Age-related delay in visual and auditory evoked responses is mediated by white- and grey-matter differences.

Slowing is a common feature of ageing, yet a direct relationship between neural slowing and brain atrophy is yet to be established in healthy humans. We combine magnetoencephalographic (MEG) measures of neural processing speed with magnetic resonance imaging (MRI) measures of white and grey matter in a large population-derived cohort to investigate the relationship between age-related structural differences and visual evoked field (VEF) and auditory evoked field (AEF) delay across two different tasks. Here we use a novel technique to show that VEFs exhibit a constant delay, whereas AEFs exhibit delay that accumulates over time. White-matter (WM) microstructure in the optic radiation partially mediates visual delay, suggesting increased transmission time, whereas grey matter (GM) in auditory cortex partially mediates auditory delay, suggesting less efficient local processing. Our results demonstrate that age has dissociable effects on neural processing speed, and that these effects relate to different types of brain atrophy.

Age-related neural reorganization during spoken word recognition: the interaction of form and meaning.

Research on language and aging typically shows that language comprehension is preserved across the life span. Recent neuroimaging results suggest that this good performance is underpinned by age-related neural reorganization [e.g., Tyler, L. K., Shafto, M. A., Randall, B., Wright, P., Marslen-Wilson, W. D., & Stamatakis, E. A. Preserving syntactic processing across the adult life span: The modulation of the frontotemporal language system in the context of age-related atrophy. Cerebral Cortex, 20, 352-364, 2010]. The current study examines how age-related reorganization affects the balance between component linguistic processes by manipulating semantic and phonological factors during spoken word recognition in younger and older adults. Participants in an fMRI study performed an auditory lexical decision task where words varied in their phonological and semantic properties as measured by degree of phonological competition and imageability. Older adults had a preserved lexicality effect, but compared with younger people, their behavioral sensitivity to phonological competition was reduced, as was competition-related activity in left inferior frontal gyrus. This was accompanied by increases in behavioral sensitivity to imageability and imageability-related activity in left middle temporal gyrus. These results support previous findings that neural compensation underpins preserved comprehension in aging and demonstrate that neural reorganization can affect the balance between semantic and phonological processing.

Conceptual structure: Towards an integrated neuro-cognitive account.

How are the meanings of concepts represented and processed? We present a cognitive model of conceptual representations and processing - the Conceptual Structure Account (CSA; Tyler & Moss, 2001) - as an example of a distributed, feature-based approach. In a first section, we describe the CSA and evaluate relevant neuropsychological and experimental behavioral data. We discuss studies using linguistic and non-linguistic stimuli, which are both presumed to access the same conceptual system. We then take the CSA as a framework for hypothesising how conceptual knowledge is represented and processed in the brain. This neuro-cognitive approach attempts to integrate the distributed feature-based characteristics of the CSA with a distributed and feature-based model of sensory object processing. Based on a review of relevant functional imaging and neuropsychological data, we argue that distributed accounts of feature-based representations have considerable explanatory power, and that a cognitive model of conceptual representations is needed to understand their neural bases.

Word retrieval failures in old age: the relationship between structure and function.

A common complaint of normal aging is the increase in word-finding failures such as tip-of-the-tongue states (TOTs). Behavioral research identifies TOTs as phonological retrieval failures, and recent findings [Shafto, M. A., Burke, D. M., Stamatakis, E. A., Tam, P., & Tyler, L. K. On the tip-of-the-tongue: Neural correlates of increased word-finding failures in normal aging. Journal of Cognitive Neuroscience, 19, 2060-2070, 2007] link age-related increases in TOTs to atrophy in left insula, a region implicated in phonological production. Here, younger and older adults performed a picture naming task in the fMRI scanner. During successful naming, left insula activity was not affected by age or gray matter integrity. Age differences only emerged during TOTs, with younger but not older adults generating a "boost" of activity during TOTs compared to successful naming. Older adults also had less activity than younger adults during TOTs compared to "don't know" responses, and across all participants, less TOT activity was affiliated with lower gray matter density. For older adults, lower levels of activity during TOTs accompanied higher TOT rates, supporting the role of an age-related neural mechanism impacting older more than younger adults. Results support a neural account of word retrieval in old age wherein, despite widespread age-related atrophy, word production processes are not universally impacted by age. However, atrophy undermines older adults' ability to modulate neural responses needed to overcome retrieval failures.

Complementary hemispheric asymmetries in object naming and recognition: a voxel-based correlational study.

