVSTM if it was a word that she could also produce successfully in picture-naming tasks. On the basis of these and additional experiments designed to exclude other interpretations, we conclude that AVSTM may be crucially supported by activation of the lexical phonological representations responsible for production of content words in speech.     

Verifying the hypothesis of disconnection syndrome in patients with conduction aphasia using diffusion tensor imaging

BACKGROUND: It is thought in disconnection theory that connection of anterior and posterior language function areas, i.e. the lesion of arcuate fasciculus causes conduction aphasia. OBJECTIVE: To verify the theory of disconnection elicited by repetition disorder in patients with conduction aphasia by comparing the characteristics of diffusion tensor imaging between healthy persons and patients with conduction aphasia. DESIGN: Case-control observation. SETTING: Department of Neurology, Hongqi Hospital Affiliated to Mudanjiang Medical College. PARTICIPANTS: Five male patients with cerebral infarction-involved arcuate fasciculus conduction aphasia, averaged （43±2）years, who hospitalized in the Department of Neurology, Hongqi Hospital Affiliated to Mudanjiang Medical College from February 2004 to February 2005 were involved in this experiment. The involved patients were all confirmed as cerebral infarction by skull CT and MRI, and met the diagnosis criteria revised in 1995 4th Cerebrovascular Conference. They were examined by the method of Aphasia Battery of Chinese (ABC) edited by Surong Gao. The results were poorer than auditory comprehension disproportionately, and consistented with the mode of conduction aphasia. Another 5 male healthy persons, averaged （43±1）years, who were physicians receiving further training in the Department of Neurology, Beijing Tiantan Hospital were also involved in this experiment. Informed consents of detected items were obtained from all the subjects. METHODS: All the subjects were performed handedness assessment with assessment criteria of handedness formulated by Department of Neurology, First Hospital Affiliated to Beijing Medical University. Arcuate fasciculus of involved patients and health controls were analyzed with diffusion tensor imaging (DTI) and divided into 3 parts (anterior, middle and posterior segments) for determining FA value (mean value was obtained after three times of measurements), and a comparison of FA value was made between two sides. MAIN OUTCOME MEASURES: Analysis results of arcuate fasciculus DTI of healthy controls and patients with conduction aphasia. RESULTS: Five patients with conduction aphasia and 5 healthy controls participated in the final analysis. ①All the subjects were right-handedness. ② The left FA value of anterior, middle and posterior segments of arcuate fasciculus was larger than the right one in most normal volunteers, i.e. arcuate fasciculus with normal function on the left side was more than that on the right side. Because the amount of healthy controls was small, so positive conclusion has not been obtained, and only above-mentioned tendency was demonstrated. Healthy controls had good bilateral arcuate fasciculus; Three patients with conduction aphasia presented left FA value of anterior segment of arcuate fasciculus smaller than the right one, and two patients presented the left FA value larger than the right one. Four patients presented the left FA value of middle segment of arcuate fasciculus smaller than the right one, and one patient presented the left FA value larger than the right one, i.e. middle segment of arcuate fasciculus of 5 patients with conduction aphasia was all involved in at different degrees. Four patients with conduction aphasia presented the left FA value of posterior segment of arcuate fasciculus smaller than the right one, and one patient presented the left FA value larger than the right one, i.e. posterior segment of arcuate fasciculus of 5 patients was all injured at different degrees. CONCLUSION: Arcuate fasciculus of patients with conduction aphasia all is involved in at different degrees, which verifies the theory of disconnection of repetition disorder in patients with conduction aphasia.     

Language processing modulated by literacy: a network analysis of verbal repetition in literate and illiterate subjects

