Decoding the Real-Time Neurobiological Properties of Incremental Semantic Interpretation.

Communication through spoken language is a central human capacity, involving a wide range of complex computations that incrementally interpret each word into meaningful sentences. However, surprisingly little is known about the spatiotemporal properties of the complex neurobiological systems that support these dynamic predictive and integrative computations. Here, we focus on prediction, a core incremental processing operation guiding the interpretation of each upcoming word with respect to its preceding context. To investigate the neurobiological basis of how semantic constraints change and evolve as each word in a sentence accumulates over time, in a spoken sentence comprehension study, we analyzed the multivariate patterns of neural activity recorded by source-localized electro/magnetoencephalography (EMEG), using computational models capturing semantic constraints derived from the prior context on each upcoming word. Our results provide insights into predictive operations subserved by different regions within a bi-hemispheric system, which over time generate, refine, and evaluate constraints on each word as it is heard.

Neural dynamics of semantic composition.

Human speech comprehension is remarkable for its immediacy and rapidity. The listener interprets an incrementally delivered auditory input, millisecond by millisecond as it is heard, in terms of complex multilevel representations of relevant linguistic and nonlinguistic knowledge. Central to this process are the neural computations involved in semantic combination, whereby the meanings of words are combined into more complex representations, as in the combination of a verb and its following direct object (DO) noun (e.g., "eat the apple"). These combinatorial processes form the backbone for incremental interpretation, enabling listeners to integrate the meaning of each word as it is heard into their dynamic interpretation of the current utterance. Focusing on the verb-DO noun relationship in simple spoken sentences, we applied multivariate pattern analysis and computational semantic modeling to source-localized electro/magnetoencephalographic data to map out the specific representational constraints that are constructed as each word is heard, and to determine how these constraints guide the interpretation of subsequent words in the utterance. Comparing context-independent semantic models of the DO noun with contextually constrained noun models reflecting the semantic properties of the preceding verb, we found that only the contextually constrained model showed a significant fit to the brain data. Pattern-based measures of directed connectivity across the left hemisphere language network revealed a continuous information flow among temporal, inferior frontal, and inferior parietal regions, underpinning the verb's modification of the DO noun's activated semantics. These results provide a plausible neural substrate for seamless real-time incremental interpretation on the observed millisecond time scales.

Balancing Prediction and Sensory Input in Speech Comprehension: The Spatiotemporal Dynamics of Word Recognition in Context.

Spoken word recognition in context is remarkably fast and accurate, with recognition times of ∼200 ms, typically well before the end of the word. The neurocomputational mechanisms underlying these contextual effects are still poorly understood. This study combines source-localized electroencephalographic and magnetoencephalographic (EMEG) measures of real-time brain activity with multivariate representational similarity analysis to determine directly the timing and computational content of the processes evoked as spoken words are heard in context, and to evaluate the respective roles of bottom-up and predictive processing mechanisms in the integration of sensory and contextual constraints. Male and female human participants heard simple (modifier-noun) English phrases that varied in the degree of semantic constraint that the modifier (W1) exerted on the noun (W2), as in pairs, such as "yellow banana." We used gating tasks to generate estimates of the probabilistic predictions generated by these constraints as well as measures of their interaction with the bottom-up perceptual input for W2. Representation similarity analysis models of these measures were tested against electroencephalographic and magnetoencephalographic brain data across a bilateral fronto-temporo-parietal language network. Consistent with probabilistic predictive processing accounts, we found early activation of semantic constraints in frontal cortex (LBA45) as W1 was heard. The effects of these constraints (at 100 ms after W2 onset in left middle temporal gyrus and at 140 ms in left Heschl's gyrus) were only detectable, however, after the initial phonemes of W2 had been heard. Within an overall predictive processing framework, bottom-up sensory inputs are still required to achieve early and robust spoken word recognition in context.SIGNIFICANCE STATEMENT Human listeners recognize spoken words in natural speech contexts with remarkable speed and accuracy, often identifying a word well before all of it has been heard. In this study, we investigate the brain systems that support this important capacity, using neuroimaging techniques that can track real-time brain activity during speech comprehension. This makes it possible to locate the brain areas that generate predictions about upcoming words and to show how these expectations are integrated with the evidence provided by the speech being heard. We use the timing and localization of these effects to provide the most specific account to date of how the brain achieves an optimal balance between prediction and sensory input in the interpretation of spoken language.

