* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download reading for language.
Survey
Document related concepts
Time perception wikipedia , lookup
Human brain wikipedia , lookup
Cognitive neuroscience wikipedia , lookup
Neuroesthetics wikipedia , lookup
Neuroplasticity wikipedia , lookup
Metastability in the brain wikipedia , lookup
Neuropsychology wikipedia , lookup
Embodied language processing wikipedia , lookup
Dual consciousness wikipedia , lookup
Cognitive neuroscience of music wikipedia , lookup
Expressive aphasia wikipedia , lookup
Broca's area wikipedia , lookup
Brodmann area 45 wikipedia , lookup
Split-brain wikipedia , lookup
Neurolinguistics wikipedia , lookup
Transcript
Brain Injury ISSN: 0269-9052 (Print) 1362-301X (Online) Journal homepage: http://www.tandfonline.com/loi/ibij20 Neurological impressions on the organization of language networks in the human brain Fabricio Ferreira de Oliveira, Sheilla de Medeiros Correia Marin & Paulo Henrique Ferreira Bertolucci To cite this article: Fabricio Ferreira de Oliveira, Sheilla de Medeiros Correia Marin & Paulo Henrique Ferreira Bertolucci (2016): Neurological impressions on the organization of language networks in the human brain, Brain Injury, DOI: 10.1080/02699052.2016.1199914 To link to this article: http://dx.doi.org/10.1080/02699052.2016.1199914 Published online: 14 Oct 2016. Submit your article to this journal Article views: 83 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ibij20 Download by: [UZH Hauptbibliothek / Zentralbibliothek Zürich] Date: 31 October 2016, At: 01:01 http://tandfonline.com/ibij ISSN: 0269-9052 (print), 1362-301X (electronic) Brain Inj, Early Online: 1–11 © 2016 Taylor & Francis Group, LLC. DOI: 10.1080/02699052.2016.1199914 REVIEW ARTICLE Neurological impressions on the organization of language networks in the human brain Fabricio Ferreira de Oliveira , Sheilla de Medeiros Correia Marin , & Paulo Henrique Ferreira Bertolucci Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil Abstract Keywords Background: More than 95% of right-handed individuals, as well as almost 80% of left-handed individuals, have left hemisphere dominance for language. The perisylvian networks of the dominant hemisphere tend to be the most important language systems in human brains, usually connected by bidirectional fibres originated from the superior longitudinal fascicle/ arcuate fascicle system and potentially modifiable by learning. Neuroplasticity mechanisms take place to preserve neural functions after brain injuries. Language is dependent on a hierarchical interlinkage of serial and parallel processing areas in distinct brain regions considered to be elementary processing units. Whereas aphasic syndromes typically result from injuries to the dominant hemisphere, the extent of the distribution of language functions seems to be variable for each individual. Method: Review of the literature Results: Several theories try to explain the organization of language networks in the human brain from a point of view that involves either modular or distributed processing or sometimes both. The most important evidence for each approach is discussed under the light of modern theories of organization of neural networks. Conclusions: Understanding the connectivity patterns of language networks may provide deeper insights into language functions, supporting evidence-based rehabilitation strategies that focus on the enhancement of language organization for patients with aphasic syndromes. Linguistics, aphasia, language, speech, disability evaluation, neural networks Towards a better understanding of language lateralization Lateralization of language functions Language is dependent on an hierarchical interlinkage of serial and parallel processing areas in distinct brain regions considered to be elementary processing units [1,2]; therefore, language processing takes place mostly in the dominant hemisphere, which is usually the left one. Development of hemisphere dominance for language processing is related to the specificity of synaptic connections established before and after birth, but it is still unknown if a specific linguistic specialization based on experience is required for the functional separation of the hemispheres [1]. The first historical evidence for localization of higher brain functions arose from studies of language disorders. Since the end of the nineteenth century, aphasic syndromes had been considered to be mostly mediated by specialized areas of the dominant hemisphere of the brain [2]. While localization of language functions shows little inter-individual variability, it Correspondence: Fabricio Ferreira de Oliveira, MD, MSc, PhD, Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina, Departamento de Neurologia e Neurocirurgia, Rua Botucatu 740, Vila Clementino, CEP 04023-900, São Paulo, SP, Brazil. E-mail: [email protected] Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/ibij. History Received 26 May 2015 Revised 22 March 2016 Accepted 6 June 2016 Published online 14 October 2016 is currently known that both hemispheres are functionally complementary, considering that several brain areas are bilaterally activated when a language task is undertaken [3–5]. Ambidextrous individuals usually have bilateral language dominance, while those with left, bilateral or right hemisphere language representation do not differ significantly with respect to verbal fluency, linguistic processing or intelligence, as well as with regard to the homology of anatomical and functional organization of language networks in either hemisphere [6]. More than 95% of right-handed individuals, as well as almost 80% of left-handed individuals, have left hemisphere dominance for language [7]. Women tend to perform better on language tasks and have bilateral language representation more often than men, who usually excel in visual-spatial abilities [8]. Whereas aphasic syndromes typically result from injuries to the dominant hemisphere [9], the extent of the distribution of language functions seems to be variable for each individual brain. A native language and a second language that shares its universal grammar can assume different region-specific processing rules according to the time when they were learned. Language lateralization seems to depend on the bilingual status of the individuals, with bilateral hemispheric involvement for both languages of early bilinguals (who learned such languages during early infancy), left hemisphere dominance for language of monolinguals and also left hemisphere dominance for both languages of late bilinguals [10]. If both 2 F. F. de Oliveira et al. Brain Inj, Early Online: 1–11 languages are learned during infancy, their fluency tends to activate indistinguishable sites in Broca’s area; however, if the second language is acquired during adulthood, it is usually represented in a separate region in Broca’s area [3,11]. The neuroanatomy of language Three large networks interact to connect language with conceptual information [1]. Broca’s and Wernicke’s areas, the insular cortex, the head of the caudate nucleus and the putamen in the dominant hemisphere form the language implementation system, which analyses auditory signals to activate conceptual knowledge and support phonemic and grammatical construction while controlling production of speech. This system is surrounded by a mediational system, composed of several regions distributed among the parietal, frontal and temporal association areas, acting as brokers between the language implementation system and the so called conceptual system, a group of regions spread throughout the association areas. It is remarkable that bidirectionality is an important attribute of the arcuate fascicle, which connects areas of the sensory cortex (including Wernicke’s area) with prefrontal and premotor areas (including Broca’s area) in the dominant hemisphere [9]. Language networks may be allocated into two different streams [12]. The dorsal stream for language is composed by the superior longitudinal fascicle/arcuate fascicle system, the most important pathway for syntactic analysis and auditory-motor transcoding in the brain [13], which is sometimes divided into a lexical-semantic pathway and a phonological pathway, but is currently considered to be domain-general rather than specialized for language [3,14]. The ventral stream for language is largely bilaterally organized for parallel processing [15], formed by the uncinate fascicle (involved in semantic processing and sound recognition), the extreme capsule (involved in the long-term storage of semantic information and phonological working memory), the middle longitudinal fascicle (involved in phonological and semantic processing) and the inferior longitudinal fascicle (involved in object recognition, face processing and visual semantic memory) [14]. The currently accepted distribution of language networks, along with trajectories of subcortical fascicles may be viewed in a simplified model (Figure 1). Subcortical structures are also known to contribute to the organization of language in view of their reciprocal connections