Previous behavioral and functional neuroimaging data indicate that certain aspects of phonological processing may not be acquired spontaneously, but are modulated by learning an alphabetic written language, that is, learning to read and write. It appears that learning an alphabetic written language modifies the auditory-verbal (spoken) language processing competence in a nontrivial way. We have previously suggested, based on behavioral and functional neuroimaging data, that auditory-verbal and written language interact not only during certain language tasks, but that learning and developing alphabetic written language capacities significantly modulates the spoken language system. Specifically, the acquisition of alphabetic orthographic knowledge has a modulatory influence on sublexical phonological processing and the awareness of sublexical phonological structure. We have suggested that developing an orthographic representation system for an alphabetic written language, and integrating a phoneme-grapheme correspondence with an existing infrastructure for auditory-verbal language processing, will result in a modified language network. Specifically, we suggest that the parallel interactive processing characteristics of the underlying language-processing brain network differ in literate and illiterate subjects. Therefore, the pattern of interactions between the regions of a suitably defined large-scale functional-anatomical network for language processing will differ between literate and illiterate subjects during certain language tasks. In order to investigate this hypothesis further, we analyzed the observed covariance structure in a PET data set from a simple auditory-verbal repetition paradigm in literate and illiterate subjects, with a network approach based on structural equation modeling (SEM). Based on a simple network model for language processing, the results of the present network analysis indicate that the network interactions during word and pseudoword repetition in the illiterate group differ, while there were no significant differences in the literate group. The differences between the two tasks in the illiterate group may reflect differences in attentional modulation of the language network, executive aspects of verbal working memory and the articulatory organization of verbal output. There were no significant differences between the literate and illiterate group during word repetition. In contrast, the network interactions differed between the literate and illiterate group during pseudoword repetition. In addition to differences similar to those observed in the illiterate group between word and pseudoword repetition, there were differences related to the interactions of the phonological loop between the groups. In particular, these differences related to the interaction between Broca's area and the inferior parietal cortex as well as the posterior-midinsula bridge between Wernicke's and Broca's area. In conclusion, the results of this network analysis are consistent with our previously presented results and support the hypothesis that learning to read and write during childhood influences the functional architecture of the adult human brain. In particular, the basic auditory-verbal language network in the human brain is modified as a consequence of acquiring orthographic language skills.     

Manipulating hemispheric attentional mechanisms to modulate word retrieval in aphasia

Background: Emerging evidence suggests that left hemisphere damage may create an attentional bias towards stimuli initially processed in the right hemisphere.

Aims: The current study aimed to investigate whether this hemispheric attentional bias influences spoken word production in a picture–word interference task.

Methods & Procedures: Two participants with aphasia and seven healthy controls named centrally presented pictures that were preceded by a distractor word which appeared in either the left or right visual field 200 ms prior to the picture. Distractor words were semantically related, phonologically related, unrelated, or the name of the picture. Results were analysed in terms of response times and accuracy.

Outcomes & Results: A greater overall facilitation effect was found in the left visual field/right hemisphere condition for both participants with aphasia, however this varied depending on distractor condition. These results are consistent with an attentional bias towards linguistic stimuli initially presented to the right hemisphere. In contrast, the results of the control group suggest a reduction in the lateralisation of language processing to the left hemisphere in healthy ageing.

Conclusions: These results suggest that spoken word production may be influenced by changes in attentional mechanisms following left hemisphere damage in aphasia, as well as changes in hemispheric lateralisation and inhibition in healthy ageing. Identifying attentional conditions that optimise language performance in aphasia may have implications for new treatments in language rehabilitation.     

Damage to temporo-parietal cortex decreases incidental activation of thematic relations during spoken word comprehension

Both taxonomic and thematic semantic relations have been studied extensively in behavioral studies and there is an emerging consensus that the anterior temporal lobe plays a particularly important role in the representation and processing of taxonomic relations, but the neural basis of thematic semantics is less clear. We used eye tracking to examine incidental activation of taxonomic and thematic relations during spoken word comprehension in participants with aphasia. Three groups of participants were tested: neurologically intact control participants (N=14), individuals with aphasia resulting from lesions in left hemisphere BA 39 and surrounding temporo-parietal cortex regions (N=7), and individuals with the same degree of aphasia severity and semantic impairment and anterior left hemisphere lesions (primarily inferior frontal gyrus and anterior temporal lobe) that spared BA 39 (N=6). The posterior lesion group showed reduced and delayed activation of thematic relations, but not taxonomic relations. In contrast, the anterior lesion group exhibited longer-lasting activation of taxonomic relations and did not differ from control participants in terms of activation of thematic relations. These results suggest that taxonomic and thematic semantic knowledge are functionally and neuroanatomically distinct, with the temporo-parietal cortex playing a particularly important role in thematic semantics.     

