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Neurological impressions on the organization oflanguage networks in the human brain

Fabricio Ferreira de Oliveira, Sheilla de Medeiros Correia Marin & PauloHenrique Ferreira Bertolucci

To cite this article: Fabricio Ferreira de Oliveira, Sheilla de Medeiros Correia Marin & PauloHenrique Ferreira Bertolucci (2016): Neurological impressions on the organization of languagenetworks 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.

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Neurological impressions on the organization of language networks inthe 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

Background: More than 95% of right-handed individuals, as well as almost 80% of left-handedindividuals, have left hemisphere dominance for language. The perisylvian networks of thedominant 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 mechanismstake place to preserve neural functions after brain injuries. Language is dependent on ahierarchical interlinkage of serial and parallel processing areas in distinct brain regions con-sidered to be elementary processing units. Whereas aphasic syndromes typically result frominjuries to the dominant hemisphere, the extent of the distribution of language functionsseems to be variable for each individual. Method: Review of the literature Results: Severaltheories try to explain the organization of language networks in the human brain from apoint of view that involves either modular or distributed processing or sometimes both. Themost important evidence for each approach is discussed under the light of modern theories oforganization of neural networks. Conclusions: Understanding the connectivity patterns oflanguage networks may provide deeper insights into language functions, supporting evi-dence-based rehabilitation strategies that focus on the enhancement of language organizationfor patients with aphasic syndromes.

Keywords

Linguistics, aphasia, language, speech,disability evaluation, neural networks

History

Received 26 May 2015Revised 22 March 2016Accepted 6 June 2016Published online 14 October 2016

Towards a better understanding of languagelateralization

Lateralization of language functions

Language is dependent on an hierarchical interlinkage ofserial and parallel processing areas in distinct brain regionsconsidered to be elementary processing units [1,2]; therefore,language processing takes place mostly in the dominant hemi-sphere, which is usually the left one. Development of hemi-sphere dominance for language processing is related to thespecificity of synaptic connections established before andafter birth, but it is still unknown if a specific linguisticspecialization based on experience is required for the func-tional separation of the hemispheres [1].

The first historical evidence for localization of higher brainfunctions arose from studies of language disorders. Since theend of the nineteenth century, aphasic syndromes had beenconsidered to be mostly mediated by specialized areas of thedominant hemisphere of the brain [2]. While localization oflanguage functions shows little inter-individual variability, it

is currently known that both hemispheres are functionallycomplementary, considering that several brain areas are bilat-erally activated when a language task is undertaken [3–5].

Ambidextrous individuals usually have bilateral languagedominance, while those with left, bilateral or right hemi-sphere language representation do not differ significantlywith respect to verbal fluency, linguistic processing or intelli-gence, as well as with regard to the homology of anatomicaland functional organization of language networks in eitherhemisphere [6]. More than 95% of right-handed individuals,as well as almost 80% of left-handed individuals, have lefthemisphere dominance for language [7]. Women tend to per-form better on language tasks and have bilateral languagerepresentation more often than men, who usually excel invisual-spatial abilities [8]. Whereas aphasic syndromes typi-cally result from injuries to the dominant hemisphere [9], theextent of the distribution of language functions seems to bevariable for each individual brain.

A native language and a second language that shares itsuniversal grammar can assume different region-specific pro-cessing rules according to the time when they were learned.Language lateralization seems to depend on the bilingualstatus of the individuals, with bilateral hemispheric involve-ment for both languages of early bilinguals (who learned suchlanguages during early infancy), left hemisphere dominancefor language of monolinguals and also left hemisphere dom-inance for both languages of late bilinguals [10]. If both

Correspondence: Fabricio Ferreira de Oliveira, MD, MSc, PhD,Universidade Federal de São Paulo (UNIFESP), Escola Paulista deMedicina, Departamento de Neurologia e Neurocirurgia, Rua Botucatu740, Vila Clementino, CEP 04023-900, São Paulo, SP, Brazil. E-mail:fabricioferreiradeoliveira@hotmail.comColor versions of one or more of the figures in the article can be foundonline at www.tandfonline.com/ibij.

http://tandfonline.com/ibijISSN: 0269-9052 (print), 1362-301X (electronic)

Brain Inj, Early Online: 1–11© 2016 Taylor & Francis Group, LLC. DOI: 10.1080/02699052.2016.1199914

languages are learned during infancy, their fluency tends toactivate indistinguishable sites in Broca’s area; however, ifthe second language is acquired during adulthood, it is usuallyrepresented in a separate region in Broca’s area [3,11].

The neuroanatomy of language

Three large networks interact to connect language with con-ceptual information [1]. Broca’s and Wernicke’s areas, theinsular cortex, the head of the caudate nucleus and the puta-men in the dominant hemisphere form the language imple-mentation system, which analyses auditory signals to activateconceptual knowledge and support phonemic and grammati-cal construction while controlling production of speech. Thissystem is surrounded by a mediational system, composed ofseveral regions distributed among the parietal, frontal andtemporal association areas, acting as brokers between thelanguage implementation system and the so called conceptualsystem, a group of regions spread throughout the associationareas. It is remarkable that bidirectionality is an importantattribute of the arcuate fascicle, which connects areas of thesensory cortex (including Wernicke’s area) with prefrontaland premotor areas (including Broca’s area) in the dominanthemisphere [9].

