Emmanuel A. Stamatakis

Modulation of motor and premotor cortices by actions, action words and action sentences.

Recent research has indicated that processing different kinds of action verbs, such as those related to arm or leg movements (e.g. grab, kick), engages regions along the motor strip responsible for the execution of the corresponding actions. It has been proposed that this activation reflects action-related meaning and that these regions are automatically triggered whenever action words are encountered. However, this view is not universally shared by cognitive studies that have shown that the representation of verbs is highly dependent on the interactions with the semantic context. We investigated these views in a set of fMRI studies, in which participants performed a movement localiser task and listened to arm- and leg-related verbs that were presented in isolation (e.g. kick), in literal sentences (as in kick the ball) and idiomatic sentences (as in kick the bucket). We found significant activation in motor regions when action verbs were presented in isolation, and, to a lesser extent, in literal sentential contexts. When the same verbs were presented in idiomatic contexts, activation was found in fronto-temporal regions, associated with language processing, but not in motor and premotor cortices. These results suggest that motor responses were context-dependent, rather than automatic and invariable. These findings lend support to cognitive theories of semantic flexibility, by showing that the nature of the semantic context determines the degree to which alternative senses and particularly relevant features are processed when a word is heard.

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 featurebased 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 coarsergrained 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.

Preserving Syntactic Processing across the Adult Life Span: The Modulation of the Frontotemporal Language System in the Context of Age-Related Atrophy

Although widespread neural atrophy is an inevitable consequence of normal aging, not all cognitive abilities decline as we age. For example, spoken language comprehension tends to be preserved, despite atrophy in neural regions involved in language function. Here, we combined measures of behavior, functional activation, and gray matter (GM) change in a younger (19–34 years) and older group (49–86 years) of participants to identify the mechanisms leading to preserved language comprehension across the adult life span. We focussed primarily on syntactic functions because these are strongly left lateralized, providing the potential for contralateral recruitment. In an functional magnetic resonance imaging study, we used a word-monitoring task to minimize working memory demands, manipulating the availability of semantics and syntax to ask whether syntax is preserved in aging because of the functional recruitment of other brain regions, which successfully compensate for neural atrophy. Performance in the older group was preserved despite GM loss. This preservation was related to increased activity in right hemisphere frontotemporal regions, which was associated with age-related atrophy in the left hemisphere frontotemporal network activated in the young. We argue that preserved syntactic processing across the life span is due to the shift from a primarily left hemisphere frontotemporal system to a bilateral functional language network.

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.

Trait impulsivity and prefrontal gray matter reductions in cocaine dependent individuals.

BACKGROUNDnImpulsivity is thought to play a key role in cocaine addiction onset and progression; therefore, we hypothesized that different facets of impulsive personality may be significantly associated with brain structural abnormalities in cocaine-dependent individuals.nnnMETHODSnThirty-eight cocaine-dependent individuals and 38 non-drug using controls completed the UPPS-P scale (measuring five different facets of impulsivity: sensation seeking, lack of premeditation, lack of perseverance, and positive and negative urgency) and were scanned on a 3T MRI scanner. We used whole-brain voxel-based morphometry analyses (VBM) to detect differences in gray matter (GM) and white matter (WM) volumes between cocaine users and controls, and to measure differences in the way that impulsivity relates to GM and WM volumes in cocaine users vs. controls.nnnRESULTSnCocaine-dependent individuals had lower GM volumes in a number of sections of the orbitofrontal cortex, right inferior frontal gyrus, right insula, left amygdala and parahippocampal gyrus, temporal gyrus, and bilateral caudate. They also had lower WM volumes in the left inferior and medial frontal gyrus, superior temporal gyrus, right anterior cingulate cortex, insula and caudate. There was a positive correlation between trait impulsivity and GM volume in the left inferior/middle frontal gyrus of cocaine-dependent individuals, a pattern directly opposed to the association in controls. Conversely, in cocaine users lack of premeditation was negatively correlated with GM volume in the insula and the putamen.nnnCONCLUSIONSnTrait impulsivity may influence cocaine dependence by impacting its neurobiological underpinnings in frontostriatal systems.

Changes in Resting Neural Connectivity during Propofol Sedation

Background The default mode network consists of a set of functionally connected brain regions (posterior cingulate, medial prefrontal cortex and bilateral parietal cortex) maximally active in functional imaging studies under “no task” conditions. It has been argued that the posterior cingulate is important in consciousness/awareness, but previous investigations of resting interactions between the posterior cingulate cortex and other brain regions during sedation and anesthesia have produced inconsistent results. Methodology/Principal Findings We examined the connectivity of the posterior cingulate at different levels of consciousness. “No task” fMRI (BOLD) data were collected from healthy volunteers while awake and at low and moderate levels of sedation, induced by the anesthetic agent propofol. Our data show that connectivity of the posterior cingulate changes during sedation to include areas that are not traditionally considered to be part of the default mode network, such as the motor/somatosensory cortices, the anterior thalamic nuclei, and the reticular activating system. Conclusions/Significance This neuroanatomical signature resembles that of non-REM sleep, and may be evidence for a system that reduces its discriminable states and switches into more stereotypic patterns of firing under sedation.