Facilitating and disrupting speech perception in word deafness

Background: Word deafness is a rare condition where pathologically degraded speech perception results in impaired repetition and comprehension but otherwise intact linguistic skills. Although impaired linguistic systems in aphasia resulting from damage to the neural language system (here termed central impairments) have consistently been shown to be amenable to external influences such as linguistic or contextual information (e.g., cueing effects in naming), it is not known whether similar influences can be shown for aphasia arising from damage to a perceptual system (here termed peripheral impairments).

Aims: This study aimed to investigate the extent to which pathologically degraded speech perception could be facilitated or disrupted by providing visual as well as auditory information.

Methods & Procedures: In three word repetition tasks, the participant with word deafness (AB) repeated words under different conditions: words were repeated in the context of a pictorial or written target, a distractor (semantic, unrelated, rhyme, or phonological neighbour) or a blank page (nothing). Accuracy and error types were analysed.

Outcomes & Results: AB was impaired at repetition in the blank condition, confirming her degraded speech perception. Repetition was significantly facilitated when accompanied by a picture or written example of the word and significantly impaired by the presence of a written rhyme. Errors in the blank condition were primarily formal, whereas errors in the rhyme condition were primarily miscues (saying the distractor word rather than the target).

Conclusions: Cross-modal input can both facilitate and further disrupt repetition in word deafness. The cognitive mechanisms behind these findings are discussed. Both top-down influence from the lexical layer on perceptual processes and intra-lexical competition within the lexical layer may play a role.     

Unravelling nonverbal cognitive performance in acquired aphasia

ABSTRACT

Background: Dissociated impairment of noun and verb retrieval has been frequently reported after vascular brain lesions: selective damage of either grammatical class allowed to test models of lexical processing and of its neuroanatomical foundation. However, vascular lesions are often quite large and do not involve brain structures uniformly. Neurosurgical lesions do not undergo such apparent limitation, being usually smaller and better distributed across the cerebral cortex.

Aims: We explored the neuroanatomical correlates of noun–verb naming processing and dissociations by means of the voxel-based lesion symptom mapping (VLSM) procedure and the subtraction of lesion volume of interests (VOIs) approach in a series of 99 neurosurgical patients.

Methods and Procedures: The VOIs and behavioral data for noun and verb naming were analyzed in a VLSM procedure. The verb (or noun) naming performance was included as a covariate control variable, which allowed testing effects on noun (or verb) naming, controlling for the verb (or noun) naming performance. The total lesion volume was also included as a covariate to avoid spurious effects.

Outcomes and Results: Eighteen patients showed a significant dissociation between noun and verb naming: seven patients showed disproportionate impairment in naming nouns, and eleven patients with disproportionate impairment in naming verbs. In addition, there were 27 undifferentiated patients, i.e. performing abnormally on nouns and/or verbs, but non-dissociating between the two word classes.VLSM in combination with the subtraction of lesion mask analyses revealed that verb naming impairments were related with lesions in the middle frontal gyrus, precentral gyrus, parietal and rolandic operculum, supplementary motor area, and the inferior parietal (supramarginal and angular gyri), whereas noun naming impairments were associated with basal temporo-occipital lesions. Furthermore, data indicate that noun and verb naming deficits also depend on a disconnection phenomenon: at subcortical level, noun naming impairments are related to damage to parts of the sagittal stratum (including the inferior fronto-occipital fasciculus and the inferior longitudinal fasciculus), the splenium of the corpus callosum, the posterior thalamic radiations (plus optic radiations), the retrorolandic part of the internal capsule, the tapetum and the fornix. On the contrary, verb naming impairments are related to damage to parts of the superior and posterior corona radiata, and of the anterior and posterior limb of the internal capsule.

Conclusions: Summing up, results point to verb-specific areas in the superior frontal as well as the inferior parietal cortex, and noun-specific basal temporo-occipital and subcortical neural circuitries.     

Longitudinal imaging and deterioration in word comprehension in primary progressive aphasia: Potential clinical significance

Background: Three variants of primary progressive aphasia (PPA), distinguished by language performance and supportive patterns of atrophy on imaging, have different clinical courses and the prognoses for specific functions. For example, semantic variant PPA alone is distinguished by impaired word comprehension. However, sometimes individuals with high education show normal performance on word-comprehension tests early on, making classification difficult. Furthermore, as the condition progresses, individuals with other variants develop word-comprehension deficits and other behavioural symptoms, making distinctions between variants less clear. Longitudinal brain imaging allows identification of specific areas of atrophy in individual patients, which identifies the location of disease in each patient.