Relating dynamic brain states to dynamic machine states: Human and machine solutions to the speech recognition problem.

There is widespread interest in the relationship between the neurobiological systems supporting human cognition and emerging computational systems capable of emulating these capacities. Human speech comprehension, poorly understood as a neurobiological process, is an important case in point. Automatic Speech Recognition (ASR) systems with near-human levels of performance are now available, which provide a computationally explicit solution for the recognition of words in continuous speech. This research aims to bridge the gap between speech recognition processes in humans and machines, using novel multivariate techniques to compare incremental 'machine states', generated as the ASR analysis progresses over time, to the incremental 'brain states', measured using combined electro- and magneto-encephalography (EMEG), generated as the same inputs are heard by human listeners. This direct comparison of dynamic human and machine internal states, as they respond to the same incrementally delivered sensory input, revealed a significant correspondence between neural response patterns in human superior temporal cortex and the structural properties of ASR-derived phonetic models. Spatially coherent patches in human temporal cortex responded selectively to individual phonetic features defined on the basis of machine-extracted regularities in the speech to lexicon mapping process. These results demonstrate the feasibility of relating human and ASR solutions to the problem of speech recognition, and suggest the potential for further studies relating complex neural computations in human speech comprehension to the rapidly evolving ASR systems that address the same problem domain.

Syntactic Complexity and Frequency in the Neurocognitive Language System.

Prominent neurobiological models of language follow the widely accepted assumption that language comprehension requires two principal mechanisms: a lexicon storing the sound-to-meaning mapping of words, primarily involving bilateral temporal regions, and a combinatorial processor for syntactically structured items, such as phrases and sentences, localized in a left-lateralized network linking left inferior frontal gyrus (LIFG) and posterior temporal areas. However, recent research showing that the processing of simple phrasal sequences may engage only bilateral temporal areas, together with the claims of distributional approaches to grammar, raise the question of whether frequent phrases are stored alongside individual words in temporal areas. In this fMRI study, we varied the frequency of words and of short and long phrases in English. If frequent phrases are indeed stored, then only less frequent items should generate selective left frontotemporal activation, because memory traces for such items would be weaker or not available in temporal cortex. Complementary univariate and multivariate analyses revealed that, overall, simple words (verbs) and long phrases engaged LIFG and temporal areas, whereas short phrases engaged bilateral temporal areas, suggesting that syntactic complexity is a key factor for LIFG activation. Although we found a robust frequency effect for words in temporal areas, no frequency effects were found for the two phrasal conditions. These findings support the conclusion that long and short phrases are analyzed, respectively, in the left frontal network and in a bilateral temporal network but are not retrieved from memory in the same way as simple words during spoken language comprehension.

Domain-specific and Domain-general Processing in Left Perisylvian Cortex: Evidence from Russian.

The processing of words containing inflectional affixes triggers morphophonological parsing and affix-related grammatical information processing. Increased perceptual complexity related to stem-affix parsing is hypothesized to create predominantly domain-general processing demands, whereas grammatical processing primarily implicates domain-specific linguistic demands. Exploiting the properties of Russian morphology and syntax, we designed an fMRI experiment to separate out the neural systems supporting these two demand types, contrasting inflectional complexity, syntactic (phrasal) complexity, and derivational complexity in three comparisons: (a) increase in parsing demands while controlling for grammatical complexity (inflections vs. phrases), (b) increase in grammatical processing demands, and (c) combined demands of morphophonological parsing and grammatical processing (inflections and phrases vs. derivations). Left inferior frontal and bilateral temporal areas are most active when the two demand types are combined, with inflectional and phrasal complexity contrasting strongly with derivational complexity (which generated only bilateral temporal activity). Increased stem-affix parsing demands alone did not produce unique activations, whereas grammatical structure processing activated bilateral superior and middle temporal areas. Selective left frontotemporal language system engagement for short phrases and inflections seems to be driven by simultaneous and interdependent domain-general and domain-specific processing demands.

Brain Network Connectivity During Language Comprehension: Interacting Linguistic and Perceptual Subsystems.