On the tip-of-the-tongue: Neural correlates of increased word-finding failures in normal aging

Tip-of-the-tongue (TOT) experiences are frustrating word-finding failures where people are temporarily unable to produce a word they are certain they know. TOT frequency increases with normal aging during adulthood, and behavioral evidence suggests that the underlying deficit is in retrieving the complete phonology of the target word during production. The present study investigated the neural correlates of this phonological retrieval deficit. We obtained 3-D T1-weighted structural magnetic resonance images (MRI) for healthy participants between 19 and 88 years old and used voxel-based morphometry to measure gray matter density throughout the brain. In a separate session, participants named celebrities cued by pictures and descriptions, indicating when they had a TOT, and also completed Ravens Progressive Matrices (RPM), a task that does not involve phonological production. The number of TOTs increased with age and also with gray matter atrophy in the left insula, an area implicated in phonological production. The relation between TOTs and left insula atrophy cannot be attributed to the correlation of each variable with age because TOTs were related to insula atrophy even with age effects removed. Moreover, errors on the RPM increased with age, but performance did not correlate with gray matter density in the insula. These results provide, for the first time, an association between a region in the neural language system and the rise in age-related word-finding failures and suggest that age-related atrophy in neural regions important for phonological production may contribute to age-related word production failures.

Dynamic Processing in the Human Language System: Synergy between the Arcuate Fascicle and Extreme Capsule

The production and comprehension of human language is thought to involve a network of frontal, parietal, and temporal cortical loci interconnected by two dominant white matter pathways. These two white matter bundles, often referred to as the dorsal and ventral processing tracts, are hypothesized to have markedly different language functions. The dorsal tract is thought to process phonological processing, while the ventral tract is considered to abet semantics. This proposed functional differentiation of tracts is similar to the ventral and dorsal dichotomy proposed for the visual and auditory systems. The present study evaluated this characterization of the language system in the context of various components involved in its function. Twenty-four chronic stroke patients completed a battery of 10 language tests designed to measure performance on the comprehension and production of phonology, morphology, semantics, and syntax. The patients also completed diffusion MRI scanning. Lesions were confined to the left hemisphere, but the size and location of the insult varied so that patients had damage to a single tract, both tracts, or neither tract. Individual FA maps were generated, and focal areas of hypointensity served as markers of white matter damage. Whole-brain voxel-by-voxel correlations revealed that only phonological and semantic tasks fit into the dual-stream model, while syntax and morphology involved both pathways. ROI analyses of the arcuate fascicle and extreme capsule supported this finding. These data suggest that natural language function is more likely to reflect a synergistic system rather than a segregated dual-stream system.

Default Mode Dynamics for Global Functional Integration

The default mode network (DMN) has been traditionally assumed to hinder behavioral performance in externally focused, goal-directed paradigms and to provide no active contribution to human cognition. However, recent evidence suggests greater DMN activity in an array of tasks, especially those that involve self-referential and memory-based processing. Although data that robustly demonstrate a comprehensive functional role for DMN remains relatively scarce, the global workspace framework, which implicates the DMN in global information integration for conscious processing, can potentially provide an explanation for the broad range of higher-order paradigms that report DMN involvement. We used graph theoretical measures to assess the contribution of the DMN to global functional connectivity dynamics in 22 healthy volunteers during an fMRI-based n-back working-memory paradigm with parametric increases in difficulty. Our predominant finding is that brain modularity decreases with greater task demands, thus adapting a more global workspace configuration, in direct relation to increases in reaction times to correct responses. Flexible default mode regions dynamically switch community memberships and display significant changes in their nodal participation coefficient and strength, which may reflect the observed whole-brain changes in functional connectivity architecture. These findings have important implications for our understanding of healthy brain function, as they suggest a central role for the DMN in higher cognitive processing. SIGNIFICANCE STATEMENT The default mode network (DMN) has been shown to increase its activity during the absence of external stimulation, and hence was historically assumed to disengage during goal-directed tasks. Recent evidence, however, implicates the DMN in self-referential and memory-based processing. We provide robust evidence for this networks active contribution to working memory by revealing dynamic reconfiguration in its interactions with other networks and offer an explanation within the global workspace theoretical framework. These promising findings may help redefine our understanding of the exact DMN role in human cognition.