Aims: We hypothesised that the areas of atrophy in individual PPA participants would be closely correlated with the decline in word comprehension over time. We propose that areas where tissue volume is correlated with word comprehension are areas that: (1) are essential for word comprehension, (2) compensate for word comprehension in some individuals with semantic variant PPA early in the course, and (3) show atrophy in individuals with logopenic and nonfluent variant PPA only late in the course.

Methods and Procedures: Fifteen participants with PPA (five logopenic variant PPA; eight semantic variant PPA; two nonfluent/agrammatic variant PPA; mean age 67.8), underwent high resolution magnetic resonance imaging and cognitive tests at least 9 months apart. The correlations between change in regional volumes and change in auditory word-comprehension scores were investigated using Spearman test.

Outcomes & Results: While scores on auditory word comprehension at Time 1 were correlated with volume loss in right and left temporal pole and left inferior temporal cortex (areas of atrophy associated with semantic variant PPA), deterioration in auditory word comprehension from Time 1 to Time 2 was associated with individual atrophy in left middle temporal cortex, left angular gyrus, and right inferior and middle temporal cortex.

Conclusions: Progressive atrophy in focal areas surrounding left temporal pole and left inferior temporal cortex, and right homologous area is closely related to progressive decline in auditory word comprehension. These correlations likely reflect areas that compensate for subtle deficits early in the course of semantic variant PPA, as well as areas that are critical for auditory word comprehension that eventually atrophy in individuals with other variants of PPA. Individual patterns of atrophy also help us understand and predict the clinical course of individuals, such as associated behavioural or motor deficits.     

The neural basis for mental state attribution: A voxel‐based lesion mapping study

The ability to infer other persons' mental states, “Theory of Mind” (ToM), is a key function of social cognition and is needed when interpreting the intention of others. ToM is associated with a network of functionally related regions, with reportedly key prominent hubs located in the dorsolateral prefrontal cortex (dlPFC) and the temporoparietal junction (TPJ). The involvement of (mainly the right) TPJ in ToM is based primarily on functional imaging studies that provide correlational evidence for brain‐behavior associations. In this lesion study, we test whether certain brain areas are necessary for intact ToM performance. We investigated individuals with penetrating traumatic brain injury (n = 170) and healthy matched controls (n = 30) using voxel‐based lesion‐symptom mapping (VLSM) and by measuring the impact of a given lesion on white matter disconnections. ToM performance was compared between five patient groups based on lesion location: right TPJ, left TPJ, right dlPFC, left dlPFC, and other lesion, as well as healthy controls. The only group to present with lower ToM abilities was the one with lesions in the right dlPFC. Similarly, VLSM analysis revealed a main cluster in the right frontal middle gyrus and a secondary cluster in the left inferior parietal gyrus. Last, we found that disconnection of the left inferior longitudinal fasciculus and right superior longitudinal fasciculus were associated with poor ToM performance. This study highlights the importance of lesion studies in complementing functional neuroimaging findings and supports the assertion that the right dlPFC is a key region mediating mental state attribution.     

Impairment of language is related to left parieto-temporal glucose metabolism in aphasic stroke patients

Summary Twenty-six aphasic patients who had an ischaemic infarct in the territory of the left middle cerebral artery (MCA) were investigated. Cranial computed tomography (CT) showed various lesion sites: infarcts restricted to cortical structures in 12 patients, combined cortical and subcortical infarcts in 7 and isolated subcortical infarcts sparing the left cortex in another 7 cases. ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography revealed remote hypometabolism of the left convexity cortex and of the left basal ganglia, which was extended further than the morphological infarct zone in all cases. Types and degrees of aphasia were classified using the Aachener Aphasie Test (AAT): 10 patients had global aphasia, 2 Broca's, 5 Wernicke's, and 5 amnesic aphasia. Four patients suffered from minimal or residual aphasic symptoms. The AAT results were compared with the regional cerebral metabolic rates of glucose of the left hemisphere. Irrespective of the infarct location all five AAT subtests (Token test, repetition, written language, confrontation naming, auditory and reading comprehension) were closely correlated among each other and with left parieto-temporal metabolic rates, whereas left frontal and left basal ganglia metabolism showed no significant correlation. The close relation between left temporo-parietal functional activity and all five AAT subtests suggests that the different aspects of aphasia tested by AAT can be related to a common disorder of language processing in those areas.     