Language networks may be allocated into two differentstreams [12]. The dorsal stream for language is composedby the superior longitudinal fascicle/arcuate fascicle system,the most important pathway for syntactic analysis and audi-tory-motor transcoding in the brain [13], which is sometimesdivided into a lexical-semantic pathway and a phonologicalpathway, but is currently considered to be domain-generalrather than specialized for language [3,14]. The ventral streamfor language is largely bilaterally organized for parallel pro-cessing [15], formed by the uncinate fascicle (involved insemantic processing and sound recognition), the extremecapsule (involved in the long-term storage of semantic infor-mation and phonological working memory), the middle long-itudinal fascicle (involved in phonological and semanticprocessing) and the inferior longitudinal fascicle (involvedin object recognition, face processing and visual semanticmemory) [14]. The currently accepted distribution of lan-guage networks, along with trajectories of subcortical fasci-cles may be viewed in a simplified model (Figure 1).

Subcortical structures are also known to contribute to theorganization of language in view of their reciprocal connec-tions with cortical language areas through networks that maybe modified by learning [1,16]. This is particularly true forthe lexical-semantic processing in inferior, lateral and poster-ior thalamic nuclei and also for the phonetic processing forfluency in the striatal structures of the dominant hemisphere[16]. Also, attention and executive functions may be affectedwhen the thalamus in the dominant hemisphere is injured andvisual-spatial orientation may be particularly impaired whenlesions occur in the thalamic nuclei of the non-dominanthemisphere [17]; such impairments may affect the linguisticperformance of patients after brain injuries. Disconnectionsyndromes may result when lesions involve the thalamusand the basal nuclei, implicating in subcortical aphasias.

Spoken language is only one of several language skillsmediated by the dominant hemisphere. Contrariwise, affective

aspects of language such as intonation (prosody) are processedin the non-dominant hemisphere, mirroring the logical organiza-tion of language content in the dominant hemisphere [7]. Irony,musical interests, metaphors and intentions can only be appre-ciated 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 gyrusof the non-dominant hemisphere for expression of emotions andthe homologue of Wernicke’s area in the non-dominant hemi-sphere, which acts in the interpretation of human emotions. Theabilities for elaboration of discourse macrostructure and for con-textual integration of information are basically non-dominanthemisphere functions, particularly related to the frontal lobe[17], as well as the ability for single word reading in patientsrecovering from aphasia. Incidentally, even though spatial orient-ing is usually a function of the visually inspired non-dominanthemisphere, neglect may also result from acute damage to areasof the dominant hemisphere that typically serve language func-tions, namely the superior and middle temporal gyri, the inferiorparietal lobule and the insula [18]; these patients may present bothcontralateral neglect and aphasia.

Definition of aphasia

Aphasia is defined as an acquired impairment in languageproduction and comprehension and in other cognitive pro-cesses that underlie language, causing problems with any orall of the following: speaking, listening, reading, writing andgesturing abilities [3]. These problems may be characterizedby: impaired fluency; difficulty to understand and/or producewords; substitution or addition of speech sounds or exchangeof semantically-related words (phonemic or semantic para-phasias, respectively); difficulty to name objects (anomia) orto recall words during conversation; and impairment in social

Figure 1. Approximate distribution of language networks in the cortex ofthe dominant hemisphere with simplified trajectories of subcortical fasci-cles. AC, primary auditory cortex; AG, angular gyrus; B, Broca’s area; M,motor networks in the precentral gyrus; PF, prefrontal networks; S, sensorynetworks in the postcentral gyrus; SM, supramarginal gyrus; T, inferiortemporal networks and temporal pole; W, Wernicke’s area.

2 F. F. de Oliveira et al. Brain Inj, Early Online: 1–11

communication skills (pragmatic language). Reading andwriting are usually affected in patients with aphasia, whilephono-articulatory function and consciousness are relativelypreserved. The most important aphasic syndromes are shownin Table I, as well as the most likely brain injury sites to resultin these language disturbances [2,19].

Plasticity in the human brain and the benefits ofneurological rehabilitation

Mechanisms of language recovery after injuries to the dominanthemisphere seem to be relatively stereotyped. There areincreased activations of homologues of language areas in thenon-dominant hemisphere and of perilesional areas of the domi-nant hemisphere, including compensatory recruitment of newareas and of language areas that were spared [20]. Sometimes,there may also be dysfunctional activation of the non-dominanthemisphere interfering with language recovery due to increasedand deleterious transcallosal inhibition of the already damageddominant hemisphere [21]. Nevertheless, uninjured languageareas in the dominant hemisphere seem to present a continu-ously increased activation, while non-dominant hemisphere

homologue areas have a biphasic course with earlier increasedand later decreased activation that is dependent on the amount ofpre-morbid language lateralization [15]. It seems that the areasrecruited for a particular language task change over the course ofrecovery, with minimal elicited activation (or haemodynamicresponse) during the language task in the acute stage, predomi-nant non-dominant hemisphere activation in the sub-acute stageand a return to predominant dominant hemisphere activation inchronic stages for patients who show good recovery of thetask [4,21].

Ictal evaluation of language may be able to localize complexpartial seizure commencement in patients with epilepsy [22] andsome studies with patients who had infancy or adolescence onsetof epilepsy have shown evidence of plastic processes affectinglanguage lateralization. While speech processes activate bilat-eral superior temporal regions, there may be convergence to aright hemisphere dominant pattern for language in some patientswith left mesial temporal sclerosis or neoplastic diseases (inter-hemispheric reorganization), contrary to what usually happensin the uninjured brains of right-handed individuals that havedeveloped left hemisphere dominance [23,24]. In some patientswith epilepsy, reorganization of language results in receptive

Table I. Traditional classification of aphasic syndromes.