Cognitive neuroscientific research proposes complementary hemispheric asymmetries in naming and recognising visual objects, with a left temporal lobe advantage for object naming and a right temporal lobe advantage for object recognition. Specifically, it has been proposed that the left inferior temporal lobe plays a mediational role linking conceptual information with word forms and vice versa, while the right inferior temporal lobe supports the retrieval of conceptual knowledge from visual input. To test these hypotheses, we administered four behavioural tasks to fifteen patients with temporal lobe brain damage, and correlated their behavioural scores with voxel-based measures of neuronal integrity (signal intensities) in whole-brain analyses. The behavioural paradigms included four tasks. Two were verbal tasks: (a) picture naming requiring the mapping of conceptual knowledge to word forms, (b) semantic categorisation of words requiring the reverse mapping of word forms to conceptual knowledge, and two were visual object tasks with no verbal component, both of which required the retrieval of conceptual information from visual objects, i.e., (c) visual object categorisation and (d) normal and chimera object decisions. Performance on the verbal tasks correlated with the neural integrity of partially overlapping left inferior and anterior temporal lobe regions, while performance on the object tasks correlated with the neural integrity of overlapping regions in right inferior and anterior temporal lobe. These findings support the notion of complementary hemispheric advantages for object naming and recognition, and further suggest that the classical language model emphasising posterior regions in the mapping between word forms and conceptual knowledge should be extended to include left inferior temporal lobe.

Longitudinal studies of semantic dementia: the relationship between structural and functional changes over time.

The pattern of brain atrophy in semantic dementia and its associated cognitive effects have attracted a considerable body of research, but the nature of core impairments remains disputed. A key issue is whether the disease encompasses one neurocognitive network (semantics) or two (language and semantics). In order to address these conflicting perspectives, we conducted a longitudinal investigation of two semantic dementia patients, in which behavioural performance across a range of measures of language and semantic performance was assessed and interpreted in the context of annually acquired MRI scans. Our results indicated a core semantic impairment in early stages of the disease, associated with atrophy of the inferior, anterior temporal cortex. Linguistic impairments emerged later, and were contingent on atrophy having spread into areas widely believed to subserve core language processes (left posterior perisylvian, inferior frontal and insular cortex). We claim, therefore, that phonological, syntactic and morphological processing deficits in semantic dementia reflect damage to core language areas. Further, we propose that much of the current controversy over the nature of deficits in semantic dementia reflect a tendency in the literature to adopt a static perspective on what is a progressive disease. An approach in which the relationship between progressive neural changes and behavioural change over time is carefully mapped, offers a more constraining data-set from which to draw inferences about the relationship between language, semantics and the brain.

Cortical differentiation for nouns and verbs depends on grammatical markers.

Here we address the contentious issue of how nouns and verbs are represented in the brain. The co-occurrence of noun and verb deficits with damage to different neural regions has led to the view that they are differentially represented in the brain. Recent neuroimaging evidence and inconsistent lesion-behavior associations challenge this view. We have suggested that nouns and verbs are not differentially represented in the brain, but that different patterns of neural activity are triggered by the different linguistic functions carried by nouns and verbs. We test these claims in a functional magnetic resonance imaging study using homophones -- words which function grammatically as nouns or verbs but have the same form and meaning -- ensuring that any neural differences reflect differences in grammatical function. Words were presented as single stems and in phrases in which each homophone was preceded by an article to create a noun phrase (NP) or a pronoun to create a verb phrase (VP), thus establishing the word's functional linguistic role. Activity for single-word homophones was not modulated by their frequency of usage as a noun or verb. In contrast, homophones marked as verbs by appearing in VPs elicited greater activity in the left posterior middle temporal gyrus (LpMTG) compared to homophones marked as nouns by occurring in NPs. Neuropsychological patients with grammatical deficits had lesions which overlapped with the greater LpMTG activity found for VPs. These results suggest that nouns and verbs do not invariably activate different neural regions; rather, differential cortical activity depends on the extent to which their different grammatical functions are engaged.

Grammatical categories in the brain: the role of morphological structure.

The current study addresses the controversial issue of how different grammatical categories are neurally processed. Several lesion-deficit studies suggest that distinct neural substrates underlie the representation of nouns and verbs, with verb deficits associated with damage to left inferior frontal gyrus (LIFG) and noun deficits with damage to left temporal cortex. However, this view is not universally shared by neuropsychological and neuroimaging studies. We have suggested that these inconsistencies may reflect interactions between the morphological structure of nouns and verbs and the processing implications of this, rather than differences in their neural representations (Tyler et al. 2004). We tested this hypothesis using event-related functional magnetic resonance imaging, to scan subjects performing a valence judgment on unambiguous nouns and verbs, presented as stems ('snail, hear') and inflected forms ('snails, hears'). We predicted that activations for noun and verb stems would not differ, whereas inflected verbs would generate more activation in left frontotemporal areas than inflected nouns. Our findings supported this hypothesis, with greater activation of this network for inflected verbs compared with inflected nouns. These results support the claim that form class is not a first-order organizing principle underlying the representation of words but rather interacts with the processes that operate over lexical representations.