with cortical language areas through networks that may be modified by learning [1,16]. This is particularly true for the lexical-semantic processing in inferior, lateral and posterior thalamic nuclei and also for the phonetic processing for fluency in the striatal structures of the dominant hemisphere [16]. Also, attention and executive functions may be affected when the thalamus in the dominant hemisphere is injured and visual-spatial orientation may be particularly impaired when lesions occur in the thalamic nuclei of the non-dominant hemisphere [17]; such impairments may affect the linguistic performance of patients after brain injuries. Disconnection syndromes may result when lesions involve the thalamus and the basal nuclei, implicating in subcortical aphasias. Spoken language is only one of several language skills mediated by the dominant hemisphere. Contrariwise, affective Figure 1. Approximate distribution of language networks in the cortex of the dominant hemisphere with simplified trajectories of subcortical fascicles. AC, primary auditory cortex; AG, angular gyrus; B, Broca’s area; M, motor networks in the precentral gyrus; PF, prefrontal networks; S, sensory networks in the postcentral gyrus; SM, supramarginal gyrus; T, inferior temporal networks and temporal pole; W, Wernicke’s area. aspects of language such as intonation (prosody) are processed in the non-dominant hemisphere, mirroring the logical organization of language content in the dominant hemisphere [7]. Irony, musical interests, metaphors and intentions can only be appreciated when the non-dominant hemisphere is intact [1]. Homologue areas in the non-dominant hemisphere contribute to ‘emotional’ aspects of language, such as the inferior frontal gyrus of the non-dominant hemisphere for expression of emotions and the homologue of Wernicke’s area in the non-dominant hemisphere, which acts in the interpretation of human emotions. The abilities for elaboration of discourse macrostructure and for contextual integration of information are basically non-dominant hemisphere functions, particularly related to the frontal lobe [17], as well as the ability for single word reading in patients recovering from aphasia. Incidentally, even though spatial orienting is usually a function of the visually inspired non-dominant hemisphere, neglect may also result from acute damage to areas of the dominant hemisphere that typically serve language functions, namely the superior and middle temporal gyri, the inferior parietal lobule and the insula [18]; these patients may present both contralateral neglect and aphasia. Definition of aphasia Aphasia is defined as an acquired impairment in language production and comprehension and in other cognitive processes that underlie language, causing problems with any or all of the following: speaking, listening, reading, writing and gesturing abilities [3]. These problems may be characterized by: impaired fluency; difficulty to understand and/or produce words; substitution or addition of speech sounds or exchange of semantically-related words (phonemic or semantic paraphasias, respectively); difficulty to name objects (anomia) or to recall words during conversation; and impairment in social Neurological organization of language networks DOI: 10.1080/02699052.2016.1199914 communication skills (pragmatic language). Reading and writing are usually affected in patients with aphasia, while phono-articulatory function and consciousness are relatively preserved. The most important aphasic syndromes are shown in Table I, as well as the most likely brain injury sites to result in these language disturbances [2,19]. Plasticity in the human brain and the benefits of neurological rehabilitation Mechanisms of language recovery after injuries to the dominant hemisphere seem to be relatively stereotyped. There are increased activations of homologues of language areas in the non-dominant hemisphere and of perilesional areas of the dominant hemisphere, including compensatory recruitment of new areas and of language areas that were spared [20]. Sometimes, there may also be dysfunctional activation of the non-dominant hemisphere interfering with language recovery due to increased and deleterious transcallosal inhibition of the already damaged dominant hemisphere [21]. Nevertheless, uninjured language areas in the dominant hemisphere seem to present a continuously increased activation, while non-dominant hemisphere 3 homologue areas have a biphasic course with earlier increased and later decreased activation that is dependent on the amount of pre-morbid language lateralization [15]. It seems that the areas recruited for a particular language task change over the course of recovery, with minimal elicited activation (or haemodynamic response) during the language task in the acute stage, predominant non-dominant hemisphere activation in the sub-acute stage and a return to predominant dominant hemisphere activation in chronic stages for patients who show good recovery of the task [4,21]. Ictal evaluation of language may be able to localize complex partial seizure commencement in patients with epilepsy [22] and some studies with patients who had infancy or adolescence onset of epilepsy have shown evidence of plastic processes affecting language lateralization. While speech processes activate bilateral superior temporal regions, there may be convergence to a right hemisphere dominant pattern for language in some patients with left mesial temporal sclerosis or neoplastic diseases (interhemispheric reorganization), contrary to what usually happens in the uninjured brains of right-handed individuals that have developed left hemisphere dominance [23,24]. In some patients with epilepsy, reorganization of language results in receptive Table I. Traditional classification of aphasic syndromes. Type of aphasia Spontaneous speech Fluency Comprehension Repetition impaired preserved preserved impaired Conduction Aphasia normal (phonemic mistakes) Global Aphasia poor (mutism), restricted to simple verbal stereotypes preserved preserved impaired impaired Semantic Aphasia preserved preserved impaired preserved preserved impaired Broca’s Aphasia Wernicke’s Aphasia Transcortical Motor Aphasia Transcortical Sensory Aphasia poor, with effort, paraphasias, agrammatism logorrheic, with paraphasias and neologisms normal (difficulty finding words) poor (mutism), with great latency at responses, echolalia, perseveration normal (semantic jargon) Mixed Transcortical Aphasia mutism impaired impaired Verbal Deafness normal preserved impaired Thalamic Aphasia normal or with paraphasias preserved preserved or discretely impaired preserved Subcortical Aphasia poor, with great latency preserved (non-thalamic) at responses, echolalia, perseveration impaired Naming Other signs impaired hemiparesis, apraxia of mouth and hand impaired impaired homonymous hemianopia, apraxia, anosognosia impaired preserved hemi-hypoesthesia, apraxia, hemianopia impaired impaired hemiparesis, hemianopia, hemihypoesthesia, apraxia preserved impaired homonymous hemianopia preserved impaired eventually hemiparesis (crural involvement) and grasp reflex preserved impaired eventually hemianopia and visual agnosia preserved impaired eventually hemianopia, visual agnosia and hemiparesis impaired preserved absent Lesion localization (dominant hemisphere) posterior-inferior frontal posterior-superior temporal arcuate fascicle— supramarginal gyrus perisylvian region (middle cerebral artery territory) inferior parietal (angular gyrus) anterior and superior to Broca’s area (supplementary motor area) preserved impaired dysarthria, initially with mutism watershed areas of middle cerebral artery and posterior cerebral artery watershed areas of middle cerebral, anterior cerebral and posterior cerebral arteries middle third of superior temporal gyrus thalamus in the dominant hemisphere preserved impaired dysarthria, hypophonia basal nuclei in the dominant hemisphere 4 F. F. de Oliveira et al. and expressive functions showing divergent hemispheric dominance [23], while in others a perilesional (intra-hemispheric) reorganization may also be seen [24]. Considering that functional communication usually improves spontaneously over the first months after an acute brain injury [25], the benefits of early aphasia rehabilitation are still uncertain. The fact that some patients show better response to speech and language therapy than others might be indicative of some unidentified cognitive impairments that impact their ability to recover from aphasia. Insight into the processes that underlie recovery from brain injuries is essential for diagnostic and therapeutic approaches, resting on the need for a deeper understanding of the organization of language networks in the brain. Several theories try to explain the organization of language networks in the human brain from a point of view that involves either modular or distributed processing or sometimes both. The most important evidences for each approach are briefly summarized in Table II. The aim of this review is to describe and confront the available theories on