Type of aphasia Spontaneous speech Fluency Comprehension Repetition Naming Other signsLesion localization

(dominant hemisphere)

Broca’s Aphasia poor, with effort,paraphasias,agrammatism

impaired preserved impaired impaired hemiparesis,apraxia of mouthand hand

posterior-inferior frontal

Wernicke’s Aphasia logorrheic, withparaphasias andneologisms

preserved impaired impaired impaired homonymoushemianopia,apraxia,anosognosia

posterior-superior temporal

Conduction Aphasia normal (phonemicmistakes)

preserved preserved impaired preserved hemi-hypoesthesia,apraxia, hemianopia

arcuate fascicle—supramarginal gyrus

Global Aphasia poor (mutism),restricted to simpleverbal stereotypes

impaired impaired impaired impaired hemiparesis,hemianopia, hemi-hypoesthesia,apraxia

perisylvian region (middlecerebral artery territory)

Semantic Aphasia normal (difficultyfinding words)

preserved preserved preserved impaired homonymoushemianopia

inferior parietal (angulargyrus)

Transcortical MotorAphasia

poor (mutism), withgreat latency atresponses, echolalia,perseveration

impaired preserved preserved impaired eventuallyhemiparesis (cruralinvolvement) andgrasp reflex

anterior and superior toBroca’s area(supplementary motor area)

TranscorticalSensory Aphasia

normal (semanticjargon)

preserved impaired preserved impaired eventuallyhemianopia andvisual agnosia

watershed areas of middlecerebral artery andposterior cerebral artery

Mixed TranscorticalAphasia

mutism impaired impaired preserved impaired eventuallyhemianopia, visualagnosia andhemiparesis

watershed areas of middlecerebral, anterior cerebraland posterior cerebralarteries

Verbal Deafness normal preserved impaired impaired preserved absent middle third of superiortemporal gyrus

Thalamic Aphasia normal or withparaphasias

preserved preserved ordiscretelyimpaired

preserved impaired dysarthria, initiallywith mutism

thalamus in the dominanthemisphere

Subcortical Aphasia(non-thalamic)

poor, with great latencyat responses, echolalia,perseveration

preserved preserved preserved impaired dysarthria,hypophonia

basal nuclei in thedominant hemisphere

DOI: 10.1080/02699052.2016.1199914 Neurological organization of language networks 3

and expressive functions showing divergent hemispheric dom-inance [23], while in others a perilesional (intra-hemispheric)reorganization may also be seen [24].

Considering that functional communication usuallyimproves spontaneously over the first months after an acutebrain injury [25], the benefits of early aphasia rehabilitationare still uncertain. The fact that some patients show betterresponse to speech and language therapy than others might beindicative of some unidentified cognitive impairments thatimpact their ability to recover from aphasia. Insight into theprocesses that underlie recovery from brain injuries is essen-tial for diagnostic and therapeutic approaches, resting on theneed for a deeper understanding of the organization of lan-guage networks in the brain.

Several theories try to explain the organization of languagenetworks in the human brain from a point of view thatinvolves either modular or distributed processing or some-times both. The most important evidences for each approachare briefly summarized in Table II. The aim of this review isto describe and confront the available theories on this subject,with the final goal to reach a clearer explanation of the innerworkings of language networks.

Evidence for modularity of language functions

Focal brain lesions affecting language functions

Many brain functions are organized on the basis of modularlocalization and activation, such as the localization of functionin sensory and motor systems. Human languages are structuredaccording to universal principles as well; therefore, why shouldlanguage not follow the same modular rules as sensory andmotor systems? In evolutionary terms, modularity of brainfunctions allows for the optimization of task performance inview of faster neural processing of information, but there issome relativity to the modularity of linguistic processes, eventhough they are independent from thought and reason.

Regardless of aetiology, focal brain lesions are the mostimportant models for the study of correlations between struc-tural changes and linguistic functions. Some focal lesions maycause aphasia while preserving other cognitive domains, thusjustifying the modular views. Whereas some patients presentwith lesions of language areas without aphasia [2], strategiclesions may produce aphasic syndromes regardless of the injurysize. The angular gyrus in the dominant hemisphere integratesfunctions from several other areas of the brain, accounting forleft–right orientation, constructional praxis, naming, readingand writing (the spatial representation of words), calculationsand finger recognition [26]. A structural asymmetry leads to analmost 15% greater cortical volume of the dominant angulargyrus in comparison with the non-dominant one, with extensivebilateral training-induced neuroplasticity when learning newskills that require spatial co-ordination and verbal memory ortheory of mind tasks [27]. Calculations are usually associatedwith the ability to spontaneously write sentences, while thesefunctions are usually impaired at the same time in patients withAlzheimer’s disease dementia, possibly due to dominant angulargyrus dysfunction [28]. While lesions to the angular gyrus mayresult in semantic aphasia, patients with brain lesions often showdouble dissociations between their abilities to name objects and

actions, suggesting that entity and event knowledge are mediatedby different neural networks [29]. The angular gyrus is involvedin phonemic discrimination and semantic feature knowledge, butnot in mapping from semantics to phonology (a role of inferiortemporal areas) or in reading in the absence of semantic associa-tions [27].

Functional impairment of the insula or subinsular area ofthe dominant hemisphere tends to produce phonemic disinte-gration and disturb speech fluency, resulting in apraxia ofspeech and transcortical motor aphasia [30]. Apraxia ofspeech has always been described with lesions to the domi-nant hemisphere, more specifically the left superior precentralgyrus of the insula, and usually follows non-fluent aphasicsyndromes rather than being a sole finding, but tends to bemore severe when premotor and supplementary motor areasof the same hemisphere are also involved [31].