Repetition suppression and semantic enhancement: an investigation of the neural correlates of priming.

The priming of a stimulus by another has become an important tool for exploring the neural underpinnings of conceptual representations. However, priming effects can derive from many different types of relationships and it is important to distinguish between them in order to be able to develop theoretical accounts of the representation of conceptual knowledge. While it is well known that repetition priming (the repeated presentation of the same stimulus) is associated with a reduced neural response, called repetition suppression (RS), the neural correlates of semantic priming (when two stimuli are related in meaning but not identical) are not so well established. We compared the neural correlates of repetition and semantic priming using written words, independently manipulating form and meaning. In an fMRI study, subjects saw single words and made a concrete-abstract decision. Two consecutive words were identical (town-town) or varied along a continuum of semantic relatedness, from highly related (cord-string) to unrelated (face-sail). We found distinct patterns of activation for repetition and semantic priming. Repetition priming was associated with RS in LIFG, bilateral parahippocampal gyrus and R fusiform gyrus. We also observed increased activation for word repetition in the RMFG and RMTG/STG, which may reflect recognition of item's earlier presentation. There was no evidence of suppression for semantic relatedness. Semantic priming was associated with enhanced activation in multiple bilateral fronto-temporal areas, i.e. semantic enhancement. The results suggest that repetition and semantic priming in visual word recognition depend on distinct cognitive processes and neural substrates.

Getting to the meaning of the regular past tense: evidence from neuropsychology.

Neuropsychological impairments of English past tense processing inform a key debate in cognitive neuroscience concerning the nature of mental mechanisms. Dual-route accounts claim that regular past tense comprehension deficits reflect a specific impairment of morphological decomposition (e.g., jump + ed), disrupting the automatic comprehension of word meaning accessed via the verb stem (e.g., jump). Single-mechanism accounts claim that the deficits reflect a general phonological impairment that affects perception of regular past tense offsets but which might preserve normal activation of verb semantics. We tested four patients with regular past tense deficits and matched controls, using a paired auditory semantic priming/lexical decision task with three conditions: uninflected verbs (hope/wish), regular past tense primes (blamed/accuse), and irregular past tense primes (shook/tremble). Both groups showed significant priming for verbs with simple morphophonology (uninflected verbs and irregular past tenses) but the patients showed no priming for verbs with complex morphophonology (regular past tenses) in contrast to controls. The findings suggest that the patients are delayed in activating the meaning of verbs if a regular past tense affix is appended, consistent with a dual-route account of their deficit.

Cingulate control of fronto-temporal integration reflects linguistic demands: a three-way interaction in functional connectivity.

In a recent fMRI language comprehension study, we asked participants to listen to word-pairs and to make same/different judgments for regularly and irregularly inflected word forms [Tyler, L.K., Stamatakis, E.A., Post, B., Randall, B., Marslen-Wilson, W.D., in press. Temporal and frontal systems in speech comprehension: an fMRI study of past tense processing. Neuropsychologia, available online.]. We found that a fronto-temporal network, including the anterior cingulate cortex (ACC), left inferior frontal gyrus (LIFG), bilateral superior temporal gyrus (STG) and middle temporal gyrus (MTG), is preferentially activated for regularly inflected words. We report a complementary re-analysis of the data seeking to understand the behavior of this network in terms of inter-regional covariances, which are taken as an index of functional connectivity. We identified regions in which activity was predicted by ACC and LIFG activity, and critically, by the interaction between these two regions. Furthermore, we determined the extent to which these inter-regional correlations were influenced differentially by the experimental context (i.e. regularly or irregularly inflected words). We found that functional connectivity between LIFG and left MTG is positively modulated by activity in the ACC and that this effect is significantly greater for regulars than irregulars. These findings suggest a monitoring role for the ACC which, in the context of processing regular inflected words, is associated with greater engagement of an integrated fronto-temporal language system.

Differentiating lexical form, meaning, and structure in the neural language system.