The dynamic neural processes underlying spoken language comprehension require the real-time integration of general perceptual and specialized linguistic information. We recorded combined electro- and magnetoencephalographic measurements of participants listening to spoken words varying in perceptual and linguistic complexity. Combinatorial linguistic complexity processing was consistently localized to left perisylvian cortices, whereas competition-based perceptual complexity triggered distributed activity over both hemispheres. Functional connectivity showed that linguistically complex words engaged a distributed network of oscillations in the gamma band (20-60 Hz), which only partially overlapped with the network supporting perceptual analysis. Both processes enhanced cross-talk between left temporal regions and bilateral pars orbitalis (BA47). The left-lateralized synchrony between temporal regions and pars opercularis (BA44) was specific to the linguistically complex words, suggesting a specific role of left frontotemporal cross-cortical interactions in morphosyntactic computations. Synchronizations in oscillatory dynamics reveal the transient coupling of functional networks that support specific computational processes in language comprehension.

Grammatical analysis as a distributed neurobiological function.

Language processing engages large-scale functional networks in both hemispheres. Although it is widely accepted that left perisylvian regions have a key role in supporting complex grammatical computations, patient data suggest that some aspects of grammatical processing could be supported bilaterally. We investigated the distribution and the nature of grammatical computations across language processing networks by comparing two types of combinatorial grammatical sequences--inflectionally complex words and minimal phrases--and contrasting them with grammatically simple words. Novel multivariate analyses revealed that they engage a coalition of separable subsystems: inflected forms triggered left-lateralized activation, dissociable into dorsal processes supporting morphophonological parsing and ventral, lexically driven morphosyntactic processes. In contrast, simple phrases activated a consistently bilateral pattern of temporal regions, overlapping with inflectional activations in L middle temporal gyrus. These data confirm the role of the left-lateralized frontotemporal network in supporting complex grammatical computations. Critically, they also point to the capacity of bilateral temporal regions to support simple, linear grammatical computations. This is consistent with a dual neurobiological framework where phylogenetically older bihemispheric systems form part of the network that supports language function in the modern human, and where significant capacities for language comprehension remain intact even following severe left hemisphere damage.

Optimally efficient neural systems for processing spoken language.

Cognitive models claim that spoken words are recognized by an optimally efficient sequential analysis process. Evidence for this is the finding that nonwords are recognized as soon as they deviate from all real words (Marslen-Wilson 1984), reflecting continuous evaluation of speech inputs against lexical representations. Here, we investigate the brain mechanisms supporting this core aspect of word recognition and examine the processes of competition and selection among multiple word candidates. Based on new behavioral support for optimal efficiency in lexical access from speech, a functional magnetic resonance imaging study showed that words with later nonword points generated increased activation in the left superior and middle temporal gyrus (Brodmann area [BA] 21/22), implicating these regions in dynamic sound-meaning mapping. We investigated competition and selection by manipulating the number of initially activated word candidates (competition) and their later drop-out rate (selection). Increased lexical competition enhanced activity in bilateral ventral inferior frontal gyrus (BA 47/45), while increased lexical selection demands activated bilateral dorsal inferior frontal gyrus (BA 44/45). These findings indicate functional differentiation of the fronto-temporal systems for processing spoken language, with left middle temporal gyrus (MTG) and superior temporal gyrus (STG) involved in mapping sounds to meaning, bilateral ventral inferior frontal gyrus (IFG) engaged in less constrained early competition processing, and bilateral dorsal IFG engaged in later, more fine-grained selection processes.

Auditory artificial grammar learning in macaque and marmoset monkeys.

Artificial grammars (AG) are designed to emulate aspects of the structure of language, and AG learning (AGL) paradigms can be used to study the extent of nonhuman animals' structure-learning capabilities. However, different AG structures have been used with nonhuman animals and are difficult to compare across studies and species. We developed a simple quantitative parameter space, which we used to summarize previous nonhuman animal AGL results. This was used to highlight an under-studied AG with a forward-branching structure, designed to model certain aspects of the nondeterministic nature of word transitions in natural language and animal song. We tested whether two monkey species could learn aspects of this auditory AG. After habituating the monkeys to the AG, analysis of video recordings showed that common marmosets (New World monkeys) differentiated between well formed, correct testing sequences and those violating the AG structure based primarily on simple learning strategies. By comparison, Rhesus macaques (Old World monkeys) showed evidence for deeper levels of AGL. A novel eye-tracking approach confirmed this result in the macaques and demonstrated evidence for more complex AGL. This study provides evidence for a previously unknown level of AGL complexity in Old World monkeys that seems less evident in New World monkeys, which are more distant evolutionary relatives to humans. The findings allow for the development of both marmosets and macaques as neurobiological model systems to study different aspects of AGL at the neuronal level.