Alexia without agraphia refers to impaired reading in thepresence of spared writing and relatively spared recognition ofwords spelled aloud, often resulting from a combination of lesionsin the left occipital cortex resulting in right homonymous hemi-anopia (such that all visual information is initially processed in theright occipital cortex) and in the splenium of the corpus callosumpreventing visual information in the right hemisphere from beingtransferred to the left hemisphere language networks [4]. Lesionsusually include connections of the visual word form area, amodular area located in the lateral occipitotemporal sulcus ofthe dominant hemisphere near the visual object form area, mostlyresponsible for orthographic reading-specific processes of thebrain independently of spatial location and partially selective forwritten strings relative to other categories such as line drawings[32,33]. Abilities involved in the rapid parallel letter processingthat is required for skilled reading are lost, but patients mayrecover the ability to read short familiar words by way of visualinputs to the occipital cortex connected to dominant hemispheremotor and premotor regions via activity in a central part of thedominant superior temporal sulcus [34]. Many of these patientsare also unable to name visual stimuli, although they can name thesame items from tactile exploration or in response to verbaldescription, a pattern known as ‘optic aphasia’ [4] (although notexactly classified as an aphasic syndrome). Overall, different net-works of the dominant hemisphere are responsible for the recog-nition of orthographic and phonologic stimuli, with predominantactivation of middle temporal and fusiform gyri during readingtasks (as well as higher connectivity of Broca’s area and of thefusiform gyrus with the parietal cortex) and of the superiortemporal gyrus during oral language tasks (with higher connec-tivity of Broca’s area and of the fusiform gyrus with the temporalcortex) [35].

In cases of lesions in the non-dominant hemisphere, patientsoften produce inappropriately stressed speech, with awkwardtiming and intonation, and flattened emotionality. Thesepatients also have difficulty to interpret the mood and emotionalcues in the speech of others and their narrative is usuallyincoherent when ordering sentences [1]. Even though dominanthemisphere involvement is the most important predictor foraphasia, dysarthria may develop when weakness is presentand may be associated with dysphagia in stroke patients whoare not alert, regardless of the affected hemisphere [36].Likewise, dysphagia tends to follow communication difficultiesin patients with primary progressive aphasia [37].

4 F. F. de Oliveira et al. Brain Inj, Early Online: 1–11

Table II. Evidences for the organization of language functions.

Evidence for modular organization Evidence for distributed processing

The dominant hemisphere is specialized in language, while the non-dominant hemisphere is skilled for visual-spatial functions.

Commissures connect both hemispheres leading to the formation of a widenetwork in which functional inter-dependence supplants lateralization.

Individuals with left, bilateral or right hemisphere language representationdo not differ significantly with respect to the anatomical and functionalorganization of language.

Converting handedness induces plasticity mechanisms that lead tore-organization of specific brain areas, while approaches that involve bothhemispheres during language rehabilitation may be more efficacious.

Aphasic syndromes result from injuries to the dominant hemisphere forlanguage, whereas some focal lesions may cause aphasia whilepreserving cognitive functions.

Language networks are distributed throughout both hemispheres in acomplementary rather than in an independent fashion.

The superior longitudinal fascicle/arcuate fascicle system connects Broca’sand Wernicke’s areas and the localization of such structures is relativelyinvariant among individuals.

Information processing in the superior longitudinal fascicle/arcuatefascicle system is bidirectional, while motor and sensory aphasias maysometimes result from injuries to areas that are not primarily involved inlanguage.

Topographic organization of cortical language areas is reproduced in sub-cortical structures, such as the thalamus.

The organization of language networks, as well as reciprocal connectionsinvolving hubs and fibres, may be modified by learning.

Human languages develop according to universal principles that mimic thelocalization of function in sensory and motor systems.

Neural networks involved in any function interact in a parallel distributionwhile preserving their independence.

Development of hemisphere dominance invariably depends on thespecificity of synaptic connections established before and after birth.

Post-natal neuronal plasticity directs the variable formation andmaintenance of active neural connections while pruning the aberrant ones.

When two languages are learned during infancy, their fluency tends toactivate indistinguishable sites in Broca’s area.

If a second language is learned during adulthood, it is usually representedin a separate region in Broca’s area.

Plasticity of language structures is critical only during infancy and earlyadolescence, characterized by its magnitude and by the ease of itstriggering, while stability overcomes flexibility in the adult brain.

Neuroplasticity may develop in adulthood due to activation of perilesionalareas and to disinhibition of the non-dominant hemisphere when braininjuries affect the dominant hemisphere.

The non-dominant hemisphere is recruited only in the sub-acute stage afteran injury to the dominant hemisphere, returning to predominantdominant hemisphere activation in chronic stages.

Activation of the non-dominant hemisphere after an injury to the dominanthemisphere may be dysfunctional and interfere with language recovery,suggesting that networks of the non-dominant hemisphere are alsoimportant for language functions.

The processing of visual information is divided between a dorsal and aventral stream that integrate modular structures and the samemechanisms may be found for the processing of auditory language.

The streams for processing of visual and auditory information aredistributed along a network of elementary processing units that are inter-dependent rather that isolated for integration of neural signals.

The compensatory potential of the non-dominant inferior frontal gyrusafter brain injuries is less effective than in patients who recover inferiorfrontal gyrus function in the dominant hemisphere.

Recruitment of the non-dominant inferior frontal gyrus reflects theactivation of mirror neurons which are apparently concentrated in theinferior frontal gyri of both hemispheres.

A structural asymmetry leads to an almost 15% greater cortical volume ofthe dominant angular gyrus in relation to the non-dominant one.

The non-dominant angular gyrus mimics the organization of the dominantone and integrates its functions during learning of new skills that requirespatial co-ordination and verbal memory or theory of mind tasks.

Different areas of the dominant hemisphere are responsible for therecognition of orthographic and phonologic stimuli.

Recognition of orthographic and phonologic stimuli depends on theorganization of language networks according to the distribution of specifichubs and fibres.

The visual word form area and the visual object form area are modularlyinvolved in reading and semantic processing of visual information,respectively.

Lesions of the inferior longitudinal fascicle that affect object recognitionor orthographic processes are usually temporary and compensated byneuroplasticity mechanisms.

Patients with brain injuries often show double dissociations between theirabilities to name objects and actions, suggesting that entity and eventknowledge are mediated by different modular systems.

Improvements in naming and comprehension may be susceptible toperformance in non-linguistic domains such as attention, abstraction andvisual-spatial working memory, translating into multiple brain regionsbeing simultaneously required for language functions.

Modularity of brain functions permits the optimization of neuralperformance in view of faster processing of information.

Performance in neural tasks is related to the connectivity between keycortical regions and a network of parallel processing areas that act in anintegrated form to support the hierarchical organization of language.

Linguistic processes are independent from thought and reason in the sameway that musical features are independent from spoken language andspeech, bringing about some patients with non-fluent aphasia being ableto sing while unable to speak.

Rhythmic acoustic and social cues mediated by the mirror neuron systemmay be responsible for the enhancement of speech networks in patientswith aphasia.

Language dysfunction in patients with primary progressive aphasias orAlzheimer’s disease depends on specific structures that are affected byneurodegeneration.

Connectivity disruption is the primary mechanism leading to languagedysfunction in neurodegenerative diseases.

In general, a direct relationship exists between lesion size and bothlanguage recovery and mortality, whereas strategic lesions may result inaphasic syndromes, regardless of lesion size.

Even though the reduced functional segregation in the ageing brain mayresult in greater susceptibility to functional impairment, languageperformance after brain injuries is modulated by mechanisms related to theformation of a ‘linguistic reserve’ (such as education and bilingualism).

Patients with injuries to the dominant hemisphere specifically present withan increased visceral-autonomic response to stimuli.

The enhancement of emotional behaviours with social communicativepurposes is mediated by the interaction between both hemispheres.

DOI: 10.1080/02699052.2016.1199914 Neurological organization of language networks 5

Processing of visual and auditory signals

It has been shown that the processing of visual information isdivided into two main streams: the ‘what’ pathway, a ventraloccipital to temporal stream specialized in object identificationand lexical activation for familiar words; and the ‘where’ and‘how’ pathways, composing a dorsal sub-lexical stream thatexamines spatial positions, motion and translations of spellingto sounds for less familiar letter strings. The dorsal stream isdivided into a pathway for spatial processing (occipital tosuperior dorsal parietal) and another pathway that representssemantic information about person–object interactions (occipi-tal to middle dorsal parietal and frontal). In other words, objectidentification modularly activates the parahippocampal andoccipitotemporal gyri, while lexical-based reading modularlyactivates the lingual, lateral occipital and posterior inferiortemporal gyri—basically, modular activation of single struc-tures with little shared activation in the ventral stream (domi-nant posterior inferior frontal gyrus); on the other hand, objectinteraction processing and phonetic decoding largely activatemodular dorsal regions in both hemispheres, as well as severalshared distributed processing regions (precentral gyri, superiorposterior temporal gyri and the following regions in the domi-nant hemisphere: inferior frontal cortex, postcentral gyrus andlateral occipital cortex) [38]. Analogically, the following dualstream model for auditory language processing has been sug-gested: a dorsal phonological stream in the superior longitudi-nal fascicle/arcuate fascicle system between superior temporaland prefrontal regions in the dominant hemisphere is the mostrelevant pathway for production of speech (mapping sound toarticulation), while a ventral semantic stream in the extremecapsule connecting the middle temporal lobe with the ventro-lateral prefrontal cortex is relevant for comprehension (map-ping sound to lexical concepts) [14,18].

Audiovisual speech comprehension is an interactive pro-cess that results from the integration of auditory and visualsignals progressively constrained by stimulus intelligibilityalong the superior temporal structures of the dominant hemi-sphere in conjunction with a spectrotemporal structure in adorsal frontotemporal circuitry [39]. Furthermore, the inferiorlongitudinal fascicle links the visual cortex with the visualobject form area, a modular area located within the basaloccipitotemporal region which is involved in object recogni-tion, but language disturbances due to lesions of this fascicleare usually temporary and compensated by neuroplasticitymechanisms [40].

Neurodegenerative mechanisms underlying modularsystems

The presentation of neurodegenerative diseases usually com-prises language disturbances as a major feature. Visual con-frontation naming, reading comprehension and auditorycomprehension are usually impaired in mild stages ofAlzheimer’s disease dementia, further leading to fluency def-icits and eventually mutism in late stages [41]. Verb produc-tion deficits in Alzheimer’s disease dementia are more drivenby semantic than by executive impairment, with double dis-sociation between verb (frontal) and noun (temporal) produc-tion [42]. Whereas lower frequency words and pseudowords

tend to elicit larger parietal activities [43], a correlationbetween cognitive decline and the loss of integrity of micro-structural white matter connectivity involving the superiorlongitudinal fascicle has been established in patients withAlzheimer’s disease [44]. Still, posterior cortical atrophy isa focal presentation of Alzheimer’s disease with occipitotem-poral hypometabolism that, when involving the dominanthemisphere, may be clinically characterized by progressivefluent aphasia with prominent visual-spatial deficits and lossof insight [45].

Primary progressive aphasias constitute models that tendto support the modular theories of language organization.These syndromes are characterized by progressive loss oflanguage functions with initial sparing of other cognitivedomains, resulting from a circumscribed atrophic process inlanguage areas leading to connectivity disruption involvingwhite matter and grey matter loss [46] and are classifiedinto the following variants: agrammatic, semantic or logo-penic [47]. The logopenic variant of primary progressiveaphasia, with hesitant anomic speech, word retrieval andsentence repetition deficits, features left posterior perisyl-vian or parietal atrophy, endorsing the role of the inferiorparietal cortex in phonological loop functions and usuallyevolves to Alzheimer’s disease dementia in advanced stages[48]. In comparison, apraxia of speech is one of the initialfeatures of agrammatic primary progressive aphasia, whichtypically involves the left posterior frontoinsular region, is abetter predictor of a tauopathy and may evolve to fronto-temporal dementia and corticobasal degeneration in laterstages [49], with initial impairments in phonological pro-cessing further leading to severe aphasia [50]. The semanticvariant of primary progressive aphasia leads to early invol-vement of the anterior temporal lobes (predominantly in theleft), is associated with ubiquitinated inclusions and usuallyevolves to the classical form of semantic dementia or tobehavioural variant frontotemporal dementia [51]. Lexical-semantic impairment is associated with greater atrophy ofthe dominant hemisphere, whereas a degradation of knowl-edge about people, including progressive prosopagnosia,has been seen in patients with more widespread temporalatrophy in the non-dominant hemisphere [52]. Features thatdifferentiate the variants of primary progressive aphasia inearly stages may lose their distinctiveness as the degenera-tion spreads [53].

Right posterior superior temporal sulcus structures haveincreased activity both in patients with primary progressiveaphasia and in those with Alzheimer’s disease dementia,correlating positively with performance in language tasks[54]. However, in view of the underlying neurodegenerativemechanisms, the effectiveness of rehabilitation strategiestends to be very limited.

Prognostic implications

Language networks are so important for daily living that adirect relationship exists between lesion size and both lan-guage recovery and mortality [21,25,55–57]. Global aphasiais usually a stronger predictor of mortality for stroke patientswhen present in the acute phase than other language disorders

6 F. F. de Oliveira et al. Brain Inj, Early Online: 1–11

[55], also bringing an unfavourable prognosis to post-strokemobility recovery, something that could be phylogeneticallyrelated to the simultaneous development of language net-works and motor gesture activity in earlier primates[25,55,58].

Age, education, depression, lesions in the dominant hemi-sphere and cortical injuries are other important prognostic fac-tors for language recovery after a first stroke [25,57,59,60],leading to some variability in language impairments accordingto lesion topography. Although healthy ageing shifts from amore distributed (in young adulthood) to a more localized topo-logical organization of language networks [61], older peopledisplay reduced modularity of neural networks that may beindicative of reduced functional segregation in the ageingbrain, with diminished connectivity in modules correspondingto executive functions and the default mode network [62], result-ing in greater susceptibility to functional impairment after braininjuries. On the other hand, education may lead to distinctcommunication forms that allow some high schooling patientswith aphasia to communicate better than low schooling indivi-duals without brain injuries. Along with other environmentaland cultural influences, schooling might modify brain organiza-tion and connections between cortical structures in both hemi-spheres, leading to better performance in language tests and alsoprotecting patients from post-stroke dementia. Bilingualism isable to delay the onset of various forms of dementia by morethan 4 years independently of education [63], probably due tostronger requirements from executive functions and attentionalnetworks that lead to greater cognitive reserve. It has also beendemonstrated that the better the response to language testsinvolving writing, the likelier it is for a patient with a non-fluentaphasia to have a good evolution [64].

When patients with aphasia present with cerebrovascularsubcortical injuries, prognosis is much more favourable theless likely one is to find that there has been cortical hypo-perfusion [25,60]. Lesion size and cortical hypoperfusion inthe acute phase are significant risk factors for bad prognosisof aphasia. Even though lesion size is an important prognosticfactor for depression and language recovery [25], more nota-bly if there is salvageable tissue (penumbra) involved [65],lacunar infarctions and leukaraiosis are also able to aggravatelanguage dysfunction [66].

It is believed that recovery of language after stroke isprimarily produced by arterial recanalization or expansionof collaterals, giving rise to an enhanced flow in the hypo-perfused cortical penumbra [67] and secondarily by mechan-isms related to the disinhibition of the uninjured hemisphere[68]. Nevertheless, the speed of language rehabilitation inadults is much slower than in children, since structural stabi-lity overcomes plasticity in the adult brain [69]. Despite thecritical role of reperfusion of ischaemic brain tissue in therestoration of normal function [7], it can paradoxically resultin reperfusion injury [70]. The dominant hemisphere suppo-sedly modulates the inhibition of the activation of arousalsystems by the non-dominant hemisphere and enhances emo-tional behaviours with social communicative purposes, so thatpatients with injuries to the dominant hemisphere have anincreased visceral-autonomic response to stimuli, more spe-cifically if aphasic syndromes are present; this leads to phe-nomena such as the catastrophic reaction, an emotional

outburst which is almost exclusively present in the acutestroke phase when the dominant hemisphere is injured andaphasia is present [71].