A technique for studying the relationship between brain and language, which involves correlating scores on two continuous variables, signal intensity across the entire brains of brain-damaged patients and behavioral priming scores, was used to investigate a central issue in cognitive neuroscience: Are the components of the neural language system organized as a single undifferentiated process, or do they respond differentially to different types of linguistic structure? Differences in lexical structure, in the form of the regular and irregular past tense, have proven to be critical in this debate by contrasting a highly predictable rule-like process (e.g., jump-jumped) with an unpredictable idiosyncratic process typified by the irregulars (e.g., think-thought). The key issue raised by these contrasts is whether processing regular and irregular past tense forms differentially engages different aspects of the neural language system or whether they are processed within a single system that distinguishes between them purely on the basis of phonological and semantic differences. The correlational analyses provide clear evidence for a functional differentiation between different brain regions associated with the processing of lexical form, meaning, and morphological structure.

Semantic processing of living and nonliving concepts across the cerebral hemispheres.

Studies of patients with category-specific semantic deficits suggest that the right and left cerebral hemispheres may be differently involved in the processing of living and nonliving domains concepts. In this study, we investigate whether there are hemisphere differences in the semantic processing of these domains in healthy volunteers. Based on the neuropsychological findings, we predicted a disadvantage for nonliving compared to living concepts in the right hemisphere. Our prediction was supported, in that semantic decisions to nonliving concepts were significantly slower and more error-prone when presented to the right hemisphere. In contrast there were no hemisphere differences for living concepts. These findings are consistent with either differential representation or processing of concepts across right and left hemispheres. However, we also found a disadvantage for nonliving things compared to living things in the left hemisphere, which is not consistent with a simple representation account. We discuss these findings in terms of qualitatively different semantic processing in right and left hemispheres within the framework of a distributed model of conceptual representation.

Selecting among competing alternatives: selection and retrieval in the left inferior frontal gyrus.

It has been widely argued that the left inferior frontal gyrus (LIFG) is involved in the control of retrieval of information from long-term memory. Recent claims that the LIFG is involved in selecting among semantic alternatives have been challenged on the grounds that the manipulation of selection demands may have been confounded with controlled retrieval. The current study used an event-related functional magnetic resonance paradigm to re-examine the possibility that LIFG activation is involved in selection processes. In order to minimize potential confounding effects of controlled retrieval, we used an automatic retrieval task (picture naming) and held retrieval demands constant, while varying selection demands by way of competitor priming from earlier semantically related trials. We found significant activation in LIFG as a function of increased selection demands; activation centred on two peaks, one in anterior LIFG and a second more superior and posterior region. These data support the view that LIFG plays a role in selection among semantic information, even in the absence of controlled retrieval processes.

The basal ganglia and rule-governed language use: evidence from vascular and degenerative conditions.

The Declarative/Procedural Model of Pinker, Ullman and colleagues claims that the basal ganglia are part of a fronto-striatal procedural memory system which applies grammatical rules to combine morphemes (the smallest meaningful units in language) into complex words (e.g. talk-ed, talk-ing). We tested this claim by investigating whether striatal damage or loss of its dopaminergic innervation is reliably associated with selective regular past tense deficits in patients with subcortical cerebrovascular damage, Parkinson's disease or Huntington's disease. We focused on past tense morphology since this allows us to contrast the regular past tense (jump-jumped), which is rule-based, with the irregular past tense (sleep-slept), which is not. We used elicitation and priming tasks to test patients' ability to comprehend and produce inflected forms. We found no evidence of a consistent association between striatal dysfunction and selective impairment of regular past tense morphology, suggesting that the basal ganglia are not essential for processing the regular past tense as a sequence of morphemes, either in comprehension or production, in contrast to the claims of the Declarative/Procedural Model. All patient groups showed normal activation of semantic and morphological representations in comprehension, despite difficulties suppressing semantically appropriate alternatives when trying to inflect novel verbs. This is consistent with previous reports that striatal dysfunction spares automatic activation of linguistic information, but disrupts later language processes that require inhibition of competing alternatives.

Anteromedial temporal cortex supports fine-grained differentiation among objects.

Patients with damage to left anteromedial temporal cortex often show a striking deficit: they fail to recognize animals and other living things. This failure of recognition presents an important challenge to theories of the neural representation of conceptual knowledge. Here we propose that this lesion-behaviour association arises because polymodal neurons in anteromedial temporal cortex integrate simple features into complex feature conjunctions, providing the neural infrastructure for differentiating among objects.

Unitary vs multiple semantics: PET studies of word and picture processing.