this subject, with the final goal to reach a clearer explanation of the inner workings of language networks. Evidence for modularity of language functions Focal brain lesions affecting language functions Many brain functions are organized on the basis of modular localization and activation, such as the localization of function in sensory and motor systems. Human languages are structured according to universal principles as well; therefore, why should language not follow the same modular rules as sensory and motor systems? In evolutionary terms, modularity of brain functions allows for the optimization of task performance in view of faster neural processing of information, but there is some relativity to the modularity of linguistic processes, even though they are independent from thought and reason. Regardless of aetiology, focal brain lesions are the most important models for the study of correlations between structural changes and linguistic functions. Some focal lesions may cause aphasia while preserving other cognitive domains, thus justifying the modular views. Whereas some patients present with lesions of language areas without aphasia [2], strategic lesions may produce aphasic syndromes regardless of the injury size. The angular gyrus in the dominant hemisphere integrates functions from several other areas of the brain, accounting for left–right orientation, constructional praxis, naming, reading and writing (the spatial representation of words), calculations and finger recognition [26]. A structural asymmetry leads to an almost 15% greater cortical volume of the dominant angular gyrus in comparison with the non-dominant one, with extensive bilateral training-induced neuroplasticity when learning new skills that require spatial co-ordination and verbal memory or theory of mind tasks [27]. Calculations are usually associated with the ability to spontaneously write sentences, while these functions are usually impaired at the same time in patients with Alzheimer’s disease dementia, possibly due to dominant angular gyrus dysfunction [28]. While lesions to the angular gyrus may result in semantic aphasia, patients with brain lesions often show double dissociations between their abilities to name objects and Brain Inj, Early Online: 1–11 actions, suggesting that entity and event knowledge are mediated by different neural networks [29]. The angular gyrus is involved in phonemic discrimination and semantic feature knowledge, but not in mapping from semantics to phonology (a role of inferior temporal areas) or in reading in the absence of semantic associations [27]. Functional impairment of the insula or subinsular area of the dominant hemisphere tends to produce phonemic disintegration and disturb speech fluency, resulting in apraxia of speech and transcortical motor aphasia [30]. Apraxia of speech has always been described with lesions to the dominant hemisphere, more specifically the left superior precentral gyrus of the insula, and usually follows non-fluent aphasic syndromes rather than being a sole finding, but tends to be more severe when premotor and supplementary motor areas of the same hemisphere are also involved [31]. Alexia without agraphia refers to impaired reading in the presence of spared writing and relatively spared recognition of words spelled aloud, often resulting from a combination of lesions in the left occipital cortex resulting in right homonymous hemianopia (such that all visual information is initially processed in the right occipital cortex) and in the splenium of the corpus callosum preventing visual information in the right hemisphere from being transferred to the left hemisphere language networks [4]. Lesions usually include connections of the visual word form area, a modular area located in the lateral occipitotemporal sulcus of the dominant hemisphere near the visual object form area, mostly responsible for orthographic reading-specific processes of the brain independently of spatial location and partially selective for written strings relative to other categories such as line drawings [32,33]. Abilities involved in the rapid parallel letter processing that is required for skilled reading are lost, but patients may recover the ability to read short familiar words by way of visual inputs to the occipital cortex connected to dominant hemisphere motor and premotor regions via activity in a central part of the dominant superior temporal sulcus [34]. Many of these patients are also unable to name visual stimuli, although they can name the same items from tactile exploration or in response to verbal description, a pattern known as ‘optic aphasia’ [4] (although not exactly classified as an aphasic syndrome). Overall, different networks of the dominant hemisphere are responsible for the recognition of orthographic and phonologic stimuli, with predominant activation of middle temporal and fusiform gyri during reading tasks (as well as higher connectivity of Broca’s area and of the fusiform gyrus with the parietal cortex) and of the superior temporal gyrus during oral language tasks (with higher connectivity of Broca’s area and of the fusiform gyrus with the temporal cortex) [35]. In cases of lesions in the non-dominant hemisphere, patients often produce inappropriately stressed speech, with awkward timing and intonation, and flattened emotionality. These patients also have difficulty to interpret the mood and emotional cues in the speech of others and their narrative is usually incoherent when ordering sentences [1]. Even though dominant hemisphere involvement is the most important predictor for aphasia, dysarthria may develop when weakness is present and may be associated with dysphagia in stroke patients who are not alert, regardless of the affected hemisphere [36]. Likewise, dysphagia tends to follow communication difficulties in patients with primary progressive aphasia [37]. DOI: 10.1080/02699052.2016.1199914 Neurological organization of language networks 5 Table II. Evidences for the organization of language functions. Evidence for modular organization The dominant hemisphere is specialized in language, while the nondominant hemisphere is skilled for visual-spatial functions. Individuals with left, bilateral or right hemisphere language representation do not differ significantly with respect to the anatomical and functional organization of language. Aphasic syndromes result from injuries to the dominant hemisphere for language, whereas some focal lesions may cause aphasia while preserving cognitive functions. The superior longitudinal fascicle/arcuate fascicle system connects Broca’s and Wernicke’s areas and the localization of such structures is relatively invariant among individuals. Topographic organization of cortical language areas is reproduced in subcortical structures, such as the thalamus. Human languages develop according to universal principles that mimic the localization of function in sensory and motor systems. Development of hemisphere dominance invariably depends on the specificity of synaptic connections established before and after birth. When two languages are learned during infancy, their fluency tends to activate indistinguishable sites in Broca’s area. Plasticity of language structures is critical only during infancy and early adolescence, characterized by its magnitude and by the ease of its triggering, while stability overcomes flexibility in the adult brain. The non-dominant hemisphere is recruited only in the sub-acute stage after an injury to the dominant hemisphere, returning to predominant dominant hemisphere activation in chronic stages. The processing of visual information is divided between a dorsal and a ventral stream that integrate modular structures and the same mechanisms may be found for the processing of auditory language. The compensatory potential of the non-dominant inferior frontal gyrus after brain injuries is less effective than in patients who recover inferior frontal gyrus function in the dominant hemisphere. A structural asymmetry leads to an almost 15% greater cortical volume of the dominant angular gyrus in relation to the non-dominant one. Different areas of the dominant hemisphere are responsible for the recognition of orthographic and phonologic stimuli. The visual word form area and the visual object form area are modularly involved in reading and semantic processing of visual information, respectively. Patients with brain injuries often show double dissociations between their abilities to name objects and actions, suggesting that entity and event knowledge are mediated by different modular systems. Modularity of brain functions permits the optimization of neural performance in view of faster processing of information. Linguistic processes are independent from thought and reason in the same way that musical features are independent from spoken language and speech, bringing about some patients with non-fluent aphasia being able to sing while unable to speak. Language dysfunction in patients with primary progressive aphasias or Alzheimer’s disease depends on specific structures that are affected by neurodegeneration. In