Phonological decoding involves left posterior fusiform gyrus

Aloud reading of novel words is achieved by phonological decoding, a process in which grapheme-to-phoneme conversion rules are applied to "sound out" a word's spoken representation. Numerous brain imaging studies have examined the neural bases of phonological decoding by contrasting pseudoword (pronounceable nonwords) to real word reading. However, only a few investigations have examined pseudoword reading under both aloud and silent conditions, task parameters that are likely to significantly alter the functional anatomy of phonological decoding. Subjects participated in an fMRI study of aloud pseudoword, aloud real word, silent pseudoword, and silent real word reading. Using this two-by-two design, we examined effects of word-type (real words vs. pseudowords) and response-modality (silent vs. aloud) and their interactions. We found 1) four regions to be invariantly active across the four reading conditions: the anterior aspect of the left precentral gyrus (Brodmann's Area (BA) 6), and three areas within the left ventral occipitotemporal cortex; 2) a main effect of word-type (pseudowords > words) in left inferior frontal gyrus and left intraparietal sulcus; 3) a main effect of response-modality (aloud > silent) that included bilateral motor, auditory, and extrastriate cortex; and 4) a single left hemisphere extrastriate region showing a word-type by response-modality interaction effect. This region, within the posterior fusiform cortex at BA 19, was uniquely modulated by varying phonological processing demands. This result suggests that when reading, word forms are subject to phonological analysis at the point they are first recognized as alphabetic stimuli and BA 19 is involved in processing the phonological properties of words.     

Long-term maintenance of novel vocabulary in persons with chronic aphasia

Background: The study of novel word learning in aphasia can shed light on the functionality of patients' learning mechanisms and potentially help in treatment planning. Previous studies have indicated that persons with aphasia are able to learn some new vocabulary. However, these learning outcomes appear short-lived and evidence for the ability to use the newly learned words in the long term is lacking.

Aims: Participants with aphasia and matched controls underwent short training where they were taught to name novel objects with novel names. We studied the participants' word learning and particularly their long-term maintenance. We also examined whether the language and verbal short-term memory impairments of the participants with aphasia related to their ability to acquire and maintain phonological and semantic information on novel words.

Methods & Procedures: Two participants with nonfluent aphasia, LL and AR, and two matched controls took part in the experiment. They were taught to name 20 unfamiliar objects by repeating the names in the presence of the object picture. Half of the items carried a definition that was used to probe incidental semantic learning. There were four training sessions, a post-training test, and follow-up tests up to 6 months post-training. Learning measures included recognition of the trained objects, as well as spontaneous and cued recall in visual confrontation naming. Incidental semantic learning was measured by spontaneous recall of the definitions.

Outcomes & Results: Combining spontaneous and phonologically cued responses, LL acquired 70% and AR 55% of the novel words. With phonological cueing, LL named 50% of the items correctly up to 6 months post-training (vs 95–100% for the controls) and AR 25% up to 8 weeks post-training. AR's lexical-semantic processing, pseudoword repetition and verbal short-term capacity were inferior to those of LL. In line with this, AR learned fewer words and showed more decline in recognition memory for the trained items, and weaker recall of the semantic definitions.

Conclusions: Our results support previous findings that people with aphasia can learn to name novel items. More importantly, the results show for the first time that, with phonological cueing, an individual with aphasia can maintain some of this learning up to 6 months post-training. Moreover the results provide further evidence for the significance of the functional status of lexical-semantic processing on word learning success.     