The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) study protocol: a cross-sectional, lifespan, multidisciplinary examination of healthy cognitive ageing.

BACKGROUND: As greater numbers of us are living longer, it is increasingly important to understand how we can age healthily. Although old age is often stereotyped as a time of declining mental abilities and inflexibility, cognitive neuroscience reveals that older adults use neural and cognitive resources flexibly, recruiting novel neural regions and cognitive processes when necessary. Our aim in this project is to understand how age-related changes to neural structure and function interact to support cognitive abilities across the lifespan. METHODS/DESIGN: We are recruiting a population-based cohort of 3000 adults aged 18 and over into Stage 1 of the project, where they complete an interview including health and lifestyle questions, a core cognitive assessment, and a self-completed questionnaire of lifetime experiences and physical activity. Of those interviewed, 700 participants aged 18-87 (100 per age decile) continue to Stage 2 where they undergo cognitive testing and provide measures of brain structure and function. Cognition is assessed across multiple domains including attention and executive control, language, memory, emotion, action control and learning. A subset of 280 adults return for in-depth neurocognitive assessment in Stage 3, using functional neuroimaging experiments across our key cognitive domains.Formal statistical models will be used to examine the changes that occur with healthy ageing, and to evaluate age-related reorganisation in terms of cognitive and neural functions invoked to compensate for overall age-related brain structural decline. Taken together the three stages provide deep phenotyping that will allow us to measure neural activity and flexibility during performance across a number of core cognitive functions. This approach offers hypothesis-driven insights into the relationship between brain and behaviour in healthy ageing that are relevant to the general population. DISCUSSION: Our study is a unique resource of neuroimaging and cognitive measures relevant to change across the adult lifespan. Because we focus on normal age-related changes, our results may contribute to changing views about the ageing process, lead to targeted interventions, and reveal how normal ageing relates to frail ageing in clinicopathological conditions such as Alzheimer's disease.

Functional organization of the neural language system: dorsal and ventral pathways are critical for syntax.

The core of human language, which differentiates it from the communicative abilities of other species, is the set of combinatorial operations called syntax. For over a century researchers have attempted to understand how this essential function is organized in the brain. Here, we combine behavioral and neuroimaging methods, with left hemisphere-damaged patients and healthy controls, to identify the pathways connecting the brain regions involved in syntactic processing. In a previous functional magnetic resonance imaging study (Tyler LK, Wright P, Randall B, Marslen-Wilson WD, Stamatakis EA. 2010b. Reorganization of syntactic processing following left-hemisphere brain damage: does right-hemisphere activity preserve function? Brain. 133(11):3396-3408.), we established that regions of left inferior frontal cortex and left posterior middle temporal cortex were activated during syntactic processing. These clusters were used here as seeds for probabilistic tractography analyses in patients and controls, allowing us to delineate, and measure the integrity of, the white matter tracts connecting the frontal and temporal regions active for syntax. We found that structural disconnection in either of 2 fiber bundles--the arcuate fasciculus or the extreme capsule fiber system--was associated with syntactic impairment in patients. The results demonstrate the causal role in syntactic analysis of these 2 major left hemisphere fiber bundles--challenging existing views about their role in language functions and providing a new basis for future research in this key area of human cognition.

Finding structure during incremental speech comprehension.

A core aspect of human speech comprehension is the ability to incrementally integrate consecutive words into a structured and coherent interpretation, aligning with the speaker's intended meaning. This rapid process is subject to multidimensional probabilistic constraints, including both linguistic knowledge and non-linguistic information within specific contexts, and it is their interpretative coherence that drives successful comprehension. To study the neural substrates of this process, we extract word-by-word measures of sentential structure from BERT, a deep language model, which effectively approximates the coherent outcomes of the dynamic interplay among various types of constraints. Using representational similarity analysis, we tested BERT parse depths and relevant corpus-based measures against the spatiotemporally resolved brain activity recorded by electro-/magnetoencephalography when participants were listening to the same sentences. Our results provide a detailed picture of the neurobiological processes involved in the incremental construction of structured interpretations. These findings show when and where coherent interpretations emerge through the evaluation and integration of multifaceted constraints in the brain, which engages bilateral brain regions extending beyond the classical fronto-temporal language system. Furthermore, this study provides empirical evidence supporting the use of artificial neural networks as computational models for revealing the neural dynamics underpinning complex cognitive processes in the brain.

Neurobiological systems for lexical representation and analysis in English.