According to the ‘modular’ view, the distributed patternsof brain activity that are observed in some studies could beexplained by the fact that other areas unoriginally related tolanguage would respond to linguistic stimuli in an incidentalway, echoing the neural processing of information with nofunctional contribution to language. Nonetheless, the hier-archical distribution of linguistic processing of informationseems to be the only model to be able to integrate all data in atimely 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 lex-ical and constructional forms of communication? It is possi-ble that the principles that organize language in the brain areshared with other cognitive domains, thus allowing for a moredistributed network of processing units that are integrated byway of such principles. For instance, individual reading per-formance may be related to the connectivity between keycortical regions both in upstream visual association areas(defining shapes of words) and in downstream visual associa-tion cortical areas (defining the lexical identity of words) anda network of parallel processing areas that act in an integratedform to define the meanings of words and support the hier-archical organization of language [35]. It has been proposedthat the ventral and dorsal processing streams for networksinvolved in visual and in auditory processing interact in aparallel distribution while preserving their dual indepen-dence [72].

Logical inference recruits neural networks that are inde-pendent of the dominant perisylvian regions traditionallyassociated with language, leading to deductive reasoning;nonetheless, some general ‘support’ areas in the frontoparietalcortex of both hemispheres tend to be commonly recruited aswell [73]. Superior parietal regions are examples of such‘support’ areas, usually associated with executive functionsrelated to information update, maintenance of order relationsand spatial attention, particularly when multi-element proces-sing is required, and possibly being implicated in representa-tions of the structure of arguments, whereas the left superiorparietal lobule contributes to letter string (identity) processingalong with the left ventral occipitotemporal area [73,74].

The meanings of words and sentences seem to begrounded in functional networks for action and perception.Somatotopic activation of the precentral gyrus has beendescribed when subjects perceive words and sentencessemantically related to bodily actions involving the face,arms or legs, whereas semantic information about constituentparts of sentences (especially action verbs) is manifest in thebrain response, suggesting that these elements contribute tothe meaning of the whole sentence [75]. A double dissocia-tion seems to exist between syntactic gender and namingprocessing, the former involving the dominant inferior frontaland posterior middle temporal gyri, while a sub-part of thedominant superior longitudinal fascicle lateral to the caudate

DOI: 10.1080/02699052.2016.1199914 Neurological organization of language networks 7

nucleus underlies a distributed cortical–subcortical circuitwhich might selectively subserve grammatical gender proces-sing [76]. Serial and parallel processing seem to be involvedin the neurophysiological indexes of lexical-syntactic, seman-tic and deep syntactic processes emerging both in sequenceand at times near simultaneously in written and spoken lan-guage processing [77].

Studies in different languages are useful for a better under-standing of word processing systems. It has been suggestedthat morpheme selection and word selection overlap in timeand influence each other in the Chinese language, whileimageability does not impact the performance of patientswith brain injuries, leading to the conclusion that there is amorphological level of representation in the Chinese wordproduction system with non-semantic routes for reading[78]. A study with Japanese morphograms (kanji) and sylla-bograms (kana) showed that alexia is complete only when thelesion involves the dominant angular gyrus together with theadjacent lateral occipital gyri; while transposition errors sug-gested disrupted sequential phonological processing from theangular and lateral occipital gyri to the supramarginal gyrus,substitution errors suggested impaired allographic conversionbetween characters attributable to dysfunction in the angularor lateral occipital gyri [79]. In any language, it seems that thedominant occipitotemporal region (the ventral pathway forreading) is specialized in automatic parallel word recognition,whereas the dominant parietal lobe (the dorsal pathway) isspecialized in serial letter-by-letter reading and both pathwaysare modulated by character spacing [80]. While imageryimpacts single-letter production, the contextual productionof words may rely mostly on retrieval of learned scripts.The study of letter position dyslexia in Arabic (an orthogra-phy in which letters have different forms in different positionsof each word) has shown that letter form in this alphabet ispart of the information encoded in the identity of the abstractletter, affecting processes for recognition of words [81]. Thus,reading and writing seem to rely upon different neural net-works that act in concert for such linguistic abilities.

Plasticity mechanisms and rehabilitation

Converting handedness tends to induce plasticity mechanismsthat lead to reorganization of specific brain areas. When forcedto use the right hand, left-handers show an increase in move-ment-related activity in the primary sensorimotor hand areas andposterior premotor cortex of the left hemisphere associated withthe relative left-to-right shift in hand preference [82]. Duringskill learning, involvement of the ipsilateral hemisphere mayinfluence the magnitude of inter-manual transfer, regardless ofthe degree of handedness, which suggests that approaches thatinvolve both hemispheres during language rehabilitation may bemore efficacious [83]. Occupation-based approaches, matchingwhat is trained with what the person has to do in daily situa-tions, also tend to be more cost-effective [84]. Similarly,patients with traumatic brain injuries seem to benefit inreading efficiency when simultaneously listening to andreading written passages (text-to-speech technology), com-bining reading and comprehension performances [85].Improvements in naming and comprehension may be sus-ceptible to performance in non-linguistic domains such as

attention, abstraction and visual-spatial working memory[86], translating into multiple brain regions being simulta-neously required for language functions, even though verbaland spatial domains activate different hemispheres whenmemory tasks are undertaken (dominant and non-dominanthemispheres, respectively).

The dominant fusiform gyrus was previously directed tospecialize in object processing for children, who learn to readby way of the recycling hypothesis: according to this hypoth-esis, plastic neuronal changes leading to word representationsin the dominant fusiform gyrus occur in the context of strongrestrictions that were evolutionarily imposed to this corticalarea [33]. For patients with aphasia, it is possible that suchmechanisms might also develop in the adult non-dominanthemisphere 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 use-dependent and must be achieved by the active participation ofpatients as much as possible [87].

Sub-acute and chronic plasticity mechanisms may bedetected in patients with insidiously evolving brain tumours.Tumour invasion, surgical stress, radiation and chemotherapyare triggers for neural reorganization that may elicit perile-sional or mostly contralateral hemisphere recruitment, withchronic reshaping of language networks [88]. Plasticity ofwhite matter language networks has also been describedfollowing anterior temporal lobe resections in patients withrefractory epilepsy [89].

Musical features are usually processed in brain areaswhich are different from the ones related to spoken languageand speech, bringing about some patients with non-fluentaphasia being able to sing, while unable to speak [90].Melodic intonation therapy results in an increase in whitematter fibres and volume in the non-dominant arcuate fasciclecorrelating with patient improvement [21]. Rhythmic acousticand social cues may be responsible for the enhancement ofspeech networks for such patients, possibly involving themirror neuron system in the context of neural networks dis-tributed throughout the non-dominant hemisphere [90,91].

The non-dominant hemisphere for language has a critical roleduring recovery from aphasia, probably related to the lexicallearning itself present in healthy subjects and to mechanisms ofbrain plasticity; recruitment of networks in the non-dominanthemisphere is believed to occur concurrently with attempts torepair the damaged original language networks in patients withaphasia [5,55]. It is generally accepted that there is greateractivity in the non-dominant hemisphere in post-stroke aphasiacompared to healthy subjects, subject to modulation by therapyand verbal learning. Nevertheless, it has been shown that thesupplementary motor area in both hemispheres, traditionallyinvolved in preparatory processing, is particularly activatedwhen patients try to speak aloud auditorily presented stimuli oreven during silent verb generation, suggesting that this area ispart of a language network that includes a sub-vocal rehearsalsystem and a phonological store [5]. The additional activation ofnon-dominant hemisphere regions may be interpreted as furtherinvolvement of functionally connected and parallel processingnetworks which, while holding some importance for speech, areusually not needed for language processing in the uninjuredbrain.

8 F. F. de Oliveira et al. Brain Inj, Early Online: 1–11

Concerning rehabilitation strategies, the theory of the mir-ror neuron system implies in understanding others’ actions bymeans of an automatic matching process that links observedand performed actions. Mirror neurons discharge during theexecution of goal-directed manual and oral actions, as well asduring the observation of the same actions undertaken byother individuals [58]. The most important areas in whichmirror neurons seem to be located in humans are those thatare activated during observation and execution of speech,such as the inferior precentral gyrus, the inferior parietallobule and the pars opercularis of the inferior frontal gyrus[92]. In view of the fact that words whose retrieval is facili-tated by gestures are more likely to be analogically encoded ina multimodal representation including sensorimotor featuresthat involve both brain hemispheres, it is likely that actionobservation leads to organizational changes in the brain andmay participate, via the mirror neuron system, in the relearn-ing of language fluency and comprehension [58,92].

The inferior frontal gyrus is an important element forlanguage recovery after a stroke. Activation of the non-domi-nant inferior frontal gyrus seems to be essential for wordretrieval from long-term memory for some patients withvascular aphasic syndromes and also for lexical learning inindividuals without brain injuries [93], although its compen-satory potential appears to be less effective than in patientswho recover inferior frontal gyrus function in the dominanthemisphere [94]. This could reflect the activation of mirrorneurons which are apparently concentrated in the inferiorfrontal gyri of both hemispheres, since patients with leftinferior frontal lesions tend to recruit the right inferior frontalgyrus more reliably than those without such lesions [20]. Inpatients with fibromyalgia, the inferior frontal gyrus of thedominant hemisphere is a key area involved in the lesseningof verbal fluency [95].

Parallel processing of linguistic codes

The parallel distributed processing model for semantic cogni-tion has a feed-forward structure, so that its activation ishierarchical and unidirectional from units that representitems and relations, passing through intermediate hubs, toan output layer that completes the tasks [96]. The knowledgein such an interactive processing system is stored in thestrength of its connections and gradually acquired throughexperience, susceptible to neurodegenerative mechanismsthat may degrade its patterns of neural activity [68].

It appears that parallel processing of linguistic data is whatdetermines the speed with which information encoding cantake place in the brain. The ability to conjure all the featuresof objects, faces and shapes, while simultaneously givingmeaning and being able to express oneself with regard tosuch elements, is a unique human characteristic that couldnot take place if serial processing were the only way to handleinformation.

Conclusions

The opposing views of localization of language functionsversus the flexibility of distributed processing find an outcomeon the fact that several elementary processing units work in an

integrated way to generate human language. Even though serialand parallel processes link these elements toward unifiedoperations, there is no doubt that little inter-individual varia-tion may be found for the localization of such units, while theperisylvian networks of the dominant hemisphere tend to be themost important language systems in human brains.Understanding the connectivity patterns of language networksmay provide deeper insights into language functions. The datacontained in this study might help substantiate evidence-basedrehabilitation strategies focusing on the enhancement of lan-guage organization for patients with aphasic syndromes.

Declaration of interest

The authors acknowledge the financial support by FAPESP – TheState of São Paulo Research Foundation (grant #2015/10109-5).The authors report no conflicts of interest. The authors alone areresponsible for the content and writing of the paper.

ORCID

Fabricio Oliveira http://orcid.org/0000-0002-8311-0859Sheilla Marin http://orcid.org/0000-0002-0381-3221Paulo Bertolucci http://orcid.org/0000-0001-7902-7502

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DOI: 10.1080/02699052.2016.1199914 Neurological organization of language networks 11