Accessing orthographic representations from speech: The role of left ventral occipitotemporal cortex in spelling

The present fMRI study used a spelling task to investigate the hypothesis that the left ventral occipitotemporal cortex (vOT) hosts neuronal representations of whole written words. Such an orthographic word lexicon is posited by cognitive dual‐route theories of reading and spelling. In the scanner, participants performed a spelling task in which they had to indicate if a visually presented letter is present in the written form of an auditorily presented word. The main experimental manipulation distinguished between an orthographic word spelling condition in which correct spelling decisions had to be based on orthographic whole‐word representations, a word spelling condition in which reliance on orthographic whole‐word representations was optional and a phonological pseudoword spelling condition in which no reliance on such representations was possible. To evaluate spelling‐specific activations the spelling conditions were contrasted with control conditions that also presented auditory words and pseudowords, but participants had to indicate if a visually presented letter corresponded to the gender of the speaker. We identified a left vOT cluster activated for the critical orthographic word spelling condition relative to both the control condition and the phonological pseudoword spelling condition. Our results suggest that activation of left vOT during spelling can be attributed to the retrieval of orthographic whole‐word representations and, thus, support the position that the left vOT potentially represents the neuronal equivalent of the cognitive orthographic word lexicon. Hum Brain Mapp, 36:1393–1406, 2015. © 2014 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Lesion analysis of language production deficits in aphasia

Background: Three aspects of language production are impaired to different degrees in individuals with post-stroke aphasia: ability to repeat words and nonwords, name pictures, and produce sentences. These impairments often persist into the chronic stages, and the neuroanatomical distribution of lesions associated with chronicity of each of these impairments is incompletely understood.

Aims: The primary objective of this study was to investigate the lesion correlates of picture naming, sentence production, and nonword repetition deficits in the same participant group because most prior lesion studies have mapped single language impairments. The broader goal of this study was to investigate the extent and degree of overlap and uniqueness among lesions resulting in these deficits in order to advance the current understanding of functional subdivision of neuroanatomical regions involved in language production.

Methods & Procedures: In this study, lesion-symptom mapping was used to determine if specific cortical regions are associated with nonword repetition, picture naming, and sentence production scores. Structural brain images and behavioural performance of 31 individuals with post-stroke left hemisphere lesions and a diagnosis of aphasia were used in the lesion analysis.

Outcomes & Results: Each impairment was associated with mostly unique, but a few shared lesions. Overall, sentence and repetition deficits were associated with left anterior perisylvian lesions, including the pars opercularis and triangularis of the inferior frontal lobe, anterior superior temporal gyrus, anterior portions of the supramarginal gyrus, the putamen, and anterior portions of the insula. In contrast, impaired picture naming was associated with posterior perisylvian lesions including major portions of the inferior parietal lobe and middle temporal gyrus. The distribution of lesions in the insula was consistent with this antero-posterior perisylvian gradient. Significant voxels in the posterior planum temporale were associated with a combination of all three deficits.

Conclusions: These findings emphasise the participation of each perisylvian region in multiple linguistic functions, suggesting a many(functions)-to-many(networks) framework while also identifying functional subdivisions within each region.     

The lonely brain: evidence from studying patients with penetrating brain injury

ABSTRACT

Loneliness is perceived as social isolation and exclusion. The neural substrate of loneliness has been investigated with functional neuroimaging; however, lesion-based studies and their associated outcomes are needed to infer causal involvement between brain regions and function. Here, we applied voxel-based lesion-symptom mapping (VLSM) analyses to investigate the causal role of brain lesions on self-report of loneliness (UCLA Loneliness Scale) in a unique sample from the Vietnam Head Injury Study, including veterans with penetrating traumatic brain injuries (pTBI) (n = 132) and healthy controls (HCs) (n = 35). Our results revealed that the right anterior insula (AI) and right prefrontal cortex (PFC) are key brain regions underpinning loneliness perception. Individuals with selective lesions to the right AI and right PFC were less likely to report loneliness compared to patients with selective lesions to the posterior cortex and HCs. Therefore, it appears that lesions to key regions involved in processing social pain act to lower the perception of loneliness. Reporting loneliness was associated with executive dysfunction, apathy, disinhibition, and lower life satisfaction. In conclusion, the reported findings broaden our understanding of how loneliness is processed in the social brain, and how behavioral and cognitive factors can influence this perception.     

Cortical and fibre tract interrelations in conduction aphasia

Background: The syndrome of conduction aphasia is an umbrella term to label clinically heterogeneous language disorders that all include a deficit of repetition due to impaired immediate memory or, in some patients, impaired speech production. The present article reviews the currently available literature on conduction aphasia. It covers aspects of the history of conduction aphasia as a fascicular disconnection syndrome and the objections to this view and discusses the proposed subtypes of this syndrome and the underlying cortical and white matter lesions.