Current research suggests that language comprehension engages two joint but functionally distinguishable neurobiological processes: a distributed bilateral system, which supports general perceptual and interpretative processes underpinning speech comprehension, and a left hemisphere (LH) frontotemporal system, selectively tuned to the processing of combinatorial grammatical sequences, such as regularly inflected verbs in English [Marslen-Wilson, W. D., & Tyler, L. K. Morphology, language and the brain: The decompositional substrate for language comprehension. Philosophical Transactions of the Royal Society: Biological Sciences, 362, 823-836, 2007]. Here we investigated how English derivationally complex words engage these systems, asking whether they selectively activate the LH system in the same way as inflections or whether they primarily engage the bilateral system that support nondecompositional access. In an fMRI study, we saw no evidence for selective activation of the LH frontotemporal system, even for highly transparent forms like bravely. Instead, a combination of univariate and multivariate analyses revealed the engagement of a distributed bilateral system, modulated by factors of perceptual complexity and semantic transparency. We discuss the implications for theories of the processing and representation of English derivational morphology and highlight the importance of neurobiological constraints in understanding these processes.

Bihemispheric foundations for human speech comprehension.

Emerging evidence from neuroimaging and neuropsychology suggests that human speech comprehension engages two types of neurocognitive processes: a distributed bilateral system underpinning general perceptual and cognitive processing, viewed as neurobiologically primary, and a more specialized left hemisphere system supporting key grammatical language functions, likely to be specific to humans. To test these hypotheses directly we covaried increases in the nonlinguistic complexity of spoken words [presence or absence of an embedded stem, e.g., claim (clay)] with variations in their linguistic complexity (presence of inflectional affixes, e.g., play+ed). Nonlinguistic complexity, generated by the on-line competition between the full word and its onset-embedded stem, was found to activate both right and left fronto-temporal brain regions, including bilateral BA45 and -47. Linguistic complexity activated left-lateralized inferior frontal areas only, primarily in BA45. This contrast reflects a differentiation between the functional roles of a bilateral system, which supports the basic mapping from sound to lexical meaning, and a language-specific left-lateralized system that supports core decompositional and combinatorial processes invoked by linguistically complex inputs. These differences can be related to the neurobiological foundations of human language and underline the importance of bihemispheric systems in supporting the dynamic processing and interpretation of spoken inputs.

Left inferior frontal cortex and syntax: function, structure and behaviour in patients with left hemisphere damage.

For the past 150 years, neurobiological models of language have debated the role of key brain regions in language function. One consistently debated set of issues concern the role of the left inferior frontal gyrus in syntactic processing. Here we combine measures of functional activity, grey matter integrity and performance in patients with left hemisphere damage and healthy participants to ask whether the left inferior frontal gyrus is essential for syntactic processing. In a functional neuroimaging study, participants listened to spoken sentences that either contained a syntactically ambiguous or matched unambiguous phrase. Behavioural data on three tests of syntactic processing were subsequently collected. In controls, syntactic processing co-activated left hemisphere Brodmann areas 45/47 and posterior middle temporal gyrus. Activity in a left parietal cluster was sensitive to working memory demands in both patients and controls. Exploiting the variability in lesion location and performance in the patients, voxel-based correlational analyses showed that tissue integrity and neural activity-primarily in left Brodmann area 45 and posterior middle temporal gyrus-were correlated with preserved syntactic performance, but unlike the controls, patients were insensitive to syntactic preferences, reflecting their syntactic deficit. These results argue for the essential contribution of the left inferior frontal gyrus in syntactic analysis and highlight the functional relationship between left Brodmann area 45 and the left posterior middle temporal gyrus, suggesting that when this relationship breaks down, through damage to either region or to the connections between them, syntactic processing is impaired. On this view, the left inferior frontal gyrus may not itself be specialized for syntactic processing, but plays an essential role in the neural network that carries out syntactic computations.

Dissociating linguistic and task-related activity in the left inferior frontal gyrus.

The left inferior frontal gyrus (LIFG) has long been claimed to play a key role in language function. However, there is considerable controversy as to whether regions within LIFG have specific linguistic or domain-general functions. Using fMRI, we contrasted linguistic and task-related effects by presenting simple and morphologically complex words while subjects performed a lexical decision (LD) task or passively listened (PL) without making an overt response. LIFG Brodmann's area 47 showed greater activation in LD than PL, whereas LIFG Brodmann's area 44 showed greater activation to complex compared with simple words in both tasks. These results dissociate task-driven and obligatory language processing in LIFG and suggest that PL is the paradigm of choice for probing the core aspects of the neural language system.