general, a direct relationship exists between lesion size and both language recovery and mortality, whereas strategic lesions may result in aphasic syndromes, regardless of lesion size. Evidence for distributed processing Commissures connect both hemispheres leading to the formation of a wide network in which functional inter-dependence supplants lateralization. Converting handedness induces plasticity mechanisms that lead to re-organization of specific brain areas, while approaches that involve both hemispheres during language rehabilitation may be more efficacious. Language networks are distributed throughout both hemispheres in a complementary rather than in an independent fashion. Information processing in the superior longitudinal fascicle/arcuate fascicle system is bidirectional, while motor and sensory aphasias may sometimes result from injuries to areas that are not primarily involved in language. The organization of language networks, as well as reciprocal connections involving hubs and fibres, may be modified by learning. Neural networks involved in any function interact in a parallel distribution while preserving their independence. Post-natal neuronal plasticity directs the variable formation and maintenance of active neural connections while pruning the aberrant ones. If a second language is learned during adulthood, it is usually represented in a separate region in Broca’s area. Neuroplasticity may develop in adulthood due to activation of perilesional areas and to disinhibition of the non-dominant hemisphere when brain injuries affect the dominant hemisphere. Activation of the non-dominant hemisphere after an injury to the dominant hemisphere may be dysfunctional and interfere with language recovery, suggesting that networks of the non-dominant hemisphere are also important for language functions. The streams for processing of visual and auditory information are distributed along a network of elementary processing units that are interdependent rather that isolated for integration of neural signals. Recruitment of the non-dominant inferior frontal gyrus reflects the activation of mirror neurons which are apparently concentrated in the inferior frontal gyri of both hemispheres. The non-dominant angular gyrus mimics the organization of the dominant one and integrates its functions during learning of new skills that require spatial co-ordination and verbal memory or theory of mind tasks. Recognition of orthographic and phonologic stimuli depends on the organization of language networks according to the distribution of specific hubs and fibres. Lesions of the inferior longitudinal fascicle that affect object recognition or orthographic processes are usually temporary and compensated by neuroplasticity mechanisms. Improvements in naming and comprehension may be susceptible to performance in non-linguistic domains such as attention, abstraction and visual-spatial working memory, translating into multiple brain regions being simultaneously required for language functions. Performance in neural tasks is related to the connectivity between key cortical regions and a network of parallel processing areas that act in an integrated form to support the hierarchical organization of language. Rhythmic acoustic and social cues mediated by the mirror neuron system may be responsible for the enhancement of speech networks in patients with aphasia. Connectivity disruption is the primary mechanism leading to language dysfunction in neurodegenerative diseases. Even though the reduced functional segregation in the ageing brain may result in greater susceptibility to functional impairment, language performance after brain injuries is modulated by mechanisms related to the formation of a ‘linguistic reserve’ (such as education and bilingualism). Patients with injuries to the dominant hemisphere specifically present with The enhancement of emotional behaviours with social communicative an increased visceral-autonomic response to stimuli. purposes is mediated by the interaction between both hemispheres. 6 F. F. de Oliveira et al. Processing of visual and auditory signals It has been shown that the processing of visual information is divided into two main streams: the ‘what’ pathway, a ventral occipital to temporal stream specialized in object identification and lexical activation for familiar words; and the ‘where’ and ‘how’ pathways, composing a dorsal sub-lexical stream that examines spatial positions, motion and translations of spelling to sounds for less familiar letter strings. The dorsal stream is divided into a pathway for spatial processing (occipital to superior dorsal parietal) and another pathway that represents semantic information about person–object interactions (occipital to middle dorsal parietal and frontal). In other words, object identification modularly activates the parahippocampal and occipitotemporal gyri, while lexical-based reading modularly activates the lingual, lateral occipital and posterior inferior temporal gyri—basically, modular activation of single structures with little shared activation in the ventral stream (dominant posterior inferior frontal gyrus); on the other hand, object interaction processing and phonetic decoding largely activate modular dorsal regions in both hemispheres, as well as several shared distributed processing regions (precentral gyri, superior posterior temporal gyri and the following regions in the dominant hemisphere: inferior frontal cortex, postcentral gyrus and lateral occipital cortex) [38]. Analogically, the following dual stream model for auditory language processing has been suggested: a dorsal phonological stream in the superior longitudinal fascicle/arcuate fascicle system between superior temporal and prefrontal regions in the dominant hemisphere is the most relevant pathway for production of speech (mapping sound to articulation), while a ventral semantic stream in the extreme capsule connecting the middle temporal lobe with the ventrolateral prefrontal cortex is relevant for comprehension (mapping sound to lexical concepts) [14,18]. Audiovisual speech comprehension is an interactive process that results from the integration of auditory and visual signals progressively constrained by stimulus intelligibility along the superior temporal structures of the dominant hemisphere in conjunction with a spectrotemporal structure in a dorsal frontotemporal circuitry [39]. Furthermore, the inferior longitudinal fascicle links the visual cortex with the visual object form area, a modular area located within the basal occipitotemporal region which is involved in object recognition, but language disturbances due to lesions of this fascicle are usually temporary and compensated by neuroplasticity mechanisms [40]. Neurodegenerative mechanisms underlying modular systems The presentation of neurodegenerative diseases usually comprises language disturbances as a major feature. Visual confrontation naming, reading comprehension and auditory comprehension are usually impaired in mild stages of Alzheimer’s disease dementia, further leading to fluency deficits and eventually mutism in late stages [41]. Verb production deficits in Alzheimer’s disease dementia are more driven by semantic than by executive impairment, with double dissociation between verb (frontal) and noun (temporal) production [42]. Whereas lower frequency words and pseudowords Brain Inj, Early Online: 1–11 tend to elicit larger parietal activities [43], a correlation between cognitive decline and the loss of integrity of microstructural white matter connectivity involving the superior longitudinal fascicle has been established in patients with Alzheimer’s disease [44]. Still, posterior cortical atrophy is a focal presentation of Alzheimer’s disease with occipitotemporal hypometabolism that, when involving the dominant hemisphere, may be clinically characterized by progressive fluent aphasia with prominent visual-spatial deficits and loss of insight [45]. Primary progressive aphasias constitute models that tend to support the modular theories of language organization. These syndromes are characterized by progressive loss of language functions with initial sparing of other cognitive domains, resulting from a circumscribed atrophic process in language areas leading to connectivity disruption involving white matter and grey matter loss [46] and are classified into the following variants: agrammatic, semantic or logopenic [47]. The logopenic variant of primary progressive aphasia, with hesitant anomic speech, word retrieval and sentence repetition deficits, features left posterior perisylvian or parietal atrophy, endorsing the role of the inferior parietal cortex in phonological loop functions and usually evolves to Alzheimer’s disease dementia in advanced stages [48]. In comparison, apraxia of speech is one of the initial features of agrammatic primary progressive aphasia, which typically involves the left posterior frontoinsular region, is a better predictor of a tauopathy and may evolve to frontotemporal dementia and corticobasal degeneration in later stages [49], with initial impairments in