Aims: The primary objectives of this article are to critically review the influence of historical concepts on recent approaches to optimise existing theoretical synergies. In addition, the article seeks to advance our understanding of the first steps of verbal auditory processing in individuals with normal and impaired language skills.

Main Contribution: We present first indications for an involvement of the left hemisphere in both short- and long-term integration of auditory information derived by examining patients with (conduction) aphasia.

Conclusions: Conduction aphasia may result from left hemisphere cortical lesions or from a disconnection of critical bundles of axons (fibre tract). The exact course of the fibre tract connections and the cortical regions involved in conduction aphasia remains controversial.     

Auditory-verbal analysis in aphasia

Background: Comprehension deficits are more pervasive in aphasic syndromes than initially believed. They affect differentially distinct levels of auditory-verbal comprehension. Current evidence from functional imaging studies in healthy subjects indicates that distinct levels of auditory-verbal analysis involve specific networks.

Aims: The aim of this study is (1) to assess the different levels of auditory-verbal analysis with real-time monitoring tasks in patients with aphasia, (2) to compare the performance profiles across aphasia types, (3) to analyse patterns of dissociations vs. co-occurrence at specific levels, and (4) to establish correlations between disturbances at specific levels of auditory-verbal analysis and sites of lesions.

Methods & Procedures: Forty-two right-handed patients with aphasia associated with a first unilateral left-hemispheric lesion underwent tests monitoring (1) phonetic-phonological, (2) lexical, (3) morphosyntactic, (4) semantic-pragmatic (at sentence level), and (5) linguistic prosody processing. Anatomo-clinical correlations were established by means of voxel-based lesion-symptom mapping.

Outcomes & Results: Widespread deficits at multiple levels occurred across aphasic syndromes. In a given patient, more levels tended to be impaired in Wernicke’s and global aphasia than in Broca’s or conduction aphasia. Syllable and word processing double-dissociated behaviourally and partially anatomically. Morphosyntactic deficits were always accompanied by semantic-pragmatic deficits. Anatomo-clinical correlations implicated the dorsal auditory stream in syllable discrimination, the ventral stream in semantic processing at lexical level and in linguistic prosody and both streams in lexical frequency effect. Basal ganglia were implicated in syntactic and semantic processing at sentence level.

Conclusions: At prelexical and lexical levels, syllable and word processing appear to be independent of each other. At sentence level, parsing of syntactic structure appears to be necessary for successful semantic-pragmatic analysis. Thus, the fine-grained evaluation of auditory-verbal processing capacities and of the integrity of specialised processing networks in brain-damaged patients provides a sensitive diagnostic tool.     

Neural intersections of the phonological,visual magnocellular and motor/cerebellar systems in normal readers: Implications for imaging studies on dyslexia

We used fMRI to explore the extent of the anatomical overlap of three neural systems that the literature on developmental dyslexia associates with reading: the auditory phonological, the visual magnocellular, and the motor/cerebellar systems. Twenty‐eight normal subjects performed four tasks during fMRI scans: word and pseudoword reading, auditory rhyming for letter names, visual motion perception, and a motor sequence learning task. We found that the left occipitotemporal cortex (OTC), which previous studies reported to be dysfunctional in dyslexia, can be fractionated into different functional areas: an anterior and lateral area that was activated by both reading and auditory rhyming tasks; a posterior area that was commonly activated by both the reading and the motion perception task and a medial/intermediate area, including the so‐called Visual Word Form Area, which was specifically activated by the reading task. These results show that the left OTC is an area of segregated convergence of different functional systems. We compared our results with the hypoactivation pattern reported for reading in a previous cross‐cultural PET study on 36 dyslexic subjects from three countries. The region of decreased activation in dyslexia overlapped with regions that are specific for reading and those activated during both the auditory rhyming task and the single word and pseudoword reading task described in the present fMRI study. No overlap was found with the activation patterns for the visual motion perception task or for the motor sequence learning task. These observations challenge current theories of dyslexia. Hum Brain Mapp 34:2669–2687, 2013. © 2012 Wiley Periodicals, Inc.