The interaction of lexical semantics and cohort competition in spoken word recognition: an fMRI study.

Spoken word recognition involves the activation of multiple word candidates on the basis of the initial speech input--the "cohort"--and selection among these competitors. Selection may be driven primarily by bottom-up acoustic-phonetic inputs or it may be modulated by other aspects of lexical representation, such as a word's meaning [Marslen-Wilson, W. D. Functional parallelism in spoken word-recognition. Cognition, 25, 71-102, 1987]. We examined these potential interactions in an fMRI study by presenting participants with words and pseudowords for lexical decision. In a factorial design, we manipulated (a) cohort competition (high/low competitive cohorts which vary the number of competing word candidates) and (b) the word's semantic properties (high/low imageability). A previous behavioral study [Tyler, L. K., Voice, J. K., & Moss, H. E. The interaction of meaning and sound in spoken word recognition. Psychonomic Bulletin & Review, 7, 320-326, 2000] showed that imageability facilitated word recognition but only for words in high competition cohorts. Here we found greater activity in the left inferior frontal gyrus (BA 45, 47) and the right inferior frontal gyrus (BA 47) with increased cohort competition, an imageability effect in the left posterior middle temporal gyrus/angular gyrus (BA 39), and a significant interaction between imageability and cohort competition in the left posterior superior temporal gyrus/middle temporal gyrus (BA 21, 22). In words with high competition cohorts, high imageability words generated stronger activity than low imageability words, indicating a facilitatory role of imageability in a highly competitive cohort context. For words in low competition cohorts, there was no effect of imageability. These results support the behavioral data in showing that selection processes do not rely solely on bottom-up acoustic-phonetic cues but rather that the semantic properties of candidate words facilitate discrimination between competitors.

Is left fronto-temporal connectivity essential for syntax? Effective connectivity, tractography and performance in left-hemisphere damaged patients.

Syntactic processing typically engages left inferior frontal gyrus and posterior middle temporal gyrus, and damage to these regions is associated with syntactic deficits. What has not been directly determined, however, is whether it is the effective connectivity between these regions - and therefore also the integrity of the white matter tracts that connect them - that underpins successful syntactic analysis. We addressed these related issues by obtaining measures of the psycho-physiological interaction between frontal and temporal regions and of the integrity of the major white matter tracts that directly connect them - the arcuate fasciculus and extreme capsule fibre system. We correlated these estimates with performance measures of syntax in a group of patients with left hemisphere damage and varying degrees of syntactic impairment. Good syntactic function was associated with enhanced effective connectivity and increased tract integrity, suggesting that intact connectivity between left frontal and temporal regions is essential for syntactic analysis rather than the activation of these regions per se.

Reorganization of syntactic processing following left-hemisphere brain damage: does right-hemisphere activity preserve function?

The extent to which the human brain shows evidence of functional plasticity across the lifespan has been addressed in the context of pathological brain changes and, more recently, of the changes that take place during healthy ageing. Here we examine the potential for plasticity by asking whether a strongly left-lateralized system can successfully reorganize to the right-hemisphere following left-hemisphere brain damage. To do this, we focus on syntax, a key linguistic function considered to be strongly left-lateralized, combining measures of tissue integrity, neural activation and behavioural performance. In a functional neuroimaging study participants heard spoken sentences that differentially loaded on syntactic and semantic information. While healthy controls activated a left-hemisphere network of correlated activity including Brodmann areas 45/47 and posterior middle temporal gyrus during syntactic processing, patients activated Brodmann areas 45/47 bilaterally and right middle temporal gyrus. However, voxel-based morphometry analyses showed that only tissue integrity in left Brodmann areas 45/47 was correlated with activity and performance; poor tissue integrity in left Brodmann area 45 was associated with reduced functional activity and increased syntactic deficits. Activity in the right-hemisphere was not correlated with damage in the left-hemisphere or with performance. Reduced neural integrity in the left-hemisphere through brain damage or healthy ageing results in increased right-hemisphere activation in homologous regions to those left-hemisphere regions typically involved in the young. However, these regions do not support the same linguistic functions as those in the left-hemisphere and only indirectly contribute to preserved syntactic capacity. This establishes the unique role of the left hemisphere in syntax, a core component in human language.