phonological processing further leading to severe aphasia [50]. The semantic variant of primary progressive aphasia leads to early involvement of the anterior temporal lobes (predominantly in the left), is associated with ubiquitinated inclusions and usually evolves to the classical form of semantic dementia or to behavioural variant frontotemporal dementia [51]. Lexicalsemantic impairment is associated with greater atrophy of the dominant hemisphere, whereas a degradation of knowledge about people, including progressive prosopagnosia, has been seen in patients with more widespread temporal atrophy in the non-dominant hemisphere [52]. Features that differentiate the variants of primary progressive aphasia in early stages may lose their distinctiveness as the degeneration spreads [53]. Right posterior superior temporal sulcus structures have increased activity both in patients with primary progressive aphasia and in those with Alzheimer’s disease dementia, correlating positively with performance in language tasks [54]. However, in view of the underlying neurodegenerative mechanisms, the effectiveness of rehabilitation strategies tends to be very limited. Prognostic implications Language networks are so important for daily living that a direct relationship exists between lesion size and both language recovery and mortality [21,25,55–57]. Global aphasia is usually a stronger predictor of mortality for stroke patients when present in the acute phase than other language disorders DOI: 10.1080/02699052.2016.1199914 [55], also bringing an unfavourable prognosis to post-stroke mobility recovery, something that could be phylogenetically related to the simultaneous development of language networks and motor gesture activity in earlier primates [25,55,58]. Age, education, depression, lesions in the dominant hemisphere and cortical injuries are other important prognostic factors for language recovery after a first stroke [25,57,59,60], leading to some variability in language impairments according to lesion topography. Although healthy ageing shifts from a more distributed (in young adulthood) to a more localized topological organization of language networks [61], older people display reduced modularity of neural networks that may be indicative of reduced functional segregation in the ageing brain, with diminished connectivity in modules corresponding to executive functions and the default mode network [62], resulting in greater susceptibility to functional impairment after brain injuries. On the other hand, education may lead to distinct communication forms that allow some high schooling patients with aphasia to communicate better than low schooling individuals without brain injuries. Along with other environmental and cultural influences, schooling might modify brain organization and connections between cortical structures in both hemispheres, leading to better performance in language tests and also protecting patients from post-stroke dementia. Bilingualism is able to delay the onset of various forms of dementia by more than 4 years independently of education [63], probably due to stronger requirements from executive functions and attentional networks that lead to greater cognitive reserve. It has also been demonstrated that the better the response to language tests involving writing, the likelier it is for a patient with a non-fluent aphasia to have a good evolution [64]. When patients with aphasia present with cerebrovascular subcortical injuries, prognosis is much more favourable the less likely one is to find that there has been cortical hypoperfusion [25,60]. Lesion size and cortical hypoperfusion in the acute phase are significant risk factors for bad prognosis of aphasia. Even though lesion size is an important prognostic factor for depression and language recovery [25], more notably if there is salvageable tissue (penumbra) involved [65], lacunar infarctions and leukaraiosis are also able to aggravate language dysfunction [66]. It is believed that recovery of language after stroke is primarily produced by arterial recanalization or expansion of collaterals, giving rise to an enhanced flow in the hypoperfused cortical penumbra [67] and secondarily by mechanisms related to the disinhibition of the uninjured hemisphere [68]. Nevertheless, the speed of language rehabilitation in adults is much slower than in children, since structural stability overcomes plasticity in the adult brain [69]. Despite the critical role of reperfusion of ischaemic brain tissue in the restoration of normal function [7], it can paradoxically result in reperfusion injury [70]. The dominant hemisphere supposedly modulates the inhibition of the activation of arousal systems by the non-dominant hemisphere and enhances emotional behaviours with social communicative purposes, so that patients with injuries to the dominant hemisphere have an increased visceral-autonomic response to stimuli, more specifically if aphasic syndromes are present; this leads to phenomena such as the catastrophic reaction, an emotional Neurological organization of language networks 7 outburst which is almost exclusively present in the acute stroke phase when the dominant hemisphere is injured and aphasia is present [71]. According to the ‘modular’ view, the distributed patterns of brain activity that are observed in some studies could be explained by the fact that other areas unoriginally related to language would respond to linguistic stimuli in an incidental way, echoing the neural processing of information with no functional contribution to language. Nonetheless, the hierarchical distribution of linguistic processing of information seems to be the only model to be able to integrate all data in a timely manner for human comprehension and expression. Evidence for distribution of language functions Shared network functioning for language Is language acquisition innate or merely the learning of lexical and constructional forms of communication? It is possible that the principles that organize language in the brain are shared with other cognitive domains, thus allowing for a more distributed network of processing units that are integrated by way of such principles. For instance, individual reading performance may be related to the connectivity between key cortical regions both in upstream visual association areas (defining shapes of words) and in downstream visual association cortical areas (defining the lexical identity of words) and a network of parallel processing areas that act in an integrated form to define the meanings of words and support the hierarchical organization of language [35]. It has been proposed that the ventral and dorsal processing streams for networks involved in visual and in auditory processing interact in a parallel distribution while preserving their dual independence [72]. Logical inference recruits neural networks that are independent of the dominant perisylvian regions traditionally associated with language, leading to deductive reasoning; nonetheless, some general ‘support’ areas in the frontoparietal cortex of both hemispheres tend to be commonly recruited as well [73]. Superior parietal regions are examples of such ‘support’ areas, usually associated with executive functions related to information update, maintenance of order relations and spatial attention, particularly when multi-element processing is required, and possibly being implicated in representations of the structure of arguments, whereas the left superior parietal lobule contributes to letter string (identity) processing along with the left ventral occipitotemporal area [73,74]. The meanings of words and sentences seem to be grounded in functional networks for action and perception. Somatotopic activation of the precentral gyrus has been described when subjects perceive words and sentences semantically related to bodily actions involving the face, arms or legs, whereas semantic information about constituent parts of sentences (especially action verbs) is manifest in the brain response, suggesting that these elements contribute to the meaning of the whole sentence [75]. A double dissociation seems to exist between syntactic gender and naming processing, the former involving the dominant inferior frontal and posterior middle temporal gyri, while a sub-part of the dominant superior longitudinal fascicle lateral to the caudate 8 F. F. de Oliveira et al. nucleus underlies a distributed cortical–subcortical circuit which might selectively subserve grammatical gender processing [76]. Serial and parallel processing seem to be involved in the neurophysiological indexes of lexical-syntactic, semantic and deep syntactic processes emerging both in sequence and at times near simultaneously in written and spoken language processing [77]. Studies in different languages are useful for a better understanding of word processing systems. It has been suggested that morpheme selection and word selection overlap in time and influence each other in the Chinese language, while imageability does not impact the performance of patients with brain injuries, leading to the conclusion that there is