In this paper we examine a central issue in cognitive neuroscience: are there separate conceptual representations associated with different input modalities (e.g., Paivio, 1971, 1986; Warrington & Shallice, 1984) or do inputs from different modalities converge on to the same set of representations (e.g., Caramazza, Hillis, Rapp, & Romani, 1990; Lambon Ralph, Graham, Patterson, & Hodges, 1999; Rapp, Hillis, & Caramazza, 1993)? We present an analysis of four PET studies (three semantic categorisation tasks and one lexical decision task), two of which employ words as stimuli and two of which employ pictures. Using conjunction analyses, we found robust semantic activation, common to both input modalities in anterior and medial aspects of the left fusiform gyrus, left parahippocampal and perirhinal cortices, and left inferior frontal gyrus (BA 47). There were modality-specific activations in both temporal poles (words) and occipitotemporal cortices (pictures). We propose that the temporal poles are involved in processing both words and pictures, but their engagement might be primarily determined by the level of specificity at which an object is processed. Activation in posterior temporal regions associated with picture processing most likely reflects intermediate, pre-semantic stages of visual processing. Our data are most consistent with a hierarchically structured, unitary system of semantic representations for both verbal and visual modalities, subserved by anterior regions of the inferior temporal cortex.

Processing objects at different levels of specificity.

How objects are represented and processed in the brain is a central topic in cognitive neuroscience. Previous studies have shown that knowledge of objects is represented in a feature-based distributed neural system primarily involving occipital and temporal cortical regions. Research with nonhuman primates suggest that these features are structured in a hierarchical system with posterior neurons in the inferior temporal cortex representing simple features and anterior neurons in the perirhinal cortex representing complex conjunctions of features (Bussey & Saksida, 2002; Murray & Bussey, 1999). On this account, the perirhinal cortex plays a crucial role in object identification by integrating information from different sensory systems into more complex polymodal feature conjunctions. We tested the implications of these claims for human object processing in an event-related fMRI study in which we presented colored pictures of common objects for 19 subjects to name at two levels of specificity - basic and domain. We reasoned that domain-level naming requires access to a coarser-grained representation of objects, thus involving only posterior regions of the inferior temporal cortex. In contrast, basic-level naming requires finer-grained discrimination to differentiate between similar objects, and thus should involve anterior temporal regions, including the perirhinal cortex. We found that object processing always activated the fusiform gyrus bilaterally, irrespective of the task, whereas the perirhinal cortex was only activated when the task required finer-grained discriminations. These results suggest that the same kind of hierarchical structure, which has been proposed for object processing in the monkey temporal cortex, functions in the human.

Neural processing of nouns and verbs: the role of inflectional morphology.

Dissociations of nouns and verbs following brain damage have been interpreted as evidence for distinct neural substrates underlying different aspects of the language system. Some neuroimaging studies have supported this claim by finding neural differentiation for nouns and verbs [Brain 122 (1999) 2337] while others have argued against neural specialisation [Brain 119 (1996) 159; Brain 124 (2001) 1619]. We suggest that one reason why these inconsistencies may have arisen is because the morphological structure of nouns and verbs has been ignored. In an event-related functional magnetic resonance imaging (fMRI) study we test the hypothesis that the neural processing of nouns and verbs differs when they are inflected. We contrasted the processing of regularly inflected nouns (dogs) with regularly inflected verbs (hitting), and found that the LIFG was more strongly activated in processing regularly inflected verbs compared to regularly inflected nouns. Moreover, regions of LIFG that were more active in the fMRI study for inflected verbs partially overlapped with the lesions in patients who have particular problems with verb morphology. Taken together with previous studies, these results suggest that noun and verb stems do not differ in terms of their representation, but when verbs are morphologically complex they differentially engage those neural systems which are involved in processes of morpho-phonology and syntax.

Objects and their actions: evidence for a neurally distributed semantic system.

An influential model of conceptual knowledge claims that objects are represented in a distributed network of cortical areas that store information about different types of attributes, such as form, colour, and motion (A. Martin et al., 2000, in: The Cognitive Neurosciences, 2nd ed., MIT Press, Cambridge). Two specific claims of this account are that (a) the motions and actions associated with objects (along with other attributes) are automatically activated whenever the object concept is evoked and (b) topographically distinct neural regions are responsible for motion/action attributes pertaining to objects in the categories of tools and animals. We used fMRI to examine the neural activation associated with conceptual processing of nouns referring to animals and tools and for verbs referring to tool-associated actions (e.g., drilling, painting) and biological actions (e.g., walking, jumping). We found that object names and their associated actions activated the same set of neural regions (left fusiform gyrus, superior and middle temporal cortex) consistent with the claim that word tool and animal concepts implicitly activate the actions associated with them. However, there was no evidence of category specificity for either objects or actions, with essentially the same activations for the form and motion attributes of both living and nonliving categories.