a morphological level of representation in the Chinese word production system with non-semantic routes for reading [78]. A study with Japanese morphograms (kanji) and syllabograms (kana) showed that alexia is complete only when the lesion involves the dominant angular gyrus together with the adjacent lateral occipital gyri; while transposition errors suggested disrupted sequential phonological processing from the angular and lateral occipital gyri to the supramarginal gyrus, substitution errors suggested impaired allographic conversion between characters attributable to dysfunction in the angular or lateral occipital gyri [79]. In any language, it seems that the dominant occipitotemporal region (the ventral pathway for reading) is specialized in automatic parallel word recognition, whereas the dominant parietal lobe (the dorsal pathway) is specialized in serial letter-by-letter reading and both pathways are modulated by character spacing [80]. While imagery impacts single-letter production, the contextual production of words may rely mostly on retrieval of learned scripts. The study of letter position dyslexia in Arabic (an orthography in which letters have different forms in different positions of each word) has shown that letter form in this alphabet is part of the information encoded in the identity of the abstract letter, affecting processes for recognition of words [81]. Thus, reading and writing seem to rely upon different neural networks that act in concert for such linguistic abilities. Plasticity mechanisms and rehabilitation Converting handedness tends to induce plasticity mechanisms that lead to reorganization of specific brain areas. When forced to use the right hand, left-handers show an increase in movement-related activity in the primary sensorimotor hand areas and posterior premotor cortex of the left hemisphere associated with the relative left-to-right shift in hand preference [82]. During skill learning, involvement of the ipsilateral hemisphere may influence the magnitude of inter-manual transfer, regardless of the degree of handedness, which suggests that approaches that involve both hemispheres during language rehabilitation may be more efficacious [83]. Occupation-based approaches, matching what is trained with what the person has to do in daily situations, also tend to be more cost-effective [84]. Similarly, patients with traumatic brain injuries seem to benefit in reading efficiency when simultaneously listening to and reading written passages (text-to-speech technology), combining reading and comprehension performances [85]. Improvements in naming and comprehension may be susceptible to performance in non-linguistic domains such as Brain Inj, Early Online: 1–11 attention, abstraction and visual-spatial working memory [86], translating into multiple brain regions being simultaneously required for language functions, even though verbal and spatial domains activate different hemispheres when memory tasks are undertaken (dominant and non-dominant hemispheres, respectively). The dominant fusiform gyrus was previously directed to specialize in object processing for children, who learn to read by way of the recycling hypothesis: according to this hypothesis, plastic neuronal changes leading to word representations in the dominant fusiform gyrus occur in the context of strong restrictions that were evolutionarily imposed to this cortical area [33]. For patients with aphasia, it is possible that such mechanisms might also develop in the adult non-dominant hemisphere when it is exposed to rehabilitation therapy. Aphasia is caused by stroke in more than 80% of all cases [2]. Recovery and reorganization of language networks is usedependent and must be achieved by the active participation of patients as much as possible [87]. Sub-acute and chronic plasticity mechanisms may be detected in patients with insidiously evolving brain tumours. Tumour invasion, surgical stress, radiation and chemotherapy are triggers for neural reorganization that may elicit perilesional or mostly contralateral hemisphere recruitment, with chronic reshaping of language networks [88]. Plasticity of white matter language networks has also been described following anterior temporal lobe resections in patients with refractory epilepsy [89]. Musical features are usually processed in brain areas which are different from the ones related to spoken language and speech, bringing about some patients with non-fluent aphasia being able to sing, while unable to speak [90]. Melodic intonation therapy results in an increase in white matter fibres and volume in the non-dominant arcuate fascicle correlating with patient improvement [21]. Rhythmic acoustic and social cues may be responsible for the enhancement of speech networks for such patients, possibly involving the mirror neuron system in the context of neural networks distributed throughout the non-dominant hemisphere [90,91]. The non-dominant hemisphere for language has a critical role during recovery from aphasia, probably related to the lexical learning itself present in healthy subjects and to mechanisms of brain plasticity; recruitment of networks in the non-dominant hemisphere is believed to occur concurrently with attempts to repair the damaged original language networks in patients with aphasia [5,55]. It is generally accepted that there is greater activity in the non-dominant hemisphere in post-stroke aphasia compared to healthy subjects, subject to modulation by therapy and verbal learning. Nevertheless, it has been shown that the supplementary motor area in both hemispheres, traditionally involved in preparatory processing, is particularly activated when patients try to speak aloud auditorily presented stimuli or even during silent verb generation, suggesting that this area is part of a language network that includes a sub-vocal rehearsal system and a phonological store [5]. The additional activation of non-dominant hemisphere regions may be interpreted as further involvement of functionally connected and parallel processing networks which, while holding some importance for speech, are usually not needed for language processing in the uninjured brain. Neurological organization of language networks DOI: 10.1080/02699052.2016.1199914 Concerning rehabilitation strategies, the theory of the mirror neuron system implies in understanding others’ actions by means of an automatic matching process that links observed and performed actions. Mirror neurons discharge during the execution of goal-directed manual and oral actions, as well as during the observation of the same actions undertaken by other individuals [58]. The most important areas in which mirror neurons seem to be located in humans are those that are activated during observation and execution of speech, such as the inferior precentral gyrus, the inferior parietal lobule and the pars opercularis of the inferior frontal gyrus [92]. In view of the fact that words whose retrieval is facilitated by gestures are more likely to be analogically encoded in a multimodal representation including sensorimotor features that involve both brain hemispheres, it is likely that action observation leads to organizational changes in the brain and may participate, via the mirror neuron system, in the relearning of language fluency and comprehension [58,92]. The inferior frontal gyrus is an important element for language recovery after a stroke. Activation of the non-dominant inferior frontal gyrus seems to be essential for word retrieval from long-term memory for some patients with vascular aphasic syndromes and also for lexical learning in individuals without brain injuries [93], although its compensatory potential appears to be less effective than in patients who recover inferior frontal gyrus function in the dominant hemisphere [94]. This could reflect the activation of mirror neurons which are apparently concentrated in the inferior frontal gyri of both hemispheres, since patients with left inferior frontal lesions tend to recruit the right inferior frontal gyrus more reliably than those without such lesions [20]. In patients with fibromyalgia, the inferior frontal gyrus of the dominant hemisphere is a key area involved in the lessening of verbal fluency [95]. Parallel processing of linguistic codes The parallel distributed processing model for semantic cognition has a feed-forward structure, so that its activation is hierarchical and unidirectional from units that represent items and relations, passing through intermediate hubs, to an output layer that completes the tasks [96]. The knowledge in such an interactive processing system is stored in the strength of its connections and gradually acquired through experience, susceptible to neurodegenerative mechanisms that may degrade its patterns of neural activity [68]. It appears that parallel processing of linguistic data is what determines the speed with which information encoding can take place in the brain. The ability to conjure all the features of objects, faces and shapes, while simultaneously giving meaning and being able to express oneself with regard to such elements, is a unique human characteristic that could not take place if serial processing were the only way to handle information. Conclusions The opposing views of localization of language functions versus the flexibility of distributed processing find an outcome on the fact that several elementary processing units work in an 9 integrated way to generate human language. Even though serial and parallel processes link these elements toward unified operations, there is no doubt that little inter-individual variation may be found for the localization of such units, while the perisylvian networks of the dominant hemisphere tend to be the most important language systems in human brains. Understanding the connectivity patterns of language networks may provide deeper insights into language functions. The data contained in this study might help substantiate evidence-based rehabilitation strategies focusing on the enhancement of language organization for patients with aphasic syndromes. Declaration of interest The authors acknowledge the financial support by FAPESP – The State of São Paulo Research Foundation (grant #2015/10109-5). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. ORCID Fabricio Oliveira http://orcid.org/0000-0002-8311-0859 Sheilla Marin http://orcid.org/0000-0002-0381-3221 Paulo Bertolucci http://orcid.org/0000-0001-7902-7502 References 1. Kandel ER, Schwartz JH, Jessell TM, Siegelbaum SA, Hudspeth AJ. Principles of Neural Science. New York: McGraw-Hill; 2013. 2. Kreisler A, Godefroy O, Delmaire C, Debachy B, Leclercq M, Pruvo JP, Leys D. The anatomy of aphasia revisited. Neurology 2000;54:1117–1123. 3. De Oliveira FF, Marin SMC, Bertolucci PHF. Communicating with the non-dominant hemisphere: implications for neurological rehabilitation. Neural Regeneration Research 2013;8:1236–1246. 4. Hillis AE. Aphasia: progress in the last quarter of a century. Neurology 2007;69:200–213. 5. Karbe H, Thiel A, Weber-Luxenburger G, Herholz K, Kessler J, Heiss WD. Brain plasticity in poststroke aphasia: what is the contribution of the right hemisphere? Brain & Language 1998;64:215–230. 6. Chang EF, Wang DD, Perry DW, Barbaro NM, Berger MS. Homotopic organization of essential language sites in right and bilateral cerebral hemispheric dominance. Journal of Neurosurgery 2011;114:893–902. 7. Anglade C, Thiel A, Ansaldo AI. The complementary role of the cerebral hemispheres in recovery from aphasia after stroke: a critical review of literature. Brain Injury 2014;28:138–145. 8. Vikingstad EM, George KP, Johnson AF, Cao Y. Cortical language lateralization in right handed normal subjects using functional magnetic resonance imaging. Journal of Neurological Sciences 2000;175:17–27. 9. Breier JI, Hasan KM, Zhang W, Men D, Papanicolaou AC. Language dysfunction after stroke and damage to white matter tracts evaluated using diffusion tensor imaging. American Journal of Neuroradiology 2008;29:483–487. 10. Peng G, Wang WSY. Hemisphere lateralization is influenced by bilingual status and composition of words. Neuropsychologia 2011;49:1981–1986. 11. Kim KSH, Relkin NR, Lee KM, Hirsch J. Distinct cortical areas associated with native and second languages. Nature 1997;388:171–174. 12. Poeppel D, Emmorey K, Hickok G, Pylkkänen L. Towards a new neurobiology of language. Journal of Neurosciences 2012;32:14125–14131. 13. Catani M, Bambini V. A model for Social Communication And Language Evolution and Development (SCALED). Current Opinion in Neurobiology 2014;28:165–171. 10 F. F. de Oliveira et al. 14. Dick AS, Tremblay P. Beyond the arcuate fasciculus: consensus and controversy in the connectional anatomy of language. Brain 2012;135:3529–3550. 15. Saur D, Hartwigsen G. Neurobiology of language recovery after stroke: lessons from neuroimaging studies. Archives of Physical Medicine & Rehabilitation 2012;93:S15–S25. 16. Kuljic-Obradovic DC. Subcortical aphasia: three different language disorder syndromes? European Journal of Neurology 2003;10:445–448. 17. Radanovic M, Azambuja M, Mansur LL, Porto CS, Scaff M. Thalamus and language: Interface with attention, memory and executive functions. Arquivos de Neuropsiquiatria 2003;61:34–42. 18. Suchan J, Karnath HO. Spatial orienting by left hemisphere language areas: a relic from the past? Brain 2011;134:3059–3070. 19. De Oliveira FF, Damasceno BP. A topographic study on the evaluation of speech and language in the acute phase of a first stroke. Arquivos de Neuropsiquiatria 2011;69:790–798. 20. Turkeltaub PE, Messing S, Norise C, Hamilton RH. Are networks for residual language function and recovery consistent across aphasic patients? Neurology 2011;76:1726–1734. 21. Hamilton RH, Chrysikou EG, Coslett B. Mechanisms of aphasia recovery after stroke and the role of noninvasive brain stimulation. Brain & Language 2011;118:40–50. 22. Privitera M, Kim KK. Postictal language function. Epilepsy & Behavior 2010;19:140–145. 23. Gage NM, Eliashiv DS, Isenberg AL, Fillmore PT, Kurelowech L, Quint PJ, Chung JM, Otis SM. Rethinking Clinical language mapping approaches: discordant receptive and expressive hemispheric language dominance in epilepsy surgery candidates. Journal of Clinical Neurophysiology 2011;28:278–288. 24. Pataraia E, Simos PG, Castillo EM, Billingsley-Marshall RL, McGregor AL, Breier JI, Sarkari S, Papanicolaou AC. Reorganization of language-specific cortex in patients with lesions or mesial temporal epilepsy. Neurology 2004;63:1825–1832. 25. Oliveira FF, Damasceno BP. Short-term prognosis for speech and language in first stroke patients. Arquivos de Neuropsiquiatria 2009;67:849–855. 26. De Oliveira FF, Avelar WM, Bichuetti DB, Felício AC, Marin LF, Morita ME, dos Santos WAC. Semantic aphasia as a sole manifestation of acute stroke. Arquivos de Neuropsiquiatria 2010;68:965–967. 27. Seghier ML. The Angular Gyrus: multiple functions and multiple subdivisions. Neuroscientist 2013;19:43–61. 28. De Oliveira FF, Wajman JR, Bertolucci PHF, Chen ES, Smith MC. Correlations among cognitive and behavioural assessments in patients with dementia due to Alzheimer’s disease. Clinical Neurology & Neurosurgery 2015;135:27–33. 29. Watson CE, Chatterjee A. The functional neuroanatomy of actions. Neurology 2011;76:1428–1434. 30. Kumral E, Ozdemirkiran T, Alper Y. Strokes in the subinsular territory: clinical, topographical, and etiological patterns. Neurology 2004;63:2429–2432. 31. Ogar J, Willock S, Baldo J, Wilkins D, Ludy C, Dronkers N. Clinical and anatomical correlates of apraxia of speech. Brain & Language 2006;97:343–350. 32. Braet W, Wagemans J, Op de Beeck HP. The visual word form area is organized according to topography. Neuroimage 2012;59:2751–2759. 33. Dehaene S, Cohen L. The unique role of the visual word form area in reading. Trends in Cognitive Sciences 2011;15:254–262. 34. Seghier ML, Neufeld NH, Zeidman P, Leff AP, Mechelli A, Nagendran A, Riddoch JM, Humphreys GW, Price CJ. Reading without the left ventral occipito-temporal cortex. Neuropsychologia 2012;50:3621–3635. 35. Mesulam M. Representation, inference, and transcendent encoding in neurocognitive networks of the human brain. Annals of Neurology 2008;64:367–378. 36. Flowers HL, Silver FL, Fang J, Rochon E, Martino R. The incidence, co-occurrence, and predictors of dysphagia, dysarthria, and aphasia after first-ever acute ischemic stroke. Journal of Communication Disorders 2013;46:238–248. 37. Marin SMC, Bertolucci PHF, Marin LF, De Oliveira FF, Wajman JR, Bahia VS, Mansur LL. Swallowing in primary progressive aphasia. Neurorehabilitation 2016;38:85–92. 38. Borowsky R, Esopenko C, Cummine J, Sarty GE. neural representations of visual words and objects: a functional MRI Study on the modularity of reading and object processing. Brain Topography 2007;20:89–96. Brain Inj, Early Online: 1–11 39. Lee HL, Noppeney U. Physical and perceptual factors shape the neural mechanisms that integrate audiovisual signals in speech comprehension. Journal of Neuroscience 2011;31:11338–11350. 40. Mandonnet E, Nouet A, Gatignol P, Capelle L, Duffau H. Does the left inferior longitudinal fasciculus play a role in language? A brain stimulation study. Brain 2007;130:623–629. 41. Ortiz KZ, Bertolucci PHF. Alterações de linguagem nas fases iniciais da doença de Alzheimer. Arquivos de Neuropsiquiatria 2005;63:311–317. 42. Beber BC, Cruz AN, Chaves ML. A behavioral study of the nature of verb production deficits in Alzheimer’s disease. Brain & Language 2015;149:128–134. 43. Londei A, D’Ausilio A, Basso D, Sestieri C, Del Gratta C, Romani GL, Belardinelli MO. Sensory-motor brain network connectivity for speech comprehension. Human Brain Mapping 2010;31:567–580. 44. Meng JZ, Guo LW, Cheng H, Chen YJ, Fang L, Qi M, Jia ZY, Mohammed W, Hong XN. Correlation between cognitive function and the association fibers in patients with Alzheimer’s disease using diffusion tensor imaging. Journal of Clinical Neurosciences 2012;19:1659–1663. 45. Wicklund MR, Duffy JR, Strand EA, Whitwell JL, Machulda MM, Josephs KA. Aphasia with left occipitotemporal hypometabolism: a novel presentation of posterior cortical atrophy? Journal of Clinical Neurosciences 2013;20:1237–1240. 46. Schwindt GC, Graham NL, Rochon E, Tang-Wai DF, Lobaugh NJ, Chow TW, Black SE. Whole-brain white matter disruption in semantic and nonfluent variants of primary progressive aphasia. Human Brain Mapping 2013;34:973–984. 47. Mesulam MM. Primary progressive aphasia and the language network. Neurology 2013;81:456–462. 48. Vaz TS, Bertolucci PHF, Oliveira FF. A patient with primary progressive aphasia developing dementia due to Alzheimer’s disease. Arquivos de Neuropsiquiatria 2012;70:551–552. 49. De Oliveira FF, Barros LAV, Bertolucci PHF. A patient with agrammatic primary progressive aphasia developing frontotemporal dementia. Acta Neurologica Belgica 2015;115:763–766. 50. Graham NL, Bak T, Patterson K, Hodges JR. Language function and dysfunction in corticobasal degeneration. Neurology 2003;61:493–499. 51. Deramecourt V, Lebert F, Debachy B, Mackowiak-Cordoliani MA, Bombois S, Kerdraon O, Buée L, Maurage CA, Pasquier F. Prediction of pathology in primary progressive language and speech disorders. Neurology 2010;74:42–49. 52. Harciarek M, Kertesz A. Primary progressive aphasias and their contribution to the contemporary knowledge about the brain-language relationship. Neuropsychology Review 2011;21:271–287. 53. Rogalski E, Cobia D, Harrison TM, Wieneke C, Weintraub S, Mesulam MM. Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia. Neurology 2011;76:1804–1810. 54. Nelissen N, Dupont P, Vandenbulcke M, Tousseyn T, Peeters R, Vandenberghe R. Right hemisphere recruitment during language processing in frontotemporal lobar degeneration and Alzheimer’s Disease. Journal of Molecular Neuroscience 2011;45:637–647. 55. De Oliveira FF, Damasceno BP. Global aphasia as a predictor of mortality in the acute phase of a first stroke. Arquivos de Neuropsiquiatria 2011;69:277–282. 56. Lazar RM, Speizer AE, Festa JR, Krakauer JW, Marshall RS. Variability in language recovery after first-time stroke. Journal of Neurology, Neurosurgery & Psychiatry 2008;79:530–534. 57. Laska AC, Hellblom A, Murray V, Kahan T, von Arbin M. Aphasia in acute stroke and relation to outcome. Journal of Internal Medicine 2001;249:413–422. 58. Ertelt D, Binkofsky F. Action observation as a tool for neurorehabilitation to moderate motor deficits and aphasia following stroke. Neural Regeneration Research 2012;7:2063–2074. 59. Soares ECS, Ortiz KZ. Influence of schooling on language abilities of adults without linguistic disorders. Sao Paulo Medical Journal 2009;127:134–139. 60. Bakheit AMO, Shaw S, Carrington S, Griffiths S. The rate and extent of improvement with therapy from the different types of aphasia in the first year after stroke. Clinical Rehabilitation 2007;21:941–949. 61. Montembeault M, Joubert S, Doyon J, Carrier J, Gagnon JF, Monchi O, Lungu O, Belleville S, Brambati SM. The impact of DOI: 10.1080/02699052.2016.1199914 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. aging on gray matter structural covariance networks. Neuroimage 2012;63:754–759. Chen ZJ, He Y, Rosa-Neto P, Gong G, Evans AC. Age-related alterations in the modular organization of structural cortical network by using cortical thickness from MRI. Neuroimage 2011;56:235–245. Alladi S, Bak TH, Duggirala V, Surampudi B, Shailaja M, Shukla AK, Chaudhuri JR, Kaul S. Bilingualism delays age at onset of dementia, independent of education and immigration status. Neurology 2013;81:1938–1944. Mohr JP, Pessin MS, Finkelstein S, Funkenstein HH, Duncan GW, Davis KR. Broca aphasia: pathologic and clinical. Neurology 1978;28:311–324. Reineck LA, Agarwal S, Hillis AE. “Diffusion-clinical mismatch” is associated with potential for early recovery of aphasia. Neurology 2005;64:828–833. Sun DJ, Zhang XQ, Liu PJ, Chen JC, Cao JX, Zhuang AX, Zeng QH, Feng SQ, Zhang Y, Jiang JD. Lacunar infarction with leukoaraiosis may aggravate cognitive dysfunction. Neural Regeneration Research 2011;6:2446–2451. Olsen S, Bruhn P, Öberg RGE. Cortical hypoperfusion as a possible cause of “subcortical aphasia”. Brain 1986;109:393–410. Fornito A, Zalesky A, Breakspear M. The connectomics of brain disorders. Nature Reviews Neuroscience 2015;16:159–172. Grefkes C, Fink GR. Connectivity-based approaches in stroke and recovery of function. Lancet Neurology 2014;13:206–216. Brouns R, De Deyn PP. The complexity of neurobiological processes in acute ischemic stroke. Clinical Neurology & Neurosurgery 2009;111:483–495. Carota A, Rossetti AO, Karapanayiotides T, Bogousslavsky J. Catastrophic reaction in acute stroke: a reflex behavior in aphasic patients. Neurology 2001;57:1902–1905. Cloutman LL. Interaction between dorsal and ventral processing streams: where, when and how? Brain & Languge 2013;127:251–263. Monti MM, Parsons LM, Osherson DN. The boundaries of language and thought in deductive inference. Proceedings of the National Academy of Sciences USA 2009;106:12554–12559. Reilhac C, Peyrin C, Démonet JF, Valdois S. Role of the superior parietal lobules in letter-identity processing within strings: FMRI evidence from skilled and dyslexic readers. Neuropsychologia 2013;51:601–612. Boulenger V, Shtyrov Y, Pulvermüller F. When do you grasp the idea? MEG evidence for instantaneous idiom understanding. Neuroimage 2012;59:3502–3513. Vidorreta JG, Garcia R, Moritz-Gasser S, Duffau H. Double dissociation between syntactic gender and picture naming processing: a brain stimulation mapping study. Human Brain Mapping 2011;32:331–340. Pulvermüller F, Shtyrov Y, Hauk O. Understanding in an instant: neurophysiological evidence for mechanistic language circuits in the brain. Brain & Language 2009;110:81–94. Crepaldi D, Che WC, Su IF, Luzzatti C. Lexical-semantic variables affecting picture and word naming in Chinese: a mixed logit model study in aphasia. Behavioral Neurology 2012;25:165–184. Sakurai Y, Asami M, Mannen T. Alexia and agraphia with lesions of the angular and supramarginal gyri: Evidence for the disruption of sequential processing. Journal of Neurological Sciences 2010;288:25–33. Neurological organization of language networks 11 80. Sun Y, Yang Y, Desroches AS, Liu L, Peng D. The role of the ventral and dorsal pathways in reading Chinese characters and English words. Brain & Language 2011;119:80–88. 81. Friedmann N, Haddad-Hanna MM. Letter position dyslexia in Arabic: from form to position. Behavioral Neurology 2012;25:193–203. 82. Klöppel S, Vongerichten A, van Eimeren T, Frackowiak RSJ, Siebner HR. Can Left–Handedness be Switched? Insights from an Early Switch of Handwriting. Journal of Neuroscience 2007;27:7847–7853. 83. Chase C, Seidler R. Degree of handedness affects intermanual transfer of skill learning. Experimental Brain Research 2008;190:317–328. 84. Clark-Wilson J, Giles GM, Baxter DM. Revisiting the neurofunctional approach: conceptualizing the core components for the rehabilitation of everyday living skills. Brain Injury 2014;28:1646–1656. 85. Harvey J, Hux K. Text-to-speech accommodations for the reading challenges of adults with traumatic brain injury. Brain Injury 2015;29:888–897. 86. Seniów J, Litwin M, Lesniak M. The relationship between nonlinguistic cognitive deficits and language recovery in patients with aphasia. Journal of Neurological Sciences 2009;283:91–94. 87. Di Luca M, Baker M, Corradetti R, Kettenmann H, Mendlewicz J, Olesen J, Ragan I, Westphal M. Consensus Document on European Brain Research. European Journal of Neuroscience 2011;33:768–818. 88. Kawashima A, Krieg SM, Faust K, Schneider H, Vajkoczy P, Picht T. Plastic reshaping of cortical language areas evaluated by navigated transcranial magnetic stimulation in a surgical case of glioblastoma multiforme. Clinical Neurology & Neurosurgery 2013;115:2226–2229. 89. Yogarajah M, Focke NK, Bonelli SB, Thompson P, Vollmar C, McEvoy AW, Alexander DC, Symms MR, Koepp MJ, Duncan JS. The structural plasticity of white matter networks following anterior temporal lobe resection. Brain 2010;133:2348–2364. 90. Zipse L, Norton A, Marchina S, Schlaug G. When right is all that is left: plasticity of right-hemisphere tracts in a young aphasic patient. Annals of the New York Academy of Sciences 2012;1252:237–245. 91. Tomaino CM. Effective music therapy techniques in the treatment of nonfluent aphasia. Annals of the New York Academy of Sciences 2012;1252:312–317. 92. Small SL, Buccino G, Solodkin A. The Mirror Neuron System and treatment of stroke. Developmental Psychobiology 2012;54:293– 310. 93. Raboyeau G, De Boissezon X, Marie N, Balduyck S, Puel M, Bézy C, Démonet JF, Cardebat D. Right hemisphere activation in recovery from aphasia: lesion effect or function recruitment? Neurology 2008;70:290–298. 94. Winhuisen L, Thiel A, Schumacher B, Kessler J, Rudolf J, Haupt WF, Heiss WD. Role of the contralateral inferior frontal gyrus in recovery of language function in poststroke aphasia: a combined repetitive transcranial magnetic stimulation and positron emission Tomography Study. Stroke 2005;36:1759–1763. 95. Bertolucci PHF, Oliveira FF. Cognitive impairment in fibromyalgia. Current Pain & Headache Reports 2013;17:344. 96. McClelland JL, Rogers TT. The parallel distributed processing approach to semantic cognition. Nature Reviews Neurology